OBJECTIVE: To assess the reversibility of the defect in glycogen synthase (GS) activity in skeletal muscle from @entity28 @entity1 with @entity2175 treated with a hypocaloric diet and @entity2449 . RESEARCH DESIGN AND METHODS: Eighteen @entity28 @entity1 newly diagnosed with @entity2175 were included in a randomized placebo-controlled double-blind parallel group trial and followed for 3 months. @entity1717 including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus @entity2449 or placebo. The @entity1 were studied at basal, low, and high insulin concentrations. RESULTS: The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia (for 8 h) or by chronic reduction of @entity4854 by diet plus @entity2449 . In both treatment groups, comparable effects on glycemic control and @entity353 were found together with marked insulin suppression of nonesterified @entity1718 and increased @entity413 oxidation. Total @entity413 disposal at @entity1717 clamp increased significantly in the @entity2449 group by 25% at high insulin level (259 +/- 31 vs. 207 +/- 21 mg x m(-2) x @entity1009 ), P < 0.05). An insignificant increase by 13% was found in the placebo group. There were no significant changes in nonoxidative @entity413 metabolism. GS activity and @entity413 utilization showed no significant differences between the two treatment groups when regression coefficients, expressed as incremental changes by increments of insulin, were compared. CONCLUSIONS: Defective GS activity in @entity28 @entity2175 @entity1 is not secondary to @entity4854 . @entity2449 and diet had no significant influence on GS activity. The added effect of @entity2449 to that of a hypocaloric diet in improving insulin-stimulated @entity413 utilization is marginal when blood @entity413 reduction is obtained by @entity353 .

Irreversibility of the defect in glycogen synthase activity in skeletal muscle from @entity28 XXXX with @entity2175 treated with diet and @entity2449 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity2175 :: ('MESH:D003924', 'Disease') :: ['NIDDM'] @entity353 :: ('MESH:D015431', 'Disease') :: ['weight loss'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obese'] @entity1009 :: ('966', 'Gene') :: ['min(-1'] @entity1717 :: ('MESH:D044903', 'Disease') :: ['euglycemic-hyperinsulinemic', 'Euglycemic-hyperinsulinemic clamp'] @entity1718 :: ('MESH:D005227', 'Chemical') :: ['fatty acids'] @entity4854 :: ('MESH:D006943', 'Disease') :: ['hyperglycemia'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose'] @entity2449 :: ('MESH:D008687', 'Chemical') :: ['Metformin', 'metformin']
@entity1 :: (9606,Species) :: ['patients']
