Diabetes Contributes to Cholesterol Metabolism Regardless of Obesity

Piia P. Simonen, MD, Helena K. Gylling, MD and Tatu A. Miettinen, MD

Disclosures

Diabetes Care. 2002;25(9) 

In This Article

Abstract and Introduction

Objective: To investigate cholesterol metabolism in obesity with and without diabetes.
Research Design and Methods: We performed cross-sectional metabolic studies in obese individuals with and without type 2 diabetes. The study population consisted of 16 obese (BMI >30 kg/m2) diabetic subjects with a mean age of 52 ± 2 years (SE) and 16 nondiabetic control subjects of similar age and weight. Cholesterol absorption efficiency was measured with peroral dual isotopes and cholesterol synthesis with sterol balance.
Results: Serum total cholesterol did not differ between the groups, but LDL and HDL cholesterol were significantly lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in the diabetic group than in the control group. Cholesterol absorption efficiency was 29 ± 1% in diabetic subjects vs. 42 ± 2% in the control subjects (P < 0.01). Cholesterol synthesis was higher (17 ± 1 vs. 14 ± 1 mg · kg-1 · day-1; P < 0.05) and neutral sterol and bile acid excretion and cholesterol turnover tended to be higher in the diabetic group than in the control group. Blood glucose was positively related to cholesterol synthesis in the diabetic group (r = +0.663, P < 0.01) and in the control group (r = +0.590, P < 0.05), suggesting that the higher blood glucose level, the higher the cholesterol synthesis. In addition, blood glucose was significantly positively related to fecal neutral sterol excretion in both groups.
Conclusions: Cholesterol absorption efficiency was lower and cholesterol synthesis was higher in obese subjects with diabetes than in those without diabetes, suggesting that diabetes modulates cholesterol metabolism more than obesity alone.

In patients with type 2 diabetes, cholesterol metabolism differs from nondiabetic patients because cholesterol synthesis is high[1,2,3,4] and is reduced by insulin.[5,6] Low cholesterol absorption efficiency has been reported earlier in a limited number of diabetic subjects with mild hyperlipidemia[4] and in moderately overweight, markedly hypertriglyceridemic subjects including both type 1 and type 2 diabetes.[7] Also, serum plant sterol levels, indicators of cholesterol absorption efficiency[8,9] are low in type 2 diabetes[10] and even in subjects with high-to-normal blood glucose levels.[11] Accordingly, cholesterol metabolism mimics that observed in obesity.[12,13,14,15]

We have shown previously that cholesterol absorption efficiency was increased by weight reduction, and the variables of glucose metabolism improved in obese diabetic subjects, suggesting that low cholesterol absorption is associated with insulin resistance and metabolic syndrome,[16] an association found earlier nondiabetic subjects.[11] The question now is whether overweight, which is frequently associated with diabetes, is responsible for the alterations observed in cholesterol metabolism in diabetes, or does diabetes have any independent role in regulating cholesterol metabolism.

To this end, we studied cholesterol absorption efficiency and sterol balance in obese subjects with and without diabetes, the latter selected by BMI from a population-based cohort.

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