Metabolic Syndrome and Insulin Resistance in Normal Glucose Tolerant Brazilian Adolescents With Family History of Type 2 Diabetes

RESEARCH DESIGN AND METHODS

Inclusion criteria were age between 10 and 19 years, good health, and family history of type 2 diabetes. The São Paulo Federal University Ethics Committee reviewed and approved the study. Informed consent and assent were obtained from all participants or relatives. BMI cut points for overweight and obesity by sex and age in children were defined as 25 and 30 kg/m², respectively, at age 18 years. These criteria were chosen because of the inclusion of Brazilian children and adolescents in the original study (7). The adolescents were stratified into three groups: G₀ (normal), G₁ (overweight), and G₂ (obese) according to the above criteria. Blood pressure was measured on the right arm using a mercury-gravity manometer with proper cuff size. Children whose systolic blood pressure (SBP) or diastolic blood pressure exceeded the 95th percentile for age and sex (8) were considered to have hypertension (high blood pressure). After a 12-h overnight fast, baseline samples were obtained for measurements of plasma glucose, lipids (total, HDL, and LDL cholesterol and triglycerides), and serum insulin. Thereafter, an oral glucose load (1.75 g/kg body wt [up to a maximum of 75 g]) was given, and after 2 h, plasma glucose and serum insulin were measured. Glucose tolerance was classified according to American Diabetes Association criteria (9). Metabolic syndrome was devised as a child-specific definition, by the presence of at least three of the following factors: BMI 97th percentile for age/sex, high blood pressure and hypertriglyceridemia (≥130 mg/dl) (10), low HDL cholesterol (≤35 mg/dl) (10), insulin resistance (defined as homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR] >2.5), impaired glucose tolerance, impaired fasting glucose, or type 2 diabetes (4). Our study was based on a child-specific definition, although we used the cutoff for obesity as the equivalent to a BMI of 30 kg/m² at age 18 years (7). HOMA, β-cell function, and insulin sensitivity were calculated by the HOMA Model Program (University of Oxford, Oxford, U.K.). HOMA-IR was calculated as (fasting serum insulin [μU/ml]) × (fasting plasma glucose [mmol · l⁻¹ · dl⁻¹])/22.5 (11). Values are expressed as means ± SD, and when not normally distributed, they were ln transformed for analysis (version 1.0, SigmaStat; Systat Software). P values <0.05 were considered statistically significant.

RESULTS

Characteristics of adolescents are presented in Table 1. There was no significant difference in birth weight, age, sex, height, Tanner stage, and physical activity among the three groups. HOMA-IR, in the whole group (n = 99), was found to be correlated with BMI (r = 0.46, P < 0.001), visceral obesity (waist) (r = 0.52, P < 0.001), SBP (r = 0.29, P < 0.005), triglycerides (r = 0.35, P < 0.005), 2-h plasma glucose (r = 0.28, P < 0.05), and 2-h serum insulin (r = 0.47, P < 0.001) on an oral glucose tolerance test. The 2-h plasma glucose, also in the whole group, was correlated with total cholesterol (r = 0.25, P < 0.05), LDL cholesterol (r = 0.25, P < 0.05), and 2-h serum insulin (r = 0.41, P < 0.005). Forward stepwise regression analysis was conducted to examine the effect of the following variables on HOMA-IR in the whole group: BMI, waist, triglycerides, SBP, 2-h plasma glucose, and 2-h serum insulin. The variables that remained significant were waist (R² = 0.275, P < 0.005) and 2-h serum insulin (R² = 0.365, P < 0.005). The same was conducted to 2-h plasma glucose (variables: total cholesterol, LDL cholesterol, and 2-h serum insulin). Variables selected in the mode were LDL cholesterol (R² = 0.172, P < 0.05) and 2-h serum insulin (R² = 0.212, P < 0.005).

The overall prevalence of metabolic syndrome was 6% (95% CI 5.9–6.1). In G₀ and G₁, none of the subjects had metabolic syndrome, while in G₂ the prevalence was 26.1% (8.2–45.6). In the whole group, the characteristics of metabolic syndrome included obesity (23.4%), HOMA-IR ≥2.5 (22.2%), high blood pressure (18.2%), hypertriglyceridemia (8.1%), and low HDL cholesterol (8.1%). In G₀, the highest prevalence was high blood pressure (13%), followed by insulin resistance (10.9%), high triglycerides (6.5%), and low HDL cholesterol (4.3%). In G₁, the more prevalent characteristic was insulin resistance (23%), followed by high blood pressure (10%), high triglycerides (6.7%) and low HDL cholesterol (6.7%). In G₂, where all of the individuals were obese, the prevalence was insulin resistance (43.5%), high blood pressure (39.1%), low HDL cholesterol (17.4%), and high triglycerides (13%).

CONCLUSIONS

We present data on metabolic syndrome in the adolescent population not well described previously, with most of the present literature focusing on the U.S. or Europe. The prevalence of metabolic syndrome was 6% in the whole group, and 24.2% of these adolescents had at least one feature of metabolic syndrome. In the obese adolescents (G₂), the prevalence of metabolic syndrome was 26.1%. Similar metabolic syndrome prevalence has been shown in diverse populations (3–5,12), despite limitations of comparison. Insulin resistance and obesity have been identified as main features of metabolic syndrome in our normal glucose tolerant adolescents. The regression analysis has shown that visceral obesity (waist) and 2-h serum insulin were the main factors for HOMA-IR and LDL cholesterol and 2-h serum insulin for 2-h plasma glucose. HOMA-IR was also correlated with triglycerides, similar to what was found in the Bogalusa Heart Study from a biracial community (13). This last study showed that blood pressure has a positive correlation with fasting insulin (even after adjustment for BMI) at as early as 5 years of age (14). The prevalence of high blood pressure in our adolescents was higher compared with other studies (15).

In summary, we show that the prevalence of metabolic syndrome in a group of normal glucose tolerant Brazilian adolescents with family history of type 2 diabetes is similar to several studies conducted in the U.S. and Europe, although there are differences in the metabolic syndrome characteristics among all groups.