Effects of growth hormone and free fatty acids on insulin sensitivity in patients with type 1 diabetes.

Author(s): Salgin B, Marcovecchio ML, Williams RM, Jackson SJ, Bluck LJ, Humphreys SM, Acerini CL, Dunger DB

Affiliation(s): University Department of Pediatrics, Addenbrooke's Hospital, Level 8, Box 116, Cambridge CB2 0QQ, United Kingdom. burak@cantab.net

Publication date & source: 2009-09, J Clin Endocrinol Metab., 94(9):3297-305. Epub 2009 Jun 30.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

CONTEXT: Because GH stimulates lipolysis, an increase in circulating free fatty acid 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 free fatty acids to the development of insulin resistance in patients with T1D. PATIENTS: Seven (four females, three males) nonobese patients with T1D aged 21-30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. MAIN OUTCOME: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia 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). Coadministration 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.