Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial

Abstract

OBJECTIVEThis study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy, including metformin. RESEARCH DESIGN AND METHODSThirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications were randomized to receive insulin glargine or liraglutide therapy for 12 weeks. The liver proton density fat fraction (PDFF) was measured by MRS. The mean liver PDFF, the total liver volume, and the total liver fat index were measured by MRI. The Student t test, the Fisher exact test, and repeated-measures ANOVA were used for statistical analysis. RESULTSInsulin treatment was associated with a significant improvement in glycated hemoglobin (7.9% to 7.2% [62.5 to 55.2 mmol/mol], P = 0.005), a trend toward a decrease in MRS-PDFF (12.6% to 9.9%, P = 0.06), and a significant decrease in liver mean MRI-PDFF (13.8% to 10.6%, P = 0.005), liver volume (2,010.6 to 1,858.7 mL, P = 0.01), and the total liver fat index (304.4 vs. 209.3 % · mL, P = 0.01). Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin (7.6% to 6.7% [59.8 to 50.2 mmol/mol], P < 0.001) but did not change MRS-PDFF (P = 0.80), liver mean MRI-PDFF (P = 0.15), liver volume (P = 0.30), or the total liver fat index (P = 0.39). CONCLUSIONSThe administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes. However, the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group.To reduce the risk of long-term microvascular and macrovascular complications, diabetes therapy should aim for tight glucose control as assessed by glycated hemoglobin (HbA 1c ) below 7% (53 mmol/mol) while minimizing hypoglycemia (1,2). However, most patients still do not achieve glycemic targets and thus require

Accelerating MR Imaging Liver Steatosis Measurement Using Combined Compressed Sensing and Parallel Imaging: A Quantitative Evaluation

“…The This range of fat fraction was similar to that in other cohorts of patients with type 2 diabetes (37,38). In the general population without nonalcoholic fatty liver disease, fat fractions of up to 45% might be observed in a few individuals (1,11).…”

Effects of insulin therapy on weight gain and fat distribution in the HF/HS-STZ rat model of type 2 diabetes

“…Insulin therapy has been reported to induce significant decrease in liver fat accumulation in humans with type 2 diabetes. 31,35 The possible discrepancies between the human studies are likely affected by the length of disease duration, the choice and intensity of insulin therapy and inclusion of insulin therapy naïve or previously insulin therapy exposed subjects. Collectively, our data tend to agree with the sparse amount of human data available, showing a favouring of fat accumulation in the subcutaneous fat compartment over the visceral compartment as a consequence of insulin therapy.…”

Response to Comment on Tang et al. Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. Diabetes Care 2015;38:1339–1346

“…Shan et al (1) raise important points regarding treatment duration, sample size, mean values of magnetic resonance (MR)-based biomarkers, and severity of liver steatosis in our study (2).…”

“…To acknowledge that the study duration was too short to address the long-term effects on liver steatosis, we preemptively stated in our discussion that "a longer study would have favored GLP-1 agonist therapy in terms of body weight loss and, possibly, a concomitant reduction in the liver fat fraction" (2).…”