5 years ago

Attenuated Suppression of Lipolysis Explains Increases in Triglyceride Secretion and Concentration with Basal Insulin Peglispro (BIL) Relative to Insulin Glargine Treatment in Patients with Type 1 Diabetes

Rakel Fuglsang Johansen, Eric Chen Quin Lam, Scott J Jacober, Esben Søndergaard, Parag Garhyan, Helle Linnebjerg, Søren Nielsen, Niels Porksen
Aims In patients with type 1 diabetes, basal insulin peglispro (BIL) lowers weight and increases plasma triglycerides (TG) and hepatic fat relative to insulin glargine (GL). To explain this, we hypothesised that BIL's attenuated peripheral effects may include increased free fatty acid flux to the liver, causing increased VLDL-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition. Materials and Methods In this open-label, randomised, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualised, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10-3H]palmitate infusion. VLDL-TG secretion, clearance and oxidation rate were assessed using primed-constant infusion of ex-vivo labelled [1-14C]VLDL-TG, while VLDL-TG storage rate was assessed using [9,10-3H]VLDL-TG bolus injection. Results VLDL-TG concentration and secretion rate, and palmitate flux were statistically significantly higher during BIL than GL treatment (58%, 51% and 35%, respectively). The ratios of least squares (LS) geometric means (95% confidence interval [CI]) for VLDL-TG clearance and oxidation were 0.92 (0.72, 1.17) and 1.31 (0.91, 1.90), respectively. The difference in LS means (95% CI) for VLDL-TG storage rate was -0.36 (-0.83, 0.12). Conclusions BIL-treated patients had higher effective lipolysis, VLDL-TG secretion and VLDL-TG concentration versus GL, explaining the increased plasma TG concentrations reported previously. Data support attenuated effects of BIL on lipolysis, in addition to the recently described hepato-preferential glucodynamic effects.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13087

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