Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study

British Medical Journal, March 14, 1998 by R.C. Turner, H. Millns, H.A.W. Neil, I.M. Stratton, S.E. Manley, D.R. Matthews, R.R. Holman

Blood pressure--Increased blood pressure was also a major risk factor for coronary artery disease, with a 15% increased risk for an increase in systolic blood pressure of 10 mm Hg, which was similar to that reported in the general population.[36] Increased blood pressure was a major risk factor for fatal myocardial infarction. This could be because hypertension is a major additional burden to the heart when myocardial infarction ensues. The hypertension in diabetes study in 1148 patients in a factorial design is evaluating whether strict blood pressure control will prevent complications.[37]

Retinopathy--Retinopathy at diagnosis was not a risk factor for cardiovascular disease in a multivariate analysis, although retinopathy was a risk factor for fatal myocardial infarction when only age and sex were adjusted for. Since both retinopathy[38] and microalbuminuria[39] are associated with hyperglycaemia and hypertension, which are also risk factors for coronary artery disease, the previously described association of retinopathy and microalbuminuria with subsequent cardiovascular mortality might reflect the longstanding hypertension and hyperglycaemia that induced both macrovascular and microvascular disease.

Risk factors in type 2 diabetes mellitus

Risk factors for development of coronary artery disease in the general population may not apply once diabetes has developed. Obesity and central obesity,[40] decreased physical activity,[41] and raised insulin concentrations[42] provide an increased risk for cardiovascular disease, but in patients with type 2 diabetes mellitus we found that none of these were major risk factors. These variables are also risk factors for diabetes,[43-45] but this study indicates that once diabetes has developed, hypertension, increased concentrations of low density lipoprotein or decreased concentrations of high density lipoprotein cholesterol and hyperglycaemia measured at baseline are greater risk factors for coronary artery disease than these precipitating factors.

Syndrome X, the association of raised concentrations of glucose, insulin, and triglyceride, decreased concentrations of high density lipoprotein cholesterol, and increased blood pressure, describes a combination of previously reported risk factors for coronary artery disease.[46] In the general population the combination of upper body obesity, glucose intolerance, hypertriglyceridaemia, and hypertension has been termed the deadly quartet.[47] However, a quintet of increased concentrations of low density lipoprotein and decreased concentrations of high density lipoprotein cholesterol, hypertension, hyperglycaemia, and smoking is probably more relevant in patients with type 2 diabetes mellitus.

The cooperation of the patients and many NHS and non-NHS staff at the centres is much appreciated. We thank Professor Eva Kohner, Mr Steve Aldington, Ms Ivy Samuel, and Mrs Caroline Wood for help with the manuscript.

Contributors: RCT and RRH coordinated the study, HM and IMS carried out the statistical analyses, HAWN provided epidemiological advice, DRM coordinated the assessment of clinical end points, and SEM provided biochemical advice. All authors wrote the paper. RCT will act as guarantor of the study. Funding: This study received grants from the Medical Research Council; British Diabetic Association; the Department of Health; the National Eye Institute and the National Institute of Digestive, Diabetes and Kidney Disease in the National Institutes of Health, United States; the British Heart Foundation; the Health Promotion Research Trust; Charles Wolfson Charitable Trust; the Alan and Babette Sainsbury Trust; the Clothworkers' Foundation; Oxford University Medical Research Fund Committee; and pharmaceutical companies, including Novo-Nordisk, Bayer, Bristol Myers Squibb, Hoechst, Lilly, Lipha, and Farmitalia Carlo Erba. Additional funding came from Boehringer Mannheim, Becton Dickinson, Owen Mumford, Securicor, Kodak, and Cortecs Diagnostics. Conflict of interest: None.