Background: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance.

Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. This study describes the natural history of classic galactosemia based on the hitherto largest data set.

OBJECTIVE—To compare the metabolic effects of fructose in healthy male and female subjects.

The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with ¹³C₆ fructose. Incorporation of ¹³C into breath CO₂, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After ¹³C fructose ingestion, 44·0 (sd 3·2) % of labelled carbons were recovered in plasma glucose in males v. 41·9 (sd 2·3) % in females (NS), and 42·9 (sd 3·7) % of labelled carbons were recovered in breath CO₂ in males v. 43·0 (sd 4·5) % in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for ¹³C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P < 0·05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16·4 (sd 5·2), P < 0·05), but it was not suppressed in females ( − 1·3 (sd 4·7) %). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation.