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Management of Type 2 Diabetic
patients in Daily Clinical Practice

KO KO
NOGH,UM(2)
©

www.bhtinfo.com


The majority of diabetic patients (greater than 90 percent) receive their care
from primary care physician.

generalist...
• A 40 years old lady is found to have
hyperglycaemia at your clinics. Her RBS is
220 mg/dl.

Is she diabetic?
• Diagnosis of DM should not be made by single
measurement of blood sugar alone.
• It is important to assess
Hyperosmolar...
AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007; 13 (Suppl 1) 2007
ADA 2012 Guidelines on
Diagnosing diabetes
Prediabetes: IFG, IGT, Increased A1C
Categories of increased risk for diabetes
(Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 m...
Definition of Diabetes

American
(mg/dL)

SI
(mmo/L)

Normal

65 - 99

3.6 – 5.5

DM

> 126

> 7.0

Random (with
symptoms)...
Millions

Number of People with Diabetes
by Age Group, 2010 and 2030
Millions

Number of People with Impaired Glucose
Tolerance by Age Group, 2010 and 2030
CHALLENGES
• Prediabetes

SOLUTIONS
• Early diagnosis &
• Life style changes

Early diagnosis
Life style changes

PREDIABE...
Criteria for Testing for Diabetes in
Asymptomatic Adult Individuals (1)
1. Testing should be considered in all adults who ...
Criteria for Testing for Diabetes in
Asymptomatic Adult Individuals (2)
2. In the absence of criteria (risk factors on
pre...
• The lady is tested again the next day. Her
FBS is 170mg/dl. So DM is diagnosed.

What should I do next?
Doctors should do
What a Doctor should do for medical care of patient
with DM?
•
•
•
•
•
•

•
•
•

Diagnosis
Screening
Evaluation of diabete...
• Diabetes never come alone
• It come in hand with

•Diabetes
•Hypertension
•IHD
•Increased Lipid
•Stroke

Obesity
Hyper...
Patient Education in Diabetes Mellitus:
10 Content Areas
Diabetes
Disease
Process

Integrating
Psychosocial
Adjustment
To ...
ATP III : General features of the Metabolic
Syndrome
• Abdominal obesity
(waist circumference)
Men
Women
• Elevated trigly...
The Metabolic Syndrome
 Low HDL cholesterol
 Borderline triglycerides
 Central obesity
 Prehypertension
 Impaired fas...
Complications
• Microvascular
 Retinopathy (Fundoscopy)
 Nephropathy (microalbuminuria, Urine RE, Urea, Cr)
 Neuropathy...
• Examination and investigations of the lady
showed
 BMI
 Waist circumference
 BP
 Total cholesterol
 LDL
 HDL
 Tri...
Problems
1.
2.
3.
4.

Newly diagnosed Type (2)DM
Obesity(BMI 32)
Hypertension
Hyperlipidaemia
Mortality in People With
Diabetes:
Causes of Death
50
40
%
of deaths

30
20
10
0

Ischemic Other DiabetesCancer Stroke Inf...
Evidence level of the recommendations

In type 2 DM management
Strategy
evidence

Evidence-based benefit

Quality of

Glyc...
Treatment of Type 2 Diabetes
Diagnosis
Therapeutic Lifestyle Change
Monotherapy
Combination Therapy - Oral Drugs Only
Comb...
Do we need to get good glycemic control?
Optimal Glycaemic Control
 Is important to prevent death ,disability &

complications of DM







-FBS
- 90-130mg%
...
Glycemic Recommendations for NonPregnant Adults with Diabetes (1)
A1C

<7.0%*

Preprandial capillary
plasma glucose

70–13...
Recommendations:
Glycemic Goals in Adults (2)
• Additional analysis from several
randomized trials suggest a small but
inc...
Recommendations:
Glycemic Goals in Adults (3)
• Conversely, less stringent A1C goals may
be appropriate for patients with
...
How Can we get good control of DM?

?
Therapeutic Lifestyle change
Diabetes food pyramid
Fats, oils, sugars, refined foods,
fatty foods: eat sparingly
Low fat m...
Plate model
Fruit
Protein

Milk/yoghurt
Vegetable

Vegetable

Starch/cereal
Rate Your Plate
Slides current until 2008
Physical activity
Recommendations
• People with diabetes should be advised to perform at
least 150 min/week of moderate-in...
Medical Nutrition
Therapy and Physical
Activity

Prevent
Diabetes
Pharmacological treatment
Diabetes And Glycemic Control: A Rational Approach
• As low as possible
• As early as possible

Lifestyle +
MET + TZD + SU...
Basic Steps in the Management of Type 2
Diabetes

d
ex iet &
er
cis
e

mo O
no ral
th
er
a

co Or
mb al
ina
tio
n
py

Or
a...
Type 2 Diabetes Medication Choices
Experience and Potency
Route

Year

Efficacy as monotherapy: %
↓ in HgbA1c

Insulin

s....
Mechanisms of Action of Pharmacologic
Agents for Diabetes

Improving Outcomes in Patients With Type 2 Diabetes Mellitus: P...
NEW IDF
2011
Early combination approach
Monitoring
• SMBG
• HbA1C

52
Glycemic control
Recommendations for A1C
• Perform the A1C test at least two times a year in patients who
are meeting trea...
Self-monitoring of Blood Glucose
(SMBG)
• SMBG should be carried out three or more times daily for patients
using multiple...
Which one is important?
• FPG ------basal for microvascular
complication
• 2HPG ----for macrovascular
complication(mainly ...
What Do We Look For In Anti-diabetic
Drug?
• Effectiveness in lowering glucose
• Extra-glycemic Effects
• Long-term compli...
An Ideal OHA should have…


Fast onset of action



To stimulate insulin secretion (including first phase)



Decrease ...
An Ideal OHA should have…



Control FPG & PPG effectively



Lowest risk of hypoglycemia



Should not produce hyperin...
ADA (antidiabetic drugs)
Sulfonylureas
Non-Sulfonylureas
Biguanides
Thiozolidinediones (Glitazones)
Alpha Glucosidase enzy...
Metformin/Glitazones

SU/Non-SU

α-glucosidase inhibitors
Effect

SU and NSU

Metformin

TZA

AGI

Mechanism

Increase in insulin
secretion

Decrease in HGO plus
increases muscle
s...
Anti-hyperglycemic agents in T2DM
Class
MET

AIC
reduction

Fasting versus
PPG

Hypoglyce
mia

Weight
change

Dosing

1.5
...
Initial Therapy with OHAs
Initial

Add

Add

SU

Metformin

Insulin

Metformin

SU

TZD/Insulin

Obese not tolerating MET
...
Metformin - Drug Profile
No hypoglycemia
Weight loss
Advantages

Cardiovascular benefit
Reduces LDL-C (approx 10 mg/dL),
r...
Sulfonylureas - Drug Profile
Advantages

Potent glucose lowering effect
Favorable adverse effect profile
Hypoglycemia, mor...
Repaglinide and Nateglinide: Drug Profiles

Advantages

Disadvantages

Less hypoglycemia than
sulfonylureas
Favorable adve...
TZDs - Drug Profile
No hypoglycemia
Advantages

May be useful in nonalcoholic fatty
liver disease
Increased fracture risk
...
Alpha Glucosidase Inhibitor (AGI) Drug Profile

Advantages

Disadvantages

No hypoglycemia
Weight neutral
Targets only pos...
Combination Therapy with OHAs
• Drug combinations should be based on
A. Therapeutic efficacy (“fire power”)
B. Complementa...
Estimated Improvements with Combination Rx
Combination

AIC% reduction

FPG reduction

SU + MET

1.7%

65 mg/dl

SU + ROS
...
Strategies for Antidiabetic Treatment

Oral Monotherapy

Metformin
Sulfonylureas
Glinides
TZDs
α-Glucosidase-Inhibitors
DP...
ADA/EASD Consensus Algorithm for the Initiation and Adjustment of
Therapy Diabetes Care 2009; 32:193–203
Master Decision Path
Type 2 Diabetes Glycemic Control
At Diagnosis
(mg/dl)

Medical Nutrition Therapy
Medical Nutrition Th...
Glitazones
• Monotherapy if
• MET contraindicated
• Intolerant to MET
• Combination Rx
• SU
• MET (high IR)
• Insulin (Bbo...
Sulfonylureas
• Which ?
• When?
• Why?

All have same MOA
All have same
1ststline in underwt/normal wt MOA2 patients
1 lin...
Comparison between 3 generations of
Sulphonylureas
Drug

2nd generation

3rd generation

Tolbutamide

Range of
dosage
500-...
Sulfonylureas: How to Choose?
• Cardiac patients: Glimepiride/GLICLAZIDE
• Elderly patients: Glimepiride/GLICLAZIDE
• Econ...
Metformin: Crucial Part of Therapy
Metformin Effects on Risk
Metformin Effects on Risk
Factors
Factors

Hundal RS, Inzucch...
No Single Class of Oral Antihyperglycemic
Monotherapy Targets All Key Pathophysiologies

Major Pathophysiologies

AlphaGlu...
TWO basic INSULIN
REGIMENS
Supplementary
Supplementary

Substitution
Substitution

(OHD +Bed time insulin)

( No OHD +Only...
Insulin Regimen for Type 2 Diabetes
Mellitus
Guidelines for Starting insulin therapy
(Asia Pacific Type 2 Diabetes Policy ...
Insulin Regimen for Type 2 Diabetes
Mellitus
Guidelines for Starting insulin therapy
(Asia Pacific Type 2 Diabetes Policy ...
Insulin Regimen for Type 2 Diabetes
Mellitus

Insulin

60

PREMIX

40

20
0

6 AM

12 AM

PREMIX 30/70

6 PM 12 PM
PREMIX ...
Basal Bolus Regimen (Substitution)
•

Mimics physiological insulin profile: starting dose
- 40% daily dose as basal insuli...
Initiation of Basal Bolus insulin regimen
Calculate Total Daily Insulin (TDI) =
0.5 units x weight (kg) OR (sum of current...
Diabetes Prevention
Can we prevent Diabetes Mellitus?
• Yes. We can

“ Small Steps. Big Rewards.
Prevent type 2 Diabetes”
Percent developing diabetes
Incidence of Diabetes
All
Placebo (n=1082)

Metformin (n=1073, p<0.001 vs. Placebo)
Lifestyle ...
Standards of Medical Care in Diabetes—2011


PREVENTION/DELAY OF TYPE 2 DIABETES



Recommendations



● Patients with ...
Are we achieving good control?
Treatment Strategies for Diabetes:
Are Patients Achieving Good Control?
Hypertension
BP <140/90 mm Hg

Hyperlipidemia
LDL-...
If RBS control is difficult
• Always ask about other medications
 Steroids
 Thiazide
 Beta-blockers
• Always check diet...
Measures to improve drug-compliance
• Patient’s education
• Promoting patient’s involvement in management
• Reducing pill ...
DRUGS
• Correct Drugs
• Correct Doses
• Correct Timing
• Correct Combination
• Compliance
• ?steroid
Correct Drugs
• Insulin
Type(1)DM/Type 2 DM with Stress/OHA Failure
• TZD/Metformin
Insulin Resistance
• Postprandial Hype...
Correct Combination
• SU+MFM
• SU + Acarbose
• SU + Thiazolidinediones
• MFM + Thiazolidinediones
• MFM + Acarbose
• SU + ...
Correct Drugs

Insulin
Resistance

• Thiazolidine
diones
• Metformin

Postprandial Hyperglycemic

Insulin Deficiency

• Gl...
Blood Pressure Management
JNC 7 and ADA recommendations
• Hypertension blood pressure: ≥140/90mmHg
• Target blood pressure...
 ACE inhibitor or ARB should be first choice
 If not controlled add diuretic (thiazide if






GFR>50ml, or loop di...
ESH/ESC Guidelines recommend initiating a
two-drug combination in high risk patients
High risk patient:
Eg Diabetes


Tre...
Management of Dyslipidiaemia
• Main predictors of CVD mortality
LDL and HDL cholesterol
• Lipid profile in type 2 diabete...
Target for lipids
• HDL

>50 mg/dl

• LDL

<100 mg/dl

• TG

<150 mg/dl

• TC

<200 mg/dl
Treatment and goal
•
•
•

Increased physical activity
Reduction of saturated fat and cholesterol
Statin therapy should be ...
Dyslipidemia Management
• Lifestyle modifications are essential. (Grade D)
•

Statins are the pharmacologic treatment of c...
Dyslipidemia Management
• Combination therapy in patients who have
not achieved the desired goals with
monotherapy. (Grade...
Diabetes UK recommends that aspirin should be offered to people with
diabetes who already have a history of CVD.
Antiplatelet Agents
• Use aspirin therapy (75-162 mg/day) as a secondary

prevention strategy in diabetic individuals with...
Antiplatelet Agents
• Aspirin therapy is not recommended in people under 30 years
of age, due to lack of evidence of benef...
Is it necessary to hospitalize the patient?
• High blood sugar alone is not an indication
for hospitalization
• When to re...
Indications for insulin therapy in
Type 2 DM
• Failure to achieve glycemic control with diet, exercise and
oral medication...
Take Home Message
 Glycemic control : HbA1c <7% ADA, <6.5% AACE
(ADVANCE)
 Blood pressure <130/ 80 mmHg
 Lipid control
...
The Pill Burger
Diabetes And Glycemic Control: A Rational Approach
• As low as possible
• As early as possible

Lifestyle +
MET + TZD + SU...
Need for global treatment to reduce complications
Exe
rcis
e

ens
p er t
Hy

Ob
es
i
y t

ion

H

cem
ly
erg ia
yp

i d e ...
Diabetes And Glycemic Control: A Rational Approach


A = Advice – Diet, Exercise, Stop smoking



B = BP – 130/80 mm Hg
...
Avoid bad habits...
jyHK;yg/
(pdwfzdpD;rIrsm; avsmhenf;EdkiforQ
avsmhenf;atmif BudK;pm;yg/
)

118
Don’t worry
I will take care of
DM
Save big Money
The end is here

Confused?

But

Thank you
Thank You for Kind Attention
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
Dm talk npt,tmo)
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  • In 1997 and 203, The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus1,2 recognized an intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are nevertheless too high to be considered normal
    This group was defined as having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
    IFG: fasting plasma glucose (FPG) of 100-125 mg/dl (5.6-5.9 mmol/l)
    IGT: two-hour plasma glucose (2-h PG) on the 75-g oral glucose tolerance test (OGTT) of 140-199 mg/dl (7.8-11.0 mmol/l)
    It should be noted that the World Health Organization (WHO) and a number of other diabetes organizations define the cutoff for IFG at 110 mg/dl (6.1 mmol)
    Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating a relatively high risk for future development of diabetes
    IFG and IGT should not be viewed as clinical entities in their own right but rather risk factors for diabetes as well as cardiovascular disease (CVD)
    IFG and IGT are associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension
    Individuals with an A1C of 5.7-6.4% should be informed of their increased risk for diabetes as well as CVD and counseled about effective strategies to lower their risks (see Prevention/Delay of Type 2 Diabetes)
  • The three primary criteria for testing for diabetes in asymptomatic adult individuals(Table 4) are summarized on two slides; this slide (Slide 1 of 2) includes:
    Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2) and have additional risk factors
    Testing should be considered in adults of any age with BMI ≥25 kg/m2 and one or more of the known risk factors listed on this slide
    It is important to know that the at-risk BMI may be lower in some ethnic groups, such as Asians
  • The three primary criteria for testing for diabetes in asymptomatic adult individuals(Table 4) are summarized on two slides; this slide (Slide 2 of 2) includes:
    In the absence of criteria (risk factors on previous slide), testing diabetes should begin at age 45 years
    If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status
    Age is a major risk factor for diabetes; therefore, testing of individuals without other risk factors should begin no later than at age 45 years
    The rationale for the 3-year interval is that false negatives will be repeated before substantial time elapses, and there is little likelihood that an individual will develop significant complications of diabetes within 3 years of a negative test result
    Given the need for follow-up and discussion of abnormal results, testing should be conducted within the health care setting
    Community screening outside a health care setting is not recommended because people with positive tests may not seek, or have access to, appropriate follow-up testing and care
    Conversely, there may be failure to ensure appropriate repeat testing for individuals who test negative
    Community screening may also be poorly targeted; i.e., it may fail to reach the groups most at risk and inappropriately test those at low risk (the worried well) or even those already diagnosed
  • Lesson Plan
    In addition to all of the risk we have discussed up to this point, when you have certain risk factors that cluster together, there is extra risk for heart disease (and diabetes.)
    Review risk factors on slide.
    3 or more of these risk factors clustering together add risk.
    This risk cluster is called The Metabolic Syndrome
    Note that extra fat in the middle—visceral fat—is more metabolically active and more dangerous than other types of fat.
    Physical activity and weight loss are effective treatments for the Metabolic Syndrome.
    Go to Next Slide: Stress Effect
  • Recommended glycemic goals for nonpregnant adults (Table 10) are shown on three slides
    Slide 1 of 3
    These recommendations are based on those for A1C values, with listed blood glucose levels that appear to correlate with achievement of an A1C of &lt;7%
    The issue of preprandial versus postprandial self-monitoring of blood glucose (SMBG) is complex; in some epidemiological studies, elevated postchallenge two-hour oral glucose tolerance test (2-h OGTT) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose (FPG)
    In diabetic subjects, some surrogate measures of vascular pathology, such as endothelial dysfunction, are negatively affected by postprandial hyperglycemia
    Postprandial hyperglycemia, like preprandial hyperglycemia, contributes to elevated A1C levels, with its relative contribution being higher at A1C levels that are closer to 7%
    However, outcome studies have clearly shown A1C to be the primary predictor of complications, and landmark trials such as the Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) relied overwhelmingly on preprandial SMBG
    For individuals who have premeal glucose values within target but A1C values above target, a reasonable recommendation for postprandial testing and targets is monitoring postprandial plasma glucose 1-2 hours after the start of the meal and treatment aimed at reducing PPG values to &lt;180 mg/dl to help lower A1C
  • Glycemic control is fundamental to the management of diabetes; recommendations for glycemic goals in nonpregnant adults are reviewed on this slide
    Lowering A1C to below or around 7% has been shown to reduce microvascular and neuropathic complications of type 1 and type 2 diabetes; therefore, for microvascular disease prevention, the A1C goal is &lt;7% (A)
    In type 1 and type 2 diabetes, randomized controlled trials of intensive versus standard glycemic control have not shown a significant reduction in cardiovascular disease (CVD) outcomes during the randomized portion. Long-term follow-up of the Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study (UKPDS) cohorts suggests treatment to A1C targets ≤7% in years soon after a diagnosis of diabetes is associated with long-term reduction in risk of macrovascular disease; until more evidence is available, a goal of &lt;7% appears reasonable for many adults for macrovascular risk reduction (B)
    Subgroup analyses of clinical trials (e.g., DCCT, UKPDS, ADVANCE) suggest a small but incremental benefit in microvascular outcomes with A1C values closer to normal; therefore, providers might reasonably suggest even lower A1C goals than &lt;7%, if achievable without significant hypoglycemia, for example. Such patients might include those with short duration of diabetes, long life expectancy, and no significant CVD (B)
    Conversely, less-stringent A1C goals than the general goal of &lt;7% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, and extensive comorbid conditions and those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin (C)
  • Glycemic control is fundamental to the management of diabetes; recommendations for glycemic goals in nonpregnant adults are reviewed on this slide
    Lowering A1C to below or around 7% has been shown to reduce microvascular and neuropathic complications of type 1 and type 2 diabetes; therefore, for microvascular disease prevention, the A1C goal is &lt;7% (A)
    In type 1 and type 2 diabetes, randomized controlled trials of intensive versus standard glycemic control have not shown a significant reduction in cardiovascular disease (CVD) outcomes during the randomized portion. Long-term follow-up of the Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study (UKPDS) cohorts suggests treatment to A1C targets ≤7% in years soon after a diagnosis of diabetes is associated with long-term reduction in risk of macrovascular disease; until more evidence is available, a goal of &lt;7% appears reasonable for many adults for macrovascular risk reduction (B)
    Subgroup analyses of clinical trials (e.g., DCCT, UKPDS, ADVANCE) suggest a small but incremental benefit in microvascular outcomes with A1C values closer to normal; therefore, providers might reasonably suggest even lower A1C goals than &lt;7%, if achievable without significant hypoglycemia, for example. Such patients might include those with short duration of diabetes, long life expectancy, and no significant CVD (B)
    Conversely, less-stringent A1C goals than the general goal of &lt;7% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, and extensive comorbid conditions and those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin (C)
  • This is another example of the diabetes food pyramid. This pyramid recommends:
    Cereals, whole grains and starch as the staple content of the diet
    one to two servings of fruit and three to four servings of vegetables
    two to three servings of milk and meat products per day
    sugars, fats, oils and fatty foods to be eaten sparingly
    The number of servings depending on the individual’s caloric requirements.
    Disadvantages associated with the food pyramid include:
    Non-specific quantities for portion sizes
    The absence of healthier alternatives in each group
    No recommendations for the cooking of foods (ie healthy/unhealthy alternatives, eg fried versus steamed)
    A lack of differentiation between healthy (monounsaturated) fats and unhealthy ones (butter and ghee)
    A uniform approach to carbohydrates that fails to distinguish between healthier (whole grains) and refined flours
    No differentiation between healthier meat/fish options.
  • The plate model is a simple way to planning a balanced diet through appropriate portion sizes.
    Foods are divided into five basic groups: 1. Starch/cereals; 2. Vegetables; 3. Fruit; 4. Milk; 5. Protein/meat.
    The plate model recommends:
    one fourth starch (potato, colocassia, yam, sweet potato, peas, etc)
    one fourth protein (meat, fish, poultry, pulses, tofu, beans, etc)
    half of the plate should consist of vegetables (preferably non-starchy, low-carbohydrate vegetables such as cabbage, broccoli, green beans, carrots, mushrooms, tomatoes, cauliflower, spinach, peppers or salad greens)
    one cup of low-fat milk or yoghurt/curd
    one piece of fruit.
    A ‘meal plan’ exercise using the plate model can be carried out in a variety of ways:
    a paper plate can be used with basic drawings showing the amount of space which should be taken up by each food group (this technique helps to reinforce consistency and prevent large amounts of carbohydrate foods being eaten on any one day)
    another simple technique is to remind people to carry a ‘Handy Meal Plan’ on their hand: hold up your hand (palm facing forward), point to your four fingers and show that most adults can have about four carbohydrates per meal, a serving of meat/meat substitute the size of the palm (about 110 g) and just a ‘thumb tip’ of fat.
  • The terms ‘exercise’ and ‘physical activity’ will both be used in this module – they are to be taken as meaning the same thing.
  • What are we looking in an antidiabetic drug
    Effectiveness of the drug: should control fasting and PP levels and at the same time should not produce hypoglycemic episodes
    Extraglycemic effects: &lt;animate&gt;
    Extra glycemic Effects such as neutral effects on body weight or even loss of weight, benefits on dyslipidemic parameters and lowering of BP are always welcome
    Should avoid long-term complications: secondary failure should not occur, or should cause hyperinsulinemia and weight gain
    Tolerability and Safety
    Ease of use: preferably once a day dose so that patients continue to remember and take the drug
    Expense
    But as we all are aware &lt;animate&gt; such an ideal drug does not really exist, at least for now.
  • ination therapy
  • Glitazones
    We have been using them for more than 6-7 yrs and these act by stimulating the PPAR-alpha receptors, a member of the nuclear receptor subfamily
    With MET, we can use when some patients have tremendous IR, therefore using full doses of PIO or ROSI may cause wt gain and fluid retention, whereas full doses of MET may result in higher GI adverse events, so we can balance these out by using moderate doses of MET and PIO or ROSI
    With insulin, it use is approved in our country but not in EUR, because of the fear that 2 drugs that cause fluid retention should not be given together because of HR risks
    We use it cautiously in elderly and patients with existing CV risks: do the ECG, do the 2D echo to assess LV function and decide
  • In 9 out of 10 cases, you can use them interchangeably.
    If a standard dose of one SU does not work, then other SUs will also not work
    Repaglinide and Nateglinide: Act similary but via a different receptor. They have quick action and shorter actions, so work well in post prandial glycemia. if an elderly patient requires avoidance of hypos, then we can use it. Shorter action time means that they will not work so well on fasting glycemia. Need to be given three times a day and are much more expensive than sulfonylureas. So they are not very popular in India.
  • Metformin
    The clinical efficacy of metformin in patients with type 2 diabetes requires the presence of insulin, but it does not stimulate insulin secretion (hence no risk of hypoglycemia). The predominant glucose-lowering mechanism of action of metformin is to reduce excessive rates of hepatic glucose production. Metformin reduces gluconeogenesis by increasing hepatic sensitivity to insulin and decreasing the hepatic extraction of certain gluconeogenic substrates (e.g. lactate). Hepatic glycogenolysis is also decreased by metformin. Insulin-stimulated glucose uptake in skeletal muscle is enhanced by metformin. This involves an increase in the movement of insulin-sensitive glucose transporter molecules to the cell membrane; an increase in the activity of the enzyme glycogen synthase promotes synthesis of glycogen. Metformin also acts in an insulin-independent manner to suppress oxidation of fatty acids and to reduce triglyceride levels in patients with hypertriglyceridemia. This reduces the energy supply for hepatic gluconeogenesis and has favourable effects on the glucose-fatty acid (Randle) cycle (in which fatty acids are held to compete with glucose as a cellular energy source). Glucose metabolism in the splanchnic bed is increased by metformin through insulin-independent mechanisms. This may contribute to the blood glucose-lowering effect of the drug, and in turn may help to prevent gains in bodyweight. Collectively, the cellular effects of metformin serve to counter insulin resistance and to reduce the putative toxic metabolic effects of hyperglycaemia (glucose toxicity) and fatty acids (lipotoxicity) in type 2diabetes.
  • No Single Class of Oral Antihyperglycemic Monotherapy Targets All Key Pathophysiologies
    Speaker Notes
    No single-agent monotherapy has an MOA that addresses all key pathophysiologies of type 2 diabetes.
    Alpha-glucosidase inhibitors decrease intestinal absorption of glucose.1,2
    Meglitinides and sulfonylureas stimulate insulin secretion.3–5
    TZDs are insulin sensitizers that also lower hepatic glucose output.6,7
    Metformin, a biguanide, lowers hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity.8
    DPP-4 inhibitors improve insulin synthesis and release and lower hepatic glucose production, both through suppressing glucagon production and release, and by improving insulin synthesis and release.
    Each class of oral antihyperglycemic agent does not address at least 1 key pathophysiology of type 2 diabetes.
  • The definition of hypertension is when the blood pressure is greater than 140/90 mmHg. However, the target in diabetes is tighter than this and a blood pressure of less than 130/80 mmHg is recommended.
    Achieving this can be difficult and it is common that three or more anti-hypertensive agents are required. However, common practice is that when the blood pressure is not reduced with one drug, the person is taken off that medication and a new one is tried. In reality what is needed is to keep adding antihypertensive agents to the regimen until the target blood pressure is achieved.
  • Targets for lipid levels in diabetes are very strict. Every effort should be made to assist a person with diabetes in reaching these targets. This should be done through adapting lifestyle and using statins and/or other lipid therapy.
  • Transcript of "Dm talk npt,tmo)"

    1. 1. Management of Type 2 Diabetic patients in Daily Clinical Practice KO KO NOGH,UM(2) © www.bhtinfo.com
    2. 2.  The majority of diabetic patients (greater than 90 percent) receive their care from primary care physician. generalist and the specialist  A large observational study (the Medical Outcomes Study) found little advantage for patients under the care of endocrinologists, when compared with family practitioners, except for improved foot care and lower infection risk [77,78] . Overall functional status at four years and mortality at seven years were similar.
    3. 3. • A 40 years old lady is found to have hyperglycaemia at your clinics. Her RBS is 220 mg/dl. Is she diabetic?
    4. 4. • Diagnosis of DM should not be made by single measurement of blood sugar alone. • It is important to assess Hyperosmolar symptoms(polyuria,polydipsia) Weight loss Previous history of poor wound healing Family history of DM Signs of DM complications (e.g. diabetic shin spots, retinopathy)
    5. 5. AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007; 13 (Suppl 1) 2007
    6. 6. ADA 2012 Guidelines on Diagnosing diabetes
    7. 7. Prediabetes: IFG, IGT, Increased A1C Categories of increased risk for diabetes (Prediabetes)* FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG or 2-h plasma glucose in the 75-g OGTT 140-199 mg/dl (7.8-11.0 mmol/l): IGT or A1C 5.7-6.4% *For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range. ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.
    8. 8. Definition of Diabetes American (mg/dL) SI (mmo/L) Normal 65 - 99 3.6 – 5.5 DM > 126 > 7.0 Random (with symptoms) DM > 200 > 11.1 GTT (2 hr.) DM > 200 > 11.1 HbA1c DM Indicator Glucose – Fasting > 6.5%
    9. 9. Millions Number of People with Diabetes by Age Group, 2010 and 2030
    10. 10. Millions Number of People with Impaired Glucose Tolerance by Age Group, 2010 and 2030
    11. 11. CHALLENGES • Prediabetes SOLUTIONS • Early diagnosis & • Life style changes Early diagnosis Life style changes PREDIABETES DIABETES
    12. 12. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1) 1. Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and have additional risk factors: •Physical inactivity •First-degree relative with diabetes •High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) •Women who delivered a baby weighing >9 lb or were diagnosed with GDM •Hypertension (≥140/90 mmHg or on therapy for hypertension) • HDL cholesterol level <35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl (2.82 mmol/l) • Women with polycystic ovarian syndrome (PCOS) • A1C ≥5.7%, IGT, or IFG on previous testing • Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) • History of CVD *At-risk BMI may be lower in some ethnic groups. ADA. Testing in Asymptomatic Patients. Diabetes Care 2011;34(suppl 1):S14. Table 4.
    13. 13. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (2) 2. In the absence of criteria (risk factors on previous slide), testing for diabetes should begin at age 45 years 3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status ADA. Testing in Asymptomatic Patients. Diabetes Care 2011;34(suppl 1):S14. Table 4.
    14. 14. • The lady is tested again the next day. Her FBS is 170mg/dl. So DM is diagnosed. What should I do next?
    15. 15. Doctors should do
    16. 16. What a Doctor should do for medical care of patient with DM? • • • • • • • • • Diagnosis Screening Evaluation of diabetes complications-macro and microvascular Detection of comobidities Reducting the risk of microvascular complications Glycemic control Reducting the risk of Macrovascular complications smoking cessation control of BP,Lipid,asprin Monitoring of complications Prevention of Diabetes DSME (Diabetes self management education)
    17. 17. • Diabetes never come alone • It come in hand with •Diabetes •Hypertension •IHD •Increased Lipid •Stroke Obesity Hypertension dyslipidemia Complications (Microvascular & Macrovascular) So look for them!
    18. 18. Patient Education in Diabetes Mellitus: 10 Content Areas Diabetes Disease Process Integrating Psychosocial Adjustment To Daily Living Preventing, Detecting & Treating Chronic Complications Diabetes SelfManagement Education Preventing, Detecting & Treating Acute Complications Promoting Care prior to and during Pregnancy Goal setting for Health & Daily Living Nutritional Management Physical Activity Monitoring Blood Glucose Funnell et. al. Diabetes Care 2010:33 (Suppl1) S89-96 Utilizing Medication
    19. 19. ATP III : General features of the Metabolic Syndrome • Abdominal obesity (waist circumference) Men Women • Elevated triglycerides • Low HDL cholesterol Men Women • Raised blood pressure • FBS > 102cm (>40inches) >88cm (>35inches) > or = 150mg/dl < 40mg/dl <50mg/dl > or = 130/85mmHg > or = 110mg/dl
    20. 20. The Metabolic Syndrome  Low HDL cholesterol  Borderline triglycerides  Central obesity  Prehypertension  Impaired fasting glucose
    21. 21. Complications • Microvascular  Retinopathy (Fundoscopy)  Nephropathy (microalbuminuria, Urine RE, Urea, Cr)  Neuropathy • Macrovascular  Stroke, TIA  IHD (ECG)  Peripherial vascular disease (pulse examination & claudication pain)
    22. 22. • Examination and investigations of the lady showed  BMI  Waist circumference  BP  Total cholesterol  LDL  HDL  Triglyceride 32 90cm 150/90mmHg 250mg/dl 160mg/dl 30mg/dl 300mg/dl How would I manage her?
    23. 23. Problems 1. 2. 3. 4. Newly diagnosed Type (2)DM Obesity(BMI 32) Hypertension Hyperlipidaemia
    24. 24. Mortality in People With Diabetes: Causes of Death 50 40 % of deaths 30 20 10 0 Ischemic Other DiabetesCancer Stroke Infection Other heart heart disease disease Geiss LS et al. In: Diabetes in America. 2nd ed. 1995; chap 11. ©2006. American College of Physicians. All Rights Reserved.
    25. 25. Evidence level of the recommendations In type 2 DM management Strategy evidence Evidence-based benefit Quality of Glycemic Control 30% decrease in microvascular complications/1% fall in HbA1c I BP control 35-58% decrease in macro & Micro vascular complications death I Lipid control 19-55% decrease in CHD events II-1 Aspirin use 28-61% decrease in AMI 15-18% decrease in CVD I
    26. 26. Treatment of Type 2 Diabetes Diagnosis Therapeutic Lifestyle Change Monotherapy Combination Therapy - Oral Drugs Only Combination Therapy - Oral Drug with Insulin
    27. 27. Do we need to get good glycemic control?
    28. 28. Optimal Glycaemic Control  Is important to prevent death ,disability & complications of DM      -FBS - 90-130mg% -2HPP - <180mg% -RBS - <200mg% -Bed time - 110-150mg% -HbA1c - <7%
    29. 29. Glycemic Recommendations for NonPregnant Adults with Diabetes (1) A1C <7.0%* Preprandial capillary plasma glucose 70–130 mg/dl* (3.9–7.2 mol/l) Peak postprandial capillary plasma glucose† <180 mg/dl* (<10.0 mmol/l) *Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes. ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S21. Table 10.
    30. 30. Recommendations: Glycemic Goals in Adults (2) • Additional analysis from several randomized trials suggest a small but incremental benefit in microvascular outcomes with A1C values closer to normal • Providers might reasonably suggest more stringent A1C goals for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment – Such patients might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease (B) ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.
    31. 31. Recommendations: Glycemic Goals in Adults (3) • Conversely, less stringent A1C goals may be appropriate for patients with – History of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions – Those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose lowering agents including insulin (C) ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.
    32. 32. How Can we get good control of DM? ?
    33. 33. Therapeutic Lifestyle change Diabetes food pyramid Fats, oils, sugars, refined foods, fatty foods: eat sparingly Low fat milk and milk products: 2-3 servings Vegetables: 3-4 servings Lean meat, fish, poultry, pulses: 1-2 servings Fruits: 12 servings Cereals, whole grains and starch: 6-11 servings Exercise for at least 30 minutes every day
    34. 34. Plate model Fruit Protein Milk/yoghurt Vegetable Vegetable Starch/cereal
    35. 35. Rate Your Plate
    36. 36. Slides current until 2008
    37. 37. Physical activity Recommendations • People with diabetes should be advised to perform at least 150 min/week of moderate-intensity aerobic physical activity (50 – 70% of maximum heart rate). (A) • In the absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance training three times per week. (A) Standard of Medical Care in Diabetes 2010
    38. 38. Medical Nutrition Therapy and Physical Activity Prevent Diabetes
    39. 39. Pharmacological treatment
    40. 40. Diabetes And Glycemic Control: A Rational Approach • As low as possible • As early as possible Lifestyle + MET + TZD + SU • For as long as possible • As safely as possible • And as rationally as possible HbA1c < 6%
    41. 41. Basic Steps in the Management of Type 2 Diabetes d ex iet & er cis e mo O no ral th er a co Or mb al ina tio n py Or al Ins plu uli s n ins uli n + + +
    42. 42. Type 2 Diabetes Medication Choices Experience and Potency Route Year Efficacy as monotherapy: % ↓ in HgbA1c Insulin s.c. 1921 ≥2.5 Sulfonylureas Oral 1946 1.5 Glinides Oral 1997 1.0-1.5 Metformin Oral 1995 1.5 α-glucosidase inhibitors Oral 1995 0.5-0.8 TZDs Oral 1999 0.8-1.0 GLP analogue s.c. 2005 0.6 DPP-IV Inhibitors Oral 2006 0.5-0.8 Amylin analogue s.c. 2005 0.6 Colesevelam Oral 2008 0.5 Bromocriptine mesylate Oral 2009 0.2-0.4 Medication
    43. 43. Mechanisms of Action of Pharmacologic Agents for Diabetes Improving Outcomes in Patients With Type 2 Diabetes Mellitus: Practical Solutions for Clinical Challenges James R. Gavin, III, MD, PhD; Mark W. Stolar, MD; Jeffrey S. Freeman, DO; Craig W. Spellman, DO, PhD JAOA • Vol 110 • No 5suppl6 • May 2010 • 2-14
    44. 44. NEW IDF 2011
    45. 45. Early combination approach
    46. 46. Monitoring • SMBG • HbA1C 52
    47. 47. Glycemic control Recommendations for A1C • Perform the A1C test at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control) (E) • Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals. (E) • Use of point-of-care testing for A1C allows for timely decisions on therapy changes, when needed. (E) Standard of Medical Care in Diabetes 2010
    48. 48. Self-monitoring of Blood Glucose (SMBG) • SMBG should be carried out three or more times daily for patients using multiple insulin injections or insulin pump therapy. • For patients using less frequent insulin injections, noninsulin therapies, or medical nutrition therapy (MNT) alone, SMBG may be useful in achieving glycaemic goals. • To achieve postprandial glucose targets, postprandial SMBG may be appropriate. 54
    49. 49. Which one is important? • FPG ------basal for microvascular complication • 2HPG ----for macrovascular complication(mainly CVS) Both are important 55
    50. 50. What Do We Look For In Anti-diabetic Drug? • Effectiveness in lowering glucose • Extra-glycemic Effects • Long-term complications • ? Effect on β cell mass • Tolerability and Safety • Easy of Use • Expense Obviously no such agent Obviously no such agent available, nor likely to be available, nor likely to be Body Wt available in near or mediumBody Wt available in near or mediumLipids term future Lipids term future BP BP Unwise to anticipate “golden” Unwise to anticipate “golden” Rx; rather, would be preferable Rx; rather, would be preferable to learn how to better use to learn how to better use available pharmacologic tools available pharmacologic tools
    51. 51. An Ideal OHA should have…  Fast onset of action  To stimulate insulin secretion (including first phase)  Decrease fasting and post prandial blood glucose  Preservation of the beta cells  Decrease insulin resistance  Prevent complications  Long duration of action (once daily administration)
    52. 52. An Ideal OHA should have…  Control FPG & PPG effectively  Lowest risk of hypoglycemia  Should not produce hyperinsulinemia & weight gain  Less drug interactions
    53. 53. ADA (antidiabetic drugs) Sulfonylureas Non-Sulfonylureas Biguanides Thiozolidinediones (Glitazones) Alpha Glucosidase enzyme inhibitors Newer Antidiabetic drugs (ADA) ▪ GLP-1 (Incretin Mimetics ) -exenatide -liraglutide ▪ DPP-IV inhibitor (Incretin enhancer) -Sitagliptin -Vildagliptin -Saxagliptin
    54. 54. Metformin/Glitazones SU/Non-SU α-glucosidase inhibitors
    55. 55. Effect SU and NSU Metformin TZA AGI Mechanism Increase in insulin secretion Decrease in HGO plus increases muscle sensitivity Decrease in HGO plus increases muscle sensitivity Decrease in glucose absorption Decrease in FPG 60-70 mg% 60-70 mg% 35-40 mg% 20-30 mg% Decrease in HbA 1.5-2.0% 1.5-2.0% 1.0-1.2% 0.7-1.0% TG level No effect Decrease Decrease No effect HDL level No effect Slight increase Increase No effect LDL level No effect Decrease Increase No effect Body weight Increase Decrease Increase No effect Insulin level Increase Decrease Decrease No effect Adverse effects Hypoglycemia GI disturbances Anemia, hepatic GI disturbances
    56. 56. Anti-hyperglycemic agents in T2DM Class MET AIC reduction Fasting versus PPG Hypoglyce mia Weight change Dosing 1.5 Fasting No Neutral 1-3 INS-LA 1.5-2.5 Fasting Yes Gain 1 INS-RA 1.5-2.5 PPG Yes Gain 1-4 1.5 Fasting Yes Gain 1-3 GLIT 0.5-1.4 Fasting No Gain 1 GLIN 1-1.5 Both Yes Gain 3 AGI 0.5-0.8 PPG No Neutral 3 PRAM 0.5-0.8 PPG No Loss 3 0.5-1 PPG No Loss 2 0.5-0.8 PPG No Neutral 1 SU EXE DPP-IV
    57. 57. Initial Therapy with OHAs Initial Add Add SU Metformin Insulin Metformin SU TZD/Insulin Obese not tolerating MET TZD SU MET contraindicated TZD SU Metformin TZD SU Insulin Thin/normal Wt Obese Severe IR Elderly PPHG prominent PPHG prominent in Sec Failure MEG/AGI AGI/Exenatid e SU
    58. 58. Metformin - Drug Profile No hypoglycemia Weight loss Advantages Cardiovascular benefit Reduces LDL-C (approx 10 mg/dL), reduces TG Diarrhea is common Disadvantages Contraindicated in renal impairment, liver failure, advanced cardiac failure Risk of lactic acidosis not increased in meta-analyses and systematic reviews Concomitant use with other drugs Can be used as monotherapy and with all classes including insulin
    59. 59. Sulfonylureas - Drug Profile Advantages Potent glucose lowering effect Favorable adverse effect profile Hypoglycemia, more with Glyburide Disadvantages Glyburide contraindicated in renal impairment ?Glyburide impairs ischemic preconditioning in heart (UKPDS did not reveal increased cardiac risk) Concomitant use with other drugs Can be used as monotherapy and with all classes including insulin
    60. 60. Repaglinide and Nateglinide: Drug Profiles Advantages Disadvantages Less hypoglycemia than sulfonylureas Favorable adverse effect profile Less potent than sulfonylureas; target mainly post-prandial glucose Nateglinide less potent than Repaglinide Concomitant use with other drugs Can be used with all classes including insulin
    61. 61. TZDs - Drug Profile No hypoglycemia Advantages May be useful in nonalcoholic fatty liver disease Increased fracture risk Weight gain Disadvantages Edema and exacerbation of CHF Rosiglitazone increases LDL-C (10mg/dL), TG (15-50mg/dL) and possible increase in MI ?? Bladder Ca Concomitant use with other drugs Can be used with other classes including insulin!. Increased fluid retention and weight gain with insulin
    62. 62. Alpha Glucosidase Inhibitor (AGI) Drug Profile Advantages Disadvantages No hypoglycemia Weight neutral Targets only postprandial glucose GI side effects Concomitant use with other drugs Can be used as monotherapy and with all classes including insulin
    63. 63. Combination Therapy with OHAs • Drug combinations should be based on A. Therapeutic efficacy (“fire power”) B. Complementary mechanisms of action C. Ancillary benefits (CVD risk factors) D. Safety and tolerability E. ? Compliance with multiple dosing regimens
    64. 64. Estimated Improvements with Combination Rx Combination AIC% reduction FPG reduction SU + MET 1.7% 65 mg/dl SU + ROS 1.4% 60 mg/dl SU + PIO 1.2% 50 mg/dl SU + ACAR 1.3% 40 mg/dl REP + MET 1.4% 40 mg/dl 0.7-0.8% 40 mg/dl Open to targets Open to targets MET + ROS/PIO INS + OHA De Fronzo, NEJM 1995 Horton, Diabetes Care 1998 Coniff, Diabetes Care 1995 Moses, Diabetes Care 1999 Schneider, Diabetes 1999 Egan, Diabetes 1999 Fonseca, Diabetes 1999
    65. 65. Strategies for Antidiabetic Treatment Oral Monotherapy Metformin Sulfonylureas Glinides TZDs α-Glucosidase-Inhibitors DPP-4 Inhibitors Oral Dual Combination Therapy Metformin + Sulfonylureas Metformin + TZDs Sulfonylureas + TZDs Metformin + DPP-4-Inhibitors Sulfonylureas + DPP-4-Inhibitors Oral Triple Combination Therapy Oral Triple Combination Therapy plus Basal Insulin or plus Metformin + Sulfonylureas + TZDs Metformin + Sulfonylureas+DPP-4Inhib. NPG, Glargine, Levemir Exenatide, Liraglutide
    66. 66. ADA/EASD Consensus Algorithm for the Initiation and Adjustment of Therapy Diabetes Care 2009; 32:193–203
    67. 67. Master Decision Path Type 2 Diabetes Glycemic Control At Diagnosis (mg/dl) Medical Nutrition Therapy Medical Nutrition Therapy & Activity Plan & Activity Plan FPG <<200 FPG 200 Casual <<250 Casual 250 If target not reached within 33 months -If target not reached within months -start oral agent start oral agent Oral Agent-Monotherapy Oral Agent-Monotherapy FPG 200-300 FPG 200-300 Casual 250-350 Casual 250-350 FPG >>300 FPG 300 Casual >>350 Casual 350 If target not reached after maximum If target not reached after maximum dose for 44- -88weeks - -- -start oral agent dose for weeks start oral agent with severe symptom with severe symptom FPG >>350 FPG 350 Casual >>350 Casual 350 Oral Combination Rx Oral Combination Rx If target not reached after maximum If target not reached after maximum doses for 44- -88weeks -- start insulin doses for weeks -- start insulin Insulin Therapy Insulin Therapy Oral Agent(s) ++Insulin Oral Agent(s) Insulin KK/ESSENTIAL DRUG/3.4.11/tAUNGGHU Targets for Targets for Glycemic Control Glycemic Control HbA1c <7% HbA1c <7% SMBG 80-140 SMBG 80-140
    68. 68. Glitazones • Monotherapy if • MET contraindicated • Intolerant to MET • Combination Rx • SU • MET (high IR) • Insulin (Bbox in US) • Disadvantages • Wt gain • Fluid retention ? CHF • Possibly hepatotoxicity • Fracture risk in • ROS/PIO • PPAR-γ agonists • Insulin action at muscle/fat cells (? liver) Pioglitazone – 15 – 45 mg OD • Pleiotropic effects Rosiglitazone – 2- 8 mg OD • Beta cell preservation
    69. 69. Sulfonylureas • Which ? • When? • Why? All have same MOA All have same 1ststline in underwt/normal wt MOA2 patients 1 line in underwt/normal wttype 2 patients type Require some viable β cell mass to work Require some viable β cell mass to work Along with insulin sensitizers: metformin or Along with insulin sensitizers: metformin or glitazones Do not work in type 1glitazones sec failure sets in type 2 Do not work in type 1and after sec failure sets in type 2 and after Along with insulin to facilitate Along with insulin toamongs SUs facilitate Differential effects amongs SUs Differential effects reduction/frequency of insulin dosing reduction/frequency of insulin dosing • Can use in heart failure, renal failure • SE - Weight gain, hypoglycemia • Choice of SU – Newer SU to prevent cardiac side effect, prolong hypoglycemia
    70. 70. Comparison between 3 generations of Sulphonylureas Drug 2nd generation 3rd generation Tolbutamide Range of dosage 500-3000 mg Relative potency 1 Doses per day 2-3 Tolazamide 1st generation Duration of action 6-12 hrs 14-16 hrs 100-1000 mg 3 1-2 Chlorpropamide Glipizide Glipizide-ER 24-72 hrs 12-24 hrs 24 hrs (lesser fluctuations compared to regular Glipizide) 100-500 mg 2.5-40 mg 2.5-20 mg 6 75 150 1-2 1-2 1 Glyburide (Glibenclamide) Micronized Glyburide Glimepiride 18-24 hrs 1.25-20 mg 150 1-2 24 hrs 3-12 mg 250 1-2 24 hrs 1-8 mg 350 1 Drugdex Evaluations; Vol.133,2007
    71. 71. Sulfonylureas: How to Choose? • Cardiac patients: Glimepiride/GLICLAZIDE • Elderly patients: Glimepiride/GLICLAZIDE • Economy: Glibenclamide • Mild renal insufficiency: Glimepiride • Severe Renal : Gliclazide and glipizide • Require high potency: Glibenclamide • Relatively younger patients: Glibenclamide
    72. 72. Metformin: Crucial Part of Therapy Metformin Effects on Risk Metformin Effects on Risk Factors Factors Hundal RS, Inzucchi SE. Metformin New Understandings, New Uses. Drugs 2003; 63(18): 1879-1894 Dose CI SE – 500 to 3000 mg - serum creatinine >1.5 mg%, Advanced Heart Failure - Reduce appetite, nausea, vomiting, diarrhoea
    73. 73. No Single Class of Oral Antihyperglycemic Monotherapy Targets All Key Pathophysiologies Major Pathophysiologies AlphaGlucosidase Inhibitors1,2 Insulin deficiency Meglitinides3  SUs4,5 TZDs6,7 Metformin8  DPP-4 Inhibitors  Insulin resistance   Excess hepatic glucose output   Intestinal glucose absorption    1. Glyset [package insert]. New York, NY: Pfizer Inc; 2004. 2. Precose [package insert]. West Haven, Conn: Bayer; 2004. 3. Prandin [package insert]. Princeton, NJ: Novo Nordisk; 2006. 4. Diabeta [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2007. 5. Glucotrol [package insert]. New York, NY: Pfizer Inc; 2006. 6. Actos [package insert]. Lincolnshire, Ill: Takeda Pharmaceuticals; 2004. 7. Avandia [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2005. 8. Glucophage [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2004.
    74. 74. TWO basic INSULIN REGIMENS Supplementary Supplementary Substitution Substitution (OHD +Bed time insulin) ( No OHD +Only insulin) Premixed/split mixed Basal bolus insulin Premixed/split mixed Basal bolus insulin
    75. 75. Insulin Regimen for Type 2 Diabetes Mellitus Guidelines for Starting insulin therapy (Asia Pacific Type 2 Diabetes Policy group) Supplementary OAD + 10 iu NDP insulin (Bedtime) Test FPG/ Adjust 3-4 days >30-40 iu – stopping OAD 0.15 units /kg /BW /Day
    76. 76. Insulin Regimen for Type 2 Diabetes Mellitus Guidelines for Starting insulin therapy (Asia Pacific Type 2 Diabetes Policy group) Substitution Pre-mixed insulin 30/70 Morning 2/3 Pre-Mix 30/70 Evening 1/3 Pre-Mix 30/70 In normal person = 0.5 units /kg /BW /Day
    77. 77. Insulin Regimen for Type 2 Diabetes Mellitus Insulin 60 PREMIX 40 20 0 6 AM 12 AM PREMIX 30/70 6 PM 12 PM PREMIX 30/70
    78. 78. Basal Bolus Regimen (Substitution) • Mimics physiological insulin profile: starting dose - 40% daily dose as basal insulin (Intermediate-acting insulin- Insulatard or Humulin N ) - 60% as short acting insulin (Actrapid or Humulin R) divided into 20% at breakfast 20% at lunch 20% at dinner • Insulin dose adjusted if needed • Requires highly motivated patients with constant monitoring 85
    79. 79. Initiation of Basal Bolus insulin regimen Calculate Total Daily Insulin (TDI) = 0.5 units x weight (kg) OR (sum of current doses) eg: if weight is 60 kg, TDI = 30 units Total Mealtime Insulin (lispro, aspart or regular) = 60% of TDI eg: 60% x 30 units = 18 units Total Basal insulin (NPH, glargine, ultralente) = 40 % of TDI eg: 40% x 30 units = 12 units Breakfast dose = 1/3 of mealtime insulin Lunch dose = 1/3 of mealtime insulin Dinner dose = 1/3 of mealtimeinsulin eg: 1/3 x 18 units = 6 units eg: 1/3 x 18 units = 6 units eg: 1/3 x 18 units = 6 units Bed-time dose = total basal insulin eg: 40% x 30 units = 12 units
    80. 80. Diabetes Prevention Can we prevent Diabetes Mellitus? • Yes. We can “ Small Steps. Big Rewards. Prevent type 2 Diabetes”
    81. 81. Percent developing diabetes Incidence of Diabetes All Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac ) Lifestyle (n=1079, p<0.001vs. Plac) Metformin (n=1073, p<0.001 vs. Metformin , Placebo (n=1082) p<0.001 vs. Placebo) Cumulative incidence (%) 40 30 participants Risk reduction 31% by metformin 58% by lifestyle 20 10 0 0 1 2 Years from randomization The DPP Research Group, NEJM 346:393-403, 2002 3 4
    82. 82. Standards of Medical Care in Diabetes—2011  PREVENTION/DELAY OF TYPE 2 DIABETES  Recommendations  ● Patients with IGT (A), IFG (E), or an A1C of 5.7–6.4% (E) should be referred to an effective ongoing support program targeting weight loss of 7% of body weight and increasing physical activity to at least 150 min/week of moderate activity such as walking.  ● Metformin therapy for prevention of type 2 diabetes may be considered in  those at the highest risk for developing diabetes, such as  those with multiple risk factors, especially if they demonstrate progression of hyperglycemia (e.g., A1C 6%) despite lifestyle interventions. (B)
    83. 83. Are we achieving good control?
    84. 84. Treatment Strategies for Diabetes: Are Patients Achieving Good Control? Hypertension BP <140/90 mm Hg Hyperlipidemia LDL-C <130 mg/dL 41% 59% A1C <7.0 41% 59% Controlled Uncontrolle d Diabetes Harris MI et al. Diabetes Care. 2000;23:754 42% 58%
    85. 85. If RBS control is difficult • Always ask about other medications  Steroids  Thiazide  Beta-blockers • Always check diets • Always check sepsis  Skin – carbuncle, abscess, gangrene  Foot – ulcer  Lungs – TB, Pneumonia  Renal – UTI, pylonephritis Compliance of drugs
    86. 86. Measures to improve drug-compliance • Patient’s education • Promoting patient’s involvement in management • Reducing pill load (longacting drugs eg.metformin XR) • Encouraging family involvement in patient’s care
    87. 87. DRUGS • Correct Drugs • Correct Doses • Correct Timing • Correct Combination • Compliance • ?steroid
    88. 88. Correct Drugs • Insulin Type(1)DM/Type 2 DM with Stress/OHA Failure • TZD/Metformin Insulin Resistance • Postprandial Hyperglycemia Glinites/Acarbose/voglibose/Soluble insulin • Insulin Deficiency SU/Glinite • Beta cell Preservation TZD
    89. 89. Correct Combination • SU+MFM • SU + Acarbose • SU + Thiazolidinediones • MFM + Thiazolidinediones • MFM + Acarbose • SU + MFM + Acarbose • SU +MFM + INSULATARD
    90. 90. Correct Drugs Insulin Resistance • Thiazolidine diones • Metformin Postprandial Hyperglycemic Insulin Deficiency • Glinides • Acarbose • Voglibos • Solube Insulin • Insulin Secretogogues • Sulphonylurea Glinides
    91. 91. Blood Pressure Management JNC 7 and ADA recommendations • Hypertension blood pressure: ≥140/90mmHg • Target blood pressure goal in diabetes: 130/80mmHg • 125/ 75 mmHg in Diabetes Nephropathy • Many people require three or more drugs to achieve the recommended target ADA 2004, JNC7
    92. 92.  ACE inhibitor or ARB should be first choice  If not controlled add diuretic (thiazide if     GFR>50ml, or loop diuretic if GFR≤) If ACE inhibitor, ARB, or diuretics are used- kidney function & serum potassium levels – closely monitor In pregnant patients BP goals 110-129/6579mmHg ACE inhibitor, ARB are contraindicated. Amlodipine,beta blocker 99
    93. 93. ESH/ESC Guidelines recommend initiating a two-drug combination in high risk patients High risk patient: Eg Diabetes  Treat as a function of total CV risk  High Risk patients: diabetes, cardio renal disease  A combination is preferred as first step treatment for patients at risk Mancia, De Backer et al. J Hypertens 2007: 25 1105-1187
    94. 94. Management of Dyslipidiaemia • Main predictors of CVD mortality LDL and HDL cholesterol • Lipid profile in type 2 diabetes raised triglycerides low HDL raised small dense LDL particles
    95. 95. Target for lipids • HDL >50 mg/dl • LDL <100 mg/dl • TG <150 mg/dl • TC <200 mg/dl
    96. 96. Treatment and goal • • • Increased physical activity Reduction of saturated fat and cholesterol Statin therapy should be added to life-style therapy, regardless of baseline lipid levels, for Diabetes patients ± CVD, > 40yrs of age • Statin therapy in addition to life style – LDL >100mg/dl • In overt CVD < 70mg/dl is goal. • TG <150mg/dl, HDL>40mg/dl in men, HDL>50mg/dl in women. • Statin is contraindicated in pregnancy. 103
    97. 97. Dyslipidemia Management • Lifestyle modifications are essential. (Grade D) • Statins are the pharmacologic treatment of choice. (Grade A) • Exetimibe in patients who are intolerant of statins or in combination therapy and other lipid modifying agent. (Grade B) • Use Fibrates as primary therapy if TG level > 400 mg/dl (Grade C) • Use low dose aspirin prophylaxis (Grade A) AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007; 13 (Suppl 1) 2007
    98. 98. Dyslipidemia Management • Combination therapy in patients who have not achieved the desired goals with monotherapy. (Grade C) • Statin + Fibrate • Statin + niacin • Statin + ezetimibe • Statin + bile-acid sequestrant • Statin + omega-3 fatty acids AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007; 13 (Suppl 1) 2007
    99. 99. Diabetes UK recommends that aspirin should be offered to people with diabetes who already have a history of CVD.
    100. 100. Antiplatelet Agents • Use aspirin therapy (75-162 mg/day) as a secondary prevention strategy in diabetic individuals with a history of CVD. • Use aspirin therapy (75-162 mg/day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk, including those who are >40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria). 107
    101. 101. Antiplatelet Agents • Aspirin therapy is not recommended in people under 30 years of age, due to lack of evidence of benefit, and is contraindicated in patients under the age of 21 years because of the associated risk of Reye's syndrome. • Combination therapy using other antiplatelet agents such as clopidogrel in addition to aspirin should be used in patients with severe and progressive CVD. 108
    102. 102. Is it necessary to hospitalize the patient? • High blood sugar alone is not an indication for hospitalization • When to refer to hospital DKA, HONK DM with sever sepsis DM with pregnancy Difficult - to - control DM
    103. 103. Indications for insulin therapy in Type 2 DM • Failure to achieve glycemic control with diet, exercise and oral medications • Before and during pregnancy • During surgery • Poor Diabetic control in any medical illness (e.g. septicaemia, TB, diabetic foot) • Critically ill patient in ICU • Glucose toxicity
    104. 104. Take Home Message  Glycemic control : HbA1c <7% ADA, <6.5% AACE (ADVANCE)  Blood pressure <130/ 80 mmHg  Lipid control  LDL-C: <100 mg/dl (<70 mg/dl in very high risk)  HDL-C: men >45 mg/dl; women >55 mg/dl  Triglycerides: <150 mg/dl  Prothrombotic state : ASA Rx (75 - 162 mg/day)  People with DM + CVD  > 40 years of age with DM + >1 other CV risk factor  Cigarette smoking : Diabetes Care. 2005; Supplement 1. Cessation
    105. 105. The Pill Burger
    106. 106. Diabetes And Glycemic Control: A Rational Approach • As low as possible • As early as possible Lifestyle + MET + TZD + SU • For as long as possible • As safely as possible • And as rationally as possible HbA1c < 6%
    107. 107. Need for global treatment to reduce complications Exe rcis e ens p er t Hy Ob es i y t ion H cem ly erg ia yp i d e mi Dyslip a Smo ki n g
    108. 108. Diabetes And Glycemic Control: A Rational Approach  A = Advice – Diet, Exercise, Stop smoking  B = BP – 130/80 mm Hg  C = Cholesterol – LDL 70 mg/dl  D = Diabetes – FBG, PP BG, HbA1c  E = Eye checkup regularly  F = Foot examination daily  G = Guardian Drugs – Aspirin, Statin, ACE-I
    109. 109. Avoid bad habits...
    110. 110. jyHK;yg/ (pdwfzdpD;rIrsm; avsmhenf;EdkiforQ avsmhenf;atmif BudK;pm;yg/ ) 118
    111. 111. Don’t worry I will take care of DM Save big Money
    112. 112. The end is here Confused? But Thank you
    113. 113. Thank You for Kind Attention
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