Effect of Ergocalciferol on ß-Cell Function in New-Onset Type 1 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial evaluates the effectiveness of ergocalciferol vs placebo in youths with newly diagnosed type 1 diabetes.

Case Report: Severe vitamin D deficiency in a girl with inflammatory myopathy and myonecrosis.

Inflammatory myopathies are a rare group of disorders that can cause significant disruption in the ability of an individual to adequately perform activities of daily living. In this case report, we present a case of a girl presenting with a substantial compromise of her ambulation with a muscle biopsy consistent with myonecrosis. She was subsequently diagnosed with an inflammatory myopathy and started on glucocorticoid and methotrexate therapy with minimal symptomatic improvement. Further in her clinical course, hypocalcemia and an undetectable 25-hydroxyvitamin D level were detected. Prompt institution of calcium and vitamin D supplementation significantly improved her myopathic condition. While there is evidence in the literature linking vitamin D deficiency with myopathy, there is a lack of data on the association between hypocalcemia and vitamin D deficiency with myonecrosis, which could represent comorbid states in myonecrosis. Therefore, vitamin D status should be established in all patients with myonecrosis, as vitamin D deficiency is easy to diagnose and treat, as exemplified in our patient's case, which shows that such treatment could lead to significant clinical improvement.

Genetic testing for maturity-onset diabetes of the young resulting in an upgraded genetic classification of an HNF1A gene variant: a case report.

The frequent misdiagnosis of MODY (Maturity-Onset Diabetes of the Young) subtypes makes it necessary to clarify the clinical spectrum of the disease phenotypes in suspected subjects so that accurate diagnosis and management plans can be introduced as early as possible in the course of the disease. We report the case of a MODY subtype that was initially characterized as variant of uncertain significance (VUS) but was later changed to a likely pathogenic variant following our report of two cases where the full expression of the clinical phenotype was described. HNF1A-MODY (Maturity Onset Diabetes of the Young type 3) is one of the most common subtypes of MODY. Due to its variable clinical presentation, and the concerns with being misdiagnosed as either type 1 or type 2 diabetes, DNA sequencing is needed to confirm the diagnosis. This case report illustrates the clinical scenario leading to the identification of the gene variant c.416T>C(p. Leu139Pro) in the HNF1A gene, initially reported as a VUS and later upgraded to a likely pathogenic variant. Though the mutation was described in two Czech family members in 2020, the clinical course and phenotype was not characterized. Therefore, there was the need to fully describe the spectrum of the disease arising from the mutation. The case report fully describes the clinical spectrum of this mutation and provides much needed clinical management approaches to the wider scientific community.

Novel duplication of the cell adhesion molecule L1-like gene in an individual with cognitive impairment, tall stature, and obesity: A case report.

The gene that codes for the close homolog of L1 (CHL1 gene) is located in the 3p26.3 cytogenetic band in the distal portion of the 3p chromosome. This gene is highly expressed in the central nervous system and plays an important role in brain formation and plasticity. Complete or partial CHL 1 gene-deficient mice have demonstrated neurocognitive deficits. In humans, mutations of the CHL 1 gene are infrequent with most mutations described in the literature as deletions. This case report describes an individual with a duplication in the CHL 1 and a presentation consistent with a syndromic form of neurocognitive impairment. To the best of our knowledge, this mutation has not been previously described in the literature.

Guidance for high-dose vitamin D supplementation for prolonging the honeymoon phase in children and adolescents with new-onset type 1 diabetes.

The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the ß-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo. The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL. If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.

Prediabetes: Adherence to Nutrition Visits Decreases HbA1c in Children and Adolescents.

Background: Prediabetes, the precursor of type 2 diabetes (T2D), is on the rise in the US, but the determinants of its progression are poorly characterized in youth. Objective: To determine the impact of nutrition visits, as a surrogate marker of lifestyle modification, on the trajectory of prediabetes over a 4-year period. Hypothesis: Adherence to nutrition visits could reduce BMI and lower HbA1c. Methods: A 4-year retrospective study of 108 youth with prediabetes who were recommended to receive medical nutrition therapy every 3 months following their diagnosis. Subjects were divided into 2 groups: the non-adherent group who had ≤1 nutrition visit/year, and the adherent group with ≥2 nutrition visits/year. Results: There were 46 male subjects, mean age 12.4 ± 3.6y; and 62 female subjects, mean age, 13.3 ± 3.0y, p=0.2. The adherent group (n=44, 41.5%) had higher BMI z-scores, but similar values for HbA1c, metformin use, and racial/ethnic composition compared to the non-adherent group. Overall, 18(17.0%) subjects progressed to T2D in 4y and consisted of 14(22.6%) of the 62 non-adherent subjects and 4(9.1%) of the 44 adherent subjects. The non-adherent subjects progressed to T2D at a mean duration of 25.8 ± 12.6 months while the adherent subjects progressed at a mean duration of 34.9 ± 11.8 months. The hazard ratio of progression from prediabetes to T2D for the non-adherent versus adherent group was 3.88 (95%CI 1.26-11.98, p=0.02). The results remained significant after adjusting for age, sex, race/ethnicity, BMI, and metformin use. Conclusion: Adherence to nutrition visits was associated with a 4-fold reduction in the likelihood to progress from prediabetes to T2D in US youth.

Partial Clinical Remission of Type 1 Diabetes: The Need for an Integrated Functional Definition Based on Insulin-Dose Adjusted A1c and Insulin Sensitivity Score.

Despite advances in the characterization of partial clinical remission (PR) of type 1 diabetes, an accurate definition of PR remains problematic. Two recent studies in children with new-onset T1D demonstrated serious limitations of the present gold standard definition of PR, a stimulated C-peptide (SCP) concentration of >300 pmol/L. The first study employed the concept of insulin sensitivity score (ISS) to show that 55% of subjects with new-onset T1D and a detectable SCP level of >300 pmol/L had low insulin sensitivity (IS) and thus might not be in remission when assessed by insulin-dose adjusted A1c (IDAA1c), an acceptable clinical marker of PR. The second study, a randomized controlled trial of vitamin D (ergocalciferol) administration in children and adolescents with new-onset T1D, demonstrated no significant difference in SCP between the ergocalciferol and placebo groups, but showed a significant blunting of the temporal trend in both A1c and IDAA1c in the ergocalciferol group. These two recent studies indicate the poor specificity and sensitivity of SCP to adequately characterize PR and thus call for a re-examination of current approaches to the definition of PR. They demonstrate the limited sensitivity of SCP, a static biochemical test, to detect the complex physiological changes that occur during PR such as changes in insulin sensitivity, insulin requirements, body weight, and physical activity. These shortcomings call for a broader definition of PR using a combination of functional markers such as IDAA1c and ISS to provide a valid assessment of PR that reaches beyond the static changes in SCP alone.

The Theory of Hyperlipidemic Memory of Type 1 Diabetes.

A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2 diabetes. Medline, EMBASE, and Ovid were searched using the following search terms: clinical remission, partial remission, partial clinical remission, honeymoon phase, C-peptide, type 1 or 2 diabetes, children, pediatric type 1 or 2 diabetes, and paediatrics type 1 or 2 diabetes, adults, adult type 1 or type 2 diabetes. Partial clinical remission (PR) of type 1 diabetes (T1D) is characterized by continued endogenous production of insulin and C-peptide following the diagnosis and the introduction of exogenous insulin therapy. PR is associated with improved glycemic control and reduced prevalence of diabetes complications. The theory of hyperglycemic memory was proposed to explain this concept of improved glycemic outcomes in remitters (those who experienced PR) versus non-remitters (those who did not experience PR). However, this theory is incomplete as it does not explain the dichotomy in early lipid phenotypes in T1D based on PR status, which is an understudied area in diabetology and lipidology. To fill this knowledge gap, we propose the Theory of Hyperlipidemic Memory of T1D. This theory is premised on our 5-year research on early post-diagnostic dichotomy in lipid phenotypes between remitters and non-remitters across the lifespan. It provides a more rigorous explanation for the differences in lifelong atherosclerotic cardiovascular disease (ASCVD) risk between remitters and non-remitters. We conducted 4 clinical studies in pediatric and adult subjects with diabetes mellitus to characterize the particulars of the hyperlipidemic memory. In the first investigation, we explored the impact of the presence or absence of PR on lipid parameters in children and adolescents with T1D. In the second, we investigated whether pubertal maturation influenced our findings in T1D; and whether these findings could be replicated in healthy, non-diabetic children and adolescents. In the third, we leveraged our findings from T1D and controls to investigate the mechanisms of early lipid changes in T2D by comparing the earliest lipid phenotype of subjects with type 2 diabetes (T2D) to those of remitters, non-remitters, and controls. In the fourth, we investigated the impact of PR on the earliest lipid phenotypes in adults with T1D and compared these early lipid data to those of T2D subjects and controls. This body of work across the lifespan in children, adolescents, and adults supports the Theory of Hyperlipidemic Memory. This new theory clarifies why PR largely determines the risks for early-phase dyslipidemia, mid-term microvascular disease risk, and long-term ASCVD risk in subjects with T1D.

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

CONTEXT: The effect 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: This work aimed to determine the effect of adjunctive ergocalciferol on residual ß-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. METHODS: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ±â€…2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ±â€…2.9 years. RESULTS: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A1c (HbA1c) (P = .09), insulin dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P = .04) and IDAA1c (P = .02) were statistically significantly blunted in the ergocalciferol group. CONCLUSION: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.

Partial Clinical Remission Reduces Lipid-Based Cardiovascular Risk in Adult Patients With Type 1 Diabetes.

Importance: Risk factors for atherosclerotic cardiovascular disease (ASCVD) are well established in type 2 diabetes (T2D), but not in type 1 diabetes (T1D). The impact of partial clinical remission (PR) on short-term ASCVD risk in T1D is unclear. Aim: To investigate the impact of PR on the earliest ASCVD risk phenotype in adult T1D using factor analysis to compare the lipid phenotypes of T1D, T2D and controls after stratifying the T1D cohort into remitters and non-remitters. Subjects and Methods: A study of 203 adults subjects consisting of 86 T2D subjects, and 77 T1D subjects stratified into remitters (n=49), and non-remitters (n=28). PR was defined as insulin-dose adjusted HbA1c of ≤9, and obesity as a BMI ≥30 kg/m2. Factor analysis was used to stratify the groups by ASCVD risk by factorizing seven lipid parameters (TC, LDL, HDL, non-HDL, TC/HDL, TG, TG/HDL) into 2 orthogonal factors (factor 1: TC*LDL; factor 2: HDL*TG) that explained 90% of the variance in the original seven parameters. Results: The analysis of individual lipid parameters showed that TC/HDL was similar between the controls and remitters (p=NS) but was significantly higher in the non-remitters compared to the remitters (p=0.026). TG/HDL was equally similar between the controls and remitters (p=NS) but was lower in the remitters compared to the non-remitters (p=0.007). TG was significantly lower in the remitters compared to T2D subjects (p<0.0001) but was similar between T2D subjects and non-remitters (p=NS). Non-HDL was significantly lower in the controls versus non-remitters (p=0.0003) but was similar between the controls and remitters (p=NS). Factor analysis showed that the means of factor 1 and factor 2 composite scores for dyslipidemia increased linearly from the controls, remitters, non-remitters to T2D, p value 0.0042 for factor 1, and <0.0001 for factor 2, with remitters having similar lipid phenotype as controls, while non-remitters were similar to T2D. Conclusions: Partial clinical remission of T1D is associated with a favorable early lipid phenotype which could translate to reduced long-term CVD risk in adults.

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 6th, 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<0.0001) 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<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.

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 ±â€…3.8 years, treated with rhGH for nonsyndromic short stature for a duration of 2 to 14 years, mean, 5.5 ±â€…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 ±â€…1.42 vs -0.69 ±â€…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 < 0.0001). IGF-I levels correlated significantly with increases in child's 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.

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 todetermine 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 ≤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.

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's 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.

Partial Clinical Remission of Type 1 Diabetes Mellitus in Children: Clinical Applications and Challenges with its Definitions.

The honeymoon phase, or partial clinical remission (PCR) phase, of Type 1 diabetes mellitus (T1DM) is a transitory period that is marked by endogenous insulin production by surviving 3 cells following a diabetes diagnosis and the introduction of insulin therapy. It is a critical window in the course of the disease that has short and long-term implications for the patient, such as a significant reduction in the risk of long-term complications of T1DM. To promote long-term cardiovascular health in children with newly diagnosed T1DM, three key steps are necessary: the generation of a predictive model for non-remission, the adoption of a user-friendly monitoring tool for remission and non-remission, and the establishment of the magnitude of the early-phase cardiovascular disease risk in these children in objective terms through changes in lipid profile. However, only about 50% of children diagnosed with T1DM experience the honeymoon phase. Accurate and prompt detection of the honeymoon phase has been hampered by the lack of an objective and easily applicable predictive model for its detection at the time of T1DM diagnosis, the complex formulas needed to confirm and monitor PCR, and the absence of a straightforward, user-friendly tool for monitoring PCR. This literature review discusses the most up-to-date information in this field by describing an objective predictive model for non-remission, an easy tool for monitoring remission or non-remission, and objective evidence for the cardiovascular protective effect of PCR in the early phase of the disease. The goal is to present non-remission as an independent clinical entity with significantly poorer long-term prognosis than partial remission.

Pubertal Lipid Levels Are Significantly Lower in Youth With Type 1 Diabetes Who Experienced Partial Clinical Remission.

IMPORTANCE: The physiologic changes in lipids during puberty in type 1 diabetes (T1D) are unclear because subjects in previous studies were not stratified by partial clinical remission status. AIM: To determine the effect of partial clinical remission on lipid changes during puberty in youth with T1D. SUBJECTS AND METHODS: A retrospective cross-sectional study of 194 subjects consisting of 71 control subjects of age 12.9 ± 1.3 years and 123 subjects with T1D stratified into remitters (n = 44; age, 13.0 ± 0.8 years) and nonremitters (n = 79; age, 11.2 ± 0.6 years). Partial clinical remission was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. RESULTS: Among the pubertal cohort, low-density lipoprotein cholesterol concentration was significantly higher in the nonremitters compared with remitters (91.1 ± 25.6 vs 77.2 ± 25.8 mg/dL, P = 0.018) and with normal-weight control subjects (91.1 ± 25.6 vs 70.4 ± 22.9 mg/dL, P = 0.009) but was similar between overweight/obese control subjects and nonremitters (89.7 ± 28.9 vs 91.1± 25.6 mg/dL, P = 0.81) and between normal-weight control subjects and remitters (70.4 ± 22.9 vs 77.2 ± 25.8 mg/dL, P = 0.39). Total cholesterol was also significantly higher in nonremitters compared with remitters (167.8 ± 30.5 vs 149.8 ± 32.1 mg/dL, P = 0.012) and with normal-weight control subjects (167.8 ± 30.5 vs 143.2 ± 30.1 mg/dL, P = 0.011) but was similar between nonremitters and overweight/obese control subjects (P = 0.098) and between remitters and normal-weight control subjects (P = 0.51). Non-high-density lipoprotein cholesterol was equally significantly higher in nonremitters compared with remitters (111.3 ± 30.1 vs 95.9 ± 29.1 mg/dL, P = 0.028) and normal-weight control subjects (111.3 ± 30.1 vs 86.2 ± 32.2 mg/dL, P = 0.028) but was similar between nonremitters and overweight/obese control subjects (P = 0.48) and between remitters vs normal-weight control subjects (P = 0.39). CONCLUSIONS: Puberty-related reductions in low-density lipoprotein, total cholesterol, and non-high-density lipoprotein occur in remitters and normal-weight control subjects but not in nonremitters and overweight/obese control subjects.

Tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children.

IMPORTANCE: The role of tobacco-smoke exposure on serum vitamin D concentration in US pediatric population is not known. We hypothesized that tobacco smoke exposure would increase the prevalence of vitamin D deficiency in US children. METHODS: Representative national data were accessed from the National Health and Nutrition Examination Survey (NHANES) 2009-2010 databank on 2,263 subjects of ages 3 to 17 years. Subjects were categorized into two groups based on their age: children, if <10 years; and youth if 10 to 17 years. Descriptive and multiple logistic regression analyses were conducted to determine the effect of serum cotinine-verified tobacco smoke exposure on vitamin D status after controlling for key sociodemographic confounders. Vitamin D deficiency was defined as 25(OH)D <20 ng/mL, insufficiency as 25(OH)D of 20-29.9 ng/mL, and sufficiency as 25(OH)D of ≥30 ng/mL. Tobacco smoke exposure status was defined by serum cotinine concentration as follows: unexposed and non-smoking (<0.05 ng/mL) and exposed (passive and active smokers combined) (≥0.05ng/mL). Specifically, passive and active smoking were defined as cotinine of 0.05-10 ng/mL, and ≥10ng/mL respectively. RESULTS: The prevalence of second-hand smoke exposure was 42.0% (95%CI, 36.7%-47.5%); while the prevalence of active smoking among teenagers was 9.0% (95%CI, 6.2%-12.5%). Vitamin D deficiency occurred at a frequency of 15.1% in children unexposed to tobacco smoke, 20.9% in children exposed to passive tobacco smoke, and 18.0% among actively smoking youth (p<0.001). Tobacco smoke exposure independently predicted vitamin D deficiency after controlling for age, sex, race, BMI, maternal education, and family socio-economic status (OR:1.50; 95%CI, 1.14-1.85, p = 0.002). CONCLUSIONS: This analysis of a nationwide database reports that tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children.

Children with type 1 diabetes who experienced a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis.

IMPORTANCE: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized. AIM: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status. SUBJECTS AND METHODS: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 ± 2.9 years, [male 11.7 ± 2.9 years, (n = 55); female 12.0 ± 2.9 years, (n = 68), p = 0.60] with type 1 diabetes of 4-5 years duration. Anthropometric and biochemical data were collected at the 4th or 5th year after diagnosis in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4-5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin-dose adjusted hemoglobin A1c (IDAA1c) of ≤9. RESULTS: There were 44 (35.8%) remitters (age 13.0 ± 2.5y; male 52.3%). Both the total cholesterol and LDL-cholesterol were significantly lower in remitters compared to non-remitters: LDL-C: 78.8 ± 28.7 mg/dL vs. 91.6 ± 26.5 mg/dL, p = 0.023; and total cholesterol: 151.5 ± 32.6 mg/dL vs. 167.0 ± 29.6 mg/dL, p = 0.015. Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, body mass index z score, thyroid function, celiac disease occurrence, or vitamin D status. A greater number of remitters were in puberty compared to non-remitters (86.4% vs. 60.8%, p = 0.006). LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p = 0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p = 0.018) after adjusting for age and duration of diabetes. CONCLUSIONS: Children with type 1 diabetes who underwent a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complication in type 1 diabetes between remitters and non-remitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing non-remission as a non-modifiable risk factor for vascular complication in type 1 diabetes.

Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of <0.3 units/kg/day to the gold standard insulin-dose adjusted hemoglobin A1c of ≤9 for the detection of partial clinical remission.

BACKGROUND: It is unclear whether the gold standard test for the detection of partial clinical remission (PCR) in new-onset type 1 diabetes (T1D), the insulin-dose adjusted Hemoglobin A1c (IDAA1c) of ≤9, is superior to a new tool, total daily dose of insulin (TDD) of <0.3 units/kg/day. The aim of the study was to test the superiority of IDAA1c over TDD of <0.3 units/kg/day for the detection of PCR. METHODS: A retrospective analysis of 204 subjects of ages 2-14 years, mean age 7.9±3.2 years, (male 7.8±3.4 years, [n=98]; female 7.9±3.0 years, [n=106], p=0.816) with new-onset T1D. Anthropometric and biochemical data were collected for the first 36 months of disease. PCR was defined by both IDAA1c≤9 and TDD<0.3 units/kg/day. RESULTS: There were 86 (42.2%) (age 9.1±3.0 years; male 57%) remitters by IDAA1c≤9 criterion, and 82 (40.2%) remitters (age 7.3±2.8 years) by TDD of <0.3 units/kg/day criterion (p=0.655). The duration of PCR was 10.0±6.1 months using TDD<0.3 units/kg/day, and 9.2±5.5 months using IDAA1c (p=0.379). Subjects in PCR as denoted by TDD<0.3 units/kg/day had 1.44 times increased probability of entering PCR than those denoted by IDAA1c of ≤9, after adjusting for BMI, bicarbonate, and HbA1c:(OR=1.44, 95% CI [1.03-2.00], p=0.033). Peak prevalence for PCR was at 6-12 months by either definition; more subjects were in PCR at 6 months by IDAA1c ≤9: 62/86 (72.1%) than by TDD<0.3 units/kg/day: 43/82 (52.4%), (p=0.011). CONCLUSIONS: There were no significant differences in the number of remitters, duration of PCR, or the time of peak remission defined by IDAA1c of ≤9 or TDD of <0.3 units/kg/day.