European Foundation for the Study of Diabetes.

No abstract

Aims: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. Subjects and methods: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). Results: Mean weight reduction was À5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0-to 6-month weight loss (b ¼ À0.222, P-value ¼ 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (b ¼ 0.505, P-valueo0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (b ¼ À0.131, P-valueo0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin ( þ 3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles ( þ 0.2% (95% confidence interval À1.1 to 1.4)); P-valueo0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P ¼ 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. Conclusion: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.

CaSR and AP2S1 sequencing is worthwhile in patients with familial hyperparathyroidism and phenotype suggesting FHH as it can diagnose up to 50% of cases. GNA11 mutations seem much rarer. Learning disabilities in these patients, associated with higher serum calcium and magnesium levels may suggest the presence of AP2S1 rather than CaSR mutation and may guide the first step in the genetic evaluation.