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J. David Schnatz, M.D.
Director, Lipid Education Service
Saint Francis Hospital and Medical Center
114 Woodland Street, Hartford, CT 06105
Telephone: (860) 714-5555
September 1997
In the last Newsbrief, 1 June 1997, I discussed "Diabetes, Coronary Heart Disease and Treatment of Hyperlipidemia," using a subset of the 4S study which showed that "cholesterol lowering with Simvastatin improves the prognosis of diabetic patients with CHD." (1) The frequency with which cardiologists see diabetic patients who have CHD and the tremendous impact of diabetes on morbidity and mortality from CHD prompts the question, does intensive control of diabetes lessen the unfavorable impact of macrovascular disease? (2,3) If so, is there a difference for intensive treatment of insulin dependent diabetes mellitus (IDDM) vs non-insulin dependent diabetes mellitus (NIDDM)?
IDDM: The Diabetes Control and Complications Trial (DCCT) has shown, convincingly, that "intensive therapy effectively delays the onset and slows the progression of diabetes retinopathy, nephropathy, and neuropathy in patients with IDDM" (4). The hemoglobin A1C in the intensive therapy group was two percentage points below that of the conventional treatment group, 7.2% vs 9.1%, p less than 0.0001, and this was maintained during the 10 years of the study. In a separate publication (5), the DCCT analyzed for reduction in macrovascular events; cardiac, cerebral and peripheral. A 42% reduction in the risk of developing macrovascular events was observed in the intensive treatment group, but this was not significant. Inability to achieve significance was probably due to the young age of the patients and the small number of major macrovascular events, making it difficult to detect a difference between the treatment groups. Further work is necessary to show a significant difference.
NIDDM: The majority of patients with CHD fall into the NIDDM category. Cardiovascular morbidity and mortality is greatly increased in NIDDM patients as described in a recent article (6). In this study, diabetic patients in the tertile with the highest glucose (greater than 214 mg/dl) had 3 times the mortality of the tertile with the lowest glucose (less than 155 mg/dl), suggesting the importance of control in those NIDDM patients.
Currently, there is a large prospective ongoing study, due to be reported in 1998, which is looking at the ability to prevent the complications of NIDDM with blood glucose control (7). However, even before the availability of that study, there are reports of metabolic control of NIDDM decreasing cardiovascular mortality.
Moss et al reported an 8-10 year follow up of 1210 younger onset diabetics (less than 30 years old) and 1,780 older onset diabetics (greater than 30 years old) (8). Hemoglobin A1C was obtained at baseline, during follow up and at the end of the study, and was significantly associated with mortality. Between the lowest and highest quartile for hemoglobin A1C, the all-cause mortality was 1.9 times greater for the highest quartile in both the younger and older onset patients. In the younger onset group, 10 year survival ranged from 96.3% in the lowest hemoglobin A1C quartile to 93.0% in the fourth quartile. In the older onset group, 10 year survival ranged from 62.8% in the lowest quartile to 41.7% in the highest quartile.
Four hundred eleven NIDDM patients were followed for 7.4 years by Andersson and Svardsudd (9). Those with a fasting blood glucose greaterv than or equal to 140 mg/dl had a 50% higher mortality compared to those with a fasting glucose of less than 140 mg/dl.
Kuusisto et al studied 1,069 non-diabetic and 229 NIDDM patients, ages 65-74 years at baseline (10). Over a 3.5 year follow-up period, both hemoglobin A1C at baseline and duration of diabetes predicted CHD death and all CHD events and this was particularly so in women. For the tertiles of hemoglobin A1C of less than 6%, 6-7.9% and greater than 7.9%, the CHD mortality was 2%, 5% and 12% respectively and the all CHD event incidence was 8%, 13% and 22%, respectively. The authors conclude that "this study gives evidence for the importance of metabolic control in the risk of CHD events in elderly subjects with NIDDM."
Dyslipidemia is a common accompaniment of uncontrolled diabetes with or without CHD. In the effort to place the patient with CHD in the most favorable metabolic setting, a major effort at controlling the diabetes should accompany all efforts to achieve NCEP-II lipid goals. In fact, control of the diabetes should help to achieve the NCEP-II lipid goals.
REFERENCES
(1) Brit J Obstet & Gynecol 103:59, 1996.
(2) Arch Int Med 156:1693, 1996.
(3) NEJ Med 316:1105, 1987.
(4) NIH Publication #93-3095.
(5) Ann Int Med 117:1038, 1992.
(6) Arch Int Med 151:67, 1991.
(7) JAMA 273:199, 1995
(8) N Eng J Med 335:453, 1996.
(9) Diabetes Care 18:1534-1543, 1995.
(10) Diabetes 43:960-967, 1994.
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