Recent advance in diabetes mellitus ppt BIOCHEMISTRY
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Recent advance in diabetes mellitus ppt BIOCHEMISTRY

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  • SmartArtcustom animation effects: vertical bullet list(Basic)To reproduce the SmartArt effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then clickBlank. On the Insert tab, in the Illustrations group, click SmartArt. In the Choose a SmartArt Graphic dialog box, in the left pane, click List. In the List pane, click Vertical Bullet List (first row, third option from the left), and then click OK to insert the graphic into the slide.To create another row, select the bottom, first-level (color-filled) rectangle, and then under SmartArtTools, on the Design tab, in the CreateGraphic group, click the arrow next to AddShape, and select AddShapeAfter.To add bullet text area, select the new first-level (color-filled) rectangle, and then under SmartArtTools, on the Design tab, in the CreateGraphic group, click AddBullet.To enter text, select the graphic, and then click one of the arrows on the left border. In the Type your text here dialog box, enter text for each level. (Note: In the example slide, the first-level text is “Topic One,” “Topic Two,” and “Topic Three.” The second-level text is “Supporting Text.”)Select the border of the SmartArt graphic. Drag the left center sizing handle to the left edge of the slide to resize the width of the SmartArt graphic.To reproduce the rectangle effects on this slide, do the following:Press and hold CTRL, and select the three color-filled rectangles (in the example above, these are the “Topic One,” “Topic Two,” and “Topic Three” rectangles).Under SmartArtTools, on the Format tab, in the Shapes group, click ChangeShape, and under Rectangles select RoundDiagonalCornerRectangle (ninth option from the left).Under SmartArtTools, on the Format tab, in the ShapeStyles group, click ShapeEffects, point to Presets and select Preset 7 (second row, third option from the left). On the Home tab, in the Font group do the following:In the Font list, select FranklinGothicDemiCond.In the FontSize box, enter 32 pt.Click Shadow.On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click TextBox in the left pane, and in the TextBox pane, under Internalmargin, in the Left box enter 3”. Select the first color-filled rectangle from the top (in the example slide, “Topic One”).On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Right(first row, fourth option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Olive Green, Accent 3 (first row, seventh option from the left). In the Transparency box, enter 90%Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Olive Green, Accent 3 (first row, seventh option from the left). In the Transparency box, enter 0%.Select the second color-filled rectangle from the top (in the example above, “Topic Two”).On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Right(first row, fourth option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Blue, Accent 1 (first row, the fifth option from the left). In the Transparency box, enter 90%Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Blue, Accent 1 (first row, the fifth option from the left). In the Transparency box, enter 0%.Select the third color-filled rectangle from the top (in the example slide, “Topic Three”).On the Home tab, in the bottom right corner of the Drawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Right(first row, fourth option from the left). Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under ThemeColors select Orange, Accent 6 (first row, 10th option from the left). In the Transparency box, enter 90%Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Orange, Accent 6 (first row, 10th option from the left). In the Transparency box, enter 0%.To reproduce the bulleted text on this slide, do the following:Press and hold CTRL, and select the three second-level, bulleted text boxes. On the Home tab, in the Font group, do the following:In the Font list, select FranklinGothicMediumCond.In the FontSize box, enter 22 pt.In the FontColor list, select White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the bottom right corner of theDrawing group, click the FormatShape dialog box launcher. In the FormatShape dialog box, select TextBox in the left pane, and in the TextBox pane do the following:Under Textlayout, in the Verticalalignment list select Middle.Under Internalmargin, do the following: In the Left box, enter 3.8”.In the Top box, enter 0.2”.In the Right box, enter 0.17”.In the Bottom box, enter 0.2”. Increase the height of the SmartArt graphic by dragging the top or bottom sizing handle. To reproduce the animation effects on this slide, do the following:On the Animations tab, in the Animations group, click CustomAnimation.Select the SmartArt graphic on the slide, and then in the CustomAnimation task pane, do the following:Click AddEffect, point to Entrance, and select MoreEffects. In the AddEntranceEffect dialog box, under Moderate,select Ascend.Click the arrow to the right of the ascend entrance effect, and then select EffectOptions. In the Ascend dialog box, do the following:On the Timing tab, in the Speed list, select 1 seconds (Fast).On the SmartArtAnimation tab, in the Groupgraphic list, select Onebyone. Click the double arrow below the animation effect to expand the list of effects.Press and hold CTRL, and select all the effects in the CustomAnimation task pane. Then under Modify: Ascend, in the Start list, select AfterPrevious.Press and hold CTRL, and select the second, fourth, and sixth effects (ascend entrance effects) in the CustomAnimation task pane. Click Change, point to Entrance, and then select MoreEffects. In the ChangeEntranceEffect dialog box, under Moderate, select EaseIn.To reproduce the background effects on this slide, do the following:Right-clickthe slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Left (first row, fifth option from the left). Under Gradient stops, click Add or Remove until three stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 60%.Click the button next to Color, and then under ThemeColors select White, Background 1 (first row, first option from the left). Select Stop 2 from the list, and then do the following: In the Stop position box, enter 90%.Click the button next to Color, and then under ThemeColors select White, Background 1, Darker 25% (fourth row, first option from the left). Select Stop 3 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under ThemeColors select Black, Text 1, Lighter 50% (second row, second option from the left).
  • SmartArt custom animation effects: upward arrow process(Basic)To reproduce the SmartArt effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then clickBlank. On the Insert tab, in the Illustrations group, click SmartArt. In the Choose a SmartArt Graphic dialog box, in the left pane, click Process. In the Process pane, click Upward Arrow (sixth row, third option from the left), and then click OK to insert the graphic into the slide.Select the graphic, and then click one of the arrows on the left border. In the Type your text here dialog box, enter text. (Note: To create a bulleted list below each heading, select the heading text box in the Type your text here dialog box, and then under SmartArtTools, on the Design tab, in the CreateGraphic group, click AddBullet. Enter text into the new bullet text box.)On the slide, select the graphic. Under SmartArtTools, on the Design tab, in the SmartArtStyles group, do the following:Click ChangeColors, and then under Colorful click Colorful Range - Accent Colors 3 to 4 (third option from the left).Click More, and then under Best Match for Document click Intense Effect (fifth option from the left).On the Home tab, in the Font group, select Calibri from the Font list, and then select 24 from the Font Size list.Select the text in the first text box from the left. Under SmartArtTools, on the Format tab, in the WordArtStyles group, click the arrow next to TextFill, and then under Theme Colors clickOliveGreen, Accent 3, Darker 25% (fifth row, seventh option from the left).Select the text in the second text box from the left. Under SmartArtTools, on the Format tab, in the WordArtStyles group, click the arrow next to TextFill, and then under Theme Colors clickAqua, Accent 5, Darker 25% (fifth row, ninth option from the left).Select the text in the third text box from the left. Under SmartArtTools, on the Format tab, in the WordArtStyles group, click the arrow next to TextFill, and then under Theme Colors clickPurple, Accent 4, Darker 25% (fifth row, eighth option from the left).To reproduce the animation effects on this slide, do the following:On the Animations tab, in the Animations group, click CustomAnimation.On the slide, select the graphic. In the CustomAnimation task pane, do the following:Click Add Effect, point to Entrance, and then click MoreEffects. In the Add Entrance Effect dialog box, under Basic, click Wipe. Under Modify: Wipe, in the Direction list, select From Left.Under Modify: Wipe, in the Speed list, select Fast.Also in the Custom Animation task pane, select the wipe effect. Click the arrow to the right of the wipe effect, and then click Effect Options. In the Wipe dialog box, on the SmartArt Animation tab, in the Group graphic list, select One by one.Also in the Custom Animation task pane, click the double arrow under the wipe effect to expand the contents of the list of effects.Also in the Custom Animation task pane, select the second wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects. In the Change Entrance Effect dialog box, under Exciting, click Curve Up.Under Modify: Curve Up,in the Start list, select With Previous. Under Modify: Curve Up,in the Speed list, select Very Fast.Also in the Custom Animation taskpane, select the third wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects.In the Change Entrance Effect dialog box, under Moderate, click Descend.Under Modify: Descend,in the Start list, select With Previous. Under Modify: Descend,in the Speed list, select Very Fast.Click the arrow to the right of the third wipe effect, and then click Timing. In the Descend dialog box, on the Timing tab, in the Delay box, enter 0.5.Also in the Custom Animation task pane, select the fourth wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects.In the Change Entrance Effect dialog box, under Exciting, click Curve Up.Under Modify: Curve Up,in the Start list, select On Click. Under Modify: Curve Up,in the Speed list, select Very Fast.Also in the Custom Animation taskpane, select the fifth wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects.In the Change Entrance Effect dialog box, under Moderate, click Descend.Under Modify: Descend,in the Start list, select After Previous. Under Modify: Descend,in the Speed list, select Very Fast.Also in the Custom Animation task pane, select the sixth wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects.In the Change Entrance Effect dialog box, under Exciting, click Curve Up.Under Modify: Curve Up,in the Start list, select On Click. Under Modify: Curve Up,in the Speed list, select Very Fast.Also in the Custom Animation task pane, select the seventh wipe effect and then do the following:Click Change, point to Entrance, and then click More Effects.In the Change Entrance Effect dialog box, under Moderate, click Descend.Under Modify: Descend,in the Start list, select After Previous. Under Modify: Descend,in the Speed list, select Very Fast.To reproduce the background effects on this slide, do the following:Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Linear.In the Direction list, click Linear Right (first row, fourth option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 39%.Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click Olive Green, Accent 3, Lighter 60%(third row, seventh option from the left).To increase the size of the SmartArt graphic so that it spans the entire slide, do the following:On the slide, select the graphic. Point to the top right corner of the graphic border, until a two-headed arrow appears. Drag the top right corner of the graphic border into the top right corner of the slide. Point to the bottom left corner of the graphic border, until a two-headed arrow appears. Drag the bottom left corner of the graphic border into the bottom left corner of the slide.
  • Custom animation effects: object spins on end(Advanced)To reproduce the background effects on this slide, do the following:On the Home tab, in theSlides group, click Layout, and then click Blank.Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, and then select Solid fill in the Fill pane. Click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left).To reproduce the rectangle on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Rectangles click Rounded Rectangle (second option from the left). On the slide, drag to draw a rounded rectangle.Select the rectangle. Drag the yellow diamond adjustment handle to the left to decrease the amount of rounding on the corners. With the rounded rectangle still selected, under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 3.5”.In the Shape Width box, enter 0.25”.Under Drawing Tools, on the Format tab, in the bottom right corner of the Shape Styles group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane. In the Fill pane, select Solid fill, click the button next to Color, and then under Theme Colors click White, Background 1, Darker 15% (third row, first option from the left).Also in the Format Shape dialog box, click Line Color in the left pane. In the Line Color pane, select No line. Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer select Offset Bottom (first row, second option from the left), and then do the following:In the Transparency box, enter 0%.In the Sizebox, enter 100%.In the Blur box, enter 8.5 pt.In the Angle box, enter 90°.In the Distance box, enter 1 pt.Also in the Format Shape dialog box, click 3-D Format in the left pane. In the 3-D Format pane, do the following:Under Bevel, click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 5 pt, and in the Height box, enter 5 pt.Under Surface, click the button next to Material, and then under Standard clickMatte (first row, first option from the left).Click the button next to Lighting, and then under Neutral click Soft (first row, third option from the left).On the slide, select the rounded rectangle. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate.Select the duplicate rectangle. On the Home tab, in the Drawing group, do the following:Click the arrow next to Shape Fill, and then click No Fill.Click the arrow next to Shape Outline, and then click No Outline.Drag the second rectangle above the first rectangle until the lower edge overlays the top edge of the first rectangle. (Note: When the spinning animation effect is created later for these rectangles, the spin will center where the edges of the rectangles meet.)Press and hold CTRL, and then select both rectangles. On the Home tab, in the Drawing group, click Arrange, and do the following:Point to Align, and then click Align Selected Objects.Point to Align, and then click Align Center.Click Group. On the slide, drag the group until it is centered horizontally on the left edge of the slide (straddling the edge).On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click Align Middle.To reproduce the dashed arc on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Basic Shapes click Arc (third row, 12th option from the left). On the slide, drag to draw an arc.Select the arc. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 7.5”.In the Shape Width box, enter 7.5”.With the arc still selected, on the Home tab, in the Drawing group, click the arrow next to Shape Outline,and then do the following:Under Theme Colors, click White, Background 1, Darker 15% (third row, first option from the left).Point to Dashes, and then click Dash (fourth option from the top).On the slide, drag the yellow diamond adjustment handle on the right side of the arc to the bottom of the arc to create a half circle.Drag the arc until the yellow diamond adjustment handles are on the left edge of the slide.With the arc still selected, on the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide. Click Align Middle. To reproduce the half circle on this slide, do the following:On the slide, select the arc. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate.Select the duplicate arc. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 3.33”.In the Shape Width box, enter 3.33”.With the second arc still selected, under Drawing Tools, on the Format tab, in the Shape Styles group, click the arrow next to Shape Fill, and then under Theme Colors click White, Background 1, Darker 5% (second row, first option from the left).Under Drawing Tools, on the Format tab, in the Shape Styles group, click the arrow next to Shape Outline,and then click No Outline.Under Drawing Tools, on the Format tab, in the Shape Styles group, click Shape Effects, point to Shadow, and then click ShadowOptions. In the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Inner click Inside Right (second row, third option from the left), and then do the following:In the Transparency box, enter 86%.In the Blur box, enter 24 pt.In the Angle box, enter 315°.In the Distance box, enter 4 pt.On the slide, drag the second arc until the yellow diamond adjustment handles are on the left edge of the slide. On the Home tab, in the Drawing group, click Arrange, and then do the following:Point to Align, and then click Align to Slide. Point to Align, and then click Align Middle. Click Send to Back.To reproduce the button shapes on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Basic Shapes click Oval (first row, second option from the left). On the slide, drag to draw an oval.Select the oval. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.34”.In the Shape Width box, enter 0.34”.Under Drawing Tools, on the Format tab, in the Shape Styles group, click More, and then click Light 1 Outline, Colored Fill – Dark 1 (third row, first option from the left).Under Drawing Tools, on the Format tab, in the bottom right corner of the Shape Styles group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane. In the Fill pane, select Solid Fill. Click the button next to Color, and then under Theme Colors click Olive Green, Accent 3, Lighter 80°(second row, seventh option from the left).Also in the Format Shape dialog box, click Line Color in the left pane. In the Line Color pane, select No line. Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click Offset Bottom (first row, second option from the left), and then do the following:In the Transparency box, enter 0%.In the Size box, enter 100%.In the Blur box, enter 8.5 pt.In the Angle box, enter 90°.In the Distance box, enter 1 pt.Also in the Format Shape dialog box, click 3-D Format in the left pane, and then do the following in the 3-D Format pane:Under Bevel, click the button next to Top, and then under Bevel click Art Deco (third row, fourth option from the left). Next to Top, in the Width box, enter 5 pt, and in the Height box, enter 5 pt.UnderContour, click the button next to Color, and then under Theme Colors click White, Background 1 (first row, first option from the left). In the Size box, enter 3.5 pt.Under Surface, click the button next to Material, and then under Standard click Matte (first row, first option from the left). Click the button next to Lighting, and then under Neutral click Soft (first row, third option from the left).On the slide, select the oval. Under Drawing Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. In the Size and Position dialog box, on the Position tab, do the following:In the Horizontal box, enter 2.98”.In the Vertical box, enter 1.5”.Select the oval. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate.Select the duplicate oval. Under Drawing Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. In the Size and Position dialog box, on the Position tab, do the following:In the Horizontal box, enter 3.52”.In the Vertical box, enter 2.98”. Repeat step 9 two more times, for a total of four ovals. Under Drawing Tools, on the Format tab, in the bottom right corner of the Size group, click the Size and Position dialog box launcher. In the Size and Position dialog box, on the Position tab, do the following to position the third and fourth ovals:Select the third oval on the slide, and then enter 3.52” in theHorizontal box and 4.27” in the Vertical box.Select the fourth oval on the slide, and then enter 2.99” in theHorizontal box and 5.66” in the Vertical box.To reproduce the text on this slide, do the following:On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box. Enter text in the text box and select the text. On the Home tab, in the Font group, do the following: In the Font list, select Corbel.In the Font Size list, select 22.Click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Align Text Left to align the text left in the text box.On the slide, drag the text box to the right of the first oval.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Click in the text box and edit the text. Drag the second text box to the right of the second oval.Repeat steps 5-7 to create the third and fourth text boxes, dragging them to the right of the third and fourth ovals. To reproduce the animation effects on this slide, do the following:On the Animations tab, in the Animations group, click Custom Animation.On the Home tab, in the Editing group, click Select, and then click Selection Pane. In the Selection and Visibility pane, select the rectangle group. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Spin. Select the animation effect (spin effect for the rectangle group). Under Modify: Spin, do the following:In theStart list, selectWith Previous. In the Amount list, in the Custom box, enter 123°,and then press ENTER. Also in the Amount list, clickCounterclockwise.In the Speedlist, select Fast. On the slide, select the first oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Change Fill Color. Select the second animation effect (change fill color effect for the first oval). Under Modify: Change Fill Color, do the following:In the Startlist, select After Previous. In the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red: 130, Green: 153, Blue: 117. In the Speedlist, select Very Fast.On the slide, select the first text box. In the CustomAnimation task pane, do the following:Click Add Effect, point to Entrance,and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade. Select the third animation effect (fade effect for the first text box). Under Modify: Fade, do the following:In theStart list, selectWith Previous.In the Speed list, select Very Fast. In the Selection and Visibility pane, select the rectangle group. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Spin. Select the fourth animation effect (spin effect for the rectangle group). Under Modify: Spin, do the following:In theStart list, selectOn Click. In the Amount list, in the Custom box, enter 22°, and then press ENTER. Also in the Amount list, click Clockwise.In the Speed list, select Very Fast.On the slide, select the second oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Change Fill Color. Select the fifth animation effect (change fill color effect for the second oval). Under Modify: Change Fill Color, do the following:In the Startlist, select After Previous. In the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red: 130, Green: 153, Blue: 117. In the Speedlist, select Very Fast.On the slide, select the second text box. In the CustomAnimation task pane, do the following:Click Add Effect, point to Entrance and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade. Select the sixth animation effect (fade effect for the second text box). Under Modify: Fade, do the following:In theStart list, selectWith Previous.In the Speed list, select Very Fast. On the slide, select the third oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Change Fill Color. Select the seventh animation effect (change fill color effect for the third oval). Under Modify: Change Fill Color, do the following:In the Startlist, select After Previous. In the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red: 130, Green: 153, Blue: 117. In the Speedlist, select Very Fast.On the slide, select the third text box. In the CustomAnimation task pane, do the following:Click Add Effect, point to Entrance and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade. Select the eighth animation effect (fade effect for the third text box). Under Modify: Fade, do the following:In theStart list, selectWith Previous.In the Speed list, select Very Fast. On the slide, select the fourth oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Change Fill Color. Select the ninth animation effect (change fill color effect for the fourth oval). Under Modify: Change Fill Color, do the following:In the Startlist, select After Previous. In the Fill Color list, click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red: 130, Green: 153, Blue: 117. In the Speedlist, select Very Fast.On the slide, select the fourth text box. In the CustomAnimation task pane, do the following:Click Add Effect, point to Entrance,and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade. Select the 10th animation effect (fade effect for the fourth text box). Under Modify: Fade, do the following:In theStart list, selectWith Previous.In the Speed list, select Very Fast.
  • I. Type 1 diabetes (-cell destruction, usually leading to absolute insulindeficiency)A. Immune-mediatedB. IdiopathicII. Type 2 diabetes (may range from predominantly insulin resistance withrelative insulin deficiency to a predominantly insulin secretory defectwith insulin resistance)III. Other specific types of diabetesA. Genetic defects of -cell function characterized by mutations in:1. Hepatocyte nuclear transcription factor (HNF) 4 (MODY 1)2. Glucokinase (MODY 2)3. HNF-1 (MODY 3)4. Insulin promoter factor (IPF) 1 (MODY 4)5. HNF-1 (MODY 5)6. NeuroD1 (MODY 6)7. Mitochondrial DNA8. Proinsulin or insulin conversionB. Genetic defects in insulin action1. Type A insulin resistance2. Leprechaunism3. Rabson-Mendenhall syndrome4. Lipodystrophy syndromesC. Diseases of the exocrine pancreas—pancreatitis, pancreatectomy,neoplasia, cystic fibrosis, hemochromatosis, fibrocalculouspancreatopathyD. Endocrinopathies—acromegaly, Cushing’s syndrome, glucagonoma,pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronomaE. Drug- or chemical-induced—Vacor, pentamidine, nicotinic acid,glucocorticoids, thyroid hormone, diazoxide, -adrenergic agonists,thiazides, phenytoin, -interferon, protease inhibitors, clozapine,beta blockersF. Infections—congenital rubella, cytomegalovirus, coxsackieG. Uncommon forms of immune-mediated diabetes—“stiff-man”syndrome, anti-insulin receptor antibodiesH. Other genetic syndromes sometimes associated with diabetes—Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome,Wolfram’s syndrome, Friedreich’s ataxia, Huntington’s chorea,Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria,Prader-Willi syndromeIV. Gestational diabetes mellitus (GDM)
  • Custom animation effects: spotlight text(Intermediate)To reproduce the text effects on this slide, do the following:On the Home tab, in theSlides group, click Layout, and then click Blank.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box. Enter text in the text box and select the text. On the Home tab, in the Font group, do the following:In the Font list, select Arial Black.In the Font Size box, enter 50.Click Bold. On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. Under Drawing Tools, on the Format tab, in bottom right corner of the WordArt Styles, click the Format Text Effects dialog box launcher. In the Format Text Effects dialog box,click Text Fill in the left pane, select Gradient fill in the Text Fill pane, and then do the following: In the Type list, select Linear.Click the button next to Direction, and then click Linear Down (first row, second option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click Black, Text 1, Lighter 35% (third row, second option from the left).Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click Black, Text 1 (first row, second option from the left).Also in the Format Text Effects dialog box,click 3-D Format in the left pane, and then do the following in the 3-D Format pane:Under Bevel, click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 10 pt, and in the Height box, enter 2.5 pt.Under Depth, click the button next to Color, and then select Automatic. Under Contour, click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 68,Green: 113,Blue: 166. In the Sizebox, enter 0.5 pt.Under Surface, click the button next to Material, and then under Standard clickMetal (fourth option from the left). Click the button next to Lighting, and then under Neutral click Contrasting (second row, second option from the left). In the Angle box, enter 75°.Under Drawing Tools, on the Format tab, in the WordArt Styles group, click Text Effects, point to Reflection, and then under Reflection Variations click Half Reflection, touching (first row, second option from the left).Drag the text box above the middle of the slide.On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.Click Align Center.To reproduce the background effects on this slide, do the following:Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Radial.Click the button next to Direction, and then click From Center (third option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 5% (second row, first option from the left).Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colors click Black, Text 1, Lighter 35% (third row, second option from the left). To reproduce the shape effects on this slide, do the following:On the Home tab, in the Drawing group, click Shapes, and then under Basic Shapes click Oval (first row, second option from the left). On the slide, drag to draw an oval.Select the oval. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 1.1”. In the Shape Width box, enter 2.31”.With the oval still selected, on the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Radial.Click the button next to Direction, and then click From Center (third option from the left).Under Gradient stops, click Add or Remove until three stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colorsclick White, Background 1 (first row, first option from the left).In the Transparency box, enter 21%.Select Stop 2 from the list, and then do the following: In the Stop position box, enter 51%.Click the button next to Color, and then under Theme Colorsclick White, Background 1 (first row, first option from the left).In the Transparency box, enter 73%.Select Stop 3 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then under Theme Colorsclick Black, Text 1 (first row, first option from the left).In the Transparency box, enter 100%.Under the Drawing Tools, on the Format tab, in the Shapes Styles group, do the following:Click the arrow next to Shape Outline, and then click No Outline.Click Shape Effects, point to Soft Edges,and then click 25 Point.On the slide, drag the oval until it is centered on the first letter in the text box.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the Animations group, click Custom Animation.On the slide, select the oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Entrance, and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade.Select the animation effect (fade entrance effect for the oval). Under Modify: Fade, do the following:In theStart box, selectWith Previous.In the Speed box, select Fast. On the slide, select the oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Exit, and then click More Effects. In the Add Exit Effect dialog box, under Subtle, clickFade.Select the second animation effect (fade exit effect for the oval). Click the arrow to the right of the animation effect, and then click Timing. In the Fade dialog box, on the Timing tab, do the following:In theStart list, selectWith Previous.In the Delay box, enter 4.In the Speed list, select 1 seconds (Fast). On the slide, select the oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Entrance, and then click More Effects. In the Add Entrance Effect dialog box, under Subtle, clickFade.Select the third animation effect (fade entrance effect for the oval). Click the arrow to the right of the animation effect, and then click Timing. In the Fade dialog box, on the Timing tab, do the following:In theStart list, selectWith Previous.In the Delay box, enter 5.In the Speed list, select 1 seconds (Fast). On the slide, select the oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Exit, and then click More Effects. In the Add Exit Effect dialog box, under Subtle, clickFade.Select the fourth animation effect (fade exit effect for the oval). Click the arrow to the right of the animation effect, and then click Timing. In the Fade dialog box, on the Timing tab, do the following:In theStart list, selectWith Previous.In the Delay box, enter 7.In the Speed list, select 1 seconds (Fast). On the slide, select the oval. In the CustomAnimation task pane, do the following:Click AddEffect, point to Motion Paths, and then click Right. Select the fifth animation effect (motion path for the oval). Click the arrow to the right of the animation effect, and then click Effect Options. In the Fade dialog box, do the following:On the Effect tab, under Path, select Auto-reverse.On the Timing tab, do the following:In theStart list, selectWith Previous.In the Delay box, enter 0.In the Speed list, select 2 seconds (Medium).In the Repeat list, select 2.On the slide, select the motion path. Point to the endpoint (red arrow) of the motion path until the cursor becomes a two-headed arrow, press and hold SHIFT, and then drag the endpoint to the center of the last letter in the text box.
  • Custom animation effects: curve up and grow(Intermediate)To reproduce the first rectangle on this slide, do the following:On the Home tab, in theSlides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Rectangles click Rounded Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rounded rectangle.Drag the yellow diamond adjustment handle to the left to reduce the size of the corner radius.Select the rounded rectangle. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 2.33”.In the Shape Width box, enter 2.32”.On the Home tab, in the Drawing group, click the arrow next to Shape Fill, and select No Fill.On the Home tab, in the Drawing group, click Shape Effects, point to Reflection, under Reflection Variations, select Tight Reflection, touching (first row, first option from the left).On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, in the left pane click Line Color, and then in the Line Color pane select Solid Line. Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 137, Green: 227, Blue: 231.Also in the Format Shape dialog box, in the left pane, click Line Style. In the Line Style pane, do the following:In the Width box, enter 10 pt.In the Cap type list, select Round.Also in the Format Text Effects dialog box, in the left pane, click 3-D Format. In the 3-D Format pane, do the following:Under Bevel, click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 10 pt, and in the Height box, enter 10 pt.Under Contour, click the button next to Color, and then under Theme Colors click Olive Green, Accent 3, Lighter 60% (third row, seventh option from the left).Under Surface, click the button next to Material, and then under Standard click Matte (first row, first option from the left). Click the button next to Lighting, and then under Neutral click Soft (first row, third option from the left). In the Angle box, enter 315°.Right-click the rounded rectangle, and then click Edit Text.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gills Sans MT Condensed from the Font list, and select 28 from the Font Size list.On the Home tab, in the Paragraph group, click Center to center the text.To reproduce the animation effects for the first rectangle on this slide, do the following:On the Animations tab, in the Animations group, click Custom Animation. On the slide, select the round diagonal corner rectangle. In the Custom Animation task pane, do the following:Click Add Effect, point to Entrance, and then click More Effects. In the Add Entrance Effect dialog box, under Exciting, click Curve Up.Select the animation effect (curve-up effect for the rectangle), and under Modify Curve Up, do the following:In the Start list, select With Previous.In the Speed list, select Fast.On the slide, select the round diagonal corner rectangle. In the Custom Animation task pane, do the following:Click Add Effect, point to Emphasis, and then click More Effects. In the Add Emphasis Effect dialog box, under Basic, click Grow/Shrink.Select the second animation effect (grow/shrink effect for the rectangle). Click the arrow next to the selected effect, and then click Effect Options. In the Grow/Shrink dialog box, do the following:On the Effect tab, do the following:In the Size list, in the Custom box, enter 5, and then press ENTER. Also in the Size list, select Vertical. Select Auto-reverse.On the Timing tab, do the following:In the Start list, select With Previous.In the Speed list, select VeryFast.To reproduce the second and third rectangle on this slide with animation effects, do the following:On the slide, select the rounded rectangle.On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Drag the second rounded rectangle next to the first rounded rectangle. Repeat this process one more time for a total of three rectangles.On the Animations tab, in the Animations group, click Custom Animation. In the Custom Animation task pane, do the following:Press and hold CTRL, and then select the third and fourth animation effects (curve up effect and grow/shrinkeffect for the second rectangle). Click the arrow next to one of the selected effects, and then click Timing. In the Effect Options dialog box, on the Timing tab, in the Delay box, enter 0.5.Press and hold CTRL, and then select the fifth and sixth animation effects (curve up effect and grow/shrink effect for the third rectangle). Click the arrow next to one of the selected effects, and then click Timing. In the Effect Options dialog box, on the Timing tab, in the Delay box, enter 1.To reproduce the background on this slide, do the following: On the Home tab, in the Drawing group, clickShapes, and then under Rectangles click Rectangle (first option from the left). On the slide, drag to draw a rectangle.Select the rectangle. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 1.62”.In the Shape Width box, enter 10”.UnderDrawing Tools, on the Format tab, in the bottom right corner of the Shape Styles group, click the Format Shape dialog box launcher.In the Format Shape dialog box, click Fill in the left pane, select Solid fill in the Fill pane, and then do the following:Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 137, Green: 227, Blue: 231.In the Transparency box, enter 70%.Also in the Format Shape dialog box, in the left pane, click Line Color, and in the Line Color pane, select No line.Drag the rectangle into the middle of the slide.On the Home tab, in the Drawing group, clickShapes, and then under Rectangles click Round Diagonal Corner Rectangle (ninth option from the left). On the slide, drag to draw a rectangle.Select the round diagonal corner rectangle. Under Drawing Tools, on the Format tab, in the Size group, do the following:In the Shape Height box enter 0.44”.In the Shape Width box enter 0.44”.UnderDrawing Tools, on the Format tab, in the Shape Styles group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Solid fill in the Fill pane, and then do the following:Click the button next to Color, and then under Theme Colors click White, Background 1, Darker 5% (second row, first option from the left).In the Transparency box, enter 60%.Also in the Format Shape dialog box, in the left pane, click Line Color, and in the Line Color pane, select No line.Select the round diagonal corner rectangle. On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate. Repeat this process until there is a total of seven round diagonal corner rectangles.On the slide, press and hold CTRL and select the seven round diagonal corner rectangles. On the Home tab, in the Drawing group, click Arrange, point to Align, and do the following:Click Align Selected Objects.Click Align Top.Click Distribute Horizontally.Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Diagonal (second row, third option from the left).Under Gradient stops, click Add or Remove until two stops appear in the drop-down list.Also under Gradient stops, customize the gradient stops that you added as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 50%.Click the button next to Color, and then click White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following: In the Stop position box, enter 100%.Click the button next to Color, and then click More Colors. In the Colors dialog box, on the Custom tab, enter values for Red: 204, Green: 244, Blue: 248.
  • Approximately one-third of the disease susceptibility is due to genes and two-thirds to environmental factors. Genes that are related to the HLA locus contribute about 40% of the genetic risk. About 95% of patients with type 1 diabetes possess either HLA-DR3 or HLA-DR4, compared with 45–50% of white controls. HLA-DQ genes are even more specific markers of type 1 susceptibility, since a particular variety (HLA-DQB1*0302) is found in the DR4 patients with type 1, while a "protective" gene (HLA-DQB1*0602) is often present in the DR4 controls. The other important gene that contributes to about 10% of the genetic risk is found at the 5' polymorphic region of the insulin gene. This polymorphic region affects the expression of the insulin gene in the thymus and results in depletion of insulin-specific T lymphocytes. In linkage studies, 16 other genetic regions of the human genome have been identified as being important to pathogenesis but less is known about them.
  • Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2-) at the time the diagnosis is made. These antibodies facilitate screening for an autoimmune cause of diabetes, particularly screening siblings of affected children, as well as adults with atypical features of type 2 diabetes (Table 27–3). Antibody levels decline with increasing duration of disease. Also, low levels of anti-insulin antibodies develop in almost all patients once they are treated with insulin.Family members of diabetic probands are at increased lifetime risk for developing type 1 diabetes. A child whose mother has type 1 diabetes has a 3% risk of developing the disease and a 6% risk if the child's father has it. The risk in siblings is related to the number of HLA haplotypes that the sibling shares with the diabetic proband. If one haplotype is shared, the risk is 6% and if two haplotypes are shared, the risk increases to 12–25%. The highest risk is for identical twins, where the concordance rate is 25–50%. Some patients with a milder expression of type 1 diabetes mellitus initially retain enough B cell function to avoid ketosis, but as their B cell mass diminishes later in life, dependence on insulin therapy develops. Islet cell antibody surveys among northern Europeans indicate that up to 15% of "type 2" diabetic patients may actually have this mild form of type 1 diabetes (latent autoimmune diabetes of adulthood; LADA). Evidence for environmental factors playing a role in the development of type 1 diabetes include the observation that the disease is more common in Scandinavian countries and becomes progressively less frequent in countries nearer and nearer to the equator. Also, the risk for type 1 diabetes increases when individuals who normally have a low risk emigrate to the Northern Hemisphere. For example, it was recently shown that Pakistani children born and raised in Bradford, England have a higher risk for developing type 1 diabetes compared with children who lived in Pakistan all their lives.Which environmental factor is responsible for the increased risk is not known. There have been a number of different hypotheses including infections with certain viruses (rubella, Coxsackie B4) and consumption of cow's milk. Also, in developed countries, childhood infections have become less frequent and so perhaps the immune system becomes dysregulated with development of autoimmunity and conditions such as asthma and diabetes. This theory is referred to as the hygiene hypothesis. None of these factors has so far been confirmed as the culprit. Part of the difficulty is that autoimmune injury undoubtedly starts many years before clinical diabetes mellitus develops.
  • Idiopathic type 1 diabetes mellitusLess than 10% of subjects have no evidence of pancreatic B cell autoimmunity to explain their insulinopenia and ketoacidosis. This subgroup has been classified as "idiopathic type 1 diabetes" and designated as "type 1B." Although only a minority of patients with type 1 diabetes fall into this group, most of these are of Asian or African origin. It was recently reported that about 4% of the West Africans with ketosis-prone diabetes are homozygous for a mutation in PAX-4 (Arg133Trp)—a gene that is essential for the development of pancreatic islets. The Pax4 gene is essential for differentiation of insulin-producing cells in the mammalian pancreasBeatriz Sosa-Pineda*, Kamal Chowdhury, Miguel Torres*, Guillermo Oliver* & Peter GrussMax Planck Institute for Biophysical Chemistry, Am Fassberg 37077 Göttingen, Germany *Present addresses: Department of Genetics, St Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, Tennessee 38101-0318, USA (B.S.-P. and G.O.); Departamento de InmunologiayOncologia, Centre Nacional de Biotecnologia, UnivesidadAutonoma, Madrid 28049, Spain (M.T.). The mammalian pancreas contains two distinct cell populations: endocrine cells which secrete hormones into the bloodstream, and exocrine cells, which secrete enzymes into the digestive tract1. The four endocrine cell types found in the adult pancreas—, , and PP—synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively2. All of these endocrine cells arise from common multipotent precursors, which coexpress several hormones when they start to differentiate3. Expression of some homeobox genes in the early developing pancreas has been reported4–7. The Pax4 gene is expressed in the early pancreas, but is later restricted to cells. Inactivation of Pax4 by homologous recombination results in the absence of mature insulin-and somatostatin-producing cells ( and , respectively) in the pancreas of Pax4 homozygous mutant mice, but glucagon-producing cells are present in considerably higher numbers. We propose that the early expression of Pax4 in a subset of endocrine progenitors is essential for the differentiation of the and cell lineages. A default pathway would explain the elevated number of cells in the absence of Pax4.
  • This subgroup is a relatively rare monogenic disorder characterized by non–insulin-dependent diabetes with autosomal dominant inheritance and an age at onset of 25 years or younger. Patients are nonobese, and their hyperglycemia is due to impaired glucose-induced secretion of insulin. Six types of MODY have been described. Except for MODY 2, in which a glucokinase gene is defective, all other types involve mutations of a nuclear transcription factor that regulates islet gene expression.MODY 2 is quite mild, associated with only slight fasting hyperglycemia and few if any microvascular diabetic complications. It generally responds well to hygienic measures or low doses of oral hypoglycemic agents. MODY 3—the most common form—accounts for two-thirds of all MODY cases. The clinical course is similar to that of idiopathic type 2 diabetes in terms of microangiopathy and failure to respond to oral agents with time.
  • Diabetes due to mutant insulinsThis is a very rare subtype of nonobese type 2 diabetes, with no more than ten families having been described. Since affected individuals were heterozygous and possessed one normal insulin gene, diabetes was mild, did not appear until middle age, and showed autosomal dominant genetic transmission. There is generally no evidence of clinical insulin resistance, and these patients respond well to standard therapy.
  • Diabetes due to mutant insulin receptorsDefects in one of their insulin receptor genes have been found in more than 40 people with diabetes, and most have extreme insulin resistance associated with acanthosisnigricans. In very rare instances when both insulin receptor genes are abnormal, newborns present with a leprechaun-like phenotype and seldom live through infancy.
  • Diabetes mellitus associated with a mutation of mitochondrial DNASince sperm do not contain mitochondria, only the mother transmits mitochondrial genes to her offspring. Diabetes due to a mutation of mitochondrial DNA that impairs the transfer of leucine or lysine into mitochondrial proteins has been described. Most patients have a mild form of diabetes that responds to oral hypoglycemic agents; some have a nonimmune form of type 1 diabetes. Two-thirds of patients with this subtype of diabetes have a hearing loss, and a smaller proportion (15%) had a syndrome of myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
  • Wolfram's syndromeWolfram's syndrome is an autosomal recessive neurodegenerative disorder first evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD. It is due to mutations in a gene named WFS1, which encodes a 100.3 KDatransmembrane protein localized in the endoplasmic reticulum. The function of the protein is not known. The diabetes mellitus, which is nonimmune and not linked to specific HLA antigens, usually presents in the first decade together with the optic atrophy. Cranial diabetes insipidus and sensorineural deafness develop during the second decade in 60–75% of patients. Ureterohydronephrosis, neurogenic bladder, cerebellar ataxia, peripheral neuropathy, and psychiatric illness develop later in many patients.
  • Insulin Resistance Syndrome (Syndrome X; Metabolic Syndrome)Twenty-five percent of the general nonobesenondiabetic population has insulin resistance of a magnitude similar to that seen in type 2 diabetes. These insulin-resistant nondiabetic individuals are at much higher risk for developing type 2 diabetes than insulin-sensitive persons. In addition to diabetes, these individuals have increased risk for elevated plasma triglycerides, lower high-density lipoproteins (HDLs), and higher blood pressure—a cluster of abnormalities termed syndrome X. These associations have now been expanded to include small, dense, low-density lipoprotein (LDL), hyperuricemia, abdominal obesity, prothrombotic state with increased levels of plasminogen activator inhibitor type 1 (PAI-1), and proinflammatory state. These clusters of abnormalities significantly increase the risk of atherosclerotic disease. It has been postulated that hyperinsulinemia and insulin resistance play a direct role in these metabolic abnormalities, but supportive evidence is inconclusive. Although hyperinsulinism and hypertension often coexist in whites, that is not the case in blacks or Pima Indians. Moreover, patients with hyperinsulinism due to insulinoma are not hypertensive, and there is no fall in blood pressure after surgical removal of the insulinoma restores normal insulin levels. The main value of grouping these disorders as a syndrome, however, is to remind clinicians that the therapeutic goals are not only to correct hyperglycemia but also to manage the elevated blood pressure and dyslipidemia that result in increased cerebrovascular and cardiac morbidity and mortality in these patients. Clinicians aware of this syndrome are more cautious in prescribing therapies that correct hypertension but may raise lipids (diuretics, beta-blockers) or that correct hyperlipidemia but increase insulin resistance, with aggravation of diabetes (niacin). Finally, the use of long-acting insulins and sulfonylureas that promote sustained hyperinsulinism may have to be moderated, with insulin-sparing drugs such as metformin or a thiazolidinedione being preferable, if the hypothesis behind the insulin resistance syndrome is ever substantiated.
  • Metabolic syndromeOften a person with abnormal glucose tolerance (IGT or diabetes) will be foundto have at least one or more of the other cardiovascular disease risk factors suchas hypertension, central (upper body) obesity, and dyslipidaemia. This clusteringhas been labelled diversely as the metabolic syndrome, syndrome X, or the insulinresistance syndrome [21]. Epidemiological studies confirm that this syndrome occurscommonly in a wide variety of ethnic groups including Caucasians, Afro-Americans,Mexican-Americans, Asian Indians, Chinese, Australian Aborigines, Polynesians andMicronesians. In 1988, Dr Gerald Reaven focused attention on this cluster, naming itSyndrome X. Central obesity was not included in the original description, so the termmetabolic syndrome is now favoured. Alone, each component of the cluster conveysincreased cardiovascular disease risk, but as a combination they become much morepowerful. This means that the management of persons with hyperglycaemia and otherfeatures of the metabolic syndrome should focus not only on blood glucose control butalso include strategies to reduce the impact of other cardiovascular disease risk factors.The metabolic syndrome with normal glucose tolerance identifies the subject as amember of a group at very high risk of future diabetes. Thus, vigorous early managementof the syndrome may have a significant impact on the prevention of both diabetes andcardiovascular disease, especially as it is well documented that the features of the metabolicsyndrome can be present for up to 10 years before glycaemic disorder is detected.Diagnosis of metabolic syndromeAt least three of the five criteria shown in Table 5 must be met to diagnose metabolicsyndrome.Several other components of the metabolic syndrome have been described (e.g.hyperuricaemia, coagulation disorders) but are not considered criteria for its diagnosis.Metabolic syndromeOften a person with abnormal glucose tolerance (IGT or diabetes) will be foundto have at least one or more of the other cardiovascular disease risk factors suchas hypertension, central (upper body) obesity, and dyslipidaemia. This clusteringhas been labelled diversely as the metabolic syndrome, syndrome X, or the insulinresistance syndrome [21]. Epidemiological studies confirm that this syndrome occurscommonly in a wide variety of ethnic groups including Caucasians, Afro-Americans,Mexican-Americans, Asian Indians, Chinese, Australian Aborigines, Polynesians andMicronesians. In 1988, Dr Gerald Reaven focused attention on this cluster, naming itSyndrome X. Central obesity was not included in the original description, so the termmetabolic syndrome is now favoured. Alone, each component of the cluster conveysincreased cardiovascular disease risk, but as a combination they become much morepowerful. This means that the management of persons with hyperglycaemia and otherfeatures of the metabolic syndrome should focus not only on blood glucose control butalso include strategies to reduce the impact of other cardiovascular disease risk factors.The metabolic syndrome with normal glucose tolerance identifies the subject as amember of a group at very high risk of future diabetes. Thus, vigorous early managementof the syndrome may have a significant impact on the prevention of both diabetes andcardiovascular disease, especially as it is well documented that the features of the metabolicsyndrome can be present for up to 10 years before glycaemic disorder is detected.Table 5. Diagnostic criteria for the metabolic syndromeCriteria Defining levelAbdominal obesityMen Waist circumference >102 cm (>40 inches)Women Waist circumference >88 cm (>35 inches)High levels of triglycerides At least 150 mg/dLLow HDL cholesterolMen 85 mmHgHigh fasting glucose At least 110 mg/dLDiagnosis of metabolic syndromeAt least three of the five criteria shown in Table 5 must be met to diagnose metabolicsyndrome.Several other components of the metabolic syndrome have been described (e.g.hyperuricaemia, coagulation disorders) but are not considered criteria for its diagnosis.
  • Box 1. Diagnostic criteria for gestational diabetes [21,23]75 g OGTT with two or more positive valuesfasting ≥95 mg/dL (5.3 mmol/L)1 hour ≥180 mg/dL (10 mmol/L)2 hours ≥155 mg/dL (8.6 mmol/L)100 g OGTT with two or more positive valuesfasting ≥95 mg/dL (5.3 mmol/L)1 hour ≥180 mg/dL (10 mmol/L)2 hours ≥155 mg/dL (8.6 mmol/L)3 hours ≥140 mg/dL (7.8 mmol/L)or50 g GCT with blood glucose value after 1 hour≥130 mg/dL (7.2 mmol/L), then confirm with 75 g or 100 g OGTT
  • Patients with type 1 diabetes have a characteristic symptom complex. An absolute deficiency of insulin results in accumulation of circulating glucose and fatty acids, with consequent hyperosmolality and hyperketonemia.Patients with type 2 diabetes may or may not have characteristic features. The presence of obesity or a strongly positive family history for mild diabetes suggests a high risk for the development of type 2 diabetes.Symptoms and SignsType 1 diabetesIncreased urination is a consequence of osmotic diuresis secondary to sustained hyperglycemia. This results in a loss of glucose as well as free water and electrolytes in the urine. Thirst is a consequence of the hyperosmolar state, as is blurred vision, which often develops as the lenses are exposed to hyperosmolar fluids.Weight loss despite normal or increased appetite is a common feature of type 1 when it develops subacutely. The weight loss is initially due to depletion of water, glycogen, and triglycerides; thereafter, reduced muscle mass occurs as amino acids are diverted to form glucose and ketone bodies.Lowered plasma volume produces symptoms of postural hypotension. Total body potassium loss and the general catabolism of muscle protein contribute to the weakness.Paresthesias may be present at the time of diagnosis, particularly when the onset is subacute. They reflect a temporary dysfunction of peripheral sensory nerves, which clears as insulin replacement restores glycemic levels closer to normal, suggesting neurotoxicity from sustained hyperglycemia.When absolute insulin deficiency is of acute onset, the above symptoms develop abruptly. Ketoacidosis exacerbates the dehydration and hyperosmolality by producing anorexia and nausea and vomiting, interfering with oral fluid replacement.The patient's level of consciousness can vary depending on the degree of hyperosmolality. When insulin deficiency develops relatively slowly and sufficient water intake is maintained, patients remain relatively alert and physical findings may be minimal. When vomiting occurs in response to worsening ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep serum osmolality below 320–330 mosm/L. Under these circumstances, stupor or even coma may occur. The fruity breath odor of acetone further suggests the diagnosis of diabetic ketoacidosis.Hypotension in the recumbent position is a serious prognostic sign. Loss of subcutaneous fat and muscle wasting are features of more slowly developing insulin deficiency. In occasional patients with slow, insidious onset of insulin deficiency, subcutaneous fat may be considerably depleted.Type 2 diabetesWhile many patients with type 2 diabetes present with increased urination and thirst, many others have an insidious onset of hyperglycemia and are asymptomatic initially. This is particularly true in obese patients, whose diabetes may be detected only after glycosuria or hyperglycemia is noted during routine laboratory studies. Occasionally, type 2 patients may present with evidence of neuropathic or cardiovascular complications because of occult disease present for some time prior to diagnosis. Chronic skin infections are common. Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women. Diabetes should be suspected in women with chronic candidalvulvovaginitis as well as in those who have delivered large babies (> 9 lb, or 4.1 kg) or have had polyhydramnios, preeclampsia, or unexplained fetal losses.Obese diabetics may have any variety of fat distribution; however, diabetes seems to be more often associated in both men and women with localization of fat deposits on the upper segment of the body (particularly the abdomen, chest, neck, and face) and relatively less fat on the appendages, which may be quite muscular. Standardized tables of waist-to-hip ratio indicate that ratios of "greater than 0.9" in men and "greater than 0.8" in women are associated with an increased risk of diabetes in obese subjects. Mild hypertension is often present in obese diabetics. Eruptive xanthomas on the flexor surface of the limbs and on the buttocks and lipemiaretinalis due to hyperchylomicronemia can occur in patients with uncontrolled type 2 diabetes who also have a familial form of hypertriglyceridemia.
  • National Diabetes Data Group (NDDG) Transition effect for timeline, slide 1(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows clickChevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 9.48”.Drag the chevron until the right end is beyond the right edge of the slide, and the left end of the chevron is approximately one inch to the right of the left edge of the slide.Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, point to Gradient, and then click MoreGradients. In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme ColorsclickWhite, Background 1 (first row, first option from the left)Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane, and then do the following in the Shadow pane: Click the button next to Presets, and then under Outer click OffsetBottom (first row, second option from the left).In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Condensedfrom the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then clickDuplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.ClickAlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.ClickDistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover clickPushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • Transition effect for timeline, slide 2(Basic)Tip: This transition works well for graphics that horizontally span more than one slide. To reproduce the shape effects on this slide, do the following:On the Home tab, in the Slides group, click Layout, and then click Blank.On the Home tab, in the Drawing group, click Shapes, and then under Block Arrows,clickChevron (second row, eighth option from the left). On the slide, drag to draw a long, horizontal chevron shape.Select the chevron. Under DrawingTools, on the Format tab, in the Size group, do the following:In the Shape Height box, enter 0.7”.In the Shape Width box, enter 11.03”.Drag the chevron until it extends past both the left and right edges of the slide. Select the chevron. Under DrawingTools, on the Format tab, in the ShapeStyles group, click the arrow next to ShapeFill, click Gradient, and then click MoreGradients.In the Format Shape dialog box, click Fill in the left pane, select Gradientfill in the Fill pane, and then do the following:In the Type list, select Linear.Click the button next to Direction, and then click Linear Up (second row, second option from the left).Under Gradient stops, click Add or Remove until a total of four gradient stops appear in the drop-down list. Also under Gradient stops, customize the gradient stops as follows:Select Stop 1 from the list, and then do the following:In the Stop position box, enter 0%.Click the button next to Color, and then under Theme Colorsclick White, Background 1 (first row, first option from the left).Select Stop 2 from the list, and then do the following:In the Stop position box, enter 36%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Select Stop 3 from the list, and then do the following:In the Stop position box, enter 73%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 178, Green: 190, Blue: 194. Select Stop 4 from the list, and then do the following:In the Stop position box, enter 100%.Click the button next to Color, click More Colors, and then in the Colors dialog box, on the Custom tab, enter values for Red: 213, Green: 219, Blue: 221. Also in the Format Shape dialog box, click LineColor in the left pane, and then select No line in the LineColor pane.Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click OffsetBottom (first row, second option from the left), and then do the following: In the Transparency box, enter 60%.In the Size box, enter 100%.In the Blur box, enter 4 pt.In the Angle box, enter 90°.In the Distance box, enter 3 pt. Also in the Format Shape dialog box, click 3-DFormat in the left pane. In the 3-D Format pane, under Bevel,click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw the text box.Enter text in the text box, select the text, and then on the Home tab, in the Font group, select Gill Sans MT Condfrom the Font list, enter 26 in the Font Size box, click Bold, click the arrow next to Font Color, and then under Theme Colors click White, Background 1, Darker 50% (sixth row, first option from the left).On the Home tab, in the Paragraph group, click Center to center the text in the text box.Select the text box. On the Home tab, in the Clipboard group, click the arrow under Paste, and then clickDuplicate. Repeat this process to create a total of three text boxes.Click in each of the two duplicate text boxes, and then edit the text.Drag the text boxes onto the chevron shape to form a row. Press CTRL+A to select all the objects on the slide. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.ClickAlignMiddle.Press and hold SHIFT, and then select all three text boxes. On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:Click Align to Slide.ClickDistributeHorizontally.To reproduce the animation effects on this slide, do the following:On the Animations tab, in the TransitiontoThisSlide group, click More, and then under Pushand Cover clickPushLeft.On the Animations tab, in the TransitionstoThisSlide group, in the Transition Speed list, select Slow.
  • Since 1965 the World Health Organization (WHO) has published guidelinesfor the diagnosis and classification of diabetes. These were lastreviewed in 1998 and were published as the guidelines for the Definition,Diagnosis and Classification of Diabetes Mellitus3. Since then moreinformation relevant to the diagnosis of diabetes has become available.In addition, in 2003, the ADA reviewed its diagnostic criteria4. While thecriteria for the diagnosis of diabetes and Impaired Glucose Tolerance (IGT)remained unchanged, the ADA recommended lowering the threshold forImpaired Fasting Glucose (IFG) from 6.1mmol/l (110mg/dl) to 5.6mmol/l(100mg/dl)4. In view of these developments WHO and the InternationalDiabetes Federation (IDF) decided that it was timely to review its existingguidelines for the definition and diagnosis of diabetes and intermediatehyperglycaemia. Guideline Development Group was held at WHO headquarters in Genevaon November 4–6, 2005. The specific aims of the meeting were to reviewrelevant data which addressed and could inform the review of thediagnostic criteria for:DiabetesImpaired glucose tolerance (IGT)Impaired fasting glucose (IFG) (in particular the 2003 ADA revisedcriteria).
  • National Glycohemoglobin StandardizationProgram (NGSP) and standardizedor traceable to the Diabetes Controland Complications Trial (DCCT)
  • Table 1. Values for diagnosis of diabetes mellitus and other categories of hyperglycaemiaGlucose concentration, mmol l–1 (mg dl–1)Whole blood Plasma*Venous Capillary VenousDiabetes Mellitus:Fasting ³ 6.1 (³ 110) ³ 6.1 (³ 110) ³ 7.0 (³ 126)or2-h post glucose loador both³ 10.0 (³ 180) ³ 11.1 (³ 200) ³ 11.1 (³ 200)Impaired Glucose Tolerance (IGT):Fasting (if measured) < 6.1 (< 110) < 6.1 (< 110) < 7.0 (< 126)and2-h post glucose load ³ 6.7 (³ 120) and ³ 7.8 (³ 140) and ³ 7.8 (³ 140) and< 10.0 (< 180) < 11.1 (< 200) < 11.1 (< 200)Impaired Fasting Glycaemia (IFG):Fasting ³ 5.6 (³ 100) and ³ 5.6 (³ 100) and ³ 6.1 (³ 110) and< 6.1 (< 110) < 6.1 (< 110) < 7.0 (< 126)and (if measured)2-h post glucose load < 6.7 (< 120) < 7.8 (< 140) < 7.8 (< 140)* Corresponding values for capillary plasma are: for Diabetes Mellitus, fasting ³ 7.0 (³ 126), 2-h ³ 12.2 (³ 220); for Impaired Glucose Tolerance,fasting < 7.0 (< 126) and2-h ³ 8.9 (³ 160) and < 12.2 (< 220); and for Impaired Fasting Glycaemia ³ 6.1 (³ 110) and < 7.0 (< 126) and if measured, 2-h < 8.9 (< 160).For epidemiological or population screening purposes, the fasting or 2-h value after 75 g oral glucose may be used alone. For clinical purposes, the diagnosis of diabetesshould always be confirmed by repeating the test on another day unless there is unequivocal hyperglycaemia with acute metabolic decompensation or obvioussymptoms.Glucose concentrations should not be determined on serum unless red cells are immediately removed, otherwise glycolysis will result in anunpredictable under-estimation of the true concentrations. It should be stressed that glucose preservatives do not totally prevent glycolysis.If whole blood is used, the sample should be kept at 0-4 °C or centrifuged immediately, or assayed immediately.
  • Recommendation 6 The oral glucose tolerance test (OGTT) should be retained as a diagnostictest for the following reasonsfasting plasma glucose alone fails to diagnose approximately 30% ofcases of previously undiagnosed diabetesan OGTT is the only means of identifying people with IGTan OGTT is frequently needed to confirm or exclude an abnormalityof glucose tolerance in asymptomatic peopleAn OGTT should be used in individuals with fasting plasma glucose6.1–6.9mmol/l (110–125mg/dl) to determine glucose tolerance status.Recommendation 7 Currently HbA1c is not considered a suitable diagnostic test for diabetesor intermediate hyperglycaemia.
  • Federation of Clinical Chemistry (IFCC) recommendation that all glucosemeasuring devices report in plasma values57.Measurement differences may also arise depending on the site of collectionof the blood sample. Venous and capillary samples will give the sameresult in the fasting state but in the non-fasting state capillary will givehigher results than venous samples.The processing of the sample after collection is important to ensure accuratemeasurement of plasma glucose. This requires rapid separation ofthe plasma after collection (within minutes) but it is recognised that thisseldom occurs. Collection into a container with glycolytic inhibitors (egNaF) is only partially effective. A minimum requirement is that the sampleshould be placed immediately in ice-water after collection and beforeseparating but even so separation should be within 30min58.Recommendation 5 1. Venous plasma glucose should be the standard method for measuringand reporting. However in recognition of the widespread use of capillarysampling, especially in under-resourced countries, conversionvalues for capillary plasma glucose are provided for post- load glucosevalues. Fasting values for venous and capillary plasma glucose areidentical.2. Glucose should be measured immediately after collection by nearpatient testing, or if a blood sample is collected, plasma shouldbe immediately separated, or the sample should be collected intoa container with glycolytic inhibitors and placed on ice-water untilseparated prior to analysis.
  • Glycated hemoglobin (hemoglobin A1) measurementsHemoglobin becomes glycated by ketoamine reactions between glucose and other sugars and the free amino groups on the and chains. Only glycation of the N-terminal valine of the beta chain imparts sufficient negative charge to the hemoglobin molecule to allow separation by charge dependent techniques. These charge separated hemoglobins are collectively referred to as hemoglobin A1 (HbA1). The major form of HbA1 is hemoglobin A1c (HbA1c) where glucose is the carbohydrate. HbA1c comprises 4–6% of total hemoglobin A1. The remaining HbA1 species contain fructose-1,6 diphosphate (HbA1a1); glucose-6-phosphate (HbA1a2); and unknown carbohydrate moiety (HbA1b). The hemoglobin A1c fraction is abnormally elevated in diabetic persons with chronic hyperglycemia. Methods for measuring HbA1c include electrophoresis, cation-exchange chromatography, boronate affinity chromatography, and immunoassays. Office-based immunoassays using capillary blood give a result in about 9 minutes and this allows for immediate feedback to the patients regarding their glycemic control.Since glycohemoglobins circulate within red blood cells whose life span lasts up to 120 days, they generally reflect the state of glycemia over the preceding 8–12 weeks, thereby providing an improved method of assessing diabetic control. The HbA1c value, however, is weighted to more recent glucose levels (previous month) and this explains why significant changes in HbA1c are observed with short-term (1 month) changes in mean plasma glucose levels. Measurements should be made in patients with either type of diabetes mellitus at 3- to 4-month intervals so that adjustments in therapy can be made if HbA1c is either subnormal or if it is more than 2% above the upper limits of normal for a particular laboratory. In patients monitoring their own blood glucose levels, HbA1c values provide a valuable check on the accuracy of monitoring. In patients who do not monitor their own blood glucose levels, HbA1c values are essential for adjusting therapy. Data from the Diabetes Control and Complications Trial (DCCT) showed that there is a linear relationship between the HbA1c and the mean of seven-point capillary blood glucose profiles (preprandial, postprandial, and bedtime). Thus, mean plasma glucose levels of 170, 205, 240, and 275 mg/dL approximately correlate with HbA1c values of 7%, 8%, 9%, and 10%, respectively. Use of HbA1c for screening is controversial. Sensitivity in detecting known diabetes cases by HbA1c measurements is only 85%, indicating that diabetes cannot be excluded by a normal value. On the other hand, elevated HbA1c assays are fairly specific (91%) in identifying the presence of diabetes.The accuracy of HbA1c values can be affected by hemoglobin variants or derivatives; the effect depends on the specific hemoglobin variant or derivative and the specific assay used. Immunoassays that use an antibody to the glycated amino terminus of globin do not recognize the terminus of the globin of hemoglobin F. Thus, in patients with high levels of hemoglobin F, immunoassays give falsely low values of HbA1c. Cation-exchange chromatography separates hemoglobin species by charge differences. Hemoglobin variants that co-elute with HbA1c can lead to an overestimation of the HbA1c value. Chemically modified derivatives of hemoglobin such as carbamoylation (in renal failure) or acetylation (high-dose aspirin therapy) can similarly co-elute with HbA1c by some assay methods.Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (eg, recovery from acute blood loss, hemolytic anemia) will falsely lower HbA1c irrespective of the assay method used. Alternative methods such as fructosamine (see below) should be considered for these patients. Vitamins C and E are reported to falsely lower test results possibly by inhibiting glycation of hemoglobin.
  • Serum fructosamineSerum fructosamine is formed by nonenzymaticglycosylation of serum proteins (predominantly albumin). Since serum albumin has a much shorter half-life than hemoglobin, serum fructosamine generally reflects the state of glycemic control for only the preceding 1–2 weeks. Reductions in serum albumin (eg, nephrotic state or hepatic disease) will lower the serum fructosamine value. When abnormal hemoglobins or hemolytic states affect the interpretation of glycohemoglobin or when a narrower time frame is required, such as for ascertaining glycemic control at the time of conception in a diabetic woman who has recently become pregnant, serum fructosamine assays offer some advantage. Normal values vary in relation to the serum albumin concentration and are 1.5–2.4 mmol/L when the serum albumin level is 5 g/dL.
  • Self-monitoring of blood glucoseCapillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful. In type 1 patients in whom "tight" metabolic control is attempted, they are indispensable. There are several paper strip (glucose oxidase, glucose dehydrogenase, or hexokinase) methods for measuring glucose on capillary blood samples. A reflectance photometer or an amperometric system is then used to measure the reaction that takes place on the reagent strip. A large number of blood glucose meters are now available. All are accurate, but they vary with regard to speed, convenience, size of blood samples required, and cost. Popular models include those manufactured by LifeScan (One Touch), Bayer Corporation (Ascencia), Roche Diagnostics (Accu-Chek), Abbott Laboratories (Precision, FreeStyle), and Home Diagnostics (Prestige). These blood glucose meters are relatively inexpensive, ranging from $50 to $100 each. Test strips remain a major expense, costing $.50 to $.75 apiece. Each glucose meter comes with a lancet device and disposable 26- to 33-gauge lancets. Some meters have been approved for measuring glucose in blood samples obtained at alternative sites such as the forearm and thigh. There is, however, a 5- to 20-minute lag in the glucose response on the arm with respect to the glucose response on the finger. Forearm blood glucose measurements could therefore result in a delay in detection of rapidly developing hypoglycemia.The clinician should be aware of the limitations of the self-monitoring glucose systems. First, a few of the older meters (such as the One Touch Profile) are calibrated against whole blood glucose concentrations even though the test strip measures the glucose in the plasma fraction. This means the displayed values are 10% to 15% lower than the laboratory glucose result. Second, increases or decreases in hematocrit can decrease or increase the measured glucose values. The mechanism underlying this effect is not known but presumably it is due to the impact of red cells on the diffusion of plasma into the reagent layer. Third, the meters and the test strips are calibrated over the glucose concentrations ranging from 60 mg/dL to 160 mg/dL, and the accuracy is not as good for higher and lower glucose levels. When the glucose is less than 60 mg/dL, the difference between the meter and the laboratory value may be as much as 20%. Fourth, glucose oxidase–based amperometric systems underestimate glucose levels in the presence of high oxygen tension. This may be important in the critically ill who are receiving supplemental oxygen; under these circumstances, a glucose dehydrogenase–based system may be preferable. The accuracy of data obtained by glucose monitoring requires education of the patient in sampling and measuring procedures as well as in proper calibration of the instruments. Bedside glucose monitoring in a hospital setting requires rigorous quality control programs and certification of personnel to avoid errors.
  • Continuous glucose monitoring systemsThree continuous glucose monitoring systems are currently available for clinical use. The DexCom and MiniMed Medtronic systems involve inserting a subcutaneous sensor (rather like an insulin pump cannula) that measures glucose concentrations in the interstitial fluid for 72 hours. In the MiniMed system, the measured glucose values are wirelessly transmitted to the screen of their insulin pump. In the DexCom system, the data are transmitted to a separate pager-like device with a screen. Both systems allow the patient to set "alerts" for low and high glucose values. Patients still have to calibrate the devices with periodic fingerstick glucose levels, and since there are concerns regarding reliability, it is still necessary to confirm the displayed glucose level with a fingerstick glucose before making interventions such as injecting extra insulin or eating extra carbohydrates. Clinical trials with these systems show that they do enable some patients to improve control without increasing the risk of hypoglycemia. The individual glucose values are not that critical—what matters is the direction and the rate at which the glucose is changing, allowing the user to take corrective action. The wearer also gains insight into the way particular foods and activities affect their glucose levels. The other main benefit is the low glucose alert warning. These systems are not covered by insurance and the initial cost is about $800 to $1000, and the sensor, which has to be changed every 3 days or so, costs about $35. This adds up to an out-of-pocket expense of about $4000 annually. The Glucowatch system from Animas Technologies measures glucose in interstitial fluid extracted through intact skin by applying a low electric current (reverse iontophoresis). This process can cause local skin irritation, and sweating distorts the glucose measurement. For these reasons, the system is not widely used.
  • Lipoprotein abnormalities in diabetesCirculating lipoproteins are just as dependent on insulin as is the plasma glucose. In type 1 diabetes, moderately deficient control of hyperglycemia is associated with only a slight elevation of LDL cholesterol and serum triglycerides and little if any change in HDL cholesterol. Once the hyperglycemia is corrected, lipoprotein levels are generally normal. However, in obese patients with type 2 diabetes, a distinct "diabetic dyslipidemia" is characteristic of the insulin resistance syndrome. Its features are a high serum triglyceride level (300–400 mg/dL), a low HDL cholesterol (less than 30 mg/dL), and a qualitative change in LDL particles, producing a smaller dense particle whose membrane carries supranormal amounts of free cholesterol. These smaller dense LDL particles are more susceptible to oxidation, which renders them more atherogenic. Since a low HDL cholesterol is a major feature predisposing to macrovascular disease, the term "dyslipidemia" has preempted the term "hyperlipidemia," which mainly denoted the elevated triglycerides. Measures designed to correct the obesity and hyperglycemia, such as exercise, diet, and hypoglycemic therapy, are the treatment of choice for diabetic dyslipidemia, and in occasional patients in whom normal weight was achieved, all features of the lipoprotein abnormalities cleared. Since primary disorders of lipid metabolism may coexist with diabetes, persistence of lipid abnormalities after restoration of normal weight and blood glucose should prompt a diagnostic workup and possible pharmacotherapy of the lipid disorder. Lipid Abnormalities discusses these matters in detail.
  • A European research team has found a molecule, CXCL5, which makes obese people develop diabetes.  Many overweight or obese people develop insulin resistance and type 2 diabetes at some phase in their lives. Now, a new research has revealed that obese people have large amounts of the molecule CXCL5, produced by certain cells in fatty tissue.  The biomedical community has known for many years that substances produced by fatty tissue are accountable for the association between diabetes and obesity.  "Chronic inflammation of the adipose tissue, which is characteristic of obese people, is a crucial stage in the development of insulin resistance and type 2 diabetes", LluisFajas, lead author of the research and a researcher at the Institute of Health and Medical Research (Inserm) in France, said.  The outcome of this new research shows that serum levels of a chemokine molecule called CXCL5, produced by certain adipose tissue cells, emerge at much high levels in the tissues of obese people than in those of individuals with normal weight.  This has helped LluisFajas's study team to come to a conclusion that is biomedically pertinent, "The CXCL5 molecule helps cause insulin resistance and type 2 diabetes".   The most vital part of this research is the discovery that an experimental treatment intended at restraining the action of CXCL5 can help to protect obese mice from developing type 2 diabetes.  "If these studies can be confirmed in humans, this treatment would represent a fundamental improvement in the quality of life of obese individuals", the researcher said.  The finding has been published in the journal Cell Metabolism
  • Insulin pills that could make blood sugar control easier for millions of diabetics worldwide are finally moving ahead in clinical trials and a step closer to the medicine cabinet. Drug manufacturers have tried for years to develop oral insulin without much success. Insulin is a peptide hormone that people with diabetes currently take by injection to bring their blood sugar within normal levels. But doing so requires uncomfortable, inconvenient injections that can make patients reluctant to use the drug frequently enough to adequately control their blood sugar. An oral form of insulin could help solve this problem. However, stomach acids and enzymes easily destroy insulin and other protein-based drugs. Scientists have had difficulty finding an effective way to eliminate this problem. They've responded to this challenge by developing special coatings for insulin pills that prevent stomach acid from destroying them. Scientists also are using additives that make it easier for the intestine to absorb large molecules like insulin. After years of setbacks, signs of success may be at hand. Several insulin pills are now in various stages of clinical trials, and proof of concept may allow them to move into late-stage and more rigorous clinical testing. Only time will tell, however, whether these much-anticipated pills will make it to the market, said a release of the American Chemical Society (ACS). These findings were reported in a two-part cover story in the current issue of Chemical and Engineering News, ACS' weekly newsmagazine.
  • Researchers have come out with new insulin that can withstand higher temperatures, a development that will bring relief to millions of diabetics across the world. Normally, insulin starts to go bad above four degrees centigrade - making its supply very difficult in areas that lack refrigeration. The poor stability of existing forms of insulin complicates the management of diabetes. However, Bianca van Lierop, Monash University chemist and her colleagues have successfully strengthened insulin's chemical structure, which can withstand higher temperatures. They have just filed a series of patents with their partner ASX-listed Circadian Technologies for marketing it. At the same time, they're using their new knowledge to develop a form of insulin that could be delivered by pill. "Over 200 million people need insulin to manage diabetes, but we still don't know how it works at a molecular level," says van Lierop. She will be presenting her work at Fresh Science, a national science talent search, at Melbourne Museum.
  • An international team co-led by scientists from the University of Michigan have discovered 12 more regions on the genome with DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38. A variant is a place on a string of DNA where one of the "letters," or nucleotides, differs between people. At most places along the DNA, any two people will have the same letter. The variable places in the DNA are important because some variants can increase predisposition to disease and other conditions, or offer drug targets. Researchers also wanted to know if people who hadn't yet developed type 2 diabetes but did have the diabetes variant showed elevated blood glucose levels, a main predictor of diabetes, said study co-leader Laura Scott, associate research scientist at the U-M School of Public Health. "What our study suggests is that many of these variants are associated with changes in glucose levels long before people get diabetes," said study co-leader Michael Boehnke, professor of biostatistics at U-M's School of Public Health. One surprising finding was that the regions with diabetes variants also seemed to be associated with nonrelated diseases. Researchers looked at a database containing a list of all the genome wide association (GWA) studies to date. They examined regions where there was a type 2 diabetes association to see if there was an increased association for other diseases and traits that have been studied thus far. "We saw surprising overlap or predisposition of not just related but also apparently unrelated traits," said Boehnke, who suggested that there could be master regulators in the genome that play a role in many different aspects of physiology and health. The next step is to take the research beyond GWA, which looks at a few million places on the genome, into genome sequencing. Genome sequencing will allow researchers to assay most of the 3 billion base pairs in the human genome and find less common variants that might be associated with disease. Currently, a three-study international team co-led by the Michigan group is sequencing 2,650 individuals with and without diabetes, in what is one of the largest sequencing projects underway in the world. Scott and Boehnke hope to have information about the variants present in individuals with and without diabetes within the next year-and-a-half. The paper, "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis," appeared online June 27 in Nature Genetics.Source: Laura BaileyUniversity of Michigan Please rate this article:(Hover over the starsthen click to rate) Patient / Public:12345orHealth Professional:12345Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.   Follow us on Twitter  Diabetes headlines  email to a friend  printer friendly version  weekly newsletter  personalize your news  rss feeds  back to topAdd Your OpinionAll opinions are moderated before being added.Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.If you write about specific medications or operations, please do not name health care professionals by name. Your Name:* E-mail Address:* Title For Opinion:* Opinion:* This is to help prevent SPAM submissions. Please enter the words exactly as they appear, including capital letters and punctuation.* * Fields marked with a * need to be filled in before you hit the submit button.Contact Our News EditorsFor any corrections of factual information, or to contact the editors please use our feedback form.Please send any medical news or health news press releases to: Back to topBack to front pageList of All Medical ArticlesPrivacy PolicyTerms and Conditions © 2010 MediLexicon International Ltd
  • January 22, 2010 — Hemoglobin A1c (HbA1c) may be useful for diabetes screening and diagnosis in routine clinical practice, according to the results of a study reported online in the January 12 issue of Diabetes Care."With current screening tools (fasting plasma glucose [FPG] ± oral glucose tolerance test [OGTT]), the prevalence of undiagnosed diabetes in Australia remains high," write Zhong X. Lu, PhD, from Melbourne Pathology Services in Australia, and colleagues. "HbA1c provides a practical alternative for screening [that] is more convenient and reproducible than is blood glucose. As optimal cut-offs are still in debate, we here explore HbA1c levels that confidently 'rule-out' and 'rule-in' diabetes in two different Australian populations."The goal of the study was to assess the value of HbA1c for screening and diagnosis of undiagnosed type 2 diabetes, as determined by OGTT, in clinical and general populations. In a clinical group (MP population) of 2494 persons, the prevalence of undiagnosed diabetes was 34.6%. This group was used to derive HbA1c cutoff values, which were 5.5% or more to "rule out" and at least 7.0% to "rule in" diabetes. These values were tested in a population-based sample (AusDiab) of 6015 persons, in which the prevalence of undiagnosed diabetes was 4.6%.Using an HbA1c cutoff value of 5.5% or less, sensitivity for diabetes was 98.7% in MP and 83.5% in AusDiab. With use of an HbA1c cutoff value of 7.0% or more, specificity was 98.2% for MP and 100% for AusDiab. In both populations, glucose status was abnormal in 61.9% to 69.3% of those with impaired HbA1c levels (5.6% - 6.9%)."HbA1c 7.0% predicts absence or presence of Type 2 diabetes while at HbA1c 6.5-6.9%, diabetes is highly probable in clinical and population settings," the study authors write. "A high proportion of people with IA1c [impaired A1c] have abnormal glucose status requiring follow-up."Limitations of HbA1c as a screening/diagnostic tool include method bias, certain confounding medical conditions such as hemoglobinopathies and anemia, and cost."Although the cost of HbA1c is slightly higher than for FPG, the overall efficiency of using HbA1c as first line for diabetes screening may facilitate early diagnosis and reduce the health burden associated with diabetes complications," the study authors conclude. "Our study supports recommendations to use HbA1c for diabetes screening and diagnosis. Using two, rather than one, cut-off values for HbA1c achieved high sensitivity for screening plus optimal specificity for diabetes diagnosis."The AusDiab study was supported by the National Health and Medical Research Council, Australian Government Department of Health and Ageing, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, AstraZeneca, Bristol-Myers Squibb, City Health Centre-Diabetes Service-Canberra, Department of Health and Community Services - Northern Territory, Department of Health and Human Services –Tasmania, Department of Health – New South Wales, Department of Health – Western Australia, Department of Health – South Australia, Department of Human Services – Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag,, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, and SanofiSynthelabo. The study authors have disclosed no relevant financial relationships.Diabetes Care. Published online January 12, 2010. Abstract[CLOSE WINDOW]Authors and DisclosuresJournalistLaurie Barclay, MDFreelance writer and reviewer, Medscape, LLCDisclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
  • What are pancreatic islets?The pancreas, an organ about the size of a hand, is located behind the lower part of the stomach. It makes insulin and enzymes that help the body digest and use food. Throughout the pancreas are clusters of cells called the islets of Langerhans. Islets are made up of several types of cells, including beta cells that make insulin.The pancreas is located in the abdomen behind the stomach. Islets within the pancreas contain beta cells, which produce insulin.Insulin is a hormone that helps the body use glucose for energy. Diabetes develops when the body doesn’t make enough insulin, cannot use insulin properly, or both, causing glucose to build up in the blood. In type 1 diabetes—an autoimmune disease—the beta cells of the pancreas no longer make insulin because the body’s immune system has attacked and destroyed them. A person who has type 1 diabetes must take insulin daily to live. Type 2 diabetes usually begins with a condition called insulin resistance, in which the body has difficulty using insulin effectively. Over time, insulin production declines as well, so many people with type 2 diabetes eventually need to take insulin.[Top]What is pancreatic islet transplantation?In an experimental procedure called islet transplantation, islets are taken from the pancreas of a deceased organ donor. The islets are purified, processed, and transferred into another person. Once implanted, the beta cells in these islets begin to make and release insulin. Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin.Research DevelopmentsScientists have made many advances in islet transplantation in recent years. Since reporting their findings in the June 2000 issue of the New England Journal of Medicine, researchers at the University of Alberta in Edmonton, Canada, have continued to use and refine a procedure called the Edmonton protocol to transplant pancreatic islets into selected patients with type 1 diabetes that is difficult to control. In 2005, the researchers published 5-year follow-up results for 65 patients who received transplants at their center and reported that about 10 percent of the patients remained free of the need for insulin injections at 5-year follow-up. Most recipients returned to using insulin because the transplanted islets lost their ability to function over time. The researchers noted, however, that many transplant recipients were able to reduce their need for insulin, achieve better glucose stability, and reduce problems with hypoglycemia, also called low blood sugar.In its 2006 annual report, the Collaborative Islet Transplant Registry, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, presented data from 23 islet transplant programs on 225 patients who received islet transplants between 1999 and 2005. According to the report, nearly two-thirds of recipients achieved “insulin independence”—defined as being able to stop insulin injections for at least 14 days—during the year following transplantation. However, other data from the report showed that insulin independence is difficult to maintain over time. Six months after their last infusion of islets, more than half of recipients were free of the need for insulin injections, but at 2-year follow-up, the proportion dropped to about one-third of recipients. The report described other benefits of islet transplantation, including reduced need for insulin among recipients who still needed insulin, improved blood glucose control, and greatly reduced risk of episodes of severe hypoglycemia.In a 2006 report of the Immune Tolerance Network’s international islet transplantation study, researchers emphasized the value of transplantation in reversing a condition known as hypoglycemia unawareness. People with hypoglycemia unawareness are vulnerable to dangerous episodes of severe hypoglycemia because they are not able to recognize that their blood glucose levels are too low. The study showed that even partial islet function after transplant can eliminate hypoglycemia unawareness.Transplant ProcedureResearchers use specialized enzymes to remove islets from the pancreas of a deceased donor. Because the islets are fragile, transplantation occurs soon after they are removed. Typically a patient receives at least 10,000 islet “equivalents” per kilogram of body weight, extracted from two donor pancreases. Patients often require two transplants to achieve insulin independence. Some transplants have used fewer islet equivalents taken from a single donated pancreas.Transplants are often performed by a radiologist, who uses x rays and ultrasound to guide placement of a catheter—a small plastic tube—through the upper abdomen and into the portal vein of the liver. The islets are then infused slowly through the catheter into the liver. The patient receives a local anesthetic and a sedative. In some cases, a surgeon may perform the transplant through a small incision, using general anesthesia.Islets extracted from a donor pancreas are infused into the liver. Once implanted, the beta cells in the islets begin to make and release insulin.Islets begin to release insulin soon after transplantation. However, full islet function and new blood vessel growth associated with the islets take time. The doctor will order many tests to check blood glucose levels after the transplant, and insulin is usually given until the islets are fully functional.[Top]What are the benefits and risks of islet transplantation?The goal of islet transplantation is to infuse enough islets to control the blood glucose level without insulin injections. Other benefits may include improved glucose control and prevention of potentially dangerous episodes of hypoglycemia. Because good control of blood glucose can slow or prevent the progression of complications associated with diabetes, such as heart disease, kidney disease, and nerve or eye damage, a successful transplant may reduce the risk of these complications.Risks of islet transplantation include the risks associated with the transplant procedure—particularly bleeding and blood clots—and side effects from the immunosuppressive drugs that transplant recipients must take to stop the immune system from rejecting the transplanted islets.Immunosuppressive DrugsRejection is the biggest problem with any transplant. The immune system is programmed to destroy bacteria, viruses, and tissue it recognizes as “foreign,” including transplanted islets. In addition, the autoimmune response that destroyed transplant recipients’ own islets in the first place can recur and attack the transplanted islets. Immunosuppressive drugs are needed to keep the transplanted islets functioning.The Edmonton protocol introduced the use of a new combination of immunosuppressive drugs, also called anti-rejection drugs, including daclizumab (Zenapax), sirolimus (Rapamune), and tacrolimus (Prograf). Daclizumab is given intravenously right after the transplant and then discontinued. Sirolimus and tacrolimus, the two main drugs that keep the immune system from destroying the transplanted islets, must be taken for life or for as long as the islets continue to function. These drugs have significant side effects and their long-term effects are still not fully known. Immediate side effects of immunosuppressive drugs may include mouth sores and gastrointestinal problems, such as stomach upset and diarrhea. Patients may also have increased blood cholesterol levels, hypertension, anemia, fatigue, decreased white blood cell counts, decreased kidney function, and increased susceptibility to bacterial and viral infections. Taking immunosuppressive drugs also increases the risk of tumors and cancer.Researchers continue to develop and study modifications to the Edmonton protocol drug regimen, including the use of new drugs and new combinations of drugs designed to help reduce destruction of transplanted islets and promote their successful implantation. These therapies may help transplant recipients achieve better function and durability of transplanted islets with fewer side effects. The ultimate goal is to achieve immune tolerance of the transplanted islets, where the patient’s immune system no longer recognizes the islets as foreign. If achieved, immune tolerance would allow patients to maintain transplanted islets without long-term immunosuppression.Researchers are also trying to find new approaches that will allow successful transplantation without the use of immunosuppressive drugs. For example, one study is testing the transplantation of islets that are encapsulated with a special coating designed to prevent rejection.Shortage of IsletsA major obstacle to widespread use of islet transplantation is the shortage of islets. Although organs from about 7,000 deceased donors become available each year in the United States, fewer than half of the donated pancreases are suitable for whole organ pancreas transplantation or for harvesting of islets—enough for only a small percentage of those with type 1 diabetes. However, researchers are pursuing various approaches to solve this problem, such as transplanting islets from a single donated pancreas, from a portion of the pancreas of a living donor, or from pigs. Researchers have transplanted pig islets into other animals, including monkeys, by encapsulating the islets or by using drugs to prevent rejection. Another approach is creating islets from other types of cells, such as stem cells. New technologies could then be employed to grow islets in the laboratory.

Recent advance in diabetes mellitus ppt BIOCHEMISTRY Recent advance in diabetes mellitus ppt BIOCHEMISTRY Presentation Transcript

  • 8/26/2013 1 Dr Vijaya Marakala MD vkunder637@gmail.com
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  • Gains • Better living conditions • Variety of foods • Better transportation • Better communication Losses • More eating • Less physical activity • More stress 8/26/2013 3
  • Obesity Diabetes Hypertension and cardiovascular diseases Leading to…. 8/26/2013 4
  • DIABETES MELLITUS Definition Classification Lab diagnosis Recent aspects 8/26/2013 5
  • A metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both . 8/26/2013 6
  • 2009(in millions) INDIA 50.8 CHINA 43.2 US 26.8 0 10 20 30 40 50 60 Inmillions Top 3 countries number of adults with diabetes, 2009 8/26/2013 7
  • One person in the world dying of diabetes every ten seconds. There will be 2 new diabetic cases in the world being identified every 10sec. In the national survey 54.1% of diabetes developed it in the most productive years of their lives IDF predicts that diabetes will cost the world economy at least US$376 billion in 2010, or 11.6% of total world healthcare expenditure.8/26/2013 8
  • Year Author Place Area Prevalence(%) Urban Rural 1971 Tripathy et al Cuttak Central 1.2 1972 Ahuja et al New Delhi North 2.3 1979 Gupta et al Multicentere 3 1.3 1984 Murthy et al Tenali South 4.7 1986 Patel Bhadran West 3.8 1988 Ramachandran et al Kudremukh South 5 1989 Kodali et al Gangavathi South 2.2 1989 Rao et al Eluru South 1.6 1991 Ahuja et al New Delhi North 6.7 1992 Ramachandran et al Madras South 8.2 2.4 1997 Ramachandran et al Madras South 11.6 2000 Ramakutty et al Kerala South 12.4 2.5 2001 Ramachandran et al National DESI 12.1 2001 Mishra et al New Delhi North 10.3 2001 Mohan et al Chennai South 12.18/26/2013 9
  • 10 Zimmet, Nature 2001 India: 2000:32 mill 2020: 81 mill 8/26/2013
  • Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational 8/26/2013 11
  • Classification of DIABETES MELLITUS Type 1 β-Cell destruction Absolute insulin deficiency Autoantibodies Type 2 Other Gestational Islet cell autoantibodies Insulin autoantibodies Glutamic acid decarboxylase autoantibodies Tyrosine phosphatase IA-2 and IA-2B b autoantibodies 8/26/2013 12
  • Classification of DIABETES MELLITUS Type 1 Type 2 Insulin resistance with an insulin secretary defect Relative insulin deficiency Other Gestational 8/26/2013 13
  • Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational Associated with secondary conditions Genetic disease of β-cell function and insulin action Pancreatic disease Endocrine disease Drug or chemical induced Insulin receptor abnormalities Other genetic syndromes 8/26/2013 14
  • Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational Glucose intolerance during pregnancy due to metabolic and hormonal changes 8/26/2013 15
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  • This form of diabetes is immune-mediated in over 90% of cases and idiopathic in less than 10%. Polyuria, polydipsia, and weight loss associated with RPG200 mg/dL. FPG>126 mg/dl more than one occasion Islet autoantibodis are frequently present. 8/26/2013 17
  • Approximately one-third of the disease susceptibility is due to genes and two-thirds to environmental factors. Genes that are related to the HLA locus contribute about 40% of the genetic risk. • About 95% of patients with type 1 diabetes possess either HLA-DR3 or HLA-DR4, compared with 45–50% of white controls. 8/26/2013 18
  • Diagnostic sensitivity and specificity of autoimmune markers in patients with newly diagnosed type 1 diabetes mellitus. Sensitivity Specificity Glutamic acid decarboxylase (GAD65) 70–90% 99% Insulin (IAA) 40–70% 99% Tyrosine phosphatase (IA-2) 50–70% 99% Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2-β ) at the time the diagnosis is made. 8/26/2013 19
  • • Less than 10% of subjects have no evidence of pancreatic β cell autoimmunity to explain their insulinopenia and ketoacidosis. It was recently reported that about 4% of the West Africans with ketosis-prone diabetes are homozygous for a mutation in PAX-4 (Arg133Trp)—a gene that is essential for the development of pancreatic islets. 8/26/2013 20
  • Most patients are over 40 years of age and obese. Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms. Hypertension, dyslipidemia, and atherosclerosis are often associated. 8/26/2013 21
  • Autosomal dominant and an age at onset of 25 years or younger. Nonobese and impaired glucose-induced secretion of insulin. Mutations of a transcription factor that regulates islet gene expression. 8/26/2013 22
  • This is a very rare subtype of nonobese type 2 diabetes, with no more than ten families having been described. Since affected individuals were heterozygous and possessed one normal insulin gene, diabetes was mild, did not appear until middle age, and showed autosomal dominant genetic transmission. 8/26/2013 23
  • Defects in one of their insulin receptor genes have been found in more than 40 people with diabetes, and most have extreme insulin resistance associated with acanthosis nigricans. Diabetes due to mutant insulin receptors Insulin Receptors 8/26/2013 24
  • Impairs the transfer of leucine or lysine into mitochondrial proteins has been described. Most patients have a mild form of diabetes Diabetes mellitus associated with a mutation of mitochondrial DNA 8/26/2013 25
  • An autosomal recessive neurodegenerative disorder first evident in childhood. It is due to mutations in a gene WFS1, which encodes a 100.3 KDa transmembrane protein localized in the ER. Wolfram's syndrome DIDMOAD 8/26/2013 26
  • Individuals are at much higher risk for developing type 2 diabetes than insulin-sensitive persons also elevated plasma triglycerides, lower high-density lipoproteins (HDLs), and higher blood pressure Twenty-five percent of the general obese nondiabetic population has insulin resistance of a magnitude similar to that seen in type 2 diabetes. 8/26/2013 27
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  • Occurs during pregnancy as a result of hormonal influences causing insulin resistance 8/26/2013 29
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  • DIABETES MELLITUS Insulin↓ and glucagon↑ ↓Glucose uptake Hyperglycemia Glucosuria • Osmotic diuresis • Dehydration • Coma • Death ↑Protein catabolism ↑Plasma amino acids ↑Nitrogen loss in urine ↑Gluconeogenesis ↑Lipolysis ↑FFA oxidation ↑Ketogenesis • Ketosis • Coma • Death Metabolic events occurring in diabetes mellitus 8/26/2013 31
  • Clinical features of diabetes at diagnosis. Type 1 Diabetes Type 2 Diabetes Polyuria and thirst ++ + Weakness or fatigue ++ + Polyphagia with weight loss ++ – Recurrent blurred vision + ++ Vulvovaginitis or pruritus + ++ Peripheral neuropathy + ++ Nocturnal enuresis ++ – Often asymptomatic – ++ 8/26/2013 32
  • Between 1979-1997Before 1979 No uniform criteria NDDG&WHO Diagnostic criteria for Diabetes Mellitus 8/26/2013 33
  • 19991997 ADA WHO Diagnostic criteria for Diabetes Mellitus 8/26/2013 34
  • Since 1965 the WHO has published guidelines for the diagnosis and classification of diabetes. These were last reviewed in 1998 In addition, in 2003, the ADA reviewed its diagnostic criteria. ADA recommended lowering the threshold for IFG from 6.1mmol/l (110mg/dl) to 5.6mmol/l(100mg/ dl) 8/26/2013 35
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  • Paper strip impregnated with glucose oxidase and a chromogen system Sensitive to as little as 0.1% glucose in urine. Urinalysis 8/26/2013 39
  • By nitroprusside tests (Acetest or Ketostix). Do not detect β- hydroxybutyric acid Urinalysis 8/26/2013 40
  • Blood testing procedures Normal carbohydrate diet for 3 days Overnight fast on the day of the test FPG is drawn Give 75gm of anhydrous glucose in about 300ml of water Blood & urine specimens are collected at half hourly for 2hours A curve is plotted for time against blood glucose 8/26/2013 41
  • The Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test.1 Normal Glucose Tolerance Impaired Glucose Tolerance Diabetes Mellitus Fasting plasma glucose (mg/dL) < 110 110–125 ≥126 Two hours after glucose load (mg/dL) < 140 ≥140–199 ≥200 Criteria for laboratory confirmation of diabetes mellitus Blood testing procedures 8/26/2013 42
  • The major form of HbA1 is hemoglobin A1c (HbA1c) where glucose is the carbohydrate. The remaining HbA1 species contain fructose-1,6 diphosphate (HbA1a1); glucose-6-phosphate (HbA1a2); and unknown carbohydrate moiety (HbA1b). Blood testing procedures 8/26/2013 43
  • Blood testing procedures Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin). 8/26/2013 44
  • Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful 8/26/2013 45
  • DexCom system MiniMed system Glucowatch system 8/26/2013 46
  • Lipoprotein abnormalities in diabetes High serum triglyceride level (300–400 mg/dL), Low HDL cholesterol (less than 30 mg/dL), and Qualitative change in LDL particles, producing a smaller dense particle 8/26/2013 47
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  • Obese people have large amounts of the molecule CXCL5, produced by certain cells in fatty tissue "The CXCL5 molecule helps cause insulin resistance and type 2 diabetes". The finding has been published in the journal Cell Metabolism 8/26/2013 49
  • ACS' weekly newsmagazine Drug manufacturers have tried for years to develop oral insulin without much success. Several insulin pills are now in various stages of clinical trials 8/26/2013 50
  • Bianca van Lierop, Monash University and her colleagues have successfully strengthened insulin's chemical structure, which can withstand higher temperatures. A development that will bring relief to millions of diabetics across the world. 8/26/2013 51
  • "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis," Appeared online June 27 in Nature Genetics. DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38. 8/26/2013 52
  • From HbA1c May Be Useful for Diabetes Screening, Diagnosis in Routine Clinical Practice .Laurie Barclay, MD January 22, 2010January 12 issue of Diabetes Care. Diabetes Care Study authors write. "A high proportion of people with IA1c [impaired A1c] have abnormal glucose status requiring follow-up." "HbA1c provides a practical alternative for screening [that] is more convenient and reproducible than is blood glucose. "HbA1c <5.5% and >7.0% predicts absence or presence of Type 2 diabetes while at HbA1c 6.5-6.9%, diabetes is highly probable in clinical and population settings," 8/26/2013 53
  • In an experimental procedure called islet transplantation, islets are taken from the pancreas of a deceased organ donor. The islets are purified, processed, and transferred into another person. Once implanted, the beta cells in these islets begin to make and release insulin. Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin. 8/26/2013 54
  • CMDT 2010 Standards of Medical Care in Diabetes—2010 American Diabetes Association Internet 8/26/2013 55