Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy
Authors' conclusion
Metreleptin treatment in patients with lipodystrophy reduced GNG likely through decreased availability of carbon sources for gluconeogenesis, such as alanine, lactate, and glycerol. Associations between alanine and GNG persisted after metreleptin treatment while correlations with glycerol and palmitate Ra did not persist, suggesting reduced importance of lipolysis as a driver of GNG in the leptin-replete state.
Study context
- Population
- Patients with lipodystrophy (NIH, 2013–2018)9 with GNG data
- Participants
- 15 patients
- Exposure
- Before vs during metreleptin administration
- Metreleptinn = 15
- Outcome
- Effects of metreleptin on GNG and GNG substrates
Main finding
As reported in the abstract
GNG
- Metreleptin decreased basal GNG and increased insulin-mediated suppression of GNG
- Metreleptin reduced GNG carbon sources (plasma alanine, lactate, glycerol rate of appearance (Ra)) and decreased palmitate Ra
Observational data: associations, not effects.
Further findings
Insulin sensitivity and glycemic control
- Improved insulin sensitivity and markers of glycemic control
Correlations with GNG
- Glycerol and palmitate Ra correlated with GNG before but not during metreleptin
- Alanine strongly correlated with GNG before and during metreleptin
Original publication
Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy. J Clin Endocrinol Metab. Published 29 July 2023. doi:10.
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