title: A family history of type 2 diabetes increases risk factors associated with overfeeding.
abstract: OBJECTIVE
  The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during experimental overfeeding.
  
  
  METHODS
  We studied the effects of 3 and 28 days of overfeeding by 5,200 kJ/day in 41 sedentary individuals with and without a family history of type 2 diabetes (FH+ and FH- respectively). Measures included body weight, fat distribution (computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp).
  
  
  RESULTS
  Body weight was increased compared with baseline at 3 and 28 days in both groups (p < 0.001), FH+ individuals having gained significantly more weight than FH- individuals at 28 days (3.4 +/- 1.6 vs 2.2 +/- 1.4 kg, p < 0.05). Fasting serum insulin and C-peptide were increased at 3 and 28 days compared with baseline in both groups, with greater increases in FH+ than in FH- for insulin at +3 and +28 days (p < 0.01) and C-peptide at +28 days (p < 0.05). Fasting glucose also increased at both time points, but without a significant group effect (p = 0.1). Peripheral insulin sensitivity decreased in the whole cohort at +28 days (54.8 +/- 17.7 to 50.3 +/- 15.6 micromol min(-1) [kg fat-free mass](-1), p = 0.03), and insulin sensitivity by HOMA-IR decreased at both time points (p < 0.001) and to a greater extent in FH+ than in FH- (p = 0.008). Liver fat, subcutaneous and visceral fat increased similarly in the two groups (p < 0.001).
  
  
  CONCLUSIONS
  Overfeeding induced weight and fat gain, insulin resistance and hepatic fat deposition in healthy individuals. However, individuals with a family history of type 2 diabetes gained more weight and greater insulin resistance by HOMA-IR. The results of this study suggest that healthy individuals with a family history of type 2 diabetes are predisposed to adverse effects of overfeeding.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00562393
  
  
  BACKGROUND
  The study was funded by the National Health and Medical Research Council (NHMRC), Australia (no. #427639).
authors.affiliation: Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Samocha-Bonet
authors.forename: L V
authors.initials: LV
authors.lastname: Campbell
authors.forename: A
authors.initials: A
authors.lastname: Viardot
authors.forename: J
authors.initials: J
authors.lastname: Freund
authors.forename: C S
authors.initials: CS
authors.lastname: Tam
authors.forename: J R
authors.initials: JR
authors.lastname: Greenfield
authors.forename: L K
authors.initials: LK
authors.lastname: Heilbronn
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001315:Australia; D001823:Body Composition; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D044343:Overnutrition / Q000097:blood / Q000503:physiopathology*; D012307:Risk Factors; D057185:Sedentary Behavior; D015430:Weight Gain / Q000502:physiology*
chemical_list: D002096:C-Peptide; D007328:Insulin; D020738:Leptin; D005947:Glucose
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