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Background: Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. Subjects and Methods: We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2, hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2, HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. Results: Obese pubertal youth were more insulin resistant than comparably obese adults (P < .001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low‐density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high‐density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤ .05 for group differences). Conclusions: Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. Clinical Trial Registration: The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Background/Objective: The extent of influence of BMI and age on C‐peptide at the diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body mass index Z‐scores (BMIZ) and age on C‐peptide measures at and soon after the diagnosis of T1D. Methods: Data from Diabetes Prevention Trial‐Type 1 (DPT‐1) participants <18.0 years at diagnosis was analyzed. Analyses examined associations of C‐peptide measures with BMIZ and age in 2 cohorts: oral glucose tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was utilized. Results: Fasting and area under the curve (AUC) C‐peptide from OGTTs (n = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age were included as independent variables in regression models (P < .001 for all). BMIZ and age explained 31%‐47% of the variance of C‐peptide measures. In an example, 2 individuals with identical AUC C‐peptide values had an approximate 5‐fold difference in values after adjustments for BMIZ and age. The association between fasting glucose and C‐peptide decreased markedly when fasting C‐peptide values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). Conclusions: C‐peptide measures are strongly and independently related to BMIZ and age at and soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial changes in C‐peptide values, and impact the association between glycemia and C‐peptide. Such adjustments can improve assessments of β‐cell impairment at diagnosis. [ABSTRACT FROM AUTHOR]