, Volume 39, Issue 7, pp 813–822

Insulin resistance in relatives of NIDDM patients: The role of physical fitness and muscle metabolism

  • B. Nyholm
  • A. Mengel
  • S. Nielsen
  • Ch. Skjærbæk
  • N. Møller
  • K. G. M. M. Alberti
  • O. Schmitz

DOI: 10.1007/s001250050515

Cite this article as:
Nyholm, B., Mengel, A., Nielsen, S. et al. Diabetologia (1996) 39: 813. doi:10.1007/s001250050515


First degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) are often reported to be insulin resistant. To examine the possible role of reduced physical fitness in this condition 21 first degree relatives of NIDDM patients and 22 control subjects without any history of diabetes were examined employing a 150-min hyper-insulinaemic (0.6 mU insulin kg−1 min−1) euglycaemic clamp combined with the isotope dilution technique (3-3H-glucose, Hot GINF), the forearm technique and indirect calorimetry. During hyperinsulinaemia glucose disposal (Rd) and forearm glucose extraction were significantly diminished in the relatives (p < 0.01 and p < 0.05), but glucose oxidation and the suppressive effect on hepatic glucose production were normal. Arteriovenous differences across the forearm of the gluconeogenic precursors lactate, alanine and glycerol as well as the increments in forearm blood flow during hyperinsulinaemia were similar in the two groups. Maximal oxygen uptake (VO2 max) was lower in the relatives than in the control subjects (36.8 ± 1.9 vs 42.1 ± 2.0 ml kg−1 min−1; p = 0.03). There was a highly significant correlation between Rd and VO2 max in both relatives and control subjects (r = 0.68 and 0.66, respectively; both p < 0.001). Comparison of the linear regression analyses of insulin-stimulated Rd on VO2 max in the two groups showed no significant differences between the slopes (0.10 ± 0.03 vs 0.09 ± 0.02) or the intercepts. In stepwise multiple linear regression analyses with insulinstimulated Rd as the dependent variable VO2 max significantly determined the level of Rd (p < 0.01), whereas forearm blood flow and anthropometric data did not. In conclusion, the insulin resistance in healthy first degree relatives of patients with NIDDM is associated with a diminished physical work capacity. Whether, this finding is ascribable to environmental or genetic factors (e.g. differences in muscle fibre types, capillary density etc) remains to be determined.


Insulin resistancerelativesnon-insulin-dependent diabetes mellitusoral glucose tolerance testphysical fitnessforearm blood flowmuscle metabolism



Body mass index

W/H ratio

waist to hip ratio


fat free mass


non-esterified fatty acids



VO2 max

maximal oxygen uptake


glucose infusion rate


isotopically determined glucose disposal


hepatic glucose production


glucose oxidation rate


non-oxidative glucose disposal


lipid oxidation rate


protein oxidation rate


non-insulin-dependent diabetes mellitus


oral glucose tolerance test.

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • B. Nyholm
    • 1
  • A. Mengel
    • 2
  • S. Nielsen
    • 1
  • Ch. Skjærbæk
    • 2
  • N. Møller
    • 1
  • K. G. M. M. Alberti
    • 3
  • O. Schmitz
    • 1
  1. 1.Department of Medicine M (Endocrinology and Diabetes)Aarhus KommunehospitalAarhus CDenmark
  2. 2.Institute of Experimental and Clinical ResearchUniversity of Aarhus, Aarhus KommunehospitalAarhusDenmark
  3. 3.Department of MedicineThe Medical SchoolNewcastle-upon-TyneUK