title: Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations.
abstract: BACKGROUND
  Earlier prospective studies have identified insulin action and secretion as predictors of T2DM in populations with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) (2-h OGTT < 7.8 and 7.8-11 mmol/L, respectively). Fasting plasma glucose (FPG), an additional and recently modified (normal <5.6 mmol/L) diagnostic criterion is associated with insulin secretion. We wanted to establish whether insulin secretion persists as an independent predictor of T2DM in individuals with no clinical evidence of impaired glucose regulation based on FPG and 2-h plasma glucose concentrations.
  
  
  METHODS
  Insulin action (M, euglycemic-hyperinsulinemic clamp), insulin secretion (acute insulin response (AIR), IVGTT), and adiposity (%Fat, DXA or densitometry) were compared at baseline in 358 Pima Indians (232M/126F, 18-44 years old) with normal glucose regulation of whom 61 (35M/26F) developed diabetes (DIAB) during a median follow-up time of 7.6 years.
  
  
  RESULTS
  In proportional-hazard analysis, % Fat (HR = 1.52, p = 0.03), M (HR = 0.51, p = 0.04) and AIR (HR = 0.64, p = 0.003) predicted the development of diabetes after adjustment for age and sex. In regression analysis adjusting for age, sex, %Fat and M at baseline, the non-diabetic group (NON-DM) had a higher AIR (p = 0.0002) than the DIAB group; the positive association of AIR with adiposity observed in the NON-DM group was absent in the DIAB group. Cumulative incidence rates (12y) for diabetes were highest (48%) in subjects with both M and AIR below the population median and lowest (11%) in subjects with both M and AIR above the population median.
  
  
  CONCLUSIONS
  AIR can predict diabetes prior to the current clinical indicators of impaired glucose regulation.
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, Arizona 85016, USA. jbunt@mail.nih.gov
authors.forename: Joy C
authors.initials: JC
authors.lastname: Bunt
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krakoff
authors.forename: Emilio
authors.initials: E
authors.lastname: Ortega
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
mesh_terms: D050154:Adiposity; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005215:Fasting / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007198:Indians, North American; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin