ContextInsulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.ObjectiveTo compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.HypothesisAdjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.Design, Setting, and ParticipantsA 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90–120 mg/dL (5.0–6.7 mmol/L). Pubertal maturation was determined by Tanner stage.ResultsOver the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.ConclusionsThis 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.Trial RegistrationClinicalTrial.gov NCT01334125

Background The impact of the anti-inflammatory and immunomodulatory actions of Vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. Objective To determine the effect of adjunctive ergocalciferol on residual β-cell function (RBCF) and PR in youth with newly-diagnosed T1D who were maintained on a standardized insulin treatment protocol. Hypothesis Ergocalciferol supplementation increases RBCF and prolongs PR. Methods A 12-month randomized, double-blind, placebo-controlled trial of 50,000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, versus placebo in 36 subjects of ages 10-21years(y), with T1D of <3 months, and a stimulated C-peptide (SCP) level of ≥0.2nmol/L (≥0.6ng/mL). The ergocalciferol group had 18 randomized subjects (10m/ 8f), mean age 13.3±2.8y; while the control group had 18 subjects (14m/4f), age 14.3±2.9y. Results The ergocalciferol treatment group had significantly higher serum 25-hydroxyvitamin D at 6 months (p=0.01) and 9 months (p=0.02) than the placebo group. At 12 months, the ergocalciferol group had a significantly lower serum TNF-α concentration (p=0.03). There were no significant differences between the groups at each timepoint from baseline to 12 months for SCP concentration (p=0.08), HbA1c (p=0.09), insulin-dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (p=0.044) and IDAA1c (p=0.015) were significantly blunted in the ergocalciferol group. Conclusions Ergocalciferol significantly reduced serum TNF-α concentration and the rates of increase in both A1c and IDAA1c suggesting a protection of RBCF and PR in youth with newly-diagnosed T1D.

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Histories of ear disease, otoscopic examinations, and audiologic, intelligence, and achievement tests were obtained from a cohort of 489 Alaskan Eskimo children who have been followed through the first ten years of life. Seventy-six per cent had experienced one or more episodes of otitis media since birth. Of these, 78% had their first attack during their first two years of life. Perforations and scars were present in 41%. A hearing loss of 26 decibels or greater was present in 16%, and an additional 25% were in the normal range but had a measurable air-bone gap. Children with a history of otitis media prior to 2 years of age and a hearing loss of 26 decibels or greater had a statistically significant loss of verbal ability and were behind in total reading, total math, and language. In addition, children who had an early onset of otitis media but now had normal hearing with a conductive component were also adversely affected in verbal areas. The number of otitis media episodes was related to tympanic membrane abnormalities, hearing loss, and low verbal and achievement scores. These findings indicate that otitis media has been a significant cause of morbidity in Alaskan Eskimo children, and its onset during the critical years of language development as well as the number of episodes play an important role in impairing verbal development.