These results support the concept that both hyperinsulinemia and a low-fat diet increase DNL, and that DNL contributes to hypertriglyceridemia.

Fluxes through intrahepatic glucose-producing metabolic pathways were measured in normal humans during overnight or prolonged (60 h) fasting. The glucuronate probe was used to measure the turnover and sources of hepatic UDP-glucose; mass isotopomer distribution analysis from

A total of 8 obese subjects with type 2 diabetes were studied while on a eucaloric diet and after reduced energy intake (25 and then 75% of requirements for 10 days each). Weight loss was 2, 3, and 3 kg after 5, 10, and 20 days, respectively; all of the weight lost was body fat. Fasting blood glucose (FBG) levels fell from 11.9 ± 1.4 at baseline to 8.9 ± 1.6, 7.9 ± 1.4, and 8.8 ± 1.3 mmol/l at days 5, 10, and 20, respectively (P < 0.05, baseline vs. 5, 10, and 20 days). Endogenous glucose production (EGP) was 22 ± 2, 18 ± 2, 17 ± 2, and 22 ± 2 µmol · kg -1 lean body mass (LBM) · min -1 (P < 0.05, days 5 and 10 vs. baseline). Gluconeogenesis measured by mass isotopomer distribution analysis provided 31 ± 4, 41 ± 5, 40 ± 4, and 33 ± 4%, respectively, of the EGP (NS); absolute glycogenolytic contribution to the EGP was 15 ± 2, 11 ± 2, 11 ± 2, and 15 ± 2 µmol · kg -1 LBM · min -1 , respectively (P < 0.001, baseline vs. days 5 and 10 and day 10 vs. day 20). The blood glucose clearance rate increased significantly at day 20 (P < 0.05). Neither lipolysis nor flux of plasma nonesterified fatty acids were altered compared with baseline. In conclusion, severe energy restriction per se independent of major changes in body composition reduces both FBG concentration and EGP in type 2 diabetes, the reduction in EGP results entirely from a reduction of glycogenolytic input into blood glucose, and the duration of reduced glycogenolysis is short-lived after relaxation of energy restriction even without weight gain, but effects on plasma glucose clearance persist and partially maintain the improvement in fasting glycemia. Diabetes 49:1691-1699, 2000 D ietary restriction of total energy intake has been shown to influence fasting blood glucose (FBG) and endogenous glucose production (EGP) before significant changes in body weight or composition occur (1-3). The changes in FBG and EGP are correlated, and most of the effects are seen within 7-10 days of starting caloric restriction (3,4).The glucose-producing pathways affected by energy restriction remain uncertain. Glycogenolysis and gluconeogenesis both contribute to EGP in the postabsorptive state. In nondiabetic humans and rodents, starvation or carbohydraterestricted diets reduce EGP (5,6); in rats, the change in EGP results entirely from reduced glycogenolytic flux to glucose, not reduced gluconeogenesis input. Some previous studies have suggested that predominantly gluconeogenesis is increased in type 2 diabetes, whereas other results suggest that the primary contribution to EGP is from hepatic glycogenolysis (7-9). FBG could also be reduced by energy restriction if the metabolic clearance of glucose were increased. This could be reflected in either increased oxidative or nonoxidative disposal of glucose under fasting conditions.Our laboratory has previously shown that fractional and absolute gluconeogenesis can be measured in rats and in humans by infusing [2-13 C 1 ]glycerol and [U-13 C 6 ]glucose using mass isotopomer distribution analysis (MIDA) to measure the fractional g...

At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia.