Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Early presentation of familial paraganglioma with SDHB mutation in a 13 year old child and its mother.

Paragangliomas are extradadrenal neuroendocrine tumors, recently associated with gene mutations in the succinate dehydrogenase complex (SDH). These mutations are thought to be responsible for the familial paraganglioma syndrome. Average age of tumor diagnosis for SDH mutation carriers is about 30 years of age, but patients younger than 10 years have been reported. We present the case of a 13 year-old boy with abdominal paraganglioma, whose mother also had a history of thoracic paraganglioma diagnosed at 14 years of age. Both were found to carry a mutation in exon 4 of the SDHB gene, heterozygous for c.418G>T, p.Val140Phe sequence. Compared to the other SDH subtypes, SDHB associated tumors have been found to be much more aggressive. This has led to current recommendations that tumor screening of asymptomatic SDHB carriers should start as early as 10 years of age. An even earlier initiation seems warranted for the identified carriers in this family.

Effect of gluten-free diet on growth and glycemic control in children with type 1 diabetes and asymptomatic celiac disease.

We aimed to evaluate the effects of a gluten-free diet on growth and glycemic control in children with type 1 diabetes mellitus (DM) and asymptomatic, biopsy-proven celiac disease (CD). Each case of CD was compared to two children with DM and no CD. We studied weight, height, and hemoglobin A1c (HgbAlc) up to 12 months pre- and post- CD diagnosis in 29 cases and 58 controls. The change in body mass index (deltaBMI Z-score) over 2 years was significantly higher in CD cases vs. controls (mean +/- SD 0.33 +/- 0.74 vs. +/- 0.08 +/- 0.46; p = 0.023). However, BMI Z-score did not change in CD patients diagnosed with DM for > 1 year. Mean HgbA1c was similar between groups throughout the study. In conclusion, children with asymptomatic CD and DM do not have significant changes in BMI, height Z-score or metabolic control 1 year post-diagnosis.

Laparoscopic excision of a familial paraganglioma.

Pheochromocytomas are rare neuroendocrine tumors that secrete catecholamines and usually arise from the adrenal medulla. Catecholamine-producing tumors that arise from extra-adrenal chromaffin tissue are referred to as paragangliomas, or extra-adrenal pheochromocytomas. Contrary to the traditional "Rule of Tens," as many as 25% of pheochromocytomas occur in hereditary tumor syndromes, such as multiple endocrine neoplasia-2, von Hippel-Lindau disease, neurofibromatosis-1, or hereditary or familial paraganglioma syndrome. Surgical resection remains the only curative therapy for pheochromocytomas, and advances in minimally invasive techniques have shown laparoscopic adrenalectomy to be safe and effective. Paragangliomas are extremely rare tumors, especially in children, and the role of laparoscopy in their treatment is evolving. This case report and the accompanying video demonstrate that the laparoscopic approach to retroperitoneal paraganglioma resection provides excellent exposure of the tumor and surrounding structures. Given proper patient preparation and perioperative monitoring, laparoscopic exploration and resection of paragangliomas can be safely and successfully accomplished in children. In addition, genetic analysis should be considered for all patients presenting with these tumors.