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Objective: To assess the efficacy and safety of DPP-4 inhibition with sitagliptin in youth with type 2 diabetes (T2D). Study Design: This was a 54-week, double-blind, randomized, controlled clinical trial evaluating the safety and efficacy of DPP-4 inhibition with sitagliptin 100 mg once daily as initial oral therapy in youth with T2D. The 190 participants, aged 10--17 years, had HbA1c 6.5%--10% (7.0%--10% if on insulin). All were negative for pancreatic autoantibodies and overweight/obese at screening or diagnosis. The trial was placebo controlled for the first 20 weeks, after which metformin replaced placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 20. Results: Treatment groups were well balanced at baseline (mean ± SD HbA1c = 7.5% ± 1.0, BMI percentile = 97.1% ± 6.8, age = 14.0 years ± 2.0 [57.4% <15], 60.5% female). At Week 20, least squares mean changes from baseline in HbA1c were -0.01% (sitagliptin) and 0.18% (placebo); between-group difference (95% CI) = -0.19% (-0.68, 0.30), p = 0.448. At Week 54, the changes in HbA1c were 0.45% (sitagliptin) and -0.11 (placebo/metformin). There were no notable between-group differences in the adverse event profiles through Week 54. Conclusions: DPP-4 inhibition with sitagliptin did not provide significant improvement in glycemic control. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01485614; EudraCT: 2011-002528-42) [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin. Study Design: Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and inadequate glycemic control on metformin ± insulin. Participants (N = 220 randomized and treated) had HbA1c 6.5%--10% (7.0%--10% if on insulin), were overweight/obese at screening or diagnosis and negative for pancreatic autoantibodies. The primary endpoint was change from baseline in HbA1c at Week 20. Results: Treatment groups were well balanced at baseline (mean HbA1c = 8.0%, BMI = 30.9 kg/m², age = 14.4 years [44.5% <15], 65.9% female). The dose of background metformin was >1500 mg/day for 71.8% of participants; 15.0% of participants were on insulin therapy. At Week 20, LS mean changes from baseline (95% CI) in HbA1c for sitagliptin/metformin and placebo/metformin were -0.58% (-0.94, -0.22) and -0.09% (-0.43, 0.26), respectively; difference = -0.49% (-0.90, -0.09), p = 0.018; at Week 54 the LS mean (95% CI) changes were 0.35% (-0.48, 1.19) and 0.73% (-0.08, 1.54), respectively. No meaningful differences between the adverse event profiles of the treatment groups emerged through Week 54. Conclusions: These results do not suggest that addition of sitagliptin to metformin provides durable improvement in glycemic control in youth with T2D. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01472367, NCT01760447; EudraCT: 2011-002529-23/2014-003583-20, 2012-004035-23). [ABSTRACT FROM AUTHOR]

Background: Obesity and type 2 diabetes (T2D) is risk factors for non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). In children with T2D and liver biopsies, we investigated correlations between NAFLD/NASH and transaminase activity, A1c, lipids, and histologic changes in repeat biopsies. Methods: Liver histology of children with T2D was evaluated using the NASH CRN scoring system and NAFLD Activity Score (NAS). We included results ≤6 months from biopsy and A1c nearest biopsy. Results: Thirty‐eight subjects (21 females, 17 males, 63.2% Hispanic, 15.8% Caucasian) had T2D diagnosed at 13.4 ± 2.7 years, 78.9% using metformin and 50% on insulin. Histological diagnosis of NAFLD occurred at mean age 14.3 ± 2.3 years, notable for NASH in 61%. Steatosis grade was higher in children with NASH than those without (mean 2.6 ± 0.7 vs 2.1 ± 0.5 (P < 0.001). Stage 3 fibrosis was noted only in subjects with NASH (26%). ALT was higher in NASH vs those without (112 ± 56 vs 85 ± 112, P = 0.016). NAS correlated with A1c (r = 0.51, P < 0.01) and triglycerides (r = 0.5, P < 0.01), and inversely with high‐density lipoprotein (HDL) (r = −0.42, P = 0.04). Males had lower HDL and higher triglycerides (P < 0.04). In eight subjects with repeat biopsies, NAS was equal (37.5%) or improved (62.5%), and steatosis decreased (68.1% to 32.8%, P = 0.027). Conclusions: In children with T2D and NAFLD, NASH is common. Having advanced fibrosis in 26% of NASH cases at this age is concerning. Better control of lipids, weight, and diabetes may help avoid worsening in NAS. [ABSTRACT FROM AUTHOR]

Background Vitamin D deficiency ( VDD) adversely affects bone health. US data on prevalence of VDD or vitamin D insufficiency ( VDI) at diagnosis of type 1 diabetes ( T1D) is lacking. Low serum 25-hydroxyvitamin D ( 25OHD) is speculated to increase the risk of developing T1D. Objectives Assess the prevalence of pediatric VDD and VDI at diagnosis of T1D, and investigate correlations with demographic and clinical parameters. Methods We performed a retrospective Institutional Review Board ( IRB)-approved chart review of all T1D cases diagnosed from January 2011 to August 2012, all having the same 25OHD assay performed at Quest Diagnostics. Definitions for VDD, VDI, and vitamin D sufficiency ( VDS) were 25OHD levels (ng/mL) ≤ 20, 21-29, and ≥ 30, respectively. We termed 25OHD <30 ng/mL as Low-D. Results We identified 185 autoantibody positive T1D subjects (51% female) with 25OHD measured, 51% Caucasian, 25% Hispanic, 4% mixed-Hispanic, 4% African American, and 16% other/mixed race. Mean age 9.8 yr (0.9-18.6). Most had Low-D (58%), 40% VDI, 18% VDD, and 42% VDS. No gender or age differences among the 25OHD groups. Low-D was more common (p < 0.0001) in Hispanics (81%) vs Caucasians (44%), but VDD rates were similar. Low-D subjects were heavier than VDS (p = 0.018). All four with elevated celiac titers were VDS. Diabetic ketoacidosis was present in 33%, but more common (44%) in Low-D vs. VDS (18%) (p < 0.0001), and trended higher in VDD (61%) vs. VDI (36%). Seventy-seven percentage with DKA had Low-D. Conclusion VDD and insufficiency are common, even in Caucasians, at onset of T1D in pediatrics, worse in those with DKA. [ABSTRACT FROM AUTHOR]