Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults

Abstract

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 http://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 http://clinicaltrials.gov

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

“…1 Compared with adults with T2D, children with T2D have more severe insulin resistance and accelerated beta cell failure, yet therapies for children are limited and less effective. 2,3 Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) was a multicenter, longitudinal study of youth-onset T2D. 4 In the primary randomized clinical trial phase of the study (N = 699), nearly half the participants reached the primary outcome of glycemic failure within 4 years.…”

“…Type 2 diabetes (T2D), once considered a disease of aging, has reached unprecedented levels among children and adolescents and disproportionately affects Black, Hispanic, and socioeconomically disadvantaged youths . Compared with adults with T2D, children with T2D have more severe insulin resistance and accelerated beta cell failure, yet therapies for children are limited and less effective . Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) was a multicenter, longitudinal study of youth-onset T2D .…”

Effect of Omega-3 Polyunsaturated Fatty Acids Combined with Dietary Intervention on Childhood Obesity and Insulin Resistance

“…Childhood obesity and its associated insulin resistance can be managed effectively through lifestyle interventions, which include a healthy diet and increased physical activity [8]. Additional adjuvant treatments like metformin treatment or omega-3 polyunsaturated FAs (PUFAs) can also promote insulin resistance [9].…”