Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients.

AIMS/HYPOTHESIS: 6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups. METHODS: One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients. RESULTS: 6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%. CONCLUSIONS/INTERPRETATION: This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.

The effect of galactose supplementation on endurance cycling performance.

OBJECTIVES: This study tested the hypothesis that supplementation with galactose before and during endurance exercise would spare carbohydrate (CHO), optimize fat utilization and improve performance compared with a typical sports drink formulation. SUBJECTS: Nine well-trained cyclists undertook three trials, each consisting of 120 min at 65 VO(2max) followed immediately by a set work, self-paced time trial (TT). Three treatments, allocated as a randomized balanced design, consisted of the following: (a) 8% (w/w) solution of galactose (Gal); (b) 8% solution of 50% galactose/50% glucose (Gluc/Gal); and (c) 8% solution of 80% glucose/20% fructose (Gluc/Fru). These were consumed as 0.67 g CHO per kg body wt 45-min pre-exercise; 1.0 g CHO per kg body wt per h for the first 120 min of exercise; 0.33 g CHO per kg body wt during the TT. Blood samples were collected before and during exercise; respiratory gas samples were collected only during fixed workload exercise. RESULTS: Mean TT power output was significantly less in Gal compared with Gluc/Gal (P=0.030). Blood glucose and insulin concentrations were lower, and free fatty acids higher in Gal compared with Gluc/Gal and Gluc/Fru. Respiratory exchange ratio was not significantly different between trials. CONCLUSIONS: Ingestion of an 8% galactose-only solution (12.5 ml per kg body wt per h) is detrimental to endurance performance compared with equivalent volumes of iso-osmotic solutions containing 50% galactose/50% glucose or 80% glucose/20% fructose. This may reflect the inability of the liver to convert galactose into glucose at a rate required to support strenuous exercise intensity.