c-peptide and lathosterol

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 x 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.

Topics: Adolescent; Adult; Aged; Apolipoproteins; Blood Glucose; C-Peptide; Child; Cholesterol; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin; Isomerism; Male; Middle Aged; Triglycerides

NIDDM and the metabolic syndrome are characterized by a low serum, HDL cholesterol content and a high triglyceride level, whereas total and LDL cholesterol concentrations are not necessarily elevated. Variable results have been reported on cholesterol absorption, elimination, and synthesis in NIDDM, but no studies are available on subjects within the normal range of blood glucose. From serum samples collected in 1985 from 203 nondiabetic men aged 51-66 years, we examined lipids, cholesterol precursors (reflecting cholesterol synthesis), and plant sterols and cholestanol (reflecting cholesterol absorption) in relation to fasting blood glucose. The findings prompted us (in 1993) to further examine 11 men from the highest and lowest glucose thirds of 203 nondiabetic men by additional dietary, serum, and fecal analyses for absorption, elimination, and synthesis of cholesterol and insulin sensitivity. In 1985, blood glucose was significantly related to LDL apolipoprotein B (P = 0.05) but not to LDL cholesterol (P = 0.19). Significantly higher serum lathosterol and desmosterol-to-cholesterol proportions and lower plant sterol and cholestanol proportions in the highest rather than the lowest glucose thirds suggested that the subjects with high normal blood glucose had decreased absorption and enhanced synthesis of cholesterol. In 1993, men with the lowest glucose versus those with the highest glucose had a lower waist-to-hip ratio, plasma HbA1c, fasting and postload insulin and glucose values, and a higher insulin sensitivity index. In agreement with the 1985 non-cholesterol sterol data, direct analyses of cholesterol metabolism showed further higher cholesterol absorption efficiency (P = 0.03) and serum plant sterol and cholestanol proportions (P < 0.001). Despite a slightly lower dietary cholesterol intake, cholesterol synthesis (P = 0.02) and serum lathosterol (P < 0.01) and desmosterol (P < 0.01) proportions were lowest in men with the lowest glucose third. We conclude that noncholesterol sterols in serum exhibits a long-lasting correlation with blood glucose level in a nondiabetic male population. Low intestinal absorption and high synthesis of cholesterol characterize men with high normal blood glucose. Differences in cholesterol metabolism could be due to underlying insulin effects associated with obesity-like fat distribution and may thus imply novel aspects in the metabolic interrelation between insulin and cholesterol in humans.

Topics: Aged; Analysis of Variance; Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Desmosterol; Fasting; Humans; Insulin; Intestinal Absorption; Male; Middle Aged; Reference Values; Triglycerides