Salgin B, Marcovecchio ML, Williams RM, Jackson SJ, Bluck LJ, Humphreys SM, Acerini CL, Dunger DB
Effects of growth hormone and free fatty acids on insulin sensitivity in patients with type 1 diabetes. [JOURNAL ARTICLE]
J Clin Endocrinol Metab 2009 Jun 30.
Context: Since growth hormone (GH) stimulates lipolysis, an increase in circulating free fatty acid (FFA) levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and FFAs to the development of insulin resistance in patients with T1D.
Patients: 7 (4female symbol/3male symbol) non-obese patients with T1D aged 21-30 years were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by Octreotide. Three 1-hour pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an anti-lipolytic drug, or a placebo were ingested every four hours on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a 2-step hyperinsulinaemic euglycaemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycaemia overnight (p=0.008), elevated basal endogenous glucose production (p=0.007), decreased basal peripheral glucose uptake (p=0.03) and reduced glucose uptake during step 1 of the clamp (p<0.0001). Co-administration of rhGH and Acipimox reversed these effects, and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity.
Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by Acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis.
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