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- Title
Effect of Nateglinide on Nonalcoholic Fatty Liver Disease as a Complication in Type 2 Diabetes.
- Authors
Matsuura, Kenichi; Mori, Yutaka; Itoh, Yohta; Tajima, Naoko
- Abstract
We previously reported that nateglinide suppresses increases in triglyceride (TG) after fat loading through suppression of not only exogenous but endogenous TG production. It is assumed that hepatic lipid metabolic disorders are implicated in increased endogenous TG, possibly leading in the long term to the development of fatty liver disease or nonalcoholic steatohepatitis (NASH). In this study, we investigated changes in hepatic fat content by using computed tomography (CT) in type 2 diabetic patients given nateglinide to evaluate the long-term effect of nateglinide on hepatic fat accumulation in these patients. Nateglinide (270 rag/day; t.i.d, before meals) was given to 18 drug-naïve patients with type 2 diabetes who were being treated on an outpatient basis (6 men, 12 women; age, 56 ± 7 years; BMI, 27.7 ± 4.4). Abdominal CT examinations were performed to evaluate liver/spleen (L/S) CT ratio, and visceral fat area (VFA) and subcutaneous fat area (SFA) at the umbilical level as assessed by slice-by-slice CT scanning, before and 6 months (M) after nateglinide administration in these patients. No significant changes were observed in BMI, VFA and SFA in the subjects. However, HbA1c values were significantly lower 3 and 6 months after the start of treatment, with the fasting glucose levels also tending to be lower, in these patients. ALT and AST values were also significantly lower in the subjects, with the L/S CT ratio by abdominal CT shown to be significantly increased 6 months after treatment compared to baseline. Of note, in 9 patients whose baseline L/S CT ratio was less than 0.8, the increase in L/S CT ratio was more pronounced (baseline: 0.58 ± 0.20 vs 6M: 0.78 ± 0.24, p < 0.01). Furthermore, there was a significant negative correlation between baseline L/S CT ratio and nateglinide-induced increases in L/S CT ratio (r = -0.58, p < 0.05). Long-term nateglinide administration suppressed hepatic fat accumulation in type 2 diabetic patients as in experimental animals. While the exact mechanisms for this remain unclear, given that this effect is not associated with changes in visceral fat area, it appears likely that nateglinide affects the liver directly.
- Subjects
DRUG efficacy; FATTY liver; DIABETES complications; TYPE 2 diabetes; TRIGLYCERIDES; PEOPLE with diabetes; BLOOD sugar
- Publication
Diabetes, 2007, Vol 56, pA555
- ISSN
0012-1797
- Publication type
Article