Summary
The Paris Prospective Study is a long-term, largescale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43–54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l, i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.
Article PDF
Similar content being viewed by others
References
Eschwège E, Richard JL, Thibult N, Ducimetière P, Warnet JM, Claude JR, Rosselin GE (1985) Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. Horm Metab Res 15 [Suppl]: 41–46
Pyörälä K, Savolainen E, Kaukola S, Haapakoski J (1985) Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2-year follow-up of the Helsinki Policemen Study population. Acta Med Scand 701 [Suppl]: 38–52
Welborn TA, Wearne K (1979) Coronary heart disease and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 2: 154–160
Stout RW (1990) Insulin and atheroma. 20-yr perspective. Diabetes Care 13: 631–654
Jarrett RJ (1988) Is insulin atherogenic? Diabetologia 31: 71–75
Hill AB (1965) The environment and disease: association or causation? Proc Roy Soc Med 58: 295–300
Ducimetière P, Richard JL, Claude JR (1981) Les cardiopathies ischémiques: incidence et facteurs de risque. L'Etude Prospective Parisienne. Editions INSERM, Paris
Rosselin G, Assan R, Yalow RS, Berson SA (1966) Separation of antibody bound and unbound peptide hormone labelled with iodine 131 by talcum powder and precipitates silica. Nature 212: 355–357
Richard JL (1973) Quelques informations sur la fréquence en France des maladies cardiovasculaires, particulièrement des cardiopathies ischémiques. In: Ducimetière P (ed) Epidémiologie et prévention des maladies cardiovasculaires. Colloques de l'INSERM, Vol 21. Editions INSERM, Paris, pp 11–46
Cox DR (1972) Regression models and life tables (with discussion). J Roy Statist Soc B 34: 187–220
SAS Institute Inc (1985) AS User's Guide: Statistics. Version 5 Edition. SAS Institute Inc, Cary NC
WHO Expert Committee (1985) Diabetes Mellitus. Technical Report Series 727, WHO, Geneva
Fontbonne A, Eschwège E, Cambien F, Richard JL, Ducimetière P, Thibult N, Warnet JM, Claude JR, Rosselin GE (1989) Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes: results from the 11-year follow-up of the Paris Prospective Study. Diabetologia 32: 300–304
Stalder M, Pometta D, Suenram A (1981) Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men. Diabetologia 21: 544–548
Laakso M, Pyörälä K, Voutilainen E, Marniemi J (1987) Plasma insulin and serum lipids and lipoproteins in middle-aged non-insulin-dependent diabetic and non-diabetic subjects. Am J Epidemiol 125: 611–621
Temple RC Carrington CA, Luzio SD, Owens DR, Schneider AE, Sobey WJ, Hales CN (1989) Insulin deficiency in non-insulin-dependent diabetes. Lancet 1: 293–295
Nagi DK, Hendra TJ, Ryle AJ, Cooper TM, Temple RC, Clark PMS, Schneider AE, Hales CN, Yudkin JS (1990) Relationships of concentrations of insulin, intact pro-insulin and 32–33 split pro-insulin with cardiovascular risk factors in Type 2 (non-insulin-dependent) diabetic subjects. Diabetologia 33: 532–537
Nikkilä EA, Miettinen TA, Vesenne MR, Pelkonen R (1965) Plasma insulin in coronary heart disease. Lancet II: 508–511
Stout RW, Vallance-Owen J (1979) Insulin and atheroma. Lancet I: 1078–1080
Pyörälä K (1979) Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 2: 131–141
Ducimetière P, Eschwège E, Papoz L, Richard JL, Claude JR, Rosselin GE (1980) Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 19: 205–210
Tobey TA, Greenfield M, Kraemer F, Reaven GM (1981) Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics and plasma triglyceride levels in normotriglyceridemic man. Metabolism 30: 165–171
Ferrannini E, Buzzigoli G, Bonnadonna R, Gioricco MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350–357
Fossati P, Romon-Rousseaux M (1987) Insulin and HDL-cholesterol metabolism. Diab Métab (Paris) 13: 390–394
Bogardus C, Lillioja S, Howard B, Reaven GM, Mott D (1984) Relationships between insulin secretion, insulin action and fasting plasma glucose concentration in non-diabetic and non-insulin-dependent diabetic subjects. J Clin Invest 74: 1238–1246
Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z (1985) Hyperinsulinemia, a link between hypertension, obesity, and glucose intolerance. J Clin Invest 75: 809–817
Zavaroni I, Bonora E, Pagliara M, Dall'Aglio E, Luchetti L, Buonanno G, Bonati PA, Bergorzani M, Gnudi L, Passeri M, Reaven GM (1989) Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 320: 702–706
Pyörälä K, Uusitupa M, Laakso M, Siitonen O, Niskanen L, Rönnemaa T (1987) Macrovascular complications in relation to hyperinsulinemia in non-insulin-dependent diabetes mellitus. Diab Métab (Paris) 13: 345–349
Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607
Foster DW (1989) Insulin resistance, a secret killer? N Engl J Med 320: 733–734
Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 256: 2835–2838
Betteridge DJ (1989) High density lipoprotein cholesterol and coronary heart disease. Br Med J 298: 975–976
Castelli WP (1986) The triglyceride issue: a view from Framingham. Am Heart J 112: 432–437
Austin MA (1989) Plasma triglyceride as a risk factor for coronary heart disease: the epidemiologic evidence and beyond. Am J Epidemiol 129: 249–259
Sicree RA, Zimmet PZ, King HOM, Coventry JS (1987) Plasma insulin response among Nauruans: prediction of deterioration in glucose tolerance over 6 years. Diabetes 36: 179–186
Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennnett PH (1988) The natural history of impaired glucose tolerance in the Pima Indians. N Engl J Med 319: 1500–1506
Charles MA, Fontbonne A, Eschwège E (1988) Risk factors of Type 2 (non-insulin-dependent) diabetes in a Caucasian population. Diabetologia 31: 479 (Abstract)
Haffner SM, Stern MP, Mitchell BD, Hazuda HP, Patterson JK (1990) Incidence of Type 2 diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body fat distribution. Diabetes 39: 283–288
Leslie RDG, Volkmann HP, Poncher M, Hanning I, Orskov H, Alberti KGMM (1986) Metabolic abnormalities in children of non-insulin-dependent diabetics. Br Med J 293: 840–842
Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK (1988) Increased insulin concentrations in non-diabetic offspring of diabetic parents. N Engl J Med 319: 1297–1301
Ho LT, Chang ZY, Wang JT, Li SH, Liu YF, Chen YDI, Reaven GM (1990) Insulin insensitivity in offspring of parents with Type 2 diabetes mellitus. Diab Med 7: 31–34
Jarrett RJ, Shipley MJ (1988) Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease — putative association via common antecedents: further evidence from the Whitehall Study. Diabetologia 31: 737–740
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fontbonne, A., Charles, M.A., Thibult, N. et al. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. Diabetologia 34, 356–361 (1991). https://doi.org/10.1007/BF00405009
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00405009