Glucose Alterations, Insulin Resistance, Arterial Hypertension, and Renin are Strictly Associated in Pediatric Obesity

Abstract

Context: Insulin resistance, glucose alterations, arterial hypertension (HTN), and the renin-angiotensin-aldosterone system (RAAS) are related in adult obesity. This crosstalk is still unexplored in childhood.

Objective: Characterize the relationships of fasting and postload glucose and insulin levels with new American Academy of Pediatrics classification of HTN and RAAS in pediatric obesity.

Methods: This was a retrospective observational study; 799 pediatric outpatients (11.4 ± 3.1 years) at a tertiary center who were overweight or obese and not yet on diet were included. The main outcome measures were mean and correlations among parameters of a complete clinical and metabolic screening (body mass index, blood pressure, and glucose and insulin levels during an oral glucose tolerance test, and renin and aldosterone levels and their ratio).

Results: 774 subjects had all the parameters, of whom 87.6% had HTN (5% elevated blood pressure, 29.2% stage I HTN, and 53.4% stage II HTN). Eighty subjects had 1 or more glucose alterations, and more frequently presented HTN. Blood pressure levels were higher in subjects with glucose alterations than in those with normal glucose levels. Fasting and stimulated glucose and insulin levels were directly related to the HTN stages, and insulin sensitivity was lower in HTN than in normal blood pressure. Aldosterone, renin, and aldosterone-renin ratio (ARR) were similar in sexes, whereas aldosterone was higher in prepubertal individuals. Subjects with impaired glucose tolerance (IGT) had higher renin and lower ARR. Renin was positively correlated with postload glucose, and ARR was negatively correlated with the Homeostatic Model Assessment for Insulin Resistance index.

Conclusion: A close relationship exists among insulin resistance, glucose alterations, HTN, and renin in childhood obesity. Specific categories of risk could provide indicators for strict clinical surveillance.

Keywords: aldosterone; glucose tolerance; hypertension; insulin resistance; obesity; renin.

Figure 1.

Flow chart of the study. Created with BioRender.com.

Figure 2.

Glucose and insulin levels during OGTT in different blood pressure stages. BP, blood pressure; HTN, hypertension. (A, B) Subjects with normal BP vs the other 3 categories together (elevated BP, HTN stages I and II). (C, D) Post hoc comparisons between groups, in which significant differences were observed between patients in HTN stage I and HTN stage II and patients with normal BP. Lines representing elevated BP are not represented in the figures to make them clearer, since patients with elevated BP did not reach significance. *Significant at multivariate analysis in A and B (glucose: fasting P < .01, 90 minutes P < .05, 120 minutes P < .01; insulin: fasting P < .04). (C, D) At multivariate analysis, + means significant in normal BP vs HTN stage I (glucose: fasting P < .02, 60 minutes P < .05, 90 minutes P < .02, 120 minutes P < .02; insulin: 60 minutes P < .05, 120 minutes P < .03); #normal BP vs HTN stage II (glucose: fasting P < .03, 60 minutes P < .05, 90 minutes P < .04, 120 minutes P < .03; insulin: 120 minutes P < .03); πHTN stage I vs HTN stage II (glucose: fasting P < .01, 60 minutes P < .05, 90 minutes P < .02, 120 minutes P < .02; insulin: fasting P < .03, 60 minutes P < .05, 120 minutes P < .03).