Insulin Resistance, β-Cell Dysfunction, and Conversion to Type 2 Diabetes in a Multiethnic Population

The association between insulin resistance and insulinemia and hypertension is controversial. We examined the relation between insulin resistance and hypertension in 564 non-Hispanic whites (NHW), 505 Hispanics (H), and 413 African Americans (AA) who participated in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity was measured with a frequently sampled intravenous glucose tolerance test with minimal model analysis. The prevalence of hypertension was 32.5%, 49.4%, and 32.3% in NHW, AA, and H, respectively (P < 0.001). When subjects without diabetes in all ethnic groups were combined, age, male sex, race (AA), body mass index (BMI), and insulin resistance, but not fasting insulin, were significantly associated with hypertension. When each ethnic group was analyzed separately, insulin resistance was significantly associated with hypertension in NHW and H, but not AA. After excluding subjects taking antihypertensive medications, male sex, BMI, fasting glucose, and insulin resistance, but not fasting insulin, were significant determinants of blood pressure. When the 3 ethnic groups were analyzed separately, insulin resistance was significantly associated with blood pressure in H, but not NHW, or AA. Neither insulin resistance nor fasting insulin was significantly associated with hypertension or blood pressure in subjects with diabetes of the 3 ethnic groups after adjusting for age, sex, BMI, and waist. In conclusion, insulin resistance, but not insulinemia, was related to hypertension and blood pressure in subjects without diabetes, but ethnic differences in these relations appear to exist. Neither insulin resistance nor insulinemia was related to hypertension or blood pressure in patients with type 2 diabetes in the 3 ethnic groups.

[1]  S. Haffner,et al.  The natural course of beta-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study. , 2006, Diabetes.

[2]  S. Fowler,et al.  Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. , 2005, Diabetes.

[3]  Peter Almgren,et al.  Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. , 2005, Diabetes.

[4]  D. Schuster,et al.  Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. , 2004, Diabetes care.

[5]  C. Hales,et al.  The relationships of concentrations of insulin, intact proinsulin and 32–33 split proinsulin with cardiovascular risk factors in Type 2 (non-insulin-dependent) diabetic subjects , 1990, Diabetologia.

[6]  A. Pezzarossa,et al.  Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects , 1987, Diabetologia.

[7]  M. Kearney,et al.  Pathophysiological implications of insulin resistance on vascular endothelial function , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[8]  R. Parker,et al.  Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Kahn,et al.  The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes , 2003, Diabetologia.

[10]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[11]  P. Home,et al.  Clinical guidelines and evidence review for Type 2 diabetes: management of blood glucose , 2002 .

[12]  C. Bogardus,et al.  Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. , 2001, Diabetes care.

[13]  L. Heinemann,et al.  Insulin resistance and the effect of insulin on blood pressure in essential hypertension. , 1998, Hypertension.

[14]  D. Yue,et al.  Does insulin therapy have a hypertensive effect in type 2 diabetes? , 1998, Journal of cardiovascular pharmacology.

[15]  R. J. Hayes,et al.  United Kingdom Prospective Diabetes Study 24: A 6-Year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet Therapy , 1998, Annals of Internal Medicine.

[16]  S. Jacob,et al.  Insulin Resistance, Hyperinsulinemia, and Blood Pressure Role of Age and Obesity , 1997 .

[17]  R. Bergman,et al.  Insulin Sensitivity and Acute Insulin Response in African-Americans, Non-Hispanic Whites, and Hispanics With NIDDM: The Insulin Resistance Atherosclerosis Study , 1997, Diabetes.

[18]  R. Bergman,et al.  Increased Insulin Resistance and Insulin Secretion in Nondiabetic African-Americans and Hispanics Compared With Non-Hispanic Whites: The Insulin Resistance Atherosclerosis Study , 1996, Diabetes.

[19]  G. Reaven,et al.  Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system. , 1996, The New England journal of medicine.

[20]  R. Bergman,et al.  The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results. , 1995, Annals of epidemiology.

[21]  D. Owens,et al.  Comparison of Estimates of Insulin Sensitivity From Minimal Model Analysis of the Insulin-Modified Frequently Sampled Intravenous Glucose Tolerance Test and the Isoglycemic Hyperinsulinemic Clamp in Subjects With NIDDM , 1995, Diabetes.

[22]  Richard M Watanabe,et al.  A Comparison Between the Minimal Model and the Glucose Clamp in the Assessment of Insulin Sensitivity Across the Spectrum of Glucose Tolerance , 1994, Diabetes.

[23]  E. Ravussin,et al.  Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. , 1993, The New England journal of medicine.

[24]  M. Matsuda,et al.  In vivo Glucose Metabolism in Obese and Type II Diabetic Subjects With or Without Hypertension , 1993, Diabetes.

[25]  R. N. Bergman,et al.  Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study , 1992, The Lancet.

[26]  G. Reaven,et al.  Prevalence of hyperinsulinaemia in patients with high blood pressure , 1992, Journal of internal medicine.

[27]  K. Berntorp,et al.  Insulin resistance and Na+/K(+)-ATPase in hypertensive women: a difference in mechanism depending on the level of glucose tolerance. , 1992, Clinical science.

[28]  B. Trimarco,et al.  Skeletal muscle is a primary site of insulin resistance in essential hypertension. , 1991, Metabolism: clinical and experimental.

[29]  H. Lebovitz,et al.  Patterns of Glucose and Lipid Abnormalities in Black NIDDM Subjects , 1991, Diabetes Care.

[30]  E. Ravussin,et al.  Racial differences in the relation between blood pressure and insulin resistance. , 1991, The New England journal of medicine.

[31]  P. Bennett,et al.  A two-step model for development of non-insulin-dependent diabetes. , 1991, The American journal of medicine.

[32]  C. Palombo,et al.  Impaired Insulin Action on Skeletal Muscle Metabolism in Essential Hypertension , 1991, Hypertension.

[33]  M. A. Abdalla Saad,et al.  Insulinemia and blood pressure responses to oral glucose load in primary hypertensive patients. , 1991, Cardiology.

[34]  R N Bergman,et al.  Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. , 1990, The Journal of clinical endocrinology and metabolism.

[35]  B. Falkner,et al.  Insulin Resistance and Blood Pressure in Young Black Men , 1990, Hypertension.

[36]  P. Bennett,et al.  Insulin and Hypertension: Relationship to Obesity and Glucose Intolerance in Pima Indians , 1990, Diabetes.

[37]  T. O'dorisio.  Panel discussion IX: Clinical application of somatostatin analogs, part I, August 9, 1989 , 1990 .

[38]  M. Laakso,et al.  Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. , 1990, The Journal of clinical investigation.

[39]  P. Savage,et al.  Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study. , 1990, Arteriosclerosis.

[40]  C. Berne,et al.  Insulin resistance is a characteristic feature of primary hypertension independent of obesity. , 1990, Metabolism: clinical and experimental.

[41]  M. Saad,et al.  Insulin resistance in essential hypertension. , 1990, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[42]  M. Laakso,et al.  Essential hypertension and insulin resistance in non‐insulin‐dependent diabetes , 1989, European journal of clinical investigation.

[43]  A. Aviv,et al.  Racial differences in ion regulation and their possible links to hypertension in blacks. , 1989, Hypertension.

[44]  A. Folsom,et al.  Relation of body fatness and its distribution to cardiovascular risk factors in young blacks and whites. The role of insulin. , 1989, American journal of epidemiology.

[45]  C. Berne,et al.  A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. , 1989, The New England journal of medicine.

[46]  P. Bennett,et al.  SEQUENTIAL CHANGES IN SERUM INSULIN CONCENTRATION DURING DEVELOPMENT OF NON-INSULIN-DEPENDENT DIABETES , 1989, The Lancet.

[47]  G. Reaven,et al.  Insulin resistance, glucose intolerance and hyperinsulinemia in patients with hypertension. , 1989, American journal of hypertension.

[48]  P. Verdecchia,et al.  HYPERINSULINAEMIA AND HYPERTENSION IN DIABETES , 1988, The Lancet.

[49]  Roy Taylor,et al.  HYPERTENSION AND HYPERINSULINAEMIA: A RELATION IN DIABETES BUT NOT ESSENTIAL HYPERTENSION , 1988, The Lancet.

[50]  S. Haffner,et al.  Hyperinsulinemia, upper body adiposity, and cardiovascular risk factors in non-diabetics. , 1988, Metabolism: clinical and experimental.

[51]  G. Reaven,et al.  Resistance to insulin-stimulated-glucose uptake in patients with hypertension. , 1988, The Journal of clinical endocrinology and metabolism.

[52]  G. Reaven,et al.  A ROLE FOR INSULIN IN THE AETIOLOGY AND COURSE OF HYPERTENSION? , 1987, The Lancet.

[53]  R N Bergman,et al.  MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. , 1986, Computer methods and programs in biomedicine.

[54]  R. Yalow,et al.  Insulin as a potential factor influencing blood pressure in amputees. , 1986, Hypertension.

[55]  E. Ferrannini,et al.  Evidence for an association of high blood pressure and hyperinsulinemia in obese man. , 1986, The Journal of clinical endocrinology and metabolism.

[56]  M. Creager,et al.  Beta adrenergic-mediated vasodilator response to insulin in the human forearm. , 1985, The Journal of pharmacology and experimental therapeutics.

[57]  P. Watkins,et al.  Provocation of Postural Hypotension by Insulin in Diabetic Autonomic Neuropathy , 1976, Diabetes.

[58]  T. Welborn,et al.  Serum-insulin in essential hypertension and in peripheral vascular disease. , 1966, Lancet.