We conducted a 12‐week trial involving 28 overweight male and female adults (BMI >25) consuming 2 or more servings/day sugar‐sweetened beverages (SSB). Participants were randomized to a 12‐week intervention replacing SSB with artificially sweetened beverages (ASB, 8M, 7F) or to a control arm without intervention (C, 6M, 7F). Intrahepatocellular lipid concentration (IHCL, 1H‐magnetic resonance spectroscopy), visceral adipose tissue volume (VAT, magnetic resonance imaging) and fasting concentrations of selected metabolic parameters were measured before and after intervention.Consumption of SSB was similar in both groups at inclusion. IHCL was reduced to 74 ±10.7% of initial values in the ASB (p<0.01) but did not change in C. ASB however did not significantly change body weight (‐1.4±1.6 vs +0.8±0.6 kg in C), VAT (‐98.4 ±78.4 vs ‐11.8 ±73.4 cc in C) or fasting glucose, insulin, uric acid, ASAT, ALAT, TG, cholesterol or HDL‐cholesterol concentrations.15 participants (8 in the ASB group, 7 in the C group) had hepatic steatosis as defined by IHCL > 60 mmol/L. They had significantly higher body weight, VAT, TG, uric acid, ASAT, ALAT, and lower HDL‐cholesterol than 13 participants without hepatic steatosis. In this subgroup, ASB was associated with significant (p<0.05) decreases in IHCL (‐43.0±12.6%), ALAT (‐19.7±7.8%) and ASAT (‐9.9±4.0 %).These results indicate that, in high SSB consumers 1) body weight and visceral fat volume are major determinants of hepatic steatosis, 2) replacing SSB with ASB reduces intrahepatic fat, most likely due to decreased total energy intake.This work was supported by the Swiss National Science Foundation and the Raymond Berger Foundation.

We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels.

BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4 h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen–glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g · kg fat free mass−1 · h−1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7±1.9 Μmol · kg fat free mass−1 · min−1 basal vs 15.9±0.9 after fructose), in obese non-diabetic subjects (12.1±0.5 basal vs 13.1±0.5 after fructose) and in lean healthy subjects (13.3±0.5 basal vs 13.8±0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232±9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p<0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors).

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55 % carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50 % of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 ± 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 ± 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.