title: β-Cell dysfunction is associated with metabolic syndrome severity in adults.
abstract: BACKGROUND
  Metabolic syndrome is prevalent in adults characterized by increased visceral adiposity and insulin resistance (IR). However, the link between pancreatic β-cell function and metabolic syndrome severity in adults across the glucose spectrum is unknown. We hypothesized that poor β-cell function would independently predict a higher metabolic syndrome Z-score (i.e., severity).
  
  
  METHODS
  Seventy (12 normal glucose tolerant, 37 prediabetic, 21 type 2 diabetic) obese adults [62.4±1.1 year; 34.6±0.6 kg/m(2); data are mean±standard error of the mean (SEM)] participated in this cross-sectional study. A 2-hr 75-gram oral glucose tolerance test (OGTT) was administered, and insulin and glucose area under the curve was determined for calculations of insulin action. Fasting and glucose-stimulated insulin secretion was calculated using homeostasis model assessment of insulin secretion (HOMA-B) and the insulinogenic index (i.e., I(0-30)/Glc(0-30) or I(60-120)/Glc(60-120)), respectively. Fasting and postprandial insulin sensitivity was assessed by HOMA-IR and the Matsuda Index, respectively. β-cell function was estimated using the disposition index via HOMA-B/HOMA-IR, I(0-30)/Glc(0-30) or I(60-120)/Glc(60-120) × Matsuda Index, which represents basal, first-, and second-phase insulin release, respectively. Body composition (via computerized tomography and dual X-ray absorptiometry) and sex-specific metabolic syndrome Z-scores were calculated from waist circumference, blood pressure, fasting glucose, triglycerides, and high-density lipoproteins.
  
  
  RESULTS
  Compared to those with normal glucose tolerance, visceral fat and IR were higher and β-cell function was lower in adults with glucose intolerance and type 2 diabetes mellitus. Elevated visceral fat and IR (HOMA-IR and Matsuda Index) correlated with elevated Z-scores (r=0.51, r=0.54, r=-0.49; all P<0.002, respectively). Basal, first-, and second-phase β-cell function correlated with low Z-scores (r=-0.59, r=-0.51, and r=-0.43, all P<0.001). Insulin secretion significantly predicted the Z-score independent of sex, body fat, blood lipids, blood pressure, IR, and glucose metabolism (P<0.005).
  
  
  CONCLUSIONS
  β-cell dysfunction is highly correlated with the severity of metabolic syndrome in adults. Future work is warranted to elucidate the mechanism by which cardiometabolic disturbances influence insulin secretion.
authors.affiliation: 1 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.forename: Stephen
authors.initials: S
authors.lastname: Finnegan
authors.forename: Ciaran E
authors.initials: CE
authors.lastname: Fealy
authors.forename: Julianne
authors.initials: J
authors.lastname: Filion
authors.forename: Michael B
authors.initials: MB
authors.lastname: Rocco
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D011236:Prediabetic State / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose