Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome
Open accessAbstract
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 less than 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.
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The main underlying risk factors for the syndrome appear to be abdominal obesity and insulin resistance.
“The predominant underlying risk factors for the syndrome appear to be abdominal obesity [2][3][4] and insulin resistance 5,6 ;”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [6]
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Cites
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154 · see citing works
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Lippa, N. C., & Sanderson, S. C. (2013) · Human Heredity · doi:10.1159/000353712 · Cited by 6,093 · see citing works
Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance.
National Diabetes Data Group (1979) · Diabetes · doi:10.2337/diab.28.12.1039 · Cited by 4,909 · see citing works
The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM
DeFronzo, R. A. (1988) · Diabetes · doi:10.2337/diab.37.6.667 · Cited by 2,456 · see citing works
Insulin Resistance in Essential Hypertension
Ferrannini, E., Buzzigoli, G., Bonadonna, R., Giorico, M. A., Oleggini, M., Graziadei, L., Pedrinelli, R., Brandi, L., & Bevilacqua, S. (1987) · New England Journal of Medicine · doi:10.1056/nejm198708063170605 · Cited by 2,344 · see citing works
Self-citationThe Metabolic Basis of Inherited Diseases
WINKELMANN, R. K. (1972) · Archives of Dermatology · doi:10.1001/archderm.1972.01620110090032 · Cited by 1,773 · see citing works
Hyperinsulinemia. A link between hypertension obesity and glucose intolerance.
Modan, M., Halkin, H., Almog, S., Lusky, A., Eshkol, A., Shefi, M., Shitrit, A., & Fuchs, Z. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111776 · Cited by 1,465 · see citing works
A Prospective Study of Obesity and Risk of Coronary Heart Disease in Women
Manson, J. E., Colditz, G. A., Stampfer, M. J., Willett, W. C., ROSNER, B. A., Monson, R. R., Speizer, F. E., & Hennekens, C. H. (1990) · New England Journal of Medicine · doi:10.1056/nejm199003293221303 · Cited by 1,403 · see citing works
An Adoption Study of Human Obesity
Stunkard, A. J., Sørensen, T. I. A., Hanis, C. L., Teasdale, T. W., Chakraborty, R., Schull, W. J., & D, F. S. M. (1986) · New England Journal of Medicine · doi:10.1056/nejm198601233140401 · Cited by 1,301 · see citing works
Epidemiology of coronary heart disease: the Framingham study.
Castelli, W. (1984) · American Journal of Medicine · doi:10.1016/0002-9343(84)90952-5 · Cited by 1,106 · see citing works
Groop, L. C., Bonadonna, R. C., DelPrato, S., Ratheiser, K., Zyck, K., Ferrannini, E., & DeFronzo, R. A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114142 · Cited by 812 · see citing works
Self-citationEarly Metabolic Defects in Persons at Increased Risk for Non-Insulin-Dependent Diabetes Mellitus
Eriksson, J., Franssila-Kallunki, A., Ekstrand, A., Saloranta, C., Widén, E., Schalin, C., & Groop, L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198908103210601 · Cited by 807 · see citing works
Pyörälà, K. (1979) · Diabetes Care · doi:10.2337/diacare.2.2.131 · Cited by 775 · see citing works
Zavaroni, I., Bonora, E., Pagliara, M., Dall’Aglio, E., Luchetti, L., Buonanno, G., Bonati, P. A., Bergonzani, M., Gnudi, L., Passeri, M., et al. (1989) · New England Journal of Medicine · doi:10.1056/nejm198903163201105 · Cited by 770 · see citing works
Ducimetière, P., Eschwège, É., Papoz, L., Richard, J. L., Claude, J., & Rosselin, G. (1980) · Diabetologia · doi:10.1007/bf00275270 · Cited by 746 · see citing works
Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects.
Kolterman, O. G., Insel, J., Saekow, M., & Olefsky, J. M. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109790 · Cited by 664 · see citing works
Impaired Glucose Tolerance as a Disorder of Insulin Action
Lillioja, S., Mott, D. M., Howard, B. V., Bennett, P. H., Yki-Järvinen, H., Freymond, D., Nyomba, B. L., Zurlo, F., Swinburn, B., & Bogardus, C. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805123181901 · Cited by 578 · see citing works
Role of Insulin in Endogenous Hypertriglyceridemia*
Reaven, G. M., Lerner, R. L., D, M. P. S. M., & Farquhar, J. W. (1967) · Journal of Clinical Investigation · doi:10.1172/jci105666 · Cited by 512 · see citing works
Resistance to Insulin-Stimulated-Glucose Uptake in Patients with Hypertension*
Shen, D. C., Shieh, S.-M., Fuh, M. M.-T., WU, D.-A., Chen, Y. I., & Reaven, G. M. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-3-580 · Cited by 420 · see citing works
Bogardus, C., Lillioja, S., Howard, B. V., Reaven, G. M., & Mott, D. M. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111533 · Cited by 397 · see citing works
Haffner, S. M., D, M. P. S. M., Mitchell, B. D., Hazuda, H. P., & Patterson, J. K. (1990) · Diabetes · doi:10.2337/diab.39.3.283 · Cited by 397 · see citing works
Self-citationHyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus.
Haffner, S., Stern, M., Hazuda, H., Pugh, J. A., & Patterson, J. (1986) · New England Journal of Medicine · doi:10.1056/nejm198607243150403 · Cited by 358 · see citing works
Self-citationIn Vivo Insulin Action Is Familial Characteristic in Nondiabetic Pima Indians
Lillioja, S., Mott, D. M., Zawadzki, J. K., Young, A. A., Abbott, W. G. H., Knowler, W. C., Bennett, P. H., Moll, P. P., & Bogardus, C. (1987) · Diabetes · doi:10.2337/diab.36.11.1329 · Cited by 268 · see citing works
Johnson, B. C., Epstein, F. H., & Kjelsberg, M. O. (1965) · Journal of Chronic Diseases · doi:10.1016/0021-9681(65)90098-6 · Cited by 265 · see citing works
Tobey, T. A., Greenfield, M. S., Kraemer, F. B., & Reaven, G. M. (1981) · Metabolism · doi:10.1016/0026-0495(81)90167-0 · Cited by 243 · see citing works
Increased Insulin Concentrations in Nondiabetic Offspring of Diabetic Parents
Haffner, S. M., Stern, M. P., Hazuda, H. P., Mitchell, B. D., & Patterson, J. K. (1988) · New England Journal of Medicine · doi:10.1056/nejm198811173192001 · Cited by 238 · see citing works
Self-citationA COMPARISON OF THREE INDICATORS FOR IDENTIFYING MEXICAN AMERICANS IN EPIDEMIOLOGIC RESEARCH
Hazuda, H. P., Comeaux, P. J., D, M. P. S. M., Haffner, S. M., Eifler, C. W., & Rosenthal, M. (1986) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a114228 · Cited by 182 · see citing works
Self-citationBlood Pressure Studies in 14 Communities
(1977) · JAMA · doi:10.1001/jama.1977.03270490025018 · Cited by 154 · see citing works
Hunt, S. C., Wu, L., Hopkins, P. N., Stults, B. M., Kuida, H., Ramirez, M. E., Lalouel, J.-M., & Williams, R. R. (1989) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.9.3.335 · Cited by 135 · see citing works
Jarrett, R. J. (1984) · Elsevier eBooks · Cited by 126 · see citing works
Epidemiology of hypertension associated with diabetes mellitus.
Fuller, J. (1985) · Hypertension · doi:10.1161/01.hyp.7.6_pt_2.ii3 · Cited by 124 · see citing works
Classification of diabetes mellitus and other categories of glucose intolerance.
Harris, M. (1992) · Medical Entomology and Zoology · Cited by 123 · see citing works
Relation of serum calcium concentration to metabolic risk factors for cardiovascular disease.
Lind, L., Jakobsson, S., Lithell, H., Wengle, B., & Ljunghall, S. (1988) · BMJ · doi:10.1136/bmj.297.6654.960 · Cited by 120 · see citing works
The Pathogenesis of Non-Insulin-Dependent Diabetes
DeFronzo, R. A., & Ferrannini, E. (1982) · Medicine · doi:10.1097/00005792-198205000-00001 · Cited by 107 · see citing works
Self-citationParental history of diabetes is associated with increased cardiovascular risk factors.
Haffner, S. M., D, M. P. S. M., Hazuda, H. P., Mitchell, B. D., Patterson, J. K., & Ferrannini, E. (1989) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.9.6.928 · Cited by 87 · see citing works
Self-citationHyperinsulinemia and hypertriglyceridemia, a vicious cycle with atherogenic potential.
Steiner, G. A., & Vranić, M. (1982) · PubMed · Cited by 83 · see citing works
Sims, E. A. H. (1982) · JAMA · doi:10.1001/jama.1982.03320260033025 · Cited by 80 · see citing works
Resistance to Insulin but Not to Glucagon in Lean Human Hypertriglyceridemics
Steiner, G. A., Morita, S., & Vranić, M. (1980) · Diabetes · doi:10.2337/diab.29.11.899 · Cited by 77 · see citing works
Epidemiology and control of hypertension
(1976) · American Heart Journal · doi:10.1016/s0002-8703(76)80164-0 · Cited by 72 · see citing works
The association of hypertension, diabetes, and obesity: A review
Ferrannini, E., & DeFronzo, R. A. (1989) · Journal of Nephrology · Cited by 70 · see citing works
Self-citationFamily Resemblance for Blood Pressure
Iselius, L., Morton, N. E., & Rao, D. C. (1983) · Human Heredity · doi:10.1159/000153391 · Cited by 64 · see citing works
Overweight and mortality in Mexican Americans.
D, M. P. S. M., Patterson, J. K., Mitchell, B. D., Haffner, S. M., & Hazuda, H. P. (1990) · PubMed · Cited by 55 · see citing works
Self-citationStamler, R., Stamler, J., Lindberg, H. A., Marquardt, J., Berkson, D. M., Paul, O., Lepper, M. H., Dyer, A. R., & Stevens, E. (1979) · Journal of Chronic Diseases · doi:10.1016/0021-9681(79)90060-2 · Cited by 46 · see citing works
(1979) · Journal of Chronic Diseases · doi:10.1016/0021-9681(79)90062-6 · Cited by 44 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., Gordon, D. J., Krauss, R. M., Savage, P. J., Smith, S. C., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.169404 · Cited by 11,961 · see citing works
Grundy, S. M., Brewer, H. B., Cleeman, J. I., Smith, S. C., & Lenfant, C. (2004) · Circulation · doi:10.1161/01.cir.0000111245.75752.c6 · Cited by 5,982 · see citing works
Barker, D. J. P., Hales, C. N., Fall, C. H. D., Osmond, C., Phipps, K., & Clark, P. M. S. (1993) · Diabetologia · doi:10.1007/bf00399095 · Cited by 2,468 · see citing works
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162 · see citing works
Park, Y.-W., Zhu, S., Palaniappan, L., Heshka, S., Carnethon, M. R., & Heymsfield, S. B. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.4.427 · Cited by 2,074 · see citing works
Alexander, C. M., Landsman, P. B., Teutsch, S. M., & Haffner, S. M. (2003) · Diabetes · doi:10.2337/diabetes.52.5.1210 · Cited by 1,475 · see citing works
Self-citationPharmacologic Therapy for Type 2 Diabetes Mellitus
DeFronzo, R. A. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-131-4-199908170-00008 · Cited by 1,173 · see citing works
Carr, D. B., Utzschneider, K. M., Hull, R. L., Kodama, K., Retzlaff, B. M., Brunzell, J. D., Shofer, J. B., Fish, B. E., Knopp, R. H., & Kahn, S. E. (2004) · Diabetes · doi:10.2337/diabetes.53.8.2087 · Cited by 993 · see citing works
Relationships of generalized and regional adiposity to insulin sensitivity in men.
Abate, N., Garg, A., Peshock, R. M., Stray-Gundersen, J., & Grundy, S. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118083 · Cited by 759 · see citing works
Components of the “Metabolic Syndrome” and Incidence of Type 2 Diabetes
Hanson, R. L., Imperatore, G., Bennett, P. H., & Knowler, W. C. (2002) · Diabetes · doi:10.2337/diabetes.51.10.3120 · Cited by 590 · see citing works
Effects of exercise and diet on chronic disease
Roberts, C. K., & Barnard, R. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00852.2004 · Cited by 556 · see citing works
Brochu, M., Tchernof, A., Dionne, I. J., Sites, C. K., Eltabbakh, G. H., Sims, E. A. H., & Poehlman, E. T. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7365 · Cited by 443 · see citing works
Del Prato, S., Leonetti, F., Simonson, D. C., Sheehan, P., Matsuda, M., & DeFronzo, R. A. (1994) · Diabetologia · doi:10.1007/bf00400466 · Cited by 322 · see citing works
Genetic and environmental determinants of non‐insulin‐dependent diabetes mellitus (NIDDM)
Hamman, R. F. (1992) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610080402 · Cited by 256 · see citing works
Insulin resistance and coronary artery disease
Bressler, P., Bailey, S. R., Matsuda, M., & DeFronzo, R. A. (1996) · Diabetologia · doi:10.1007/s001250050581 · Cited by 226 · see citing works
Hanefeld, M. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00059-3 · Cited by 222 · see citing works
Prevalence of the metabolic syndrome in drug‐treated hypertensive patients and control subjects
Rantala, A. O., Kauma, H., Lilja, M., Savolainen, M. J., Reunanen, A., & Kesäniemi, Y. A. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00429.x · Cited by 211 · see citing works
Insulin resistance, insulin response, and obesity as indicators of metabolic risk
Ferrannini, E., Balkau, B., Coppack, S. W., Dekker, J. M., Mari, A., Nolan, J., Walker, M., Natali, A., & Beck-Nielsen, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0334 · Cited by 193 · see citing works
Self-citationShimada, M., Hasegawa, T., Nishimura, C., Kan, H., Kanno, T., Nakamura, T., & Matsubayashi, T. (2009) · Clinical and Experimental Hypertension · doi:10.1080/10641960902977908 · Cited by 124 · see citing works
Low glycaemic index diets for coronary heart disease
Kelly, S. A., Frost, G., Whittaker, V., & Summerbell, C. D. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004467.pub2 · Cited by 122 · see citing works
Osei, K., Rhinesmith, S., Gaillard, T., & Schuster, D. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030686 · Cited by 86 · see citing works
Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology
Yudkin, J. S. (2007) · Diabetologia · doi:10.1007/s00125-007-0711-3 · Cited by 75 · see citing works
Stewart, K. J. (2004) · Cardiology Clinics · doi:10.1016/j.ccl.2004.06.007 · Cited by 72 · see citing works
Brevetti, G., Schiano, V., Sirico, G., Giugliano, G., Laurenzano, E., & Chiariello, M. (2006) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2006.02.048 · Cited by 55 · see citing works
MARTELL, N., RODRIGUEZ-CERRILLO, M., GROBBEE, D. E., LÓPEZ-EADY, M. D., FERNÁNDEZ-PINILLA, C., AVILA, M., FERNANDEZ-CRUZ, A., & LUQUE, M. (2003) · Blood Pressure · doi:10.1080/08037050310009950 · Cited by 49 · see citing works
Koopmans, S. J., Kushwaha, R. S., & DeFronzo, R. A. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90081-1 · Cited by 48 · see citing works
de Leeuw, A. E., & de Boer, R. A. (2016) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvw009 · Cited by 46 · see citing works
Phenotypic, genetic, and genome-wide structure in the metabolic syndrome
Martin, L. J., North, K. E., Dyer, T., Blangero, J., Comuzzie, A. G., & Williams, J. (2003) · BMC Genetics · doi:10.1186/1471-2156-4-s1-s95 · Cited by 31 · see citing works
Wijsman, C. A., van Opstal, A. M., Kan, H. E., Maier, A. B., Westendorp, R. G. J., Slagboom, P. E., Webb, A. G., Mooijaart, S. P., & van Heemst, D. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00455.2011 · Cited by 24 · see citing works
- Authors
- Ferrannini, E., Haffner, S. M., Mitchell, B. D., & Stern, M. P.
- Affiliations
- University of Pisa (IT)
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- Diabetologia
- Published
- 1991-06
- Volume
- 34
- Issue
- 6
- Pages
- 416-422
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2014318859
- Cited by
- 898
- References
- 45
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 9 · 2022: 7 · 2021: 17 · 2020: 12 · 2019: 17 · 2018: 12 · 2017: 20 · 2016: 26 · 2015: 27 · 2014: 19 · 2013: 19 · 2012: 28
- FWCI
- 17.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL024799, HL24799)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- hyperinsulinemia, insulin resistance, metabolic syndrome, cardiovascular risk, obesity, type 2 diabetes, impaired glucose tolerance, hypertension, hypertriglyceridemia, hypercholesterolemia, HDL cholesterol, body fat distribution, waist-to-hip ratio, coronary artery disease, comorbidity prevalence
- MeSH terms
- Adult, Blood Pressure, Body Weight, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Hypercholesterolemia, Hyperinsulinism, Hypertension, Insulin Resistance, Male, Metabolic Diseases, Middle Aged, Syndrome, Hypertriglyceridemia, Prevalence
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