title: Family history of type 2 diabetes increases the risk of both obesity and its complications: is type 2 diabetes a disease of inappropriate lipid storage?
abstract: OBJECTIVE
  The aim of this study was to characterize diabetes risk in relation to amount and distribution of body fat (environmental factors) and genetic risk defined as having first-degree (FH1) or second-degree relatives with diabetes.
  
  
  METHODS
  We analysed the METSIM population of 10 197 middle-aged, randomly selected men. At baseline, information about family history of diabetes was registered and all individuals underwent extensive phenotyping. A follow-up study was conducted after 6 years. The metabolic consequences of increased visceral versus subcutaneous fat were characterized in a separate cohort of 158 healthy men (the Kuopio Cohort of the EUGENE2 study).
  
  
  RESULTS
  At baseline, individuals with a family history of diabetes (FH+) had approximately a twofold increase in the prevalence of type 2 diabetes compared with individuals without a family history of the disease (FH-) (18.0% vs. 9.9%; P = 1.3 × 10(-31) ). FH1 individuals were more commonly overweight and obese compared with FH- (69.2% vs. 64.8%; P = 1.3 × 10(-4) ) and, for a given body mass index, showed an increased risk profile for both type 2 diabetes and cardiovascular disease as well as a greater susceptibility to the negative consequences of increased body fat also when nonobese. Subgroup analyses indicated that the metabolic consequences were due primarily to increased ectopic/visceral fat rather than subcutaneous fat. The increased risk profile in FH+ individuals was not altered by adjusting for 43 major diabetes risk genes.
  
  
  CONCLUSIONS
  Family history of type 2 diabetes (particularly FH1) is associated with both increased risk of becoming overweight/obese and with a greater susceptibility to the negative consequences of increasing body fat, probably as a consequence of an increased propensity to accumulate ectopic (nonsubcutaneous) fat.
authors.affiliation: Department of Medicine, Kuopio and Kuopio University Hospital 2, University of Eastern Finland, Kuopio, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Cederberg
authors.forename: A
authors.initials: A
authors.lastname: Stančáková
authors.forename: J
authors.initials: J
authors.lastname: Kuusisto
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: U
authors.initials: U
authors.lastname: Smith
mesh_terms: D050218:Body Fat Distribution; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050152:Intra-Abdominal Fat / Q000473:pathology; D052439:Lipid Metabolism Disorders / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000473:pathology; D050177:Overweight / Q000209:etiology* / Q000473:pathology; D010375:Pedigree; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000473:pathology; D055105:Waist Circumference
chemical_list: D007328:Insulin
keywords: diabetes; family history; genetics; insulin resistance; insulin secretion; obesity