Effect of Insulin-metformin Combination on Hepatic Steatosis in Patients with Type 2 Diabetes

Overview

Journal J Diabetes Complications

Specialty Endocrinology

Date 2007 May 12

PMID 17493545

Citations 14

Authors

Ildiko Lingvay

Philip Raskin

Lidia S Szczepaniak

Affiliations

Soon will be listed here.

Abstract

Objective: Hepatic steatosis occurs in up to 78% of patients with type 2 diabetes. Studies evaluating the effect of metformin on hepatic steatosis are conflicting. Insulin is believed to be detrimental due to its lipogenic effect. Since insulin-metformin combination is commonly used for the treatment of diabetes, it is important to assess the effect of this combined therapy on hepatic steatosis. We evaluated the change in hepatic steatosis following the initiation of insulin and metformin in patients with type 2 diabetes.

Methods: Newly diagnosed treatment-naïve patients with type 2 diabetes had their hepatic triglyceride (TG) content measured by magnetic resonance spectroscopy at baseline and after 3 months of treatment with BiAsp 30 insulin, in combination with metformin. Insulin was administered twice daily and titrated to achieve normal capillary blood glucose levels. Metformin was titrated during the first month from 500 mg daily to 1000 mg bid.

Results: The average hepatic TG content in 19 enrolled subjects was 11.83+/-7.61% (range, 0.93-23.16%) and correlated with body mass index (r=.567). Three months of treatment reduced hepatic steatosis by 45%, with 75% of the study subjects achieving a normal level. The change in hepatic TG content was partially explained by changes in HbA1c (P=.006) and cholesterol (P=.003) levels.

Conclusions: The combined treatment with insulin and metformin significantly reduced hepatic steatosis in patients with newly diagnosed type 2 diabetes.

Citing Articles

Assessment of fatty liver and its correlation with glycemic control in patients with type 2 diabetes mellitus attending Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.

Abebe G, Ayanaw D, Mengstie T, Dessie G, Malik T SAGE Open Med. 2022; 10:20503121221124762.

PMID: 36161212 PMC: 9490463. DOI: 10.1177/20503121221124762.

Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD.

Svop Jensen V, Fledelius C, Zachodnik C, Damgaard J, Nygaard H, Tornqvist K J Transl Med. 2021; 19(1):80.

PMID: 33596938 PMC: 7890970. DOI: 10.1186/s12967-021-02729-1.

Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review.

Pan C, Stanley T Front Endocrinol (Lausanne). 2020; 11:70.

PMID: 32153507 PMC: 7046622. DOI: 10.3389/fendo.2020.00070.

Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells.

Yousuf Y, Datu A, Barnes B, Amini-Nik S, Jeschke M Stem Cell Res Ther. 2020; 11(1):18.

PMID: 31915055 PMC: 6950874. DOI: 10.1186/s13287-019-1480-x.

Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

Bergenstal R, Lunt H, Franek E, Travert F, Mou J, Qu Y Diabetes Obes Metab. 2016; 18(11):1081-1088.

PMID: 27265390 PMC: 5096008. DOI: 10.1111/dom.12698.

References

Luyckx F, Lefebvre P, Scheen A . Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. Diabetes Metab. 2000; 26(2):98-106. View

Belfort R, Harrison S, Brown K, Darland C, Finch J, Hardies J . A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006; 355(22):2297-307. DOI: 10.1056/NEJMoa060326. View

Mayerson A, Hundal R, Dufour S, Lebon V, Befroy D, Cline G . The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes. 2002; 51(3):797-802. PMC: 2995527. DOI: 10.2337/diabetes.51.3.797. View

Anderwald C, Bernroider E, Krssak M, Stingl H, Brehm A, Bischof M . Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes. 2002; 51(10):3025-32. DOI: 10.2337/diabetes.51.10.3025. View

Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies L, Pratipanawatr W, Glass L . Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes. 2003; 52(6):1364-70. DOI: 10.2337/diabetes.52.6.1364. View

Promrat K, Lutchman G, Uwaifo G, Freedman R, Soza A, Heller T . A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004; 39(1):188-96. DOI: 10.1002/hep.20012. View

Uygun A, Kadayifci A, Isik A, Ozgurtas T, Deveci S, Tuzun A . Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004; 19(5):537-44. DOI: 10.1111/j.1365-2036.2004.01888.x. View

Duseja A, Murlidharan R, Bhansali A, Sharma S, Das A, Das R . Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report. Indian J Gastroenterol. 2004; 23(1):12-5. View

Nair S, Diehl A, Wiseman M, Farr Jr G, Perrillo R . Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004; 20(1):23-8. DOI: 10.1111/j.1365-2036.2004.02025.x. View

10.

Tiikkainen M, Hakkinen A, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H . Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004; 53(8):2169-76. DOI: 10.2337/diabetes.53.8.2169. View

11.

Longo R, Pollesello P, Ricci C, Masutti F, Kvam B, Bercich L . Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J Magn Reson Imaging. 1995; 5(3):281-5. DOI: 10.1002/jmri.1880050311. View

12.

Sheth S, Gordon F, Chopra S . Nonalcoholic steatohepatitis. Ann Intern Med. 1997; 126(2):137-45. DOI: 10.7326/0003-4819-126-2-199701150-00008. View

13.

Younossi Z, Gramlich T, Liu Y, Matteoni C, Petrelli M, Goldblum J . Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod Pathol. 1998; 11(6):560-5. View

14.

Szczepaniak L, Babcock E, Schick F, Dobbins R, Garg A, Burns D . Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol. 1999; 276(5):E977-89. DOI: 10.1152/ajpendo.1999.276.5.E977. View

15.

Browning J, Szczepaniak L, Dobbins R, Nuremberg P, Horton J, Cohen J . Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004; 40(6):1387-95. DOI: 10.1002/hep.20466. View

16.

Szczepaniak L, Nurenberg P, Leonard D, Browning J, Reingold J, Grundy S . Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2004; 288(2):E462-8. DOI: 10.1152/ajpendo.00064.2004. View

17.

Schwimmer J, Middleton M, Deutsch R, Lavine J . A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2005; 21(7):871-9. DOI: 10.1111/j.1365-2036.2005.02420.x. View

18.

Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N . A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005; 100(5):1082-90. DOI: 10.1111/j.1572-0241.2005.41583.x. View

19.

Kleiner D, Brunt E, Van Natta M, Behling C, Contos M, Cummings O . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41(6):1313-21. DOI: 10.1002/hep.20701. View

20.

Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E . Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005; 128(7):1898-906. DOI: 10.1053/j.gastro.2005.03.084. View