Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes
Abstract
UNLABELLED: We determined whether insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes (age 51+/-2 yr, body mass index 33.1+/-1.4 kg/m2) treated with metformin alone received additional basal insulin for 7 mo. Liver fat (proton magnetic resonance spectroscopy), fat distribution (MRI), fat-free and fat mass, and whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose) were measured. The insulin dose averaged 75+/-10 IU/day (0.69+/-0.08 IU/kg, range 24-132 IU/day). Glycosylated hemoglobin A1c (Hb A1c) decreased from 8.9+/-0.3 to 7.4+/-0.2% (P<0.001). Whole body insulin sensitivity increased from 2.21+/-0.38 to 3.08+/-0.40 mg/kg fat-free mass (FFM).min (P<0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production (HGP) by insulin (HGP 1.04+/-0.28 vs. 0.21+/-0.19 mg/kg FFM.min, P<0.01). The percent suppression of HGP by insulin increased from 72+/-8 to 105+/-11% (P<0.01). LFAT decreased from 17+/-3 to 14+/-3% (P<0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity (r=0.56, P<0.05). Body weight increased by 3.0+/-1.1 kg (P<0.05). Of this, 83% was due to an increase in fat-free mass (P<0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly. CONCLUSIONS: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.
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The associations between liver fat and hepatic insulin resistance have previously been reported by Bajaj et al in 14 type 2 diabetic patients, and by us in nondiabetic subjects and type 2 diabetic patients treated with insulin.
“The associations between liver fat and hepatic insulin resistance have previously been reported by Bajaj et al, 62 who studied 14 type 2 diabetic patients, and by us in nondiabetic subjects 24,39 and type 2 diabetic patients treated with insulin. 36,38”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [36]
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- Authors
- Juurinen, L., Tiikkainen, M., Häkkinen, A.-M., Hakkarainen, A., & Yki-Järvinen, H.
- ORCID
- Hakkarainen, Antti
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-03
- Volume
- 292
- Issue
- 3
- Pages
- E829-E835
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2062583781
- Cited by
- 141
- References
- 54
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 9
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin therapy, type 2 diabetes, hepatic insulin sensitivity, liver fat, hepatic glucose production, basal insulin, metformin, fat-free mass, free fatty acids, adiponectin, weight gain, hyperinsulinemic-euglycemic clamp, 1H NMR
- MeSH terms
- Alanine Transaminase, Basal Metabolism, Diabetes Mellitus, Type 2, Drug Combinations, Fatty Acids, Nonesterified, Glucose, Humans, Insulin, Insulin Resistance, Lipids, Liver, Metformin, Middle Aged, Oxidation-Reduction
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