Insulin secretion and resistance in nondiabetic Mexican Americans and non-Hispanic whites with a parental history of diabetes.

Both insulin resistance and decreased insulin secretion have been hypothesized as precursors of noninsulin-dependent diabetes mellitus (NIDDM). However, there are few data on insulin resistance and secretion in relationship to parental history of diabetes in ethnic groups at different risks for NIDDM. We examined the relationship of fasting insulin (as a marker of insulin resistance) and the ratio of the 30-min change in insulin to the 30-min change in glucose (delta I30/delta G30) during an oral glucose tolerance test (as a marker of insulin secretion) in relation to parental history of diabetes in 1672 nondiabetic Mexican Americans and 894 nondiabetic non-Hispanic whites. A parental history of diabetes was associated with increased fasting insulin concentrations. The association between decreased insulin secretion and parental history of diabetes was not significant. However, when insulin resistance and insulin secretion were included in the same regression model, both fasting insulin (odds ratio = 1.80; 95% confidence interval = 1.17, 2.76) and decreased insulin secretion (odds ratio = 0.70, 95% confidence interval = 0.52, 0.95) were significantly associated with a parental history of diabetes. These results were little changed after adjustment for obesity, body fat distribution, and glucose tolerance. These results were similar in both Mexican Americans and non-Hispanic whites and in both subjects with impaired and those with normal glucose tolerance. A parental history of diabetes in both Mexican Americans and non-Hispanic whites is associated with both increased fasting insulin and decreased delta I30/delta G30. These data suggest that both increased insulin resistance and early decreased insulin secretion in response to an oral glucose challenge may be important factors in the pathogenesis of NIDDM in populations at high and low risk of NIDDM. Our results also emphasize the importance of adjusting for insulin resistance in evaluating insulin secretion.

[1]  S. Efendić,et al.  Aspects of the pathogenesis of type 2 diabetes. , 1984, Endocrine reviews.

[2]  W. Sheu,et al.  Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance. , 1993, The Journal of clinical endocrinology and metabolism.

[3]  P. Bennett,et al.  Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. , 1990, The Journal of clinical endocrinology and metabolism.

[4]  S. Haffner,et al.  Increased insulin concentrations in nondiabetic offspring of diabetic parents. , 1988, The New England journal of medicine.

[5]  R. DeFronzo.  The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM , 1988, Diabetes.

[6]  S. Haffner,et al.  Decreased Insulin Secretion and Increased Insulin Resistance Are Independently Related to the 7-Year Risk of NIDDM in Mexican-Americans , 1995, Diabetes.

[7]  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.

[8]  M Rosenthal,et al.  Sex difference in the effects of sociocultural status on diabetes and cardiovascular risk factors in Mexican Americans. The San Antonio Heart Study. , 1984, American journal of epidemiology.

[9]  S. Haffner,et al.  Incidence of Type II Diabetes in Mexican Americans Predicted by Fasting Insulin and Glucose Levels, Obesity, and Body-Fat Distribution , 1990, Diabetes.

[10]  R. Bergman,et al.  Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function , 1993, Diabetes.

[11]  R. DeFronzo,et al.  The Metabolic Profile of NIDDM Is Fully Established in Glucose-Tolerant Offspring of Two Mexican-American NIDDM Parents , 1992, Diabetes.

[12]  G. Dailey,et al.  Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. , 1995, JAMA.

[13]  P. Bennett,et al.  The natural history of impaired glucose tolerance in the Pima Indians. , 1988, The New England journal of medicine.

[14]  R. Sicree,et al.  Plasma Insulin Response Among Nauruans: Prediction of Deterioration in Glucose Tolerance Over 6 Yr , 1987, Diabetes.

[15]  E. Cerasi,et al.  Dose-response relation between plasma-insulin and blood-glucose levels during oral glucose loads in prediabetic and diabetic subjects. , 1973, Lancet.

[16]  A. Krolewski,et al.  Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. , 1990, Annals of internal medicine.

[17]  L. Groop,et al.  Hyperproinsulinemia of Type II Diabetes Is Not Present Before the Development of Hyperglycemia , 1994, Diabetes Care.

[18]  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.

[19]  A. Fontbonne,et al.  Risk Factors for NIDDM in White Population: Paris Prospective Study , 1991, Diabetes.

[20]  D. Owens,et al.  INSULIN DEFICIENCY IN NON-INSULIN-DEPENDENT DIABETES , 1989, The Lancet.

[21]  G. Reaven,et al.  Insulin resistance and hypertriglyceridemia in nondiabetic relatives of patients with noninsulin-dependent diabetes mellitus. , 1989, The Journal of clinical endocrinology and metabolism.

[22]  D. Kelley,et al.  Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. , 1992, The New England journal of medicine.

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

[24]  P. Wahl,et al.  Association of Elevated Fasting C-Peptide Level and Increased Intra-Abdominal Fat Distribution With Development of NIDDM in Japanese-American Men , 1990, Diabetes.

[25]  S. Haffner,et al.  Higher Proinsulin and Specific Insulin Are Both Associated With a Parental History of Diabetes in Nondiabetic Mexican-American Subjects , 1995, Diabetes.

[26]  S. O’Rahilly,et al.  BETA-CELL DYSFUNCTION, RATHER THAN INSULIN INSENSITIVITY, IS THE PRIMARY DEFECT IN FAMILIAL TYPE 2 DIABETES , 1986, The Lancet.

[27]  C. Osmond,et al.  Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion , 1994, Diabetic medicine : a journal of the British Diabetic Association.

[28]  M. Davies,et al.  Insulin Deficiency and Increased Plasma Concentration of Intact and 32/33 Split Proinsulin in Subjects with Impaired Glucose Tolerance , 1993, Diabetic medicine : a journal of the British Diabetic Association.

[29]  L. Groop,et al.  Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. , 1989, The New England journal of medicine.

[30]  S. Haffner,et al.  Hyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus. , 1986, The New England journal of medicine.

[31]  P. Wahl,et al.  Earlier Appearance of Impaired Insulin Secretion Than of Visceral Adiposity in the Pathogenesis of NIDDM: 5-Year Follow-up of Initially Nondiabetic Japanese-American Men , 1995, Diabetes Care.

[32]  S. Haffner,et al.  A comparison of three indicators for identifying Mexican Americans in epidemiologic research. Methodological findings from the San Antonio Heart Study. , 1986, American journal of epidemiology.