Hyperinsulinemia in african-american children: decreased insulin clearance and increased insulin secretion and its relationship to insulin sensitivity.

African-American (AA) children are hyperinsulinemic and insulin resistant compared with American White (AW) children. This study investigated 1) whether AA/AW differences in insulinemia are associated with differences in insulin clearance; 2) whether dietary patterns, mainly carbohydrate and fat intake, play a role; and 3) whether the quantitative relationship between insulin sensitivity and secretion is similar between AA and AW children. Forty-four prepubertal children (22 AA and 22 AW) with comparable body composition and visceral adiposity were studied. All underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp to calculate insulin sensitivity and insulin clearance and a 2-h hyperglycemic clamp (12.5 mmol/l) to assess first- and second-phase insulin responses. Twenty-four-hour food recalls were analyzed for macronutrient intake. Insulin clearance (19.5 +/- 0.7 vs. 22.9 +/- 1.1 ml x min(-1) x kg(-1) fat-free mass [FFM]; P = 0.011) and insulin sensitivity were lower in AA versus AW children (14.8 +/- 1.0 vs. 18.9 +/- 1.4 micro mol x min(-1) x kg(-1) FFM; P = 0.021). Both insulin clearance and insulin sensitivity correlated inversely with dietary fat/carbohydrate ratio, which was higher in AA than in white children. Fasting C-peptide and insulin were higher in AA children with no difference in proinsulin levels. First- and second-phase insulin concentrations and glucose disposition index (insulin sensitivity x first-phase insulin) were higher in AA than in white children (12.8 +/- 2.1 vs. 7.2 +/- 0.6 micro mol. min(-1) x kg(-1) FFM; P = 0.019). In conclusion, the hyperinsulinemia observed in AA children is due to both lower insulin clearance and higher insulin secretion compared with their white peers. The quantitative relationship between insulin secretion and sensitivity is upregulated in AA children. This suggests that increased insulin secretion in AA children is not merely a compensatory response to lower insulin sensitivity. Dietary factors may have a role. Additional studies are needed to determine whether metabolic/nutritional factors, possibly mediated through free fatty acids, may play a role in the hyperinsulinism observed in AA children.

[1]  J. McGarry.  Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. , 2002, Diabetes.

[2]  S. Arslanian,et al.  Lipolysis in African-American children: is it a metabolic risk factor predisposing to obesity? , 2001, The Journal of clinical endocrinology and metabolism.

[3]  J. McGarry.  Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes , 2001 .

[4]  R. Bergman,et al.  Longitudinal Compensation for Fat-induced Insulin Resistance Includes Reduced Insulin Clearance and Enhanced ␤-cell Response Research Design and Methods , 2022 .

[5]  G. Hunter,et al.  Racial differences in insulin secretion and sensitivity in prepubertal children: role of physical fitness and physical activity. , 2000, Obesity research.

[6]  B. Gower,et al.  Role of dietary factors in ethnic differences in early risk of cardiovascular disease and type 2 diabetes. , 2000, The American journal of clinical nutrition.

[7]  K. Jones,et al.  Type 2 diabetes mellitus in minority children and adolescents. An emerging problem. , 1999, Endocrinology and metabolism clinics of North America.

[8]  G. Balasekaran,et al.  Insulin sensitivity in African-American children with and without family history of type 2 diabetes. , 1999 .

[9]  B. Gower,et al.  Visceral fat, insulin sensitivity, and lipids in prepubertal children. , 1999, Diabetes.

[10]  A. Rosenbloom,et al.  Emerging epidemic of type 2 diabetes in youth. , 1999, Diabetes care.

[11]  J. McGarry,et al.  Fatty acids, lipotoxicity and insulin secretion , 1999, Diabetologia.

[12]  J. Rood,et al.  Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women. , 1998, Metabolism: clinical and experimental.

[13]  P. J. Randle,et al.  Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. , 1998, Diabetes/metabolism reviews.

[14]  D. Schuster,et al.  Differential impact of obesity on glucose metabolism in black and white American adolescents. , 1998, The American journal of the medical sciences.

[15]  G. Boden,et al.  Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. , 1998, Diabetes.

[16]  J. McGarry,et al.  Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. , 1998, Diabetes.

[17]  M. Walker,et al.  Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications. , 1997, The American journal of clinical nutrition.

[18]  S. Arslanian,et al.  Testosterone treatment in adolescents with delayed puberty: changes in body composition, protein, fat, and glucose metabolism. , 1997, The Journal of clinical endocrinology and metabolism.

[19]  J. Janosky,et al.  Insulin secretion and sensitivity in black versus white prepubertal healthy children. , 1997, The Journal of clinical endocrinology and metabolism.

[20]  K. Polonsky,et al.  Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals. , 1997, The Journal of clinical endocrinology and metabolism.

[21]  D. Schuster,et al.  Race and ethnicity determine serum insulin and C-peptide concentrations and hepatic insulin extraction and insulin clearance: comparative studies of three populations of West African ancestry and white Americans. , 1997, Metabolism: clinical and experimental.

[22]  R. Bergman,et al.  Dietary fat and insulin sensitivity in a triethnic population: the role of obesity. The Insulin Resistance Atherosclerosis Study (IRAS) , 1997, The American journal of clinical nutrition.

[23]  S. Arslanian,et al.  Differences in the in vivo insulin secretion and sensitivity of healthy black versus white adolescents. , 1996, The Journal of pediatrics.

[24]  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.

[25]  S. Srinivasan,et al.  Racial (black-white) differences in insulin secretion and clearance in adolescents: the Bogalusa heart study. , 1996, Pediatrics.

[26]  K. Polonsky,et al.  Report of the American Diabetes Association's Task Force on Standardization of the Insulin Assay , 1996, Diabetes.

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

[28]  R. Unger.  Lipotoxicity in the Pathogenesis of Obesity-Dependent NIDDM: Genetic and Clinical Implications , 1995, Diabetes.

[29]  A. Tremblay.  Nutritional determinants of the insulin resistance syndrome. , 1995, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[30]  J. Pivarnik,et al.  Ethnicity affects aerobic fitness in US adolescent girls. , 1994, Medicine and science in sports and exercise.

[31]  M. Stachura,et al.  Relation of percentage of body fat and maximal aerobic capacity to risk factors for atherosclerosis and diabetes in black and white seven- to eleven-year-old children. , 1994, The Journal of pediatrics.

[32]  S. Schiffman,et al.  Effect of race on perception of fat alone and in combination with sugar , 1994, Physiology & Behavior.

[33]  L. Snetselaar,et al.  The Dietary Intervention Study in Children (DISC): dietary assessment methods for 8- to 10-year-olds. , 1993, Journal of the American Dietetic Association.

[34]  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.

[35]  C. Quesenberry,et al.  Usual Dietary Fat Intake and Insulin Concentrations in Healthy Women Twins , 1993, Diabetes Care.

[36]  A. Kriska,et al.  The epidemiology of leisure physical activity in an adolescent population. , 1993, Medicine and science in sports and exercise.

[37]  M. Harris,et al.  Effect of multiple risk factors on differences between blacks and whites in the prevalence of non-insulin-dependent diabetes mellitus in the United States. , 1993, American journal of epidemiology.

[38]  K. Osei,et al.  Differences in basal and poststimulation glucose homeostasis in nondiabetic first degree relatives of black and white patients with type 2 diabetes mellitus. , 1992, The Journal of clinical endocrinology and metabolism.

[39]  G. Berenson,et al.  Black-White Contrasts In Insulin Levels During Pubertal Development: The Bogalusa Heart Study , 1992, Diabetes.

[40]  W. Haskell,et al.  Saturated Fat Intake and Insulin Resistance in Men With Coronary Artery Disease , 1991, Circulation.

[41]  P. Gergen,et al.  Dietary patterns of U.S. children: implications for disease prevention. , 1990, Preventive medicine.

[42]  M. Harris.  Noninsulin-dependent diabetes mellitus in black and white Americans. , 1990, Diabetes/metabolism reviews.

[43]  I M Buzzard,et al.  Sources of data for developing and maintaining a nutrient database. , 1988, Journal of the American Dietetic Association.

[44]  B H Frank,et al.  Quantitative study of insulin secretion and clearance in normal and obese subjects. , 1988, The Journal of clinical investigation.

[45]  J M Tanner,et al.  Growth and maturation during adolescence. , 2009, Nutrition reviews.

[46]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.