RISE Coordinating Center, Rockville, Maryland.
Pediatr Diabetes. 2019 Nov;20(7):849-860. doi: 10.1111/pedi.12883. Epub 2019 Jul 29.
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.
We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m , 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/m , 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.
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).
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.
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.
肥胖和青春期胰岛素抵抗会使青少年的心血管（CV）危险因素恶化。目前尚不清楚肥胖和胰岛素抵抗与 CV 风险的关系与成年人相比如何。
我们评估了 66 名青春期青少年（平均年龄±标准差：14.2±2.0 岁，体重指数 [BMI]36.6±6.0kg/m2，糖化血红蛋白 [HbA1c]38.5±6.1mmol/mol）和 355 名具有相似 BMI（年龄 52.7±9.4 岁，BMI35.1±5.1kg/m2，HbA1c39.8±4.2mmol/mol）的成年人，他们参加了一项多中心研究。使用高血糖钳夹术量化胰岛素敏感性。对 CV 危险因素的评估在各站点进行了标准化。回归分析比较了青少年和成年人胰岛素敏感性和 CV 危险因素的影响。
肥胖的青春期青少年比肥胖程度相当的成年人更胰岛素抵抗（P<.001），但胰岛素敏感性与肥胖之间的负相关斜率相似。肥胖对 CV 危险因素的影响可通过胰岛素敏感性来解释（调整敏感性后 P=NS）。在调整肥胖因素后，两组之间胰岛素敏感性与舒张压、总胆固醇和低密度脂蛋白（LDL）胆固醇之间的关系没有差异。然而，虽然成年人的收缩压（SBP）和高密度脂蛋白（HDL）胆固醇与胰岛素敏感性呈预期的直接和负相关，但在整个胰岛素敏感性范围内，青少年的这些斜率都是平坦的（组间差异 P≤.05）。
两组中肥胖对 CV 危险因素的影响归因于胰岛素敏感性。肥胖青少年和成年人群体中，胰岛素敏感性与 CV 危险因素之间的关系相似，除了 SBP 和 HDL 胆固醇。
