Overweight/obesity in adolescents with type 1 diabetes belonging to an admixed population. A Brazilian multicenter study

This study had a cross-sectional design and was conducted in 10 Brazilian cities, from all geographic regions of the country, with patients followed in 14 public clinics between 2011/2014.

All patients received free health care (NPH and regular insulins, syringes, needles, glucometers and strips for blood glucose monitoring) from the Brazilian National Health Care System (BNHCS) Each clinic provided data for at least 50 T1D outpatients that were treated by an endocrinologist in secondary or tertiary care settings. Included patients were those with the diagnosis of T1D done by a physician, the need for continuous insulin use since the diagnosis, at least 13 years of age, and followed at each diabetes center for at least 6 months. Pregnant or lactating women, patients who had an acute infection or ketoacidosis in the three preceding months or had a history of renal transplantation were excluded [14].

The total sample was composed of 1760 patients. They were diagnosed as having T1D between 1960 and 2014. 367 patients (20.9%) were adolescents, according to the World Health Organization criteria [15] (10 to 19 years old) and formed the sample of this study. Each center had a local ethics committee that approved the study. Patients and/or their parents where necessary, signed a written informed consent agreeing with the participation in the study.

The collected data were: current age, age at diagnosis, self-reported color-race (White, Black, Brown (“parda”), Asian (“amarela”) and Indigenous (“indígena”)) [16], diabetes duration, years of school attendance, frequency of self-monitoring of blood glucose (SMBG), smoking status, type of prescribed insulin therapeutic regimens (ITR), self-reported adherence to diet (following at least 80% of the time the prescribed diet) [17] and to prescribed ITRs [14], BMI and self-reported frequency of physical activity (at least three times a week). Family history of diabetes, obesity, hypertension and coronary diseases in first degree relatives were also assessed. The coexistence of another health care insurance, besides that offered by the BNHCS was also assessed.

Adequate glycemic control was defined as the presence of HbA1c levels < 7.5% (58 mmol/mol) [18], and inadequate glycemic control was defined as HbA1c levels  ≥ 7.5% (58 mmol/mol). HbA1c was measured using high-performance liquid chromatography HPLC (Bio-Rad Laboratories, Hercules, California, USA). The last value of HbA1c in the previous year was obtained from the medical records. Fasting triglycerides, HDL cholesterol, total cholesterol and laboratorial markers of NAFLD such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase, were measured using enzymatic techniques and serum uric acid by an uricase-based commercial (mg/dl). Creatinine was measured using a colorimetric assay kit, corrected for standardized creatinine assay by mass spectrometry. All the above measurements were performed with BioSystem (model A25; Barcelona, Spain). Friedewald’s equation was used to calculate LDL cholesterol values [19]. ITRs were stratified as follows: exclusive use of intermediate insulin (NPH) or regular insulin, long-acting insulin analogs plus short acting insulin or the use of continuous subcutaneous insulin infusion (CSII). Normal weight was defined as a BMI of percentile ≥ 3 and ≤ 85, underweight as a BMI of percentile < 3, overweight as a BMI of > 85th percentile, and obesity as a BMI of > 97th percentile according to age and gender [20] and current smoking as the use of more than one cigarette per day. Elevated blood pressure and hypertension for adolescents were defined according to age, sex and height. Elevated blood pressure was considered as blood pressure values ≥ 90th percentile to < 95th percentile or 120/80 mm Hg to < 95th percentile for children aged 10 to < 13 years, and 120/ < 80 to 129/ < 80 mm Hg for those ≥ 13 years old [21]. Hypertension was defined as systolic blood pressure and/or diastolic blood pressure ≥ 95^th percentile or 130/80 to 139/89 mm Hg for children aged 10 to < 13 years and ≥ 130/80 for those with ≥ 13 years old [18, 21]. Undesirable levels of LDL-Cholesterol were considered as ≥ 100 mg/dl [18].

The definition of MS was done according to the International Diabetes Federation criteria [31]. Adolescents aged 10 to < 16 years old were classified according to the following criteria: (1) abdominal obesity: waist circumference (WC) ≥ 90th percentile for age and gender; (2) triglycerides ≥ 150 mg/dL (1.7 mmol/L); (3) HDL-c < 40 mg/dL (1.03 mmol/L); (4) elevated BP ≥ 130 × 85 mmHg [22]. As there are no reference values of percentiles on abdominal waist in the Brazilian population, we used the same criterion (≥ 90th percentile) for each age and gender group of our sample. Considering that all participants had T1D, central obesity plus an additional factor was necessary for diagnosing MS [32]. Adolescents aged 16 years or older were classified according to the same criteria adopted for adults as follows: central obesity: WC ≥ 90 cm for South American men or ≥ 80 cm in South American women; triglycerides ≥ 150 mg/dL (1.7 mmol/L) or on drug therapy for elevated triglycerides; HDL < 40 mg/dL (1.03 mmol/L) in men or < 50 mg/dL (1.29 mmol/L) in women or on drug therapy for low HDL; elevated BP ≥ 130 × 85 mmHg or using antihypertensive drugs.

For statistical analysis purpose, normal weight and underweight were grouped together as well as overweight and obesity [33]. An exploratory analysis was initially performed, and the data were presented as mean (± SD) or median, interquartile range [IQR] for continuous variables and percentage for discrete variables. Parametric and non-parametric tests were used for comparison between the groups as indicated. Pearson’s correlation coefficient was calculated when applicable.

Overall, 251 patients (68.4%) had normal weight, 21 (5.7%) were underweight and 95 (25.9%) presented overweight/obesity, with 79 patients (21.5%) presenting overweight and 16 (4.4%) obesity (Fig. 1). The sociodemographic data of the studied population are listed in Table 1.

Clinical, demographic and laboratory data stratified according to the presence of overweight/obesity are described in Table 2. Overall, patients with overweight/obesity were female, older, had longer diabetes duration, had more frequently acanthosis nigricans, were attended at a tertiary care level center and used lower insulin doses (U/kg/day) but higher total daily insulin dose (U/day) than those patients without overweight/obesity. No difference was noted concerning the level of HbA1c in the year of the evaluation as well in the previous year. A strong correlation was noted between the last values of HbA1c in the previous year with HbA1c values measured during the study (r = 0.74, p < 0.001). A weak correlation between HbA1c values measured during the study with the levels of total cholesterol (r = 0.244, p < 0.001), triglycerides (r = 0.265, p < 0.001), ALT (r = 0.143, p = 0.007) and AST (r = 0.113, p < 0.035) was noted. No correlation was found with LDL-C and HDL-C values.

The presence of hypertension, family history of hypertension in first degree relatives and MS were higher in patients with overweight/obesityin comparison to patients without this condition. These patients also had higher levels of total and LDL-cholesterol, high frequency of undesirable levels of LDL-Cholesterol, lower level of GFR and were more frequently under the use of metformin, statins and anti-hypertensive drugs. No difference was observed in the levels of ALT, AST, GGT, uric acid, HDL-cholesterol and triglycerides. A similar prevalence of retinopathy and CKD was observed in patients with and without overweight/obesity. Data described in Table 2

Multivariate analysis performed with the presence of overweight/obesity as a dependent variable, showed that all the independent variables which entered in the model, could explain 20.7% (Nagelkerke R-squared) of a given patient having overweight/obesity. 73.8% of the patients were correctly classified by the model. The presence of overweight/obesity was associated with female gender, age, sBP, and showed a tendency to be associated with geographic region of the country and with the use of anti-hypertensive drugs. Data described in Table 3.