3. Managing Diabetes and Metabolic syndrome Treatment Perspectives by Professor Dr Intekhab Alam Department of Medicine PGMI, Khyber Medical University Lady Reading Hospital, Peshawar.
This slide module will:
Discuss the importance of glycosylated haemoglobin A1c as a marker for blood glucose control in both type 1 and type 2 diabetes management
Review the Diabetes Control and Complications Trial, United Kingdom Prospective Diabetes Study, and other studies to identify the link between good glycaemic control and long-term clinical outcomes
Demonstrate the need for aggressive therapy to achieve glycaemic control, thereby reducing the risk of microvascular and macrovascular complications

4. Dual defect of type 2 diabetes: treating a moving target
Insulin
Resistance
Type 2
Diabetes
b-cell
Dysfunction
Hyperglycaemia
Insulin Action
b-cell Failure
Insulin
Concentration
Insulin
Resistance
Dual defect of type 2 diabetes: treating a moving target
The pathophysiology of type 2 diabetes is complex, and characterised by remorseless progression of the dual metabolic defects of insulin resistance and b-cell dysfunction.
Initially, insulin resistance causes the glucose-lowering actions of insulin to be blunted, so that the pancreas secretes more insulin to overcome the deficit. At this stage the subject may develop impaired glucose tolerance, but is not yet diabetic.
As insulin resistance progresses, however, the pancreas is no longer able to secrete enough insulin to control glycaemia, and increased hepatic glucose output and reduced glucose disposal by muscle and fat contribute to the chronic fasting and postprandial hyperglycaemia characteristic of type 2 diabetes. Eventually, insulin secretion from the b-cell begins to decline and the severity of the hyperglycaemia increases further.
Adapted from DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992;15:
Euglycaemia
Normal
IGT ± Obesity
Diagnosis of type 2 diabetes
Progression of type 2 diabetes
DeFronzo et al. Diabetes Care 1992;15:318-68

5. IGT is driving the worldwide diabetes pandemic50 45 40 35 30 25 20 15 10 5
IGT
Undiagnosed type 2 diabetes
% of population
Diagnosed type 2 diabetes
IGT is driving the worldwide diabetes pandemic
Data from the USA suggest that type 2 diabetes is only the tip of the iceberg, in terms of the prevalence of glucose intolerance. Individuals with either undiagnosed type 2 diabetes or impaired glucose tolerance (IGT) are thought to be far more numerous than the type 2 diabetic population.
This is especially so in older individuals (>65 years), of whom about two-fifths may have IGT or undiagnosed type 2 diabetes.
Harris MI et al. Consultant 1997;37 (Suppl): S9.
20-44
45-54
55-64
65
Age (years)
Harris. Consultant. 1997;37 Suppl:S9

6. Type 2 Diabetes : Tip of the Iceberg
Stage III
Diabetes
Macroangiopathy 
Microangiopathy 
Postprandial
Plasma glucose 
Glucose production 
Glucose transport 
Insulin secretory deficiency
Stage II
Impaired glucose
tolerance
Stage I
Normal glucose
tolerance
Atherogenesis
Hyperinsulinaemia
Insulin Resistance
Tg 
HDL 
Hypertension
Lipogenesis 
Obesity
Waist-hip ratio
Diabetes Genes

7. “Genetics loads the gun But the environment pulls the trigger”
Joslin, 1927

8. • • • • • • • • • ◄ Principles of Diabetes Care Life Style
Hypertension •
Exercise
Diet •
Hyperlipidaemia
Isulin Secretagogues •
Sulfonylureas
Meglitinides
Microalbuminuria • •
Insulin Sensitizers
Metformin •
Thiazolidenediones
Insulin • ◄
Incretin mimetics • •
Pramlintide
Glycosidase Inhibitors

9. Treatment of the Metabolic Syndrome in Overweight or Obese Patients
Weight loss induced by diet and increased physical activity is the cornerstone of therapy
Weight loss induced by drug therapy can also improve specific features of the metabolic syndrome
Bariatric surgery is the most effective weight loss therapy for extremely obese subjects and improves all features of the metabolic syndrome
Treatment of the metabolic syndrome in overweight or obese patients
The principal strategy for the treatment of the metabolic syndrome should be weight loss and increased physical activity. While there are no randomized clinical trials showing the effectiveness of these behavioral therapies for reducing cardiovascular disease, there are several randomized controlled trials showing that modest weight loss (around 5%) and increased physical activity may reduce the risk of type 2 diabetes by > 50% (Diabetes Prevention Program and Finnish Prevention Study.)
References:
Diabetes Prevention Program Research Group. Reduction in the incidence of Type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):
2.Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:

10. Treatment of Metabolic Syndrome in Patients with Diabetes
80-85% of diabetic subjects in North America and Europe have the metabolic syndrome
However, most subjects with the metabolic syndrome do not have diabetes
Statin therapy has been shown to be effective in diabetic subjects (4S, HPS, CARE, CARDS).
Treatment of Hypertension is also crucially important in diabetic subjects (UKPDS, SYST-Euro, HOT).
Treatment of metabolic syndrome in patients with diabetes
There is a great deal of data showing the effectiveness of blood pressure and lipid therapy in subjects with type 2 diabetes. Since 80-85% of diabetic subjects have the metabolic syndrome, this might be considered to be a good model for assessing whether traditional cardiovascular interventions might work in subjects with the metabolic syndrome. However, most subjects with the metabolic syndrome do not have type 2 diabetes.

11. >20% fall in total mortality
OBESITY CO-MORBIDITY
WEIGHT LOSS
BENEFIT OF WEIGHT LOSS
Mortality
10 kg
>20% fall in total mortality
>30% fall in diabetes-related deaths
Fall in obesity-related cancer deaths
Diabetes
Fall in 50% fasting glucose
Blood pressure
Fall of 10 mmHg systolic
Fall of 20 mmHg diastolic
Blood lipids
Fall of 10 % total cholesterol
Fall of 15% LDL
Fall of 30% triglycerides
Increase of 8% HDL
Blood clotting indices
Reduced red cell aggregability
Improved fibrinolytic capacity
Physical complications
5 – 10 kg
Improved back and joint pain
Improved lung function
Decreased breathlessness
Reduced frequency of sleep apnoea
Ovarian function
>5%
Improved ovarian function

12. Goal for Glycemic Control
HbA1C less than 7% (6.5%?)
Fasting sugars less than 110
Two-hour postprandial sugars
less than 140
Blood pressure less than 130/80 (125/75 if renal impairment)

13. KEY CONCEPTS IN SETTING GLYCEMIC CONTROL
Goals should be individualized
Certain populations(children, pregnant women,elderly) require special considerations
Less intensive glycemic goals for patients with frequent hypoglycemia
Postprandial goals may be targeted if A1C goals are not met despite reaching pre-prandial glucose goals

14. Principles of Diabetes Care
Life Style
Exercise
Diet
How much?
2½ hours weekly or 30 min a day for 5 days a wk
Moderate exertion like brisk walk, light exercise….
Increase activity rather than stressing on exercise.

15. Exercise!

16. Principles of Diabetes Care
Life Style
Exercise
Diet
Outline
Maintain Ideal Body Weight.
Maximum 25 (men) 24 (women)
“Limit” total fat
“Limit” free sugars

17. “From an excess of FAT diabetes begins & from an excess of FAT diabetics die.”

18. Take Home Messages “if you love them don’t stuff them”
Don’t allow your children to get obese.
Eat less and remain healthy.
Physical activity or exercise doesn’t play a great role in weight loss.
It is possible to remain slim after overeating but it is not possible to get obese without overeating.

19. 2-hour plasma glucose (mmol/l) Fasting plasma glucose (mmol/l)
Relative risk for death increases with 2-hour blood glucose irrespective of the FPG level
2.5
2.0
1.5
1.0
0.5
0.0
Hazard ratio
³11.1
7.8–11.0
Results from the DECODE study show that the relative risk for death increases with 2-hour blood glucose irrespective of fasting plasma glucose (FPG) levels.
It can clearly be seen that within each FPG category, the hazard ratio for death increased with increasing 2-hour blood glucose. However, increasing FPG levels appear to have a minimal effect on the relative risk of death.
This indicates that increases in 2-hour blood glucose levels are closely associated with the relative risk of mortality, irrespective of the FPG level.
Fasting plasma glucose categories were defined as: normal <6.1 mmol/l (<110 mg/dl), impaired fasting glucose (IFG) 6.1–6.9 mmol/l (110–124 mg/dl) and fasting diabetes 7.0 mmol/l ( 126 mg/dl).
Two-hour plasma glucose categories were defined as: normal <7.8 mmol/l (<140 mg/dl), impaired glucose tolerance (IGT) 7.8–11 mmol/l (140–198 mg/dl) and diabetes  11.1mmol/l ( 200 mg/dl).
<7.8
2-hour plasma glucose (mmol/l)
< –6.9 ³7.0
Fasting plasma glucose (mmol/l)
Adjusted for age, centre, gender
DECODE Study Group. Lancet 1999;354:617–621

20. Knowledge from UKPDS and DECODE
Hyperglycaemia
Tissue damage
Diabetes complication
Total load (HbA1c)
Chronic glucose toxicity
Microangiopathy
UKPDS1
Postprandial
peaks
Acute glucose toxicity
Macroangiopathy
DECODE2
DECODE: Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe, HbA1c: haemoglobin A1c, UKPDS: UK Prospective Diabetes Study
1. Stratton IM, et al. BMJ 2000;321:405–12.
2. DECODE. Diabetes Care 2003;26:688–96.
Knowledge from DECODE and UKPDS
The UK Prospective Diabetes Study (UKPDS) showed that interventions directed at lowering fasting plasma glucose (FPG) levels were far more effective at reducing the risk of micro- than macrovascular complications.1 In contrast, the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) demonstrated that the risk of CVD is more strongly associated with 2-hour postchallenge plasma glucose (2hPG) levels, than with FPG levels.2
Both fasting and postprandial hyperglycaemia must be addressed to prevent diabetes complications. However, as the majority of diabetes patients die from CV causes, the current focus on pharmacological agents that target FPG levels may not offer optimal CV risk reduction.
1. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35). BMJ 2000;321:405–12.
2. DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 2003;26:688–96.

21. Postprandial Glucose Monitoring Take-home messages
Epidemiological data supports relationship between postprandial glycemia and mortality including cardiovascular mortality.
Outcomes trials show benefit of reducing HbA1c for microvascular and macrovascular disease with no threshold for glycemic control
Emerging evidence that targeting postprandial glucose reduces adverse outcomes

22. Pharmacological Therapy
Matching pathophysiology to pharmacology

23. Type 2 Diabetes Standard “Stepped” Approach to Treatment
Step1: Education, Diet, Exercise & SMBG
Step2: Oral Antidiabetic Agents (Monotherapay)
Step3: Oral Antidiabetic Agents
“Combination therapy”.
Step4: Bedtime NPH or Glargine + Daytime OAD
Step5: BID Split / Mixed Insulin
Step6: Multiple daily Injections

24. Targeting Insulin Resistance: A Strategy for Improving Glycemic Control in Type 2 Diabetes

25. Insulin Resistance: Definition
Condition in which greater than normal amounts of insulin are required to produce a normal biological response
Olefsky JM. In: Ellenberg and Rifkin’s Diabetes Mellitus. 5th ed. 1997:

26. Consequences of Insulin Resistance
Insulin resistance interferes with the insulin signal...
Insulin
Pancreas
Insulin resistance, a key factor in the pathogenesis of type 2 diabetes, is a condition in which the cells of various body tissues fail to respond efficiently to insulin. For example, muscle tissue fails to increase its uptake of blood glucose, and hepatic production of glucose is not inhibited as it normally would be by insulin. As insulin resistance develops, the beta-cells of the pancreas attempt to compensate by producing more insulin.
Following the onset of beta-cell dysfunction, the pancreas is no longer able to compensate for insulin resistance by relative hypersecretion of insulin. As a consequence, control of blood glucose worsens, leading to impaired glucose tolerance, increased fasting and post-prandial glucose levels, and then to type 2 diabetes.
Liver
Fat
Muscle
…hepatic glucose output increases
FFA output increases
...and glucose uptake in fat and muscle decreases
Reaven. Physiol Rev 1995;75:

27. Insulin resistance exposes patients to.....
Excessive calorific intake
Obesity
Inherited genetic susceptibility
Insulin Resistance
Hyperinsulinemia
Dyslipidaemia
Hypertension
Atherosclerosis
Insulin resistance can result from genetic and/or environmental influences which ultimately result in hyperinsulinaemia defined as raised levels of insulin in the blood.
Insulin resistance has emerged as a potentially important risk factor for vascular disease. In separate investigations it has been associated with risk for coronary artery disease, atherosclerosis and stroke. Although the mechanism for this association is not totally understood but may involve hyperglycemia, dyslipidaemia, hypertension, hypercoaguability and endothelial dysfunction.
Thus dyslipidaemia, hypertension and atherosclerosis are all associated with insulin resistance through different cellular mechanisms. The good news is that scientific and clinical research programs have proven that pioglitazone has a positive effect on diabetic dyslipidaemia, hypertension and markers of atherosclerosis in patients with type 2 diabetes through direct effects of the agent rather than through its ability to lower blood sugar.
You may be asking yourselves what is the relevance of this and of the various published papers, well the remainder of this presentation will put all of that into context…hopefully.
Raised TG
Raised LDL-C
Lowered HDL-C
Reduced nitric
oxide production
Raised
inflammatory
markers
Modified from Reaven G. In: LeRoith D, et al, eds.
Diabetes Mellitus: A Fundamental and Clinical Text. 2000;Philadelphia, PA: LWW pp .

28. Insulin Resistance and Type 2 Diabetes
40% of older people are insulin resistant mostly secondary to obesity and inactivity (important in prevention and treatment)
20% of the elderly have type 2 diabetes
8.5% of all adults have type 2 diabetes
90% of diabetics are managed in primary care

29. One Approach to Selecting Medication for Type 2 Diabetics
Check a fasting insulin C-peptide level
If high or high-normal use an insulin sensitizer – biguanine or glitazone or a combination of the two
If low or low-normal use an insulin secretagogue
Consider changing patients who were put on insulin before the new oral diabetes medications to insulin sensitizers

30. • • • • • • • • • ◄ Principles of Diabetes Care Life Style
Hypertension •
Exercise
Diet •
Hyperlipidaemia
Isulin Secretagogues •
Sulfonylureas
Meglitinides
Microalbuminuria • •
Insulin Sensitizers
Metformin •
Thiazolidenediones
Insulin • ◄
Incretin mimetics • •
Pramlintide
Glycosidase Inhibitors

31. Insulin sensitizers
BIGUANIDES
THIAZOLIDINEDIONES.

32. BIGUANIDES
Metformin

33. First Line Drug for Type 2 Diabetes
Biguanides (Metformin)
Decreases hepatic glucose output
Increases insulin sensitivity
Decreases LDL and triglycerides
Decreases C-reactive protein
Causes weight loss or stabilization
No risk of hypoglycemia
Causes nausea, cramps and diarrhea
Lactic acidosis rare (contraindications –
CHF, renal impairment, age greater than 80)

34. UKPDS - 1998 Traditional glycemic control (secretagogues)
reduced microvascular complications
Retinopathy -29%
Nephropathy -33%
Neuropathy -40%
But not macrovascular complications
MI’s -16%
Stroke +11%
Deaths -6%

35. UKPDS 1998 Metformin decreased macrovascular
complicatons (lower insulin levels)
MI %
Coronary Deaths -50%
Diabetes Related
Deaths %
All Cause Mortality -36%

36. Risk reductions from intervention studies in type 2 diabetes
Clinical Outcomes
Diabetes-related deaths (%)
All-cause mortality (%)
All MI (%)
Fatal MI (%)
All stroke (%)
Fatal stroke (%)
Follow-up (years)
UKPDS
Metformin
n=753 42 36 39 50 41 25
10.7
UKPDS
SU/Ins
n=3867 10 6 16
(+)11
(+)17
10.7
UKPDS
Captopril
Atenolol
n=1148 32 18 21 28 44 58
8.4
HOT
Felodipine
Aspirin
n=1501 67 43 51 - 30
3.8 4S
Simva- statin
n=202 36 43 55 - 62
5.4
HOPE
Ramipril
n=3577 37 24 22 - 33
4.5
Risk reductions from intervention studies in type 2 diabetes
The magnitudes of the outcome benefits in the study of metformin in overweight patients compare well with the results of other major clinical trials, which recruited substantial proportions of diabetic subjects and addressed the prognostic effects of controlling blood pressure or lipids.
A total of 1148 hypertensive patients enrolled in the UKPDS were randomised to tight blood pressure control with the antihypertensive agents atenolol (n=358) or captopril (n=400), or to less tight blood pressure control (n=390).
The Hypertension Optimal Treatment (HOT) study randomised patients to three target blood pressures (< 90 mmHg, < 85 mmHg or < 80 mmHg), achieved using a calcium channel blocker, felodipine, plus additional antihypertensive therapy as needed.
The Heart Outcomes Prevention Evaluation (HOPE) study evaluated the effects of an angiotensin converting enzyme inhibitor, ramipril, in patients at high cardiovascular risk, i.e. patients with atherosclerosis or diabetes with at least one additional cardiovascular risk factor.
The Scandinavian Simvastatin Survival Study (4S) showed that aggressive lipid- lowering therapy significantly reduced the incidence of major cardiovascular events.
In summary, type 2 diabetic patients have multiple risk factors, which if corrected are likely to lead to reduced morbidity and mortality. The evidence base points towards the need for multiple interventions to minimise cardiovascular risk and premature mortality.

37. Thiazolidinediones Pioglitazone Rosiglitazone

38. THIAZOLIDINEDIONES MECHANISM OF ACTION
Peroxisome Proliferator Acivated Receptor-gamma
(PPAR-γ) agonists.
Expression of number of genes
↑glucose transporter expression(GLUT 4)
↓FFA
↓hepatic gluconeogenesis
↑differentiation of preadipocytes into adipocytes

39. THE PPAR FAMILY OF NUCLEAR RECEPTORS
FIBRATES
THIOZOLIDINEDIONES
FATTY ACIDS
LIGAND
PPAR α
PPAR δ
PPAR γ
RECEPTOR
EFFECT
LIPOPROTEIN EXPRESSION
PEROXISOME PROLIFERATION
LIPID SYNTHESIS
CARBOHYDRATE METABOLISM

40. PPARg Increases Glucose Disposal: Potential Site of Action
Slide IV.4
PPARg Increases Glucose Disposal: Potential Site of Action
PPARg Increases Glucose Disposal: Potential Site of Action*
Through their activation of PPARg, the thiazolidinediones improve insulin-stimulated glucose disposal.
Impaired glucose transport in adipose tissue and skeletal muscle is an important defect in patients with type 2 diabetes. Under normal circumstances, this process is initiated when insulin binds to surface receptors on fat and muscle cells and transmits a signal (signal transduction) across the cell membrane. GLUT4, which is the only one of several glucose transporters known to be insulin-sensitive, is translocated to the cell membrane where it facilitates the movement of glucose across the membrane into the cell. After insulin leaves its receptor, GLUT4 reenters the cell and returns to its storage vesicle.
In patients with insulin resistance, the insulin signal is not propagated. Activation of PPARg by the thiazolidinediones enhances insulin signal transduction, increases the recruitment of GLUT4 to the cell membrane, and increases glucose uptake and transport into the cell.
*An animated version of this slide is located in the folder “Animated Slides.”

41. SITES OF ACTION OF ORAL ANTIDIABETIC AGENTS
Delay
Carbohydrate absorption
Acarbose
Reduce excessive
Hepatic glucose output
Stimulate Impaired
Insulin secretion
Reduce
Hyperglycemia
TZD’s 20%
Metformin 80%
Sulfonylureas
TZD’s
80%
Metformin
20%
Reduce peripheral
Insulin resistance

42. THIAZOLIDINEDIONES DURATION OF ACTION 24-30 Hours SIDE EFFECTS
Hepatotoxicity
Weight gain
Fluid retention
Anemia
CONTRAINDICATIONS
Liver disease
Heart Failure (NYHA class 3 &4)

43. Indications
As an adjunct to diet & exercise to improve glycemic control in patients with type 2 diabetes.
Indicated as monotherapy
Also indicated for use in combination with a sulfonylurea, metformin or insulin.

44. Insulin Sensitizers Do More Than Just Lower Glucose
Improve lipid (TZDs >> Metformin)
Decrease TG, Increase HDL, Increase LDL – bigger particle
Lower CRP (TZD > Metformin)
Lower PAI-1 (TZD & Metformin)
Decrease intra abdominal fat (TZD)
? Protect beta cell (TZD)
Prevent restenosis after stenting.

45. Fixed-Dose Monotherapy Study Change in HbA1c at Endpoint
HbA1c at week 26 (% points)
Change from baseline
Difference from placebo
Baseline mean HbA1c: 9.5%
*p<0.05 vs baseline
†p<0.05 vs placebo
adapted from: Aronoff S, et al., Diabetes Care 2000;23:

46. Pioglitazone + Sulphonylurea Study Mean Changes in FPG at Endpoint
FPG at week 16 (mmol/L)
Placebo + SU (n=182)
Plo 15mg + SU (n=179)
Plo 30mg + SU (n=186)
Mean Change from baseline
Baseline mean FPG placebo: 13.1 mmol/L, pioglitazone: 13.5mmol/L *p=0.05 vs baseline †p=0.05 vs placebo +SU
Kipnes MS, et al. Am J Med 2001;111:10-17.

47. Pioglitazone + Metformin Study Mean Changes in FPG at Endpoint
FPG at week 16 (mmol/L)
Placebo + Met (n=157)
Plo 30mg + Met (n=167)
Mean Change from baseline
Baseline mean FPG:placebo 14.4 mmol/L, pioglitazone 14.0 mmol/L *p<0.05 vs baseline †p<0.05 vs placebo + Met
Einhorn D, et al. Clin Ther 2000;22:

48. Pioglitazone: Favorable effects on serum lipids

49. Study Objective
To evaluate the impact of pioglitazone and rosiglitazone on lipid profiles and glycemic control in patients with type 2 diabetes
pioglitazone
rosiglitazone

50. Mean Change in Triglyceride
Pioglitazone
Rosiglitazone
-13.3
P = vs. baseline
-6%
-10
Mean change in TG (mg/dL)
-20
-55.2
P <0.001 vs. baseline
-23%
-30
-40
-50
Pioglitazone vs. Rosiglitazone: P <0.001
-60

51. Mean Change in Total Cholesterol
Pioglitazone
Rosiglitazone 6
4.8 2%
P = vs. baseline 4
Mean change in TC (mg/dL) 2 -2
-8.5
-4%
P <0.001 vs. baseline -4 -6 -8
Pioglitazone vs. Rosiglitazone: P <0.001
-10

52. Mean change in HDL-C (mg/dL) Pioglitazone vs. Rosiglitazone: P = 0.064
3.0
2.7 6%
P <0.001 vs. baseline
2.5
Mean change in HDL-C (mg/dL)
2.0
Pioglitazone vs. Rosiglitazone: P = 0.064
1.5
1.0
0.5
-0.1
-0.3%
P = vs. baseline
0.0
-0.5

53. Mean Change in LDL-C 3% -4% Pioglitazone Rosiglitazone6
3.6 3%
P = vs. baseline 4
Mean change in LDL-C (mg/dL) 2
-5.1
-4%
P = vs. baseline -2 -4
Pioglitazone vs. Rosiglitazone: P <0.001 -6

54. Conclusions
Blood lipid levels changed more favorably with pioglitazone than with rosiglitazone
Changes in HbA1c and weight gain were equivalent
pioglitazone
rosiglitazone

55. A new armament against Type 2 DM
Pioglitazone.
A new armament against Type 2 DM
An insulin sensitizer that reduces insulin
resistance
Provides excellent glycemic control
Less risk of Hypoglycemia
Improves lipid profile
Reduces the risk of CVD.
Indicated as mono therapy as well as in
combination with Metformin, Sulfonylureas &
Insulin

56. Non Glycemic Goals: Treat All Cardiovascular Risks Factors Aggressively
Smoking
Hypertension
BP less than 130/80
Lipids
LDL Cholesterol < 100 mg/dl
LDL less than 70 mg/dl in “high risk” cases
HDL cholesterol > 40 mg/dl
Triglycerides < 150 mg/dl
Aspirin

57. Case History 30 y.o. woman with a history of gestational
diabetes with her first pregnancy at age 21
presents with frequent urination, thirst, weight
loss and a random glucose of She has an
IUD in place. Her BMI is 33. BP is 140/80.
Is this enough information to diagnose diabetes?
What other tests would you order?

58. Test Results HbA1C 9.2 Alb/Cr 0.010 Cr 0.6 LFT’s WNL CBC WNL TSH 2.3
Fasting Insulin
C-peptide 3.5
b-HCG Neg

59. What will you do now?
Educate your patient about diabetes and set goals together for her care
Diabetic diet counseling and a weight loss program
Educate her in use of a glucometer.
Devise exercise program for physical fitness.

60. Anything else? Refer to ophthalmologist
Do microfilament check for neuropathy
See frequently to reinforce diet, exercise, home glucose monitering
Start Metformin.
Treat BP with ACEI if remains over 130/80

61. Eight Months Later
Despite modest weight loss and compliance with her medications your patient still has a HbA1C of Her blood pressue is 120/75 and her Alb/Cr is LFT’s remain normal.
What would you do now?

62. Second Oral Medication
Add a
Glitazone or
Sulfonylurea

63. Summary Type 2 diabetes affects many organs
Type 2 diabetes changes over time
Diabetes treatment changes over time
Medications can now be selected to work where the problem is
Combinations of medications, because they work at different sites, in the body usually work better than monotherapy

64. THANK YOU