Follistatins in glucose regulation in healthy and obese individuals.

AIMS: It has been suggested recently that follistatin (FST) and its homologous protein, follistatin-like 3 (FSTL3), may be a therapeutic target in the treatment of type 2 diabetes because of their glucose-regulatory effects in rodents. MATERIALS AND METHODS: We investigated this hypothesis in humans by studying the physiology of a possible glycaemia-follistatin feedback loop, that is, whether glucose, but not lipid intake (oral or intravenous), can regulate circulating FST and FSTL3 in healthy humans (n = 32), whether the levels of follistatins change in response to various types of bariatric operation in morbidly obese individuals, with or without type 2 diabetes (n = 41), and whether such changes are associated prospectively with improvement of glucose homeostasis/insulin sensitivity. RESULTS: In healthy individuals, circulating FST decreases after intravenous or oral glucose intake compared to controls, indicating the presence of a negative feedback mechanism. In morbid obesity, insulin resistance, glycaemia, circulating FST and FSTL3 are all reduced (by 22%-33%) after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. Importantly, the changes in circulating FST 3 months after bariatric surgery are associated prospectively with the changes in glucose, insulin, HOMA-IR and HbA1c observed 6 months postoperatively in individuals with and without type 2 diabetes. CONCLUSIONS: Our findings provide evidence of an important role of FST in glucose homeostasis in healthy individuals as well as in severely obese individuals with insulin resistance and type 2 diabetes. Our data extend recent results from animal studies to humans and support the need for further evaluation of FST inactivation strategies for targeting hyperglycaemia and insulin resistance.

Determinants of Secondary Hyperparathyroidism in Bariatric Patients after Roux-en-Y Gastric Bypass or Sleeve Gastrectomy: A Pilot Study.

Objective. Nutritional deficiencies are common after bariatric surgery. We aimed to assess the prevalence and possible predictors of secondary hyperparathyroidism (SHPT) in bariatric patients. Methods. A total of 95 patients who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were assessed after a median of 3 years after surgery. Anthropometric/demographic and weight-loss parameters were compared according to the presence of SHPT, independently for men/premenopausal women and postmenopausal women. Results. SHPT was highly prevalent (men/premenopausal women, 52.1%; postmenopausal women, 31.9%). Among men/premenopausal women, multivariate analysis indicated that SHPT was predicted by (a) 25-hydroxyvitamin D levels (Exp(B) = 0.869, P-value = 0.037), independently of age, sex, smoking; (b) calcium (Exp(B) = 0.159, P-value = 0.033) and smoking, independently of age and sex; (c) magnesium (Exp(B) = 0.026, P-value = 0.046) and smoking, independently of age and sex. Among postmenopausal women, SHPT was predicted by menopausal age independently of age, smoking, and levels of 25-hydroxyvitamin D or calcium. The development of SHPT was not associated with the type of surgery. Conclusions. RYGB and SG exhibited similar effects regarding the regulation of the hypothalamus-pituitary-parathyroid axis after surgery. Vitamin D status and menopausal age appear to determine SHPT on the long term. SHPT should be sought and vigorously treated with calcium and vitamin D supplementation.

Cross-sectional long-term micronutrient deficiencies after sleeve gastrectomy versus Roux-en-Y gastric bypass: a pilot study.

BACKGROUND: Nutritional deficiencies are highly prevalent in obese patients. Bariatric surgery has been associated with adverse effects on homeostasis of significant vitamins and micronutrients, mainly after gastric bypass. The aim of the present study was to compare the extent of long-term postsurgical nutritional deficiencies between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: This cross-sectional, pilot study included 95 patients who underwent RYGB or SG surgery with a mean follow-up of 4 years. Demographic, anthropometric, and biochemical parameters were compared according to the type of surgery. RESULTS: Both types of surgery were associated with significant nutritional deficiencies. Vitamin B12 deficiency was significantly higher in patients with RYGB compared with SG (42.1% versus 5%, P = .003). The type of surgery was associated neither with anemia nor with iron or folate deficiency (SG versus RYGB: anemia, 54.2% versus 64.3%, P = .418; folate deficiency, 20% versus 18.4%, P = .884; iron deficiency, 30% versus 36.4%, P = .635). CONCLUSION: During a mean follow up period of 4 years postRYGB or SG, patients were identified with several micronutrient deficiencies, including vitamin D, folate, and vitamin B12. SG may have a more favorable effect on the metabolism of vitamin B12 compared with RYGB, being associated with less malabsorption. Adherence to supplemental iron and vitamin intake is of primary significance in all cases of bariatric surgery.

The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: a pilot study.

AIM: The purpose of our study was to investigate the possible effect of BsmI vitamin D receptor (VDR's) polymorphism on changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women receiving different treatments. MATERIAL AND METHODS: This pilot study included 42 postmenopausal women with elevated fracture risk, randomized into 1-year treatment with weekly oral alendronate or daily subcutaneous teriparatide. Both groups received daily supplements of 1000 mg calcium and 800 IU vitamin D. Blood samples were obtained for biochemical evaluation and genotyping. BMD at the lumbar spine and femoral neck were assessed with dual energy X-ray absorptiometry. Baseline, follow-up BMD and markers of bone turnover were assessed according to the BsmI genotype. RESULTS: BMD at the lumbar spine increased in patients carrying at least one b allele, while it decreased in patients with the BB genotype (P = 0.041). Whereas no gene-treatment interaction was observed in teriparatide-receiving patients, women with the BB genotype receiving alendronate resulted in negative BMD (-0.056 ± 0.032 g/m(2) ) and T-score (-0.295 ± 0.190) gradient, compared to carriers of the b allele (BMD: +0.020 ± 0.017 g/m(2) , P = 0.054; T-score: +0.217 ± 0.100, P = 0.030). No effect of genotype was apparent with respect to gradients of biochemical bone markers. CONCLUSIONS: These preliminary results indicate that alendronate has a differential effect on BMD, depending on the VDR genotype. Carriers of the b allele may be more responsive to treatment compared to patients with the BB genotype. The interaction of VDR's BsmI polymorphism with the efficacy of the anti-osteoporotic treatment needs further investigation by larger prospective studies.