Endocrine Abstracts (2001) 2 P4

Acute regulation of bone collagen turnover and PTH by insulin and glucose: Hyperinsulinemic euglycaemic and hypoglycaemic clamp studies

JC Clowes, RT Robinson, SR Heller, R Eastell & A Blumsohn


Division of Clinical Sciences (NGHT), University of Sheffield, UK.


Bone turnover decreases markedly following both oral glucose and feeding. The mechanism for this is unclear. The aim of this study was to examine whether insulin itself could be responsible for the effect of feeding. We examined the acute effect of a hyperinsulinemic euglycemic clamp (E) and stepwise hyperinsulinemic hypoglycemic clamp (H) on bone turnover and PTH. Sixteen healthy male volunteers (mean age 22) attended on two occasions at 0800 after an overnight fast. The study was approved by the local ethics committee. They were randomised in a double blind crossover study to H or E clamp protocols. At each visit subjects received an intravenous insulin infusion at a constant rate (1.5 mUnits/kg/min). 20% dextrose was infused at a variable rate to maintain plasma glucose at 5 mmol/l (E clamp) or 2.5 mmol/l (H clamp). Samples were collected at baseline (-40 min), 0, 45, 75 and 105 or 120 minutes for measurement of PTH, serum C-terminal telopeptide of type I collagen (beta CTX) a marker of bone resorption, serum procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC), markers of bone formation.

During induction of the clamp (-40 to 0 minutes), plasma insulin increased more than ten fold with no change in plasma glucose. This was associated with a significant decrease in OC (8%), PINP (3%) and PTH by 27% (all P<0.01). The H clamp resulted in decreases in CTX (37%,) OC (5%), PINP by 15% (all P<0.001) and PTH by 12% (P<0.05). E Clamp resulted in increased PINP (4%) and PTH (23%) P<0.01, but no change in CTX.

We conclude that hyperinsulinemia is not likely to be responsible for the acute effect of feeding on bone resorption . However, hyperinsulinemic hypoglycemia is associated with acute suppression of bone turnover. This may be related to acute changes in PTH, hypoglycemia itself, or other hormones released in response to hypoglycemia.

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