EPIDEMIOLOGY

The prevalence of obesity and type 2 diabetes mellitus (T2DM) has increased considerably in recent decades. Recent data (Nhanes, 2001) suggest that 35% of the American adult population is overweight (BMI ≥ 25 kg/m ² ). In childhood and adolescence, obesity and overweight are defined as BMI values ​​above the 95th and 85th percentiles, respectively, for age and sex, according to the World Health Organization tables (WHO, 1998).

The incidence of overweight has tripled among American children in the last three decades, and 15% of the population between six and 19 years of age falls into this category(2).

The incidence of T2DM in childhood and adolescence has increased significantly in the last decade, especially in racial minorities. Until 1990, less than 5% of cases of diabetes diagnosed in the population under 20 years of age were T2DM. Currently, these values ​​affect 20% of obese Americans in this age group(3,7). Similar to adults, the pathology is underdiagnosed because it is asymptomatic. Furthermore, adolescents do not seek medical care, especially males, which falsely increases the number of cases diagnosed in females (op. cit.).

The average age at diagnosis of DM2 usually varies from ten to 18 years, coinciding with puberty (op. cit.).

Currently, the DM2 epidemic does not affect only ethnic minorities, with global reports of an increase in incidence and prevalence(4). In 2010, there will be 221 million individuals with DM2 in the world population, an increase of 46% in prevalence relative to the year 2000(5). In Brazil, 2.7% of DM2 carriers are under 40 years old(6).

The risk of micro and macrovascular complications in these patients is extremely high due to the early age of diagnosis, leading to a huge economic impact in the long term, with a great burden on the health system, society and the individual.

RISK FACTORS

The main risk factor is excess weight: the average BMI demonstrated ranges from 26 to 40 kg/m2 ^, and obesity in these patients is typically of a central pattern, reinforcing the importance of metabolic syndrome in the etiopathogenesis. Other components of the syndrome are usually present, such as systemic arterial hypertension in 17% to 32% and hypertriglyceridemia in 4% to 32% (op. cit).

A positive family history of DM2 is strongly associated with its development in this age group, especially on the maternal side, since the diabetogenic intrauterine environment(7) favors the loss of the first phase of insulin secretion, involved in the pathophysiology. It is usually present in 74% to 100% of the cases studied(3).

Acanthosis nigricansconsists of skin hyperpigmentation with thickening of the flexural regions of the neck, armpits and inguinal region, with a velvety appearance, characterized by papillomatosis and hyperkeratosis(16), and is present in 60% to 95% of cases (op. cit.). It is found in approximately 20% of the black and Latin American population, and does not always mean alteration of glucose metabolism (op. cit.).

Female sex is a risk factor, regardless of ethnicity, with a ratio of 1/1.7 of males to females. However, this difference can be attributed to the higher proportion of undiagnosed cases among boys, who seek medical care less than girls.

Ethnic minorities such as the Latino, black and indigenous populations in the United States and Canada have a higher prevalence of DM2, although the increase in recent decades has been global, and, for the individual, ethnicity is not a useful predictive parameter (op. cit.).

A diet high in fat and low in fiber, in addition to a sedentary lifestyle, in any age group and population, is associated with a higher prevalence of DM2.

Lack of breastfeeding is an important risk factor for obesity in childhood and adolescence(9) and, indirectly, for DM2.

Low birth weight and macrosomia increase the risk for DM2, dyslipidemia and systemic arterial hypertension (SAH) in adolescents and adults(10,11).

INSULIN RESISTANCE (IR)

Metabolic syndrome, or insulin resistance syndrome, implicated in the pathophysiology of DM2, comprises at least three of the following criteria:

• HAS;
• low HDL cholesterol;
• high triglycerides;
• hyperglycemia;
• abdominal obesity;
• hyperuricemia;
• hyperinsulinemia.

This syndrome already affects 22% of the adult population worldwide, including 7% of young people between 20 and 29 years of age. In the medium term, its impact on mortality from premature coronary disease will be greater than that of smoking (op. cit.). The pathophysiology of IR is explained by a reduction in insulin action in peripheral tissues, resulting in a compensatory increase in insulin secretion (hyperinsulinemia).

IR occurs in adolescence due to the peak of growth hormone (GH) and other counter-regulatory hormones. Females have a higher IR for any Tanner stage compared to males. Insulin sensitivity is 30% lower in Tanner stage III compared to children and adults, with full recovery in stage V(10).

The deterioration of glucose tolerance and the development of DM2 reflect IR combined with relative insulinopenia. IR is documented as fasting hyperinsulinemia or hyper-insulin response to the oral glucose tolerance test (OGTT), even in normoglycemic individuals, who maintain an increase in insulin secretion during IR(7). There is no standardization in the literature regarding ideal insulin values.

The transient decrease in insulin sensitivity that occurs at puberty is not related to changes in body fat, as this increases continuously before and after puberty (op. cit.).

Both IR and pancreatic beta cell capacity can be programmed in utero : fetal malnutrition and maternal diabetes contribute equally to the higher incidence of IR in childhood and adolescence, increasing the risk of DM2 in this population. This hypothesis is known in the literature as the thrifty phenotype (op. cit.).

Early diagnosis of IR is of crucial importance, since these changes can be present up to ten years before the diagnosis of DM2.

SCREENING

The American Diabetes Association (ADA) recommends screening for T2DM in children ≥ 10 years of age who are overweight or obese and have at least two risk factors, including(13):

1) family history of T2DM in first- or second-degree relatives;

2) ethnic minorities (Latin American, Native American, African American);

3) conditions associated with IR, such as acanthosis nigricans , hypertension, dyslipidemia, and polycystic ovary syndrome (PCOS).

The test to be used is fasting blood glucose. However, most multicenter studies related to the diagnosis of T2DM or oral glucose intolerance in children and adolescents have used OGTT(4). Diabetes mellitusIt is defined by fasting blood glucose ≥ 126 mg/dL or > 200 mg/dL two hours after administration of 75 g of glucose (OGTT). Oral glucose intolerance is defined by blood glucose ≥ 140 mg/dL and < 200 mg/dL after the same period of time.

In some cases, it is initially difficult to classify diabetes as type 1 or 2. With the increase in the prevalence of obesity, the number of obese type 1 diabetics is already high, and it is not uncommon for patients with DM2 to have diabetic ketoacidosis at diagnosis, requiring insulin as initial therapy. In these cases, laboratory testing of pancreatic autoantibodies, C-peptide and fasting insulin levels help in classification(8).

TREATMENT

Treatment of DM2 in adolescents is similar to that in adults, and should begin with a calorie-restricted diet and increase physical activity, aiming to improve energy balance and weight loss. In adults, weight loss of 10% to 15% brings great benefits to metabolic control (op. cit.).

Regarding oral antidiabetic agents, metformin is the drug of choice, being effective and safe in this age group (12). Doses range from 1,000 to 2,550 mg/day, divided into meals. The use of metformin can lead to the normalization of anovulatory cycles in girls with PCOS, increasing the risk of unplanned pregnancy. For this reason, counseling regarding prevention of conception should be part of the therapeutic regimen for these patients (ADA, 2002). The main side effects are gastrointestinal, generally self-limiting in two to three weeks.

The therapeutic objective in relation to glycemic control is to maintain glycosylated hemoglobin below the upper limit of the method, fasting blood glucose between 90 and 110 mg/dl and postprandial blood glucose below 140 mg/dl(13).

When monotherapy fails in three to six months, several alternatives are possible, such as the addition of sulfonylureas or meglitinides (op. cit.). There is no approval for the use of glitazones in children or adolescents. The use of insulin in DM2 should be restricted to symptomatic patients, with extremely high blood glucose levels or contraindications to the use of oral agents.

Control of comorbidities such as hypertension and dyslipidemia is also essential.

The primary objective of diabetes treatment is to reduce acute and chronic, micro and macrovascular complications.

PREVENTION

Type 2 diabetes can be prevented or its onset delayed in high-risk individuals through lifestyle changes, such as reducing sedentary lifestyle and saturated fat intake. The adoption of physical activity for 150 minutes per week for less than three years led to a 58% reduction in the incidence of DM2(14). This probably occurs due to a reduction in insulinemia and an increase in insulin sensitivity, which has also been demonstrated in adolescents (op. cit.).

The use of metformin has also proven useful in high-risk populations for the prevention of DM2, reducing its incidence by 31% (op. cit.), with direct effects on insulinemia and glycemia, based on clinical studies already successfully conducted in younger age groups(15).

The first step in the prophylaxis of metabolic syndrome should be the prevention of childhood obesity.

CONCLUSION

With the increasing prevalence of obesity in our population, DM2 in childhood and adolescence has become an increasingly frequent pathology. The presence of acanthosis nigricans, a positive family history, and other risk factors associated with insulin resistance should alert the health care professional dealing with the adolescent to the need for screening and to alert the patient and their family to its prevention.