Effect of exposure to non-esterified fatty acid on progressive deterioration of insulin secretion in patients with Type 2 diabetes: a long-term follow-up study.

Objective: The aim of the study was to determine whether fasting serum non-esterified fatty acid (NEFA) could be associated with long-term progressive deterioration of insulin secretion in patients with Type 2 diabetes.

Methods: Seventy-seven Japanese patients with Type 2 diabetes (mean BMI 23.3 kg/m(2) ) were followed for 10 years. We measured fasting C-peptide level every 1-2 years. By using the slope of regression line between fasting C-peptide level and duration, we calculated its individual annual decline as an index of insulin secretion. During the follow-up periods of C-peptide, the patients were evaluated for fasting serum non-esterified fatty acid, LDL cholesterol, HDL cholesterol and HbA(1c) levels for the last 8 years. We excluded patients who had renal dysfunction or anti-insulin antibodies from among the insulin-treated patients. Association between the individual annual decline of fasting C-peptide level and related factors were evaluated.

Results: The mean individual annual decline of fasting serum C-peptide level was -0.013 ± 0.027 nmol/l/year. Fasting serum non-esterified fatty acid level had no significant difference between the first and the last 2 years of the 8-year observation period of non-esterified fatty acid. Using multiple regression analysis, mean fasting serum non-esterified fatty acid level was associated with the individual annual decline of fasting serum C-peptide level (standardized regression coefficient -0.358, P=0.0056), although other related factors, including HbA(1c) level, were not associated.

Conclusions: Mean fasting serum non-esterified fatty acid level during an 8-year observation was independently associated with long-term progressive deterioration of insulin secretion in Japanese patients with Type 2 diabetes.