title: Metabolic consequences of a family history of NIDDM (the Botnia study): evidence for sex-specific parental effects.
abstract: Although a strong genetic susceptibility has been established for NIDDM and a maternal transmission of the disease predominates in some populations, a relationship between parental diabetes status and metabolic abnormalities in nondiabetic offspring has not been shown in humans. To address this question, we studied 2,152 first-degree relatives of patients with NIDDM (FH+) and 528 age- and weight-matched spouses without a family history of NIDDM (FH-) in Western Finland (the Botnia study). A subset of the subjects underwent a euglycemic insulin clamp combined with indirect calorimetry to measure insulin sensitivity and energy expenditure. Despite similar amounts of total body fat, persons with a family history of NIDDM had a greater waist-to-hip ratio (WHR) than spouses without a family history of diabetes (P < 0.003). They also had a decreased resting metabolic rate (P = 0.005), but this difference disappeared when adjusted for the difference in WHR. Insulin-stimulated glucose metabolism (P = 0.002), particularly nonoxidative glucose metabolism (P = 0.009), was reduced in FH+ compared with FH- subjects, and this difference remained after adjustment for WHR. A parental history of NIDDM influenced the insulin response to the oral glucose load, with male offspring of diabetic mothers showing the lowest insulin values (P = 0.011). Moreover, a parental effect was also observed on HDL and HDL2 cholesterol concentrations with female offspring of diabetic mothers showing lower values than female offspring of diabetic fathers (both P < 0.002). We conclude that abdominal obesity, insulin resistance, and decreased resting metabolic rate are characteristic features of first-degree relatives of patients with NIDDM and that the decrease in resting metabolic rate is partially related to the degree of abdominal obesity. A sex-specific paternal effect was observed on insulin and HDL cholesterol concentrations. Therefore, one has to consider the possibility of unprecedented maternal or paternal inheritance of different NIDDM phenotypes.
authors.affiliation: Department of Endocrinology, University of Lund, Malmö General Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Groop
authors.forename: C
authors.initials: C
authors.lastname: Forsblom
authors.forename: M
authors.initials: M
authors.lastname: Lehtovirta
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
authors.forename: S
authors.initials: S
authors.lastname: Karanko
authors.forename: M
authors.initials: M
authors.lastname: Nissén
authors.forename: B O
authors.initials: BO
authors.lastname: Ehrnström
authors.forename: B
authors.initials: B
authors.lastname: Forsén
authors.forename: B
authors.initials: B
authors.lastname: Isomaa
authors.forename: B
authors.initials: B
authors.lastname: Snickars
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001827:Body Height; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D005387:Finland; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D005947:Glucose