Ergocalciferol in New-onset Type 1 diabetes: A Randomized Controlled Trial

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 ofmonths, 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

Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes

Background: Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study\u27s aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 +/- 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 +/- 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 +/- 1.1% vs 8.3 +/- 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 +/- 1.1% vs. 8.7 +/- 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 +/- 0.98% vs. 0.38 +/- 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 +/- 1.4 vs -0.22 +/- 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users

COVID-19 Pandemic and Pediatric Type 1 Diabetes: No Significant Change in Glycemic Control During The Pandemic Lockdown of 2020

Importance: There is no consensus on the impact of the 2020 COVID-19 pandemic lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) in the US. Aim: To determine the impact of the pandemic lockdown of March 15th through July 6(th), 2020 on glycemic control after controlling for confounders. Subjects and Methods: An observational study of 110 subjects of mean age 14.8 +/- 4.9 years(y), [male 15.4 +/- 4.0y, (n=57); female 14.1 +/- 3.8y, (n=53), p=0.07] with T1D of 6.31 +/- 4.3y (95% CI 1.0-19.7y). Data were collected at 1-4 months before the lockdown and 1-4 months following the lifting of the lockdown at their first post-lockdown clinic visit. Results: There was no significant change in A1c between the pre- and post-pandemic lockdown periods, 0.18 +/- 1.2%, (95% CI -0.05 to 0.41), p=0.13. There were equally no significant differences in A1c between the male and female subjects, -0.16 +/- 1.2 vs -0.19 +/- 1.2%, p=0.8; insulin pump users and non-pump users, -0.25 +/- 1.0 vs -0.12 +/- 1.4%, p=0.5; and pubertal vs prepubertal subjects, 0.18 +/- 1.3 vs -0.11 +/- 0.3%, p=0.6. The significant predictors of decrease in A1c were pre-lockdown A1c (p \u3c .0001) and the use of CGM (p=0.019). The CGM users had significant reductions in point-of-care A1c (0.4 +/- 0.6%, p=0.0012), the CGM-estimated A1c (p=0.0076), mean glucose concentration (p=0.022), a significant increase in sensor usage (p=0.012), with no change in total daily dose of insulin (TDDI). The non-CGM users had significantly increased TDDI (p \u3c 0.0001) but no change in HbA1c, 0.06 +/- 1.8%, p=0.86. Conclusions: There was no change in glycemic control during the pandemic lockdown of 2020 in US children

Mechanisms and early patterns of dyslipidemia in pediatric type 1 and type 2 diabetes

Objectives: The is no consensus on the early patterns of lipid-based cardiovascular disease (CVD) risk in youth with either type 1 diabetes (T1D) or type 2 diabetes (T2D). The aim was to determine the differences in CVD risk, using lipid profiles, in children and adolescents with either T1D or T2D at the time of their first lipid assessment, after stratifying the T1D cohort into remitters and non-remitters based on their honeymoon history. Methods: A cross-sectional study of 249 subjects consisting of 73 controls, 53 T2D subjects, and 123 T1D subjects stratified into remitters (n=44), and non-remitters (n=79). Partial clinical remission (PCR) was defined as insulin-dose adjusted HbA1c of \u3c /=9. Pubertal status was determined by Tanner staging. Results: After adjusting for age, sex, BMI, race, and pubertal status, T2D patients had significantly higher LDL-C compared to the controls (p=0.022), the remitters (p=0.029), but not the non-remitters (103.1 +/- 5.9 mg/dL vs. 91.4 +/- 4.2 mg/dL, p=0.49). Similarly, T2D patients had significantly higher non-HDL-C compared to the controls (p=0.006), the remitters (p=0.0002), but not the non-remitters (137.6 +/- 7.1 mg/dL vs. 111.71 +/- 5.0 mg/dL, p=0.053). Total cholesterol was also significantly higher in T2D patients compared to the controls (p=0.0005), the remitters (p=0.006) but not the non-remitters (183.5 +/- 6.6 mg/dL vs. 166.2 +/- 4.8 mg/dL, p=0.27). Conclusions: Lack of the honeymoon phase in children and adolescents with T1D confers early and significantly increased lipid-based cardiovascular risk to these patients that is similar to the elevated cardiovascular risk seen in T2D

Long-term GH Therapy Does Not Advance Skeletal Maturation in Children and Adolescents

Context: There is no consensus on the effect of recombinant human GH (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age-predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods: A retrospective longitudinal study of 71 subjects aged 2 to 16 years, mean 9.9 +/- 3.8 years, treated with rhGH for nonsyndromic short stature for a duration of 2 to 14 years, mean, 5.5 +/- 2.6 years. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 +/- 1.42 vs -0.69 +/- 1.63, P = 0.09). Piecewise regression, however, showed a quantifiable catch-up phenomenon in BA of 1.5 months per year of rhGH therapy in the first 6.5 years (P = 0.017) that plateaued thereafter (P = 0.88). BAPAH overestimated near-adult height in younger subjects but became more accurate in older subjects (P \u3c 0.0001). IGF-I levels correlated significantly with increases in child\u27s height and BA-CA. Conclusion: Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5 years that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and support strategic, but not the insurance company mandated reflexive annual monitoring of skeletal maturation with bone age in children receiving rhGH therapy