(Circulation. 1999;100:e118.)
© 1999 American Heart Association, Inc.
Circulation Electronic Pages |
Hyperinsulinemia Predicts Coronary Heart Disease Risk in Healthy Middle-Aged Men
3rd Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary
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To the Editor:
In a recent article, Pyörälä et al1 have stated that hyperinsulinemia/area under the plasma insulin response curve (AUC insulin) during an oral glucose tolerance test (OGTT) was a statistically significant predictor of coronary heart disease (CHD) risk over the 22-year follow-up in the Helsinki Policemen Study. In addition, the authors had another interesting observation that AUC glucose also predicted CHD risk in the first 5 years of follow-up. However, subjects with diabetes mellitus were excluded, and it would seem that subjects with impaired glucose tolerance (IGT) might have been involved in the study. Besides plasma cholesterol level, AUC glucose was the only significant independent predictor of CHD risk during this period.
To assess major risk factors and to provide secondary prevention
for patients with recent myocardial infarction, we performed OGTTs in
28 patients free of diabetes who had a fasting plasma glucose level
<6.1 mmol/L (23 males, 5 females). Thirteen patients had IGT
based on the 2-hour postload glucose level (
7.8 mmol/L). Fifteen
patients had normal glucose tolerance (NGT) according to World Health
Organization and American Diabetes Association
criteria.2 3 We also performed OGTTs in 14 age- and body
mass index–matched control subjects free of CHD and diabetes who had a
fasting plasma glucose level <6.1 mmol/L. None of these control
subjects had IGT. AUC glucose was higher in the patients with CHD and
NGT than in controls (15.9±2.9 versus 13.2±2.1 mmol ·
L-1 · h-1,
P=0.013). Fasting plasma glucose level was also higher
within the normal range in the CHD patients with NGT compared with the
controls (5.3±0.5 versus 4.8±0.5 mmol/L, P=0.015).
Two-hour postload glucose level and Hb A1c
concentrations tended to be higher in the patients with CHD and NGT
than in the controls (6.5±1.0 versus 5.6±1.1 mmol/L,
P=0.055, and 4.8±0.6% versus 4.0±0.6%,
P=0.069, respectively). All mean data ±SD were compared by
Mann-Whitney test.
Our observation that a high normal blood glucose level is associated with CHD provides additional support to the observations of Pyörälä et al. We emphasize that at least for secondary prevention, it appears worthwhile to perform an OGTT in CHD patients and to have these patients begin the necessary lifestyle and dietary changes long before their plasma glucose levels would reach the criteria of diabetes or IGT.
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1. Pyörälä M, Miettinen H, Laakso M, Pyörälä K. Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Circulation. 1998;98:398–404.
2. World Health Organization. Diabetes Mellitus: Report of a WHO Study Group. Geneva, Switzerland: World Health Organization; 1985. Technical Report Series No. 727.
3. Committee Report. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–1197. 14,1999[Medline] [Order article via Infotrieve]
Response
Department of Medicine, University of Kuopio, Kuopio, Finland
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The primary aim of our study1 was to investigate the predictive value of hyperinsulinemia with regard to the risk of coronary heart disease (CHD) and its independence with regard to other CHD risk factors over the 22-year follow-up of a cohort of 970 Helsinki policemen who were free of CHD, other cardiovascular disease, and diabetes mellitus at baseline. As Dr Hosszúfalusi and colleagues presumed, we did not exclude men with impaired glucose tolerance (IGT). Our study cohort included 40 men who fulfilled the World Health Organization (WHO) criteria for IGT2 and, in addition, 39 men with "impaired fasting glucose" (fasting blood glucose
5.6
mmol/L) according to the American Diabetes Association’s (ADA)
criteria.2 When these 79 men were excluded, leaving a
study cohort of 891 men with normal glucose tolerance (NGT) according
to the WHO and ADA criteria, our results with regard to the association
of insulin and the risk of CHD, as reported in Tables 3 and 4 of our
article, was even slightly strengthened. Dr Hosszúfalusi and colleagues noted our finding that area under the glucose response curve (AUC glucose) during an oral glucose tolerance test was a significant predictor of CHD risk during the first 5 years of the follow-up of our study cohort. They also report their own interesting observation in a cross-sectional case-control study that in patients with myocardial infarction and NGT according to the WHO and ADA criteria,2 3 AUC glucose, as well as fasting and 2-hour postload glucose and Hb A1C levels, was higher than in age- and body mass index–matched healthy control subjects. Their findings are in accordance with observations from another, larger cross-sectional case-control comparison of patients with myocardial infarction and matched healthy control subjects.4 A recent metaregression analysis of 20 prospective studies in >95 000 individuals not known to have diabetes mellitus at baseline demonstrated an exponential and continuous relationship between blood glucose levels and the risk of cardiovascular events, which extended to the range of NGT.5
Stimulated by the comments of Dr Hosszúfalusi and colleagues, we have now investigated the association of AUC glucose and the risk of CHD in the cohort of 891 Helsinki policemen with NGT. Age-adjusted Cox model hazard ratios (and their 95% CIs) for a 1-SD difference in AUC glucose with regard to major CHD events during 5-, 10-, 15-, and 22-year follow-up periods were 1.68 (1.11 to 2.53), 1.39 (1.07 to 1.81), 1.22 (1.00 to 1.50), and 1.23 (1.04 to 1.45), respectively. Further adjustment for other risk factors (area under the plasma insulin response curve, body mass index, subscapular skinfold, systolic blood pressure, cholesterol, triglycerides, smoking, and physical activity), however, reduced these hazard ratios to 1.38 (0.85 to 2.22), 1.12 (0.83 to 1.52), 0.95 (0.75 to 1.21), and 1.02 (0.84 to 1.23), respectively. Thus, our findings in healthy middle-aged Helsinki policemen are compatible with the view that the association between blood glucose and CHD risk extends to the "normoglycemic" range but may to a large extent be explained by close links of blood glucose with other risk factors, particularly those clustering with hyperinsulinemia and insulin resistance.
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References |
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TopIntroductionReferencesIntroduction References |
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1. Pyörälä M, Miettinen H, Laakso M, Pyörälä K. Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Circulation. 1998;98:398–404.
2. Diabetes Mellitus: Report of a WHO Study Group. Geneva, Switzerland: World Health Organization; 1985. Technical Report Series No. 727.
3. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–1197.
4.
Gerstein HC, Pais P, Pogue J, Yusuf S.
Relationship of glucose and insulin levels to the risk of myocardial
infarction: a case-control study. J Am Coll Cardiol. 1999;33:612–619.
5.
Coutinho M, Gerstein HC, Wang Y, Yusuf S. The
relationship between glucose and incident
cardiovascular events: a metaregression
analysis of published data from 20 studies of 95,783
individuals followed for 12.4 years. Diabetes Care. 1999;22:233–240.
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