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 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.
Feillet
C
C
Department of Metabolic Diseases, Lapeyronie Hospital, Montpellier, France.
Monnier
L H
LH
Barjon
J N
JN
Perrin
M
M
Descomps
B
B
Crastes de Paulet
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002648:Child; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D001786:Blood Glucose; D002096:C-Peptide; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides; C001521:lathosterol