The Relationship of Concentrations of Insulin and Proinsulin-Like Molecules With Coronary Heart Disease Prevalence and Incidence: A study of two ethnic groups
- John S Yudkin, MD, FRCP,
- A Elizabeth Denver, RGN,
- Vidya Mohamed-Ali, PHD,
- Kaushik L Ramaiya, MMED,
- Dinesh K Nagi, PHD,
- Stephanie Goubet, MSC,
- Donald G McLarty, FRCP† and
- Andrew Swai, BM, MMED
- Departments of Medicine, University College London Medical School London
- Primary Health Care, University College London Medical School London
- Edna Coates Centre, Pinderfields Hospital Trust, Wakefield U.K.
- Hindu Mandal Hospital Dar es Salaam, Tanzania
- Department of Medicine, University of Dar es Salaam, Muhimbili Medical Center Dar es Salaam, Tanzania
- Address correspondence and reprint requests to John S. Yudkin, MD, FRCP, Department of Medicine, University College London Medical School, Whittington Hospital, “G” Block, Archway Wing, Archway Road, London N19 3UA, U.K.
Abstract
OBJECTIVE To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease.
RESEARCH DESIGN AND METHODS Fasting concentrations of proinsulin, des-31,32-proinsulin, and insulin, and of insulin 2 h after a 75-g glucose load, were measured in 1,034 nondiabetic europid subjects and 257 south Asian subjects and related to prevalent coronary heart disease (Minnesota-coded electrocardiographic criteria or ischemic chest pain). In 137 south Asian subjects, the fasting concentrations were related to incident coronary heart disease over a 6.5-year follow-up.
RESULTS The standardized odds ratios for prevalent coronary heart disease were as follows: fasting insulin, 1.29 (1.11–1.49), P = 0.0006; 2-h insulin, 1.25 (1.08–1.45), P = 0.003; proinsulin, 1.23 (0.99–1.53), P = 0.058; and des-31,32-proinsulin, 1.32 (1.03–1.69), P = 0.026. The odds ratios were similar in the two ethnic groups. These relationships became insignificant when controlling for age, sex, and BMI. The standardized odds ratios for incident coronary heart disease were as follows: fasting insulin, 0.99 (0.63–1.55), P = 0.97; proinsulin, 1.13 (0.72–1.78), P = 0.59; and des-31,32-proinsulin, 1.00 (0.61–1.63), P = 1.00.
CONCLUSIONS We have found similar relationships between concentrations of proinsulin-like molecules and prevalent coronary heart disease, as are observed for insulin in these nondiabetic subjects, although these molecules comprise only ∼ 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.
- Received September 18, 1996.
- Revision received March 19, 1997.
- Accepted March 19, 1997.
- Copyright © 1997 by the American Diabetes Association
