Thalidomide impairs insulin action on glucose uptake and glycogen synthesis in patients with type 2 diabetes.
OBJECTIVE
To investigate the effect of thalidomide on glucose turnover (glucose production and uptake), on intracellular pathways of glucose utilization (glycogen synthesis [GS], glycolysis [GLS], carbohydrate oxidation, and nonoxidative GLS), and on free fatty acid (FFA) turnover (lipolysis, FFA oxidation, and FFA reesterification).


METHODS
A total of 6 patients with type 2 diabetes were studied with 4-h isoglycemic-hyperinsulinemic clamps (approximately 8 mmol/l and 500-600 pmol/l, respectively) before treatment (Prestudy), after 3 weeks of thalidomide (150 mg orally at bedtime), and after 3 weeks of placebo.


RESULTS
Thalidomide reduced insulin-stimulated glucose uptake by 31% (from 27.7 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 21% (from 24.2 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with placebo. Thalidomide also reduced insulin-stimulated GS by 48% (from 14.1 to 8.2 micromol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 40% (from 13.6 to 8.2 micromol x kg(-1) x min(-1), P < 0.5) compared with placebo. Thalidomide had no effect on rates of GLS, carbohydrate oxidation, nonoxidative GLS, lipolysis, FFA oxidation, and reesterification.


CONCLUSIONS
We conclude that thalidomide increased insulin resistance in obese patients with type 2 diabetes by inhibiting insulin-stimulated GS and that patients taking thalidomide should be monitored for possible deterioration in their glucose tolerance.
Division of Endocrinology, Diabetes, and Metabolism and the General Clinical Research Center, Temple University Hospital, Philadelphia, Pennsylvania 19140, USA.
N
N
Iqbal
M
M
Zayed
G
G
Boden
D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011865:Radioisotope Dilution Technique; D016037:Single-Blind Method; D013792:Thalidomide / Q000494:pharmacology*; D014316:Tritium
D001786:Blood Glucose; D007328:Insulin; D010919:Placebos; D014316:Tritium; D013792:Thalidomide; D006003:Glycogen; D005947:Glucose