ObjectiveObesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens.Research Design and MethodsFasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio.ResultsBranched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R2 = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R2 = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males.ConclusionsBCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.
Context
The effects of the COVID-19 pandemic on the incident cases of pediatric Type 1 (T1D) and Type 2 diabetes (T2D) are not clear.
Objective
To identify trends in incidence and presentation of pediatric new-onset T1D and T2D during the COVID-19 pandemic.
Methods
A retrospective chart review was conducted. Demographics, anthropometrics, and initial labs from patients ages 0-21 who presented with new-onset diabetes to a pediatric tertiary care center were recorded.
Results
During the pandemic incident cases of pediatric T1D increased from 31 in each of the prior two years to 46; an increase of 48%. Incident cases of pediatric T2D increased by 231% from 2019 to 2020. The number of incident cases of pediatric T2D increased significantly more than the number of incident cases of pediatric T1D (p-value = 0.009). Patients with T2D were more likely to present in DKA, though this was not statistically significant (p-value=0.093). Severe DKA was higher compared to moderate DKA (p-value = 0.036) in incident cases of pediatric T2D. During the pandemic, for the first time, incident cases of T2D accounted for more than half of the all newly diagnosed pediatric diabetes cases (53%).
Conclusions
There were more incident pediatric T1D and T2D cases as well as an increase in DKA severity in T2D at presentation during the COVID-19 pandemic. More importantly, incident T2D cases were higher than the incident T1D during the pandemic. This clearly suggests a disruption and change in the pediatric diabetes trends with profound individual and community health consequences.
Results: Weight reduction was associated with reductions in BCAA, glutamate, and C3/C5 (p = .002) and increases in urea cycle AA (p = .029), suggesting an increase in BCAA catabolism. Increases in urea cycle AA during weight reduction were associated with increases in adiponectin, a marker of insulin sensitivity. Markers of insulin resistance (high BCAA, glutamate, and C3/C5 and low urea cycle AA
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