Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes

Cusi, Kenneth; Sanyal, Arun J.; Zhang, S.; Hoogwerf, Byron J.; Chang, Annette M.; Jacober, Scott J.; Bue-Valleskey, JulieM.; Higdon, A. N.; Bastyr, Edward J.; Haupt, Axel; Hartman, Mark L.

doi:10.1111/dom.12751

Cited by 30 publications

(68 citation statements)

References 37 publications

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“…In insulin-naïve patients with T2D, glargine reduced LFC while BIL treatment was associated with no change. In previously insulin-treated patients with T2D, glargine had no effect while LFC increased with BIL 7. Similar results were seen in serum triglycerides, suggesting differences in lipid flux between the two insulins and different patient types 42…”

Section: Discussionsupporting

confidence: 52%

“…BIL has different effects on LFC than glargine 7. In insulin-naïve patients with T2D, glargine reduced LFC while BIL treatment was associated with no change.…”

Section: Discussionmentioning

confidence: 89%

“…7 †Least squares mean±SE.n, number of patients randomized; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BIL, basal insulin peglispro; ELF, enhanced liver fibrosis; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; K-18, cytokeratin-18; LDL, low-density lipoprotein; LFC, liver fat content; T1D, type 1 diabetes; T2D, type 2 diabetes.…”

Section: Resultsmentioning

confidence: 99%

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Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

Sanyal

Cusi

Hartman

et al. 2018

Journal of Investigative Medicine

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Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin-treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are limited. This study analyzed phase III data comparing basal insulin peglispro (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin-naïve and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and liver fat content (LFC), measured by MRI, were obtained longitudinally. Baseline K-18 (U/L) was higher in T2D (range: 207‒247) than T1D (range: 148‒183), correlated with ALT in all populations (r (range) 0.264‒0.637, p<0.05), but with LFC only in T2D (r (range) 0.474‒0.586, p<0.05). K-18 increased significantly from baseline in BIL-treated, but not glargine-treated patients. Change from baseline (CFB) K-18 was significantly correlated with CFB in ALT in BIL-treated T2D populations. Baseline ELF scores were higher in T2D (range: 9.12‒9.20) than T1D (range: 8.24‒8.36), correlated with ALT in T1D only (0.209, p<0.05), and not correlated with LFC in any population. ELF scores increased significantly from baseline in BIL-treated but not glargine-treated patients. There were no correlations between CFB in LFC and ELF score at week 52 in any treatment group/population. In all BIL-treated populations, CFB in ALT and CFB in ELF score at week 52 were positively correlated. These data characterize associations of K-18 and ELF score with ALT and LFC in insulin-treated patients with T1D and T2D. Hepatopreferential insulins may be associated with increased K-18 and ELF scores but mechanisms and clinical significance are unknown. ClinicalTrials.gov identifiers are NCT01481779, NCT01435616, NCT01454284 and NCT01582451.

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Section: Discussionsupporting

confidence: 52%

“…BIL has different effects on LFC than glargine 7. In insulin-naïve patients with T2D, glargine reduced LFC while BIL treatment was associated with no change.…”

Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

Sanyal

Cusi

Hartman

et al. 2018

Journal of Investigative Medicine

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“…The primary LFC and routine blood lipid results are reported elsewhere [8, 11]. Here we report the results of the lipoprotein particle and related lipid analyses by cohort (type 1 diabetes, type 2 insulin naïve, or type 2 previously on insulin) and treatment (insulin glargine or BIL) at baseline and follow-up.…”

Section: Introductionmentioning

confidence: 99%

“…Changes in particle size of LDL, HDL, and VLDL were also compared. The objectives and results of the LFC study have been reported elsewhere [11, 12]. …”

Section: Introductionmentioning

confidence: 99%

The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

Orchard

Cariou

Connelly

et al. 2017

Cardiovasc Diabetol

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BackgroundIn Phase 2/3 studies of basal insulin peglispro (BIL) compared to insulin glargine, patients with type 1 or type 2 diabetes previously treated with insulin and randomized to BIL had an increase in serum triglycerides (TGs). To further understand lipoprotein changes, a lipid substudy which included liver fat content was designed to assess relationships among the measured variables for each diabetes cohort and compare the hepato-preferential insulin BIL to glargine.MethodsIn three cohorts of patients with diabetes (type 1, type 2 insulin naïve, and type 2 previously on insulin; n = 652), liver fat content (LFC) was determined by magnetic resonance imaging (MRI) and blood lipids were analyzed by nuclear magnetic resonance (NMR) spectroscopy at baseline, 26 and 52 weeks of treatment. Apolipoproteins, adiponectin, and other lipid parameters were also measured. Descriptive statistics were done, as well as correlation analyses to look for relationships among LFC and lipoproteins or other lipid measures.ResultsIn patients with type 1 diabetes treated with BIL, but not glargine, small LDL and medium and large VLDL subclass concentrations increased from baseline. In patients with type 2 diabetes previously on insulin and treated with BIL, large VLDL concentration increased from baseline. In insulin naïve patients with type 2 diabetes treated with BIL, there were very few changes, while in those treated with glargine, small LDL and large VLDL decreased from baseline. Baseline LFC correlated significantly in one or more cohorts with baseline large VLDL, small LDL, VLDL size, and Apo C3. Changes in LFC by treatment showed generally weak correlations with lipoprotein changes, except for positive correlations with large VLDL and VLDL size. Adiponectin was higher in patients with type 1 diabetes compared to patients with type 2 diabetes, but decreased with treatment with both BIL and glargine.ConclusionsThe lipoprotein changes were in line with the observed changes in serum TGs; i.e., the cohorts experiencing increased TGs and LFC with BIL treatment had decreased LDL size and increased VLDL size. These data and analyses add to the currently available information on the metabolic effects of insulins in a very carefully characterized cohort of patients with diabetes. Clinicaltrials.gov registration numbers and dates NCT01481779 (2011), NCT01435616 (2011), NCT01454284 (2011), NCT01582451 (2012)Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0555-1) contains supplementary material, which is available to authorized users.

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Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes

Liu

Yan

Xia

et al. 2020

Diabetes Metabolism Res

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BackgroundThe aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a 24‐week randomized controlled multicentre clinical trial. Seventy‐six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis‐4 index (FIB‐4).ResultsLFC, VAT, SAT, and FIB‐4 were significantly reduced after exenatide treatment (ΔLFC, −17.55 ± 12.93%; ΔVAT, −43.57 ± 68.20 cm2; ΔSAT, −28.44 ± 51.48 cm2; ΔFIB‐4, −0.10 ± 0.26; all P < .05). In comparison, only LFC (ΔLFC, −10.49 ± 11.38%; P < .05), and not VAT, SAT, or FIB‐4 index (all P > .05), was reduced after insulin glargine treatment. Moreover, exenatide treatment resulted in greater reductions in alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transpeptidase (GGT) than insulin glargine (P < 0.05). The body weight, waist circumference, postprandial plasma glucose, and low‐density lipoprotein cholesterol (LDL‐C) in the exenatide group also presented greater reductions than the insulin glargine group (P < .05). The proportion of adverse events were comparable between the two groups.ConclusionBoth exenatide and insulin glargine reduced LFC in patients with drug‐naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB‐4, postprandial plasma glucose, and LDL‐C.

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Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes

Cited by 30 publications

References 37 publications

Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes

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