Persistence of Pre-Diabetes in Overweight and Obese Hispanic Children

OBJECTIVE—To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS—We recruited 128 overweight/obese Hispanic children with a family history of type 2 diabetes primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying American Diabetes Association criteria to define diabetes and pre-diabetes. Insulin sensitivity (Si), acute insulin response (AIR) to glucose, and β-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, and total body fat by dual-energy X-ray absorptiometry and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by magnetic resonance imaging were assessed in years 1, 2, and 4. RESULTS—No subjects developed type 2 diabetes, 40% never had pre-diabetes, 47% had intermittent pre-diabetes with no clear pattern over time, and 13% had persistent pre-diabetes. At baseline, those with persistent pre-diabetes had lower BCF and higher IAAT. In repeated measures, Si deteriorated regardless of pre-diabetes, and there was a significant effect of pre-diabetes on AIR (42% lower in pre-diabetes; P = 0.01) and disposition index (34% lower in pre-diabetes; P = 0.021) and a significant interaction of pre-diabetes and time on IAAT (greater increase over time in those with pre-diabetes; P = 0.034). CONCLUSIONS—In this group of Hispanic children at high risk of type 2 diabetes, 1) pre-diabetes is highly variable from year to year; 2) the prevalence of persistent pre-diabetes over 3 years is 13%; and 3) children with persistent pre-diabetes have lower BCF, due to a lower AIR, and increasing visceral fat over time.

[1]  J. Silverstein,et al.  Type 2 diabetes in children and adolescents , 2003, Pediatric diabetes.

[2]  M. Goran,et al.  Deterioration of insulin sensitivity and beta-cell function in overweight Hispanic children during pubertal transition: a longitudinal assessment. , 2006, International journal of pediatric obesity : IJPO : an official journal of the International Association for the Study of Obesity.

[3]  T. Buchanan,et al.  Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes. , 2006, Diabetes.

[4]  M. Goran,et al.  Decreased β-Cell Function in Overweight Latino Children With Impaired Fasting Glucose , 2005 .

[5]  W. Tamborlane,et al.  Predictors of changes in glucose tolerance status in obese youth. , 2005, Diabetes care.

[6]  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.

[7]  R. Bergman,et al.  Impaired Glucose Tolerance and Reduced β-Cell Function in Overweight Latino Children with a Positive Family History for Type 2 Diabetes , 2004 .

[8]  M. Goran,et al.  The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. , 2004, The Journal of clinical endocrinology and metabolism.

[9]  R. Moldawsky Prescription drug benefits and health status among Medicare patients. , 2003, JAMA.

[10]  Stephen W. Sorensen,et al.  Lifetime risk for diabetes mellitus in the United States. , 2003, JAMA.

[11]  L. Kuller,et al.  Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. , 2003, American journal of physiology. Endocrinology and metabolism.

[12]  R. Ross,et al.  Visceral fat and liver fat are independent predictors of metabolic risk factors in men. , 2003, American journal of physiology. Endocrinology and metabolism.

[13]  R. Bergman,et al.  Insulin resistance and associated compensatory responses in african-american and Hispanic children. , 2002, Diabetes care.

[14]  Katherine M Flegal,et al.  Prevalence and trends in overweight among US children and adolescents, 1999-2000. , 2002, JAMA.

[15]  A. Häkkinen,et al.  Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. , 2002, The Journal of clinical endocrinology and metabolism.

[16]  W. Tamborlane,et al.  Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. , 2002, The New England journal of medicine.

[17]  R. Bergman,et al.  Accurate Assessment of β-Cell Function: The Hyperbolic Correction , 2002 .

[18]  S. Kahn,et al.  The Importance of β-Cell Failure in the Development and Progression of Type 2 Diabetes , 2001 .

[19]  R. Pratley,et al.  The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus , 2001, Diabetologia.

[20]  G. Marchesini,et al.  Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. , 2001, Diabetes.

[21]  G. Smith,et al.  Munchausen's syndrome manifesting as factitious hypoglycaemia. , 2001 .

[22]  T. Buchanan Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. , 2001, The Journal of clinical endocrinology and metabolism.

[23]  C. Bogardus,et al.  A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. , 2000, Diabetes.

[24]  R. N. Bergman,et al.  Non-esterified fatty acids and the liver: why is insulin secreted into the portal vein? , 2000, Diabetologia.

[25]  C. Bogardus,et al.  The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. , 1999, The Journal of clinical investigation.

[26]  T. Buchanan,et al.  Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. , 1999, Diabetes.

[27]  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.

[28]  A. Perez-Atayde,et al.  Idiopathic steatohepatitis in childhood: a multicenter retrospective study. , 1995, The Journal of pediatrics.

[29]  R. Bergman Toward Physiological Understanding of Glucose Tolerance: Minimal-Model Approach , 1989, Diabetes.

[30]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.

[31]  F. Ginsberg-Fellner,et al.  Plasma Glucose, Free Fatty Acids, and Immunoreactive Insulin in Sixty-six Obese Children: Studies in Reference to a Family History of Diabetes Mellitus , 1968, Diabetes.