Diabetes and Cardiovascular Disease

1
Diabetes and Cardiovascular Disease

• Epidemiology
• Clinical Trials
• Management

Nathan Wong
2
Diabetes Scope of Problem

• At least 10.3 million Americans have been
  diagnosed with diabetes mellitus, and another 5.4
  million are estimated to have undiagnosed
  diabetes. Onset often precedes diagnosis by
  several years.
• About 90 of diabetic patients have Type II
  diabetes
• Hispanics, blacks, Native Americans, and Asians
  (especially South Asians) are especially
  susceptible to diabetes.
• Diabetes in women essentially cancels out any
  hormonal protection.

3
Diabetes Type II Diabetes and Insulin
Resistance

• Type II diabetes is most common form, occurring
  later in life, and involving combination of
  impaired insulin-mediated glucose disposal
  (insulin resistance) and defective secretion of
  insulin by pancreatic beta cells
• Insulin resistance develops from obesity and
  physical inactivity and insulin secretion
  declines with advancing age (and accelerated by
  genetic factors)

4
Insulin Resistance and Atherosclerosis Posited
Relationships
5
Diabetes and the Dysmetabolic Syndrome

• Insulin resistance often precedes type II
  diabetes and is often accompanied by other risk
  factors-- dyslipidemia, hypertension, and
  prothrombotic factors, the dysmetabolic
  syndrome
• Impaired fasting glucose (110-125 mg/dl) often
  accompanies the dysmetabolic syndrome.
• The threshold for fasting plasma glucose for
  diagnosis of diabetes has been lowered from 140
  mg/dl to 126 mg/dl.

6
Diabetes Complications

• Cardiovascular diseases (CVD) account for about
  65 of all deaths in diabetics those with CVD
  have a worse prognosis than CVD patients without
  diabetes.
• Complications include CHD, stroke, peripheral
  arterial disease, nephropathy, retinopathy, and
  possibly neuropathy and cardiomyopathy.
• Stroke mortality 3-fold in diabetics vs.
  nondiabetics. Carotid atherosclerosis and
  likelihood of irreverisible brain damage from
  stroke more common in diabetics.
• Renal impairment is a severe complication of
  diabetes about 35 of pts with Type I diabetes
  have some renal impairment. End stage renal
  disease (ESRD) carries a high mortality (20/year
  in dialysis pts) and is more common in Hispanics,
  blacks, and Native Americans

7
Framingham Heart Study 30-Year Follow-UpCVD
Events in Patients With Diabetes (Ages 35-64)
10
10
9
Men
Women
8
11
Risk ratio
6
30
19
4
9
6
38
20
3
2
0
Total CVD
CHD
Cardiac failure
Intermittent claudication
Stroke
Age-adjusted annual rate/1,000
Plt0.001 for all values except Plt0.05.
8
Risk Similar in Patients With Type 2 Diabetes and
No Prior MI vs Nondiabetic Subjects With Prior MI
100
80
60
Survival()
40
Nondiabetic subjects without prior MI
(n1,304)Diabetic subjects without prior MI
(n890)Nondiabetic subjects with prior MI
(n69)Diabetic subjects with prior MI (n169)
20
0
0
1
2
3
4
5
6
7
8
Year
Haffner SM et al. N Engl J Med. 1998339229-234.
9
Atherosclerosis in Diabetes

• 80 of all diabetic mortality
• 75 from coronary atherosclerosis
• 25 from cerebral or peripheral vascular disease
• gt75 of all hospitalizations for diabetic
  complications
• gt50 of patients with newly diagnosed type 2
  diabetes have CHD

National Diabetes Data Group. Diabetes in
America. 2nd ed. NIH1995.
10
Potential Mechanisms of Atherogenesis in Diabetes

• Abnormalities in apoprotein and lipoprotein
  particle distribution
• Glycosylation and advanced glycation of proteins
  in plasma and arterial wall
• Glycoxidation and oxidation
• Procoagulant state
• Insulin resistance and hyperinsulinemia
• Hormone-, growth-factor, and cytokine-enhanced
  SMC proliferation and foam cell formation

SMCsmooth muscle cell. Adapted from Bierman EL.
Arterioscler Thromb. 199212647-656.
11
Women, Diabetes, and CHD

• Diabetic women are at high risk for CHD
• Diabetes eliminates relative cardioprotective
  effect of being premenopausal
• risk of recurrent MI in diabetic women is three
  times that of nondiabetic women
• Age-adjusted mean time to recurrent MI or fatal
  CHD event is 5.1 yr for diabetic women vs 8.1 yr
  for nondiabetic women

Kannel WB. Am Heart J. 19851101100-1107. Abbott
RD et al. JAMA. 19882603456-3460.
12
Diabetes in California

• Diabetes has increased more than 28 since 1987,
  corresponding with a more than 50 increase in
  the prevalence of overweight / obesity during the
  same time period
• 12.9 of Hispanics, 14.5 of Blacks, compared to
  4.3 in Whites report diabetes in California.
• 4.6 of Men and 6.3 of Women report diabetes in
  California.
• Prevalence of diabetes increases with age and is
  inversely related to educational attainment.

13
Evaluation of Risk Factors Affecting Diabetes
and CVD

• Body weight and fat distribution - assess
  history, BMI (obesity gt30 Obesity) and waist
  circumference (abdominal obesity gt40 in. in men
  and gt36 in. in women)
• Physical activity - assess past and current
  levels
• Family history of CVD (lt65 female,lt55 male
  relative)
• Dyslipidemia (esp. low HDL-C and high TG)
• Hypertension (treshold for treatment 130/80 mmHg)
• Cigarette Smoking - current, past habits, and
  intensity
• Albuminuria - measure serum creatinine and test
  urine with dipstick for protein (do alb/creat if
  neg)
• Glycemic status - age of onset of hyperglycemia,
  family history of diabetes, complications,
  measure fasting plasma glucose, periodic measures
  of HgbA1c

14
Abnormal Lipid Levels in Men With Type 2 Diabetes
50
Men without diabetes
Men with diabetes
40
34
30
26
Prevalence()
21
19
20
14
13
12
11
9
9
10
0
TC ?260
TG ?235
VLDL-C ?40
LDL-C ?190
HDL-C ?31
Plt0.05. LRC approximate 90th percentile age- and
sex-matched values, except for HDL-C (10th
percentile).
15
Abnormal Lipid Levels in Women With Type 2
Diabetes
50
Women without diabetes
Women with diabetes
38
40
31
30
25
Prevalence()
24
21
17
20
16
15
10
8
10
0
TC ?275
TG ?200
VLDL-C ?35
LDL-C ?190
HDL-C ?41
Plt0.05. LRC approximate 90th percentile age- and
sex-matched values, except for HDL-C (10th
percentile).
16
(No Transcript)
17
Significance of Small, Dense LDL

• Low cholesterol content of LDL particles
• ? particle number for given LDL-C level
• Associated with ? levels of TG and LDL-C, and ?
  levels of HDL2
• Marker for common genetic trait associated with
  ? risk of coronary disease (LDL subclass pattern
  B)
• Possible mechanisms of ? atherogenicity
• greater arterial uptake
• ? uptake by macrophages
• ? oxidation susceptibility

18
Hypertension in Persons with Diabetes

• Up to 75 of persons with Type II diabetes have
  hypertension if defined as gt140 / 90 mmHg

19
Treatment of Hypertension in Diabetics

• The JNC-VI recommends pharmacologic treatment
  concurrently with lifestyle management for
  hypertension in diabetics with a systolic blood
  pressure of 130mmHg or higher, or a diastolic
  blood pressure of 85 mmHg or higher.
• An angiotensin converting enzyme (ACE)-inhibitor
  is recommended as first line therapy also because
  of renal-protective effects in preventing
  progression of microalbuminuria / proteinuria.

20
(No Transcript)
21
(No Transcript)
22
Primary CHD Prevention in Patients With Type 2
Diabetes The Helsinki Heart Study
Type 2 (n135)
15
Others (n3,946)
PNS
Type 2 on placebo (n76)
10.5
Plt0.02
Type 2 on gemfibrozil (n59)
10
5-Yr incidenceof CHD ()
7.4
5
3.4
3.3
0
Myocardial infarction or cardiac death. NSnot
significant. Koskinen P et al. Diabetes Care.
199215820-825.
23
(No Transcript)