Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion or action. Chronic hyperglycemia can cause long term damage to organs like the eyes, kidneys, nerves, heart, and blood vessels. The disease is defined by symptoms of high blood glucose plus a plasma glucose level over 200 mg/dL, a fasting plasma glucose over 126 mg/dL, or a two hour post-glucose load over 200 mg/dL during an oral glucose tolerance test. The main causes of death for people with diabetes are cardiovascular disease and renal failure. Treatment involves lifestyle changes like diet, exercise and education combined with oral medications or insulin to lower blood glucose levels.

1. Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia
resulting from defects in insulin
secretion, insulin action, or both. The
chronic hyperglycemia of diabetes is
associated with long term damage,
dysfunction, and failure of various
organs, especially the eyes, kidneys,
nerves, heart and blood vessels.
Definition of Diabetes Mellitus

2. 1. Symptoms of diabetes plus casual plasma glucose
concentration ≥ 200 mg/dl (11.1 mmol/l)
Casual is defined as any time of day without regard to
time since last meal. The classic symptoms of diabetes
include polyuria,polydipsia,and unexplained weight loss.
or
2. FPG ≥ 126 mg/dl (7.0 mmol/l). Fasting is defined as no
caloric intake for at least 8 h.
or
3. 2-h post load glucose ≥ 200 mg/dl (11.1 mmol/l) during an
OGTT.The test should be performed as described by WHO.
In the absence of unequivocal hyperglycemia, these criteria should be confirmed by
repeat testing on a different day. The third measure (OGTT) is not recommended for
routine clinical use. Diabetes Care, Jan 2009
Criteria for the diagnosis of
diabetes mellitus

4. Causes of Death in People with Diabetes
● Cardiovascular disease 70%
● Renal failure 10%
● Cancer 10%
● Infections 06%
● Diabetic ketoacidosis 01%
● Other 03%

5. Insulin
Monitoring
Education &
Motivation
Diet
Exercise
Oral Agents
Treatment of Type 2 Diabetes

6. Traditional Food Pyramid
• High Carb/low
fat 55%
carbohydrate,
• 25% protein,
• 20% fat

7. Balanced Discuss with your client the effect of high GI carb foods
versus low GI-carb foods
35-40% carbohydrates,
20--25%
protein
35-40% fat

8. Low Glycemic Carbohydrates
• More Protein
• Low GI Carbs
• Appropriate Fats

9. Regular 30
minutes
exercise
Prevent diabetes
Prevent blood
pressure
Prevent
Dislipidemia
Prevent heart
attack
Prevent stroke
Prevent
Obesity
Make cheerful
Strengthen
immune
system
Make sound
Sleep
Keep body fit

10. Diabetes
Management
Algorithm

11. SITES OF ACTION OF DRUGS USED TO TREAT NON-INSULIN-DEPENDENT
DIABETES.

12. SIDE EFFECTS OF ORAL ANTIHYPERGLYCEMIC AGENTS
Liver
Toxicity
Lactic
Acidosis
GI
Effects
Edema
Wt.
Gain
Hypo-
glycemia
Drug
±
0
±
0
1+
1+
Glipizide XL
±
0
±
0
1+
2+
Glimepiride
±
0
±
0
1+
2+
Gliclazide
±
0
±
0
2+
4+
Glibenclamide
0
0
0
0
1+
1+
Repaglinide
0
0
0
0
?
1+
Nateglinide
0
1+
2+
0
0
Metformin
±
0
3+
0
0
0
Acarbose
0
0
3+
0
0
0
Miglitol
0*
0
0
2+
3+
0
Rosiglitazone
0*
0
0
2+
3+
0
Pioglitazone
0
0
±
0
0
0
DPP4 i
0
0
0
0
2-
0
SGLT2 i

13. Insulin Secretagogues: Sulfonylureas (Generic
Glyburide, Glibenclamide, Gliclazide) Repaglinide,
Nateglinide
 Action
– Release of insulin from
pancreas in response to a
glucose challenge
– Repaglinide and
Nateglinide have short
half-life (~1 hour)
 Clinical Indicators
– Insulin Deficiency
– BMI <27 kg/m2
– HbA1c <9%
– High postprandial BG 200-
300 mg/dL (11.1-16.7
mmol/L)
 Side effects
– Weight gain
– Hypoglycemia
 Precautions and
Contraindications
– Kidney Disease: No dosage
adjustment required
– Liver Disease: Use caution, not
well studied with liver disease
– Known hypersensitivity to the drug
 Pregnancy
– Contraindicated, initiate insulin
therapy

14. Beta cells produce insulin and
store it in secretory vesicles
ATP
ADP
Pyruvate
Voltage-gated
Calcium Channel
Ca++
Ca+
+
G
G G
G
G
G
Glucose
Transporter
(Glut 2) G
G
G
G
G
G
G
G
G
G
G
Potassium
Channel
K
+
Insulin Secretagogues:
Beta Cell Function
N
X
K+ Channel Blocked- membrane becomes depolarized
S
R
K +

15. Insulin Sensitizer:
Metformin
 Action
– Overcomes liver insulin
resistance resulting in lower
gluconeogenesis
– Improve insulin sensitivity in
peripheral tissue
 Clinical Indicators
– Insulin Resistance
– BMI > 27 kg/m2
– HbA1c <9% as monotherapy
– High fasting blood glucose
(160-250 mg/dL or 8.9-13.9
mmol/L)
– Dyslipidemia
 Side effects
– GI distress (effecting weight
loss?)
– Metallic taste
 Precautions and
Contraindications
– Kidney Disease: serum
creatinine >1.4 F, >1.5 M
– Liver Disease: if present or if
excessive alcohol intake,
metabolic acidosis
– Heart Disease: Active
cardiac or pulmonary disease
– Hold Metformin at time of, or
prior to, iodinated contrast
dye or surgical procedures
 Pregnancy
– passes placental barrier,
initiate insulin therapy

16. Insulin Sensitizer: Thiazolidindione
Pioglitazone and Rosiglitazone
 Action
– Overcomes insulin resistance
insulin sensitive tissue
 Clinical Indicators
– Insulin Resistance
– BMI > 27 kg/m2
– HbA1c <9% as monotherapy
– High fasting blood glucose
(160-250 mg/dL or 8.9-13.9
mmol/L)
– Insulin Resistance Syndrome
 Side effects
– Edema
– Weight gain
 Precautions and
Contraindications
– Kidney Disease: none
– Liver Disease: don’t initiate
therapy if ALT>2.5X upper
limit of normal, more
monitoring for mildly elevated
ALTs
– Heart Disease: Evidence of
ischemic heart disease or CHF
 Pregnancy
– passes placental barrier,
initiate insulin therapy

17. Overcoming Insulin
Resistance
Nucleus
Insulin Sensitive Cell
(Muscle or Fat)
Insulin
Glucose
Insulin
Receptor
Glucose
Transporter
(GLUT4)
G
G G G
G TZD
G G G

18. α-Glucosidase Inhibitor:
Acarbose and Miglitol
 Action
– Delays carbohydrates
absorption by interfering with
their breakdown
 Clinical Indicators
– Insulin
Deficiency/Insulin
Resistance
– HbA1c<8% as monotherapy
– High post prandial blood
glucose (180-225 mg/dL or
10.0-12.5 mmol/L))
 Side effects
– Flatulence, abdominal pain and
diarrhea
 Precautions and
Contraindications
– Kidney Disease: Serum
creatinine >2.0 mg/dL
– Liver Disease: Evidence of
severe disease
– Heart Disease: none
– Inflammatory bowel
disease
 Pregnancy
– passes placental barrier,
initiate insulin therapy

19. Properties of commonly prescribed insulin
secretogouges
Comments
Duration
of action
Daily
dose
Generic
name
Relatively short acting
Hypoglycemia less severe
>12 h
2.5-20 mg
Glipizide
Hypoglycemia and weight gain
reported to be quite High
24 h
5-20 mg
Glibenclamide
Hypoglycemia frequency and
severity less
No interference with ischemic
preconditioning
24 h
1-8 mg
Glimepiride
Hypoglycemia less severe
24 h
80-320
Gliclazide
Low incidence of
hypoglycemia
Weight gain less than with
sulfonylureas
5-6 h
1-4 mg
with each
meal
Repaglinide
Very low incidence of
hypoglycemia
Little data on weight gain
3-4 h
60-120 mg
with each
meal
Nateglinide

22. SIDE EFFECTS OF ORAL ANTIHYPERGLYCEMIC AGENTS
Liver
Toxicity
Lactic
Acidosis
GI
Effects
Edema
Wt.
Gain
Hypo-
glycemia
Drug
±
0
±
0
1+
1+
Glipizide XL
±
0
±
0
1+
2+
Glimepiride
±
0
±
0
1+
2+
Gliclazide
±
0
±
0
2+
4+
Glibenclamide
0
0
0
0
1+
1+
Repaglinide
0
0
0
0
?
1+
Nateglinide
0
1+
2+
0
0
Metformin
±
0
3+
0
0
0
Acarbose
0
0
3+
0
0
0
Miglitol
0*
0
0
2+
3+
0
Rosiglitazone
0*
0
0
2+
3+
0
Pioglitazone

23. Incretin: GLP-1
GLP-1 secreted upon
the ingestion of food
1.β-cell:
Enhances glucose-dependent
insulin secretion in the
pancreas1
3.Liver:
reduces hepatic glucose
output2
2.α-cell:
Suppresses postprandial
glucagon secretion1
4.Stomach:
slows the rate of
gastric emptying3
5.Brain:
Promotes satiety and
reduces appetite4,5
Problem: GLP-1 rapidly degraded by DPPIV
Long-term effects
in animal models:
• Increase of β-cell mass
and improved β-cell function

24. Mechanisms of β-cell secretion

28. INDICATION FOR INSULIN
THERAPY IN TYPE 2 DIABETES
Acute metabolic complications
Pregnancy and lactation
Acute illness
Fasting plasma glucose >300 mg/dl
Failure of oral hypoglycemic agents
Severe infection

29. Types Examples
Bolus (Meal) Insulin
Rapid-actingInsulin lispro,
Insulin aspart
Short-acting Regular
Basal (Background) Insulin
Intermediate-acting NPH, Lente
Long-acting Glargine, Detemir
Pre-Mixed Insulin
NPH/Regular 70/30, 50/50
NPL/Lispro Mix 75/25
NPA/Aspart Mix 70/30
Insulin

30. 0 2 4 8 10 12 14 16 18 20 22 24
Plasma
Insulin
Levels
Hours
NPH (12–16 hr)
Regular (6–8 hr)
Glargine (~22 hr)
ASAspart, Lispro (4–5 hr)
Ultralente (~16–20 hr )
Insulin Profiles – schematic (duration)
Detemir (~20 hr)
INSULIN THERAPY in Diabetes Mellitus
6

31. 0
10
20
30
40
50
0 2 4 6 8 10 12 14 16 18 20 22 24
Normal Insulin Secretion
Serum
insulin
(mU/L)
Time (Hours)
Meal Meal Meal
Basal Insulin Needs
Bolus insulin needs