The short-term use of intravenous unacylated ghrelin infusion does not appear to have an effect on either substrate metabolism or insulin sensitivity in men with type 2 diabetes (T2D), according to findings from a study published in The Journal of Clinical Endocrinology & Metabolism.

Some data suggest that unacylated ghrelin may improve insulin sensitivity in individuals with T2D. In the current study, researchers evaluated the effects of intravenous unacylated ghrelin infusion on glucose and lipid metabolism, insulin sensitivity, and energy expenditure in a small cohort of men with T2D. A randomized double-blind and placebo-controlled crossover study was conducted at a hospital clinical research center in which 10 men with T2D (mean age, 52.4 years) completed 2 study days. During day 1, they received a 6-hour unacylated ghrelin infusion (1 µg/kg/hour) and on day 2 they received a 6-hour placebo infusion. Participants were investigated in the basal postabsorptive state for 4 hours, which was followed by a hyperinsulinemic clamp for 2 hours.

Results showed that plasma unacylated ghrelin was 64.1 ± 11.3 pg/mL at baseline but increased more than 50-fold during the unacylated ghrelin infusion. Baseline fasting plasma glucose was 7.0 ± 0.3 mmol/L before the unacylated ghrelin infusion vs 6.7 ± 0.4 mmol/L for placebo (P =.43) but remained unaffected by the unacylated ghrelin infusion. Measuring insulin sensitivity, glucose rates were 4.69 ± 0.56 mg/kg/minute for the unacylated ghrelin infusion and 4.98 ± 0.43 mg/kg/minute for the placebo infusion (P =.66) during the hyperinsulinemic clamp, and unacylated ghrelin infusion did not affect glucose oxidation, nonoxidative glucose disposal, lipolysis, energy expenditure, or respiratory exchange rate.

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“Our results do not support that [short-term unacylated ghrelin] exposure elicits either ghrelin-dependent or direct effects, but higher [unacylated ghrelin] concentrations and more prolonged [unacylated ghrelin] exposition may be required to detect an effect,” wrote the researchers. “Studies on long-term effects of [unacylated ghrelin] or its analogs on glucose and lipid metabolism remain to be conducted to determine if modulation of the ghrelin system could play a role in future diabetes treatment.”

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Vestergaard ET, Jessen N, Møller N, Jørgensen JOL. Unacylated ghrelin does not acutely affect substrate metabolism or insulin sensitivity in men with type 2 diabetes [published online February 4, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-02601