Cardiovascular Events and Correlates in the Veterans Affairs Diabetes Feasibility Trial Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes

BACKGROUND The risks and benefits of intensive therapy in non-insulin-dependent diabetes mellitus (NIDDM) need to be defined. In preparation for a long-term trial, a feasibility study of 153 men in 5 medical centers compared standard vs intensive insulin therapy. OBJECTIVE To assess the rate of development of new cardiovascular events and their correlates. METHODS Patients with a mean +/- SD age of 60 +/- 6 years and diagnosis of NIDDM for 7.8 +/- 4.0 years were randomly assigned to a standard (1 insulin injection every morning) or to an intensive treatment arm (stepped plan from 1 evening injection of insulin, alone or with glipizide, to multiple daily injections) designed to attain near-normal glycemia levels. A 2.07% separation of glycosylated hemoglobin (HbA1c) was sustained for a mean follow-up of 27 months (P < .001). Predefined cardiovascular events were assessed by a committee unaware of treatment assignment. RESULTS Mild and moderate hypoglycemic events were more frequent in the intensive than in the standard treatment arm (16.5 vs 1.5 per patient per year, respectively). Mean insulin dose was 23% lower in the standard treatment arm (P < .001). There were 61 new cardiovascular events in 24 patients (32%) in the intensive treatment arm and in 16 patients (20%) in the standard treatment arm (P = .10). There was no difference in total and cardiovascular mortality (n = 5 and n = 3 in the intensive and standard treatment arms, respectively) or in new events in patients with cardiovascular history (n = 10 in each arm). In Cox regression analysis, the only significant correlate for new cardiovascular events was previous cardiovascular disease (P = .04). Entering in the analysis any baseline cardiovascular abnormality, the regression model indicated a lower HbA1c level prior to the event as the only correlate for new cardiovascular events (P = .05). CONCLUSION A long-term prospective trial is needed to assess the risk-benefit ratio of intensive insulin therapy for NIDDM in patients who require it.

[1]  F. Nuttall,et al.  Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM): Results of the feasibility trial , 1995, Diabetes Care.

[2]  J. Manson,et al.  Glycosylated hemoglobin and the risk of retinopathy in insulin-dependent diabetes mellitus. , 1995, The New England journal of medicine.

[3]  A. Krolewski,et al.  Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. , 1995, The New England journal of medicine.

[4]  G. Viberti.  A glycemic threshold for diabetic complications? , 1995, The New England journal of medicine.

[5]  M. Feinglos,et al.  Hypoglycemia-Induced Angina Pectoris in a Patient with Diabetes Mellitus , 1994, Annals of Internal Medicine.

[6]  R. Klein,et al.  The association of glycemia and cause-specific mortality in a diabetic population. , 1994, Archives of internal medicine.

[7]  M. Laakso,et al.  NIDDM and Its Metabolic Control Predict Coronary Heart Disease in Elderly Subjects , 1994, Diabetes.

[8]  G. Viberti,et al.  Relationship between insulin resistance and coronary heart disease in diabetes mellitus and the general population: a critical appraisal. , 1993, Bailliere's clinical endocrinology and metabolism.

[9]  G. Reaven,et al.  Insulin resistance and risk factors for coronary heart disease. , 1993, Bailliere's clinical endocrinology and metabolism.

[10]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[11]  G. Bakris.  Angiotensin-Converting Enzyme Inhibitors and Progression of Diabetic Nephropathy , 1993, Annals of Internal Medicine.

[12]  F. Ferris,et al.  How effective are treatments for diabetic retinopathy? , 1993, JAMA.

[13]  T. Tai,et al.  Development of Macrovascular Diseases in NIDDM Patients in Northern Taiwan: A 4-yr follow-up study , 1993, Diabetes Care.

[14]  R. Henry,et al.  Intensive Conventional Insulin Therapy for Type II Diabetes: Metabolic effects during a 6-mo outpatient trial , 1993, Diabetes Care.

[15]  D. Levy,et al.  Prognostic Implications of Asymptomatic Ventricular Arrhythmias: The Framingham Heart Study , 1992, Annals of Internal Medicine.

[16]  F. Nuttall,et al.  Glycemic Control and Complications in Type II Diabetes: Design of a feasibility trial , 1992, Diabetes Care.

[17]  A. Motala,et al.  Effect of Insulin Therapy on Blood Pressure in NIDDM Patients With Secondary Failure , 1992, Diabetes Care.

[18]  T. Orchard,et al.  Diabetes Mellitus and Macrovascular Complications: An epidemiological perspective , 1992, Diabetes Care.

[19]  T. Koepsell,et al.  Risk Factors for Amputation in Patients with Diabetes Mellitus , 1992, Annals of Internal Medicine.

[20]  J. Manson,et al.  A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. , 1991, Archives of internal medicine.

[21]  M. Hanefeld,et al.  Diabetes Intervention Study: Multi-Intervention Trial in Newly Diagnosed NIDDM , 1991, Diabetes Care.

[22]  T. Meyer,et al.  Diabetic nephropathy: hemodynamic basis and implications for disease management. , 1989, Annals of internal medicine.

[23]  D L DeMets,et al.  Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. , 1988, JAMA.

[24]  A. LaCroix,et al.  Electrocardiographic estimate of left ventricular mass versus radiographic cardiac size and the risk of cardiovascular disease mortality in the epidemiologic follow-up study of the First National Health and Nutrition Examination Survey. , 1988, The American journal of cardiology.

[25]  J. Huttunen,et al.  Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. , 1987, The New England journal of medicine.

[26]  R. Klein,et al.  Glycosylated hemoglobin in a population-based study of diabetes. , 1987, American journal of epidemiology.

[27]  A. Ziegler,et al.  Daily insulin dose as a predictor of macrovascular disease in insulin treated non-insulin-dependent diabetics. , 1987, Diabete & metabolisme.

[28]  J. Cutler,et al.  Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). , 1987, The American journal of cardiology.

[29]  R. Newton,et al.  Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction. , 1985 .

[30]  K. Dahl-Jørgensen,et al.  Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study. , 1985, British medical journal.

[31]  C. Abraira,et al.  A Four-year Prospective Trial of Unmeasured Diet In Lean Diabetic Adults , 1984, Diabetes Care.

[32]  J. Halter,et al.  Acute and chronic effects of sulfonylurea drugs on pancreatic islet function in man. , 1984, Diabetes care.

[33]  R. Klein,et al.  Visual impairment in diabetes. , 1984, Ophthalmology.

[34]  G. Gerritsen.  The Chinese Hamster as a Model for the Study of Diabetes Mellitus , 1982, Diabetes.

[35]  Ronald J. Prineas,et al.  The Minnesota code manual of electrocardiographic findings : standards and procedures for measurement and classification , 1982 .

[36]  J. Colwell.  Atherosclerosis in diabetes mellitus. , 1981, Journal of chronic diseases.

[37]  R. Santen,et al.  Atherosclerosis in diabetes mellitus. Correlations with serum lipid levels, adiposity, and serum insulin level. , 1972, Archives of internal medicine.

[38]  C. Meinert,et al.  A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. , 1970, Diabetes.