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Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin‐10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism
Author(s) -
George Jyothis T.,
Veldhuis Johannes D.,
TenaSempere Manuel,
Millar Robert P.,
Anderson Richard A.
Publication year - 2013
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12103
Subject(s) - kisspeptin , endocrinology , medicine , testosterone (patch) , luteinizing hormone , type 2 diabetes , pathophysiology , diabetes mellitus , hypothalamic–pituitary–gonadal axis , hormone
Rationale Low serum testosterone is commonly observed in men with type 2 diabetes (T2 DM ), but the neuroendocrine pathophysiology remains to be elucidated. Objectives The hypothalamic neuropeptide kisspeptin integrates metabolic signals with the reproductive axis in animal models. We hypothesized that administration of exogenous kisspeptin‐10 will restore luteinizing hormone ( LH ) and testosterone secretion in hypotestosteronaemic men with T2 DM . Participants Five hypotestosteronaemic men with T2 DM (age 33·6 ± 3 years, BMI 40·6 ± 6·3, total testosterone 8·5 ± 1·0 nmol/l, LH 4·7 ± 0·7 IU /l, HbA 1c 7·4±2%, duration of diabetes <5 years) and seven age‐matched healthy men. Experiment 1 Mean LH increased in response to intravenous administration of kisspeptin‐10 (0·3 mcg/kg bolus) both in healthy men (5·5 ± 0·8 to 13·9 ± 1·7 IU /l P < 0·001) and in men with T2 DM (4·7 ± 0·7 to 10·7 ± 1·2 IU /l P = 0·02) with comparable Δ LH ( P = 0·18). Experiment 2 Baseline 10‐min serum sampling for LH and hourly testosterone measurements were performed in four T2 DM men over 12 h. An intravenous infusion of kisspeptin‐10 (4 mcg/kg/h) was administered for 11 h, 5 days later. There were increases in LH (3·9 ± 0·1 IU /l to 20·7 ± 1·1 IU /l P = 0·03) and testosterone (8·5 ± 1·0 to 11·4 ± 0·9 nmol/l, P = 0·002). LH pulse frequency increased from 0·6 ± 0·1 to 0·9 ± 0 pulses/h ( P = 0·05) and pulsatile component of LH secretion from 32·1 ± 8·0 IU /l to 140·2 ± 23·0 IU /l ( P = 0·007). Conclusions Kisspeptin‐10 administration increased LH pulse frequency and LH secretion in hypotestosteronaemic men with T2 DM in this proof‐of‐concept study, with associated increases in serum testosterone. These data suggest a potential novel therapeutic role for kisspeptin agonists in enhancing endogenous testosterone secretion in men with T2 DM and central hypogonadism.