Evidence for a short-term stimulatory effect of insulin on cholesterol synthesis in newly insulin-treated diabetic patients

To gain further insight into the effects of insulin on cholesterol synthesis in humans, 19 newly insulin-treated diabetic patients were studied before any insulin treatment (study day 1) and after a few days of optimized glycemic control with a continuous intravenous insulin infusion (study day 2). The patients were divided into two groups according to their clinical characteristics and laboratory disorders. Groups I and II consisted, respectively, of 10 newly diagnosed type I diabetic patients and nine type II diabetic patients with secondary failure to oral antidiabetic drugs. Cholesterol synthesis was estimated from the determination of serum lathosterol, a metabolic precursor in the cholesterol pathway, and from the serum lathosterol to cholesterol ratio. Serum cholesterol (millimolar, mean ± SEM) remained unchanged in both groups. After insulin therapy (study day 2), serum lathosterol (micromolar) and the serum lathosterol to cholesterol ratio (molar ratio × 10 3) were significantly increased as compared with baseline (study day 1). Serum lathosterol levels were as follows: 9.9 ± 2.0 versus 4.1 ± 0.4 ( P < .02) in group I, and 9.9 ± 0.8 versus 5.7 ± 0.7 ( P < .005) in group II; serum lathosterol to cholesterol ratios were 2.10 ± 0.39 versus 0.86 ± 0.11 ( P < .005) in group I, and 1.92 ± 0.12 versus 0.98 ± 0.10 ( P < .001) in group II. The data indicate that in newly insulin-treated diabetic patients, short-term intensive insulin therapy has a stimulatory effect on cholesterol synthesis and even results in cholesterol overproduction.