, Volume 34, Issue 6, pp 416–422 | Cite as

Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome

  • E. Ferrannini
  • S. M. Haffner
  • B. D. Mitchell
  • M. P. Stern


In a population-based survey of 2,930 subjects, prevalence rates for obesity, Type 2 (non-insulin-dependent) diabetes mellitus, impaired glucose tolerance, hypertension, hypertriglyceridaemia, and hypercholesterolaemia were 54.3, 9.3, 11.1, 9.8, 10.3 and 9.2%, respectively. The prevalence, however, of each of these conditions in its isolated form (free of the other five) was 29.0% for obesity, 1.3% for Type 2 diabetes, 1.8% for impaired glucose tolerance, 1.5% for hypertension, 1.0% for hypertriglyceridaemia, and 1.7% for hypercholesterolaemia. Two-by-two associations were even rarer. The large differences in prevalence between isolated and mixed forms indicate a major overlap among the six disorders in multiple combinations. In the isolated form, each condition was characterized by hyperinsulinaemia (both fasting and 2 h after oral glucose), suggesting the presence of insulin resistance. In addition, in any isolated condition most of the variables categorising other members of the sextet were still significantly altered in comparison with 1,049 normal subjects. In the whole of the subjects who presented with one or another disorder (1,881 of 2,930 or 64%), marked fasting and post-glucose hyperinsulinaemia was associated with higher body mass index, waist:hip ratio, fasting and post-glucose glycaemia, systolic and diastolic blood pressure, serum triglycerides and total cholesterol levels, and with lower HDL-cholesterol concentrations (all p <0.001). We conclude that (1) insulin sensitivity, glucose tolerance, blood pressure, body fat mass and distribution, and serum lipids are a network of mutually interrelated functions; and (2) an insulin resistance syndrome underlies each and all of the six disorders carrying an increased risk of coronary artery disease.

Key words

Hyperinsulinaemia insulin resistance syndrome X San Antonio Heart Study 


  1. 1.
    Sims EAH, Berchtold P (1982) Obesity and hypertension. Mechanisms and implications for management. JAMA 247: 49–52PubMedGoogle Scholar
  2. 2.
    National Diabetes Data Group (1979) Classification of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1055PubMedGoogle Scholar
  3. 3.
    Fuller JH (1985) Epidemiology of hypertension associated with diabetes mellitus. Hypertension 7 [Suppl. II]: II3–7PubMedGoogle Scholar
  4. 4.
    Nikkila EA (1984) Plasma lipid and lipoprotein abnormalities in diabetes. In: Jarrett RJ (ed) Diabetes and heart disease. Elsevier, Amsterdam, pp 133–167Google Scholar
  5. 5.
    Stamler J, Berkson D, Dyer A, Lindberg HA (1975) Relationship of multiple variables to blood pressure findings from four Chicago epidemiologic studies. In: Paul O (ed) Epidemiology and control of hypertension. Stratton, New York, pp 307–356Google Scholar
  6. 6.
    Modan M, Halkin H, Almog S, Lusky A, Eskol A, Shefi M, Shitrit A, Fuchs L (1985) Hyperinsulinaemia. A link between hypertension obesity and glucose intolerance. J Clin Invest 75: 809–817PubMedGoogle Scholar
  7. 7.
    DeFronzo RA, Ferrannini E (1982) The pathogenesis of non-insulin dependent diabetes. An update. Medicine 61: 125–135PubMedGoogle Scholar
  8. 8.
    Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi LS, Bevilacqua S (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350–357PubMedGoogle Scholar
  9. 9.
    Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607PubMedGoogle Scholar
  10. 10.
    Castelli WP (1984) Epidemiology of coronary heart disease: the Framingham study. Am J Med 76 [Suppl. 2A]: 4–12CrossRefPubMedGoogle Scholar
  11. 11.
    Stamler R, Stamler J (1979) Asymptomatic hyperglycemia and coronary heart disease. J Chron Dis 32: 829–837CrossRefPubMedGoogle Scholar
  12. 12.
    Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, Speizer FE, Hennekens CH (1990) A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 322: 882–889PubMedGoogle Scholar
  13. 13.
    Pyőrala 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: 121–141Google Scholar
  14. 14.
    Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G (1980) Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 19: 205–210CrossRefPubMedGoogle Scholar
  15. 15.
    Haffner SM, Stern MP, Hazuda HP, Pugh JA, Patterson JK (1986) Hyperinsulinaemia in a population at high risk for non-insulin-dependent diabetes mellitus. N Engl J Med 315: 220–224PubMedGoogle Scholar
  16. 16.
    Hazuda HP, Comeaux PJ, Stern MP, Haffner SM, Eifler CW, Rosenthal M (1986) A comparison of three indicators for identifying Mexican Americans in epidemiologic research: methodological findings from the San Antonio Heart Study. Am J Epidemiol 123: 96–112PubMedGoogle Scholar
  17. 17.
    Stern MP, Patterson JK, Mitchell BD, Haffner SM, Hazuda HP (1990) Overweight and mortality in Mexican Americans. Int J Obes 14: 623–629PubMedGoogle Scholar
  18. 18.
    Hypertension Detection and Follow-up Program Cooperative Group (1977) Blood pressure studies in 14 communities: a two-stage screen for hypertension. JAMA 237: 2385–2391Google Scholar
  19. 19.
    World Health Organization Expert Committee (1980) Second Report on Diabetes Mellitus. Geneva, WHO, Tech. Rep. Ser. No. 646Google Scholar
  20. 20.
    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: 165–171CrossRefPubMedGoogle Scholar
  21. 21.
    Reaven GM, Lerner RL, Stern MP, Farquhar JW (1967) Role of insulin in endogenous hypertriglyceridemia. J Clin Invest 46: 1756–1767PubMedGoogle Scholar
  22. 22.
    Steiner G, Vranic M (1982) Hyperinsulinemia and hypertriglyceridemia, a vicious circle with atherogenic potential. Int J Obes 6 [Suppl. 1]: 117–124PubMedGoogle Scholar
  23. 23.
    Ferrannini E, DeFronzo RA (1989) The association of hypertension, diabetes, and obesity: a review. J Nephrol 1: 3–15Google Scholar
  24. 24.
    DeFronzo RA (1988) The triumvirate: ß-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 37: 667–687PubMedGoogle Scholar
  25. 25.
    DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214-E223PubMedGoogle Scholar
  26. 26.
    Kolterman OG, Insel J, Saekow M, Olefsky JM (1980) Mechanisms of insulin resistance in human obesity. Evidence for receptor and postreceptor defects. J Clin Invest 65: 1272–1284PubMedGoogle Scholar
  27. 27.
    Groop LC, Bonadonna RC, Del Prato S, Ratheiser K, Zyck K, Ferrannini E, DeFronzo RA (1989) Glucose and free fatty acid metabolism in non-insulin dependent diabetes mellitus: evidence for multiple sites of insulin resistance. J Clin Invest 84: 205–213PubMedGoogle Scholar
  28. 28.
    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: 1238–1246PubMedGoogle Scholar
  29. 29.
    Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C (1988) Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 318: 1217–1225PubMedGoogle Scholar
  30. 30.
    Steiner G, Morita S, Vranic M (1980) Resistance to insulin but not glucagon in lean human hypertriglyceridemics. Diabetes 29: 899–905PubMedGoogle Scholar
  31. 31.
    Shen DC, Shieh S-M, Fuh MT, Chen Y-DI, Reaven GM (1988) Resistance to insulin-stimulated glucose uptake in patients with hypertension. J Clin Endocrinol Metab 66: 580–583PubMedGoogle Scholar
  32. 32.
    Lind L, Jakobsson S, Lithell H, Wengle B, Ljunghall S (1988) Relation of serum calcium to metabolic risk factors for cardiovascular disease. Br Med J 297: 960–963Google Scholar
  33. 33.
    Lillioja S, Mott DM, Zawadzki JK, Young AA, Abbott WGH, Knowler WC, Bennett PH, Moll P, Bogardus C (1987) In vivo insulin action is familial characteristic in nondiabetic Pima Indians. Diabetes 36: 1329–1335PubMedGoogle Scholar
  34. 34.
    Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK (1988) Increased insulin concentrations in nondiabetic offspring of diabetic parents. N Engl J Med 319: 1297–1301PubMedGoogle Scholar
  35. 35.
    Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widen E, Schalin C, Groop L (1989) Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 321: 337–343PubMedGoogle Scholar
  36. 36.
    Haffner SM, Stern MP, Mitchell BD, Hazuda HP, Patterson JK (1990) Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes 39: 283–288PubMedGoogle Scholar
  37. 37.
    Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK, Ferrannini E (1989) Parental history of diabetes is associated with increased cardiovascular risk factors. Arteriosclerosis 9: 928–933PubMedGoogle Scholar
  38. 38.
    Zavaroni I, Bonora E, Pagliara M et al. (1989) Risk factors for coronary artery disease in healthy people with hyperinsulinaemia and normal glucose tolerance. N Engl J Med 320: 202–206Google Scholar
  39. 39.
    Hurt SC, Wu LL, Hopkins PN et al. (1989) Apolipoprotein, low density lipoprotein subfraction, and insulin associations with familial combined hyperlipidemia. Study of Utah patients with familial dyslipidemic hypertension. Arteriosclerosis 9: 335–344PubMedGoogle Scholar
  40. 40.
    Stunkard AJ, Sorensen TIA, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, Schulsinger F (1986) An adoption study of human obesity. N Engl J Med 314: 193–198PubMedGoogle Scholar
  41. 41.
    Foster DW (1989) Diabetes mellitus. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited diseases, 6th edn. McGraw-Hill, New York, p 384Google Scholar
  42. 42.
    Johnson BC, Epstein FH, Kjelsberg M (1965) Distribution and familial studies of blood pressure and serum cholesterol levels in a total community, Tecumseh, Michigan. J Chronic Dis 18: 147–160CrossRefPubMedGoogle Scholar
  43. 43.
    Iselius L, Morton NE, Rao DC (1983) Family resemblance for blood pressure. Hum Hered 33: 277–286PubMedGoogle Scholar
  44. 44.
    Grundy SM (1987) Disorders of lipids and lipoproteins. In: Stein JH (ed) Internal medicine, 2nd edn. Little, Brown and Company, Boston, pp 2035–2052Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • E. Ferrannini
    • 2
    • 3
  • S. M. Haffner
    • 1
  • B. D. Mitchell
    • 1
  • M. P. Stern
    • 1
  1. 1.Division of Clinical Epidemiology, Department of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  2. 2.Division of Diabetes, Department of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  3. 3.Metabolism Unit of the C.N.R. Institute of Clinical PhysiologyUniversity of PisaPisaItaly

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