title: Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM.
abstract: Insulin resistance is a common feature in first-degree relatives of NIDDM patients. To explore the mechanism(s) behind this condition in more detail, a percutaneous muscle biopsy (vastus lateralis) was performed in 25 first-degree relatives of NIDDM patients and 21 control subjects to examine muscle fiber composition and capillary density. Insulin-stimulated glucose disposal (Rd) was determined employing a hyperinsulinemic-(insulin infusion rate 0.6 mU x kg[-1] x min[-1]) euglycemic clamp. Rd (5.76 +/- 0.35 vs. 8.06 +/- 0.36 mg x kg lean body weight [LBW]-1 x min[-], P < 0.001) and estimated VO2max (49.3 +/- 2.8 vs. 57.2 +/- 3.5 mg x kg LBW[-1] x min[-1], 0.05 < P < 0.10) were decreased in the relatives. The number of type IIb fibers (29.5 +/- 2.5 vs. 21.0 +/- 2.8%, P < 0.05) was increased in the relatives, whereas no significant differences were found in other fiber types or capillary density between the groups. Correlations were observed between number of type I fibers (positive), number of type IIb fibers (negative), and capillary density (positive) versus Rd as well as estimated VO2max (P < 0.05). In a multiple linear regression analysis with Rd as a dependent variable, estimated VO2max, family history of NIDDM, and number of type IIb fibers (P < 0.001, r2 = 0.64) significantly determined the level of Rd, whereas capillary density did not. In conclusion, insulin-resistant first-degree relatives of NIDDM patients are characterized by an increased number of type IIb muscle fibers. Whether this finding reflects a reduced physical activity level and fitness in the relatives or is of primary genetic origin remains to be determined.
authors.affiliation: Department of Medicine (Endocrinology and Diabetes), Institute for Experimental Clinical Research, University of Aarhus, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Nyholm
authors.forename: Z
authors.initials: Z
authors.lastname: Qu
authors.forename: A
authors.initials: A
authors.lastname: Kaal
authors.forename: S B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: C H
authors.initials: CH
authors.lastname: Gravholt
authors.forename: J L
authors.initials: JL
authors.lastname: Andersen
authors.forename: B
authors.initials: B
authors.lastname: Saltin
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D002196:Capillaries / Q000033:anatomy & histology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology*; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology; D009679:Nuclear Family; D012016:Reference Values; D012044:Regression Analysis