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Endocrine abnormalities in healthy first‐degree relatives of type 2 diabetes patients – potential role of steroid hormones and leptin in the development of insulin resistance
Author(s) -
Jansson PA.,
Eliasson B.,
Lindmark S.,
Eriksson J. W.
Publication year - 2002
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2002.00963.x
Subject(s) - medicine , endocrinology , leptin , insulin resistance , type 2 diabetes , hormone , body mass index , diabetes mellitus , insulin , testosterone (patch) , first degree relatives , endocrine system , obesity , family history
Background First‐degree relatives of type 2 diabetes patients are at risk of developing diabetes and they display several metabolic and hormonal perturbations. The interplay between insulin resistance, steroid hormones and circulating leptin is, however, still not fully explored in this group. Design Thirty‐three healthy first‐degree relatives of type 2 diabetic patients (relatives; M/F 19/14) were compared to 33 healthy subjects without a family history of diabetes (controls) and the groups were matched for gender, age and body mass index (BMI). We performed euglycaemic hyperinsulinaemic clamps and blood was sampled for hormone analyses. Results Relatives exhibited decreased insulin sensitivity (index of metabolic clearance rate of glucose; MCRI) but when genders were analysed separately, this difference was significant only in males (11·3 ± 1·3 vs. 15·0 ± 1·5 units, means ± SEM, P = 0·030). In male relatives morning cortisol and testosterone levels were lower, whereas leptin was higher than in male controls ( P = 0·018, 0·008 and 0·063, respectively). In male relatives plasma testosterone levels were significantly associated with insulin sensitivity ( r = 0·48, P = 0·040). Circulating leptin levels were inversely correlated with insulin sensitivity in all subject groups ( r ‐values –0·49 to –0·66; P < 0·05, except in female control subjects P = 0·063). These associations were present also when age and BMI or waist : hip ratio were included in stepwise multiple regression analyses. Conclusion Male subjects genetically predisposed for type 2 diabetes display several endocrine abnormalities including leptin, cortisol and testosterone levels. Dysregulation of these hormones may be important in the development of insulin resistance and type 2 diabetes.