Fasting Plasma Glucose and Cardiometabolic Risk in Normoglycemic Children

In outpatient children and adolescents, higher FPG within the normal range is associated with several CMRF, independent of obesity.…

The study was done to evaluate whether fasting plasma glucose (FPG) within a normoglycemic range is associated with cardiometabolic risk factors (CMRF) among children and adolescents in an outpatient setting.  

Subjects (780; age 6-16 years) with FPG <100 mg/dL were divided into tertiles of FPG.

BMI, waist circumference, homeostasis model assessment-insulin resistance, systolic blood pressure, and white blood cell (WBC) count (P < 0.0001) increased across tertiles of FPG. Subjects with high-normal FPG (89-99 mg/dL) showed a higher risk of insulin resistance, hypertension, and high WBC count compared with subjects with low-normal FPG, independent of BMI z score.

This study demonstrates that in an outpatient setting of normoglycemic Caucasian children and adolescents, FPG is associated with several CMRF, independent of obesity. In adults, a high but normal FPG is a risk factor for development of type 2 diabetes and cardiovascular disease . Previous studies exploring the clinical significance of high-normal FPG in children have been performed in obese subjects. In a sample of 323 obese children, Grandone et al. showed that high normal FPG (87–99 mg/dL) is associated with a sevenfold higher risk of presenting IGT and IR. More recently, O’Malley et al. reported a reduction in both insulin sensitivity and b-cell function at increasing FPG in normoglycemic multiethnic obese youth, thus demonstrating that some deterioration of glucose homeostasis is already present at apparently normal FPG. Our study extends this observation by demonstrating that FPG is associated with a cluster of CMRF and demonstrates that this relation is independent of BMI. 

Actually, subjects with FPG between 89 and 99 mg/dL not only present IR but also show a 60% increased risk of hypertension and a 30% increased risk of high WBC count than those with FPG 82 mg/dL.

A positive association between FPG and BP has been previously demonstrated in children with IFG. Our study provides the novel evidence that this relation is also present at FPG within the normal range. Thus the finding of a high-normal FPG in a clinical setting could contribute to an early detection of elevated BP levels, a condition frequently underestimated in childhood.

An increased WBC count has been recently reported in children and adolescents with the metabolic syndrome. We show that this trait is detectable also in children with high-normal FPG, indicating that systemic inflammation may appear early in life and be related to subclinical abnormalities of glucose metabolism.

In conclusion, in an outpatient setting of Caucasian children and adolescents, FPG within the normal range is associated with several CMRF, independent of obesity. Subjects with high-normal FPG show a worse cardiometabolic profile than those with low-normal FPG. Although our observations need to be confirmed in the general pediatric population, the simple measurement of FPG may help in identifying children who warrant some monitoring.

Longitudinal studies will confirm whether high-normal FBG in childhood could be considered a marker of cardiovascular risk and a predictor of hard outcomes in adulthood.