The relationship of concentrations of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. A study of two ethnic groups.
OBJECTIVE
To define the potential role of proinsulin-like molecules as risk factors for cardiovascular disease.


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 approximately 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.
Yudkin
J S
JS
Department of Medicine, University College London Medical School, U.K.
Denver
A E
AE
Mohamed-Ali
V
V
Ramaiya
K L
KL
Nagi
D K
DK
Goubet
S
S
McLarty
D G
DG
Swai
A
A
D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern / Q000208:ethnology; D000368:Aged; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology* / Q000208:ethnology; D003430:Cross-Sectional Studies; D005060:Europe / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007194:India / Q000208:ethnology; D007328:Insulin / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010154:Pakistan / Q000208:ethnology; D015995:Prevalence; D011384:Proinsulin / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D044469:Racial Groups; D012044:Regression Analysis; D006113:United Kingdom / Q000453:epidemiology
D007328:Insulin; D011498:Protein Precursors; C070703:proinsulin, des(31,32)-; D011384:Proinsulin