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

Posted on: Wednesday, 16 March 2005, 03:00 CST

Abbreviations: HOMA, homeostasis model assessment; HOMA-IR, HOMA of insulin resistance; SBP, systolic blood pressure.

A table elsewhere in this issue shows conventional and Systme International (SI) units and conversion factors for many substances.

2005 by the American Diabetes Association.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Metabolic syndrome increases risk for cardiovascular disease (1,2). The diagnosis of metabolic syndromc in patients might hold promise for enhanced prevention of cardiovascular disease. Currently, there is no consensus on the diagnosis of metabolic syndrome in children and adolescents, with variable prevalence of metabolic syndrome from 4.2 to 32% in several populations (3-5). The highest rates of metabolic syndrome were lound in adolescents with Latino or African backgrounds (3,6). However, this racial/ethnic predisposition to metabolic syndrome is not well defined. The Brazilian population has a high degree of miscegenation that includes a mix of indigenous people, Afro- and Euro-Brazilians, and a widespread Latin ancestry. We do not know if this genetic and environmental diversity can modify the prevalence of metabolic syndrome or its relationship to obesity. In this study, we determine the prevalence of metabolic syndrome in a group of Brazilian adolescents with a 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 So 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/ m^sup 2^, 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: G^sub 0^ (normal), G^sub 1^ (overweight), and G^sub 2^ (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 gl) 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/m^sup 2^ 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 [U/ml]) (fasting plasma glucose [mmol . 1^sup -1^ . dl^sup -1^)/22.5 (1.1). Values are expressed as means SD, and when not normally distributed, they were ln transformed for analysis (version 1.0, Sigma-Stat; 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 (R^sup 2^ = 0.275, P < 0.005) and 2-h serum insulin (R^sup 2^ = 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 (R^sup 2^ = 0.172, P < 0.05) and 2-h serum insulin (R^sup 2^ = 0.212, P < 0.005).

Table 1-Characteristics of normal BMI (G^sub 0^), overweight (G^sub 1^), and obese (G^sub 2^) groups

The overall prevalence of metabolic syndrome was 6% (95% CI 5.9- 6.1). In G^sub 0^ and G^sub 1^, none of the subjects had metabolic syndrome, while in G^sub 2^ 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 G^sub 0^, 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 G^sub 1^, 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 G^sub 2^, 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 (G^sub 2^), 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 ol 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.

References

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14. Jiang X, Srinivasan SR, Bao W: Association of fasting insulin with blood pressure in young individuals: the Bogalusa Heart Study. Arch Intern Med 153:323-328,1993

15. Oliveira RG, Lamounier JA, Oliveira ADB, Castro MDR, Oliveira JS: Arterial hypertension in children and adolescents: the Belo Horizonte City Study. J Pediatr (Rio J) 75:256-266, 1999

REGINA C.Q. DA SILVA, MD, MSC

WALKIRIA L. MIRANDA, MSC

ANTONIO R. CHACRA, MD, PHD

SERGIO A. DIB, MD, PHD

From the Diabetes Center, Sa Paulo Federal University, So Paulo, SP, Brazil.

Address correspondence and reprint requests to Srgio Atala Dib, MD, PhD, Escola Paulista de Medicina, Disciplina de Endocrinologia, Rua Botucatu 740 CEP:04034-970, So Paulo, SP, Brasil. E-mail: sadib@endocrino.epm.br.

Received for publication 3 December 2004 and accepted 6 December 2004.

Copyright American Diabetes Association Mar 2005

Source: Diabetes Care

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