Cellular β function in type 2 prediabetes. Growth and development during childhood and adolescence of Iris and its association with β cell function

Abstract

The risk factors for the development of prediabetes and type 2 diabetes present in childhood and adolescence -obesity, family history of type-2 diabetes, and association with other variables, such as arterial hypertension, dyslipidemia acanthosis, and polycystic ovary syndrome (PCOS)- have been widely described.. To these classical factors, recently low birth weight and intrauterine growth retardation (IUGR) have been added.

During growth and development, there are periods that are considered critical or vulnerable, in which different factors that modify normal growth patterns have a greater impact affecting future health. These periods are characterized by a high growth rate or marked changes in the composition or distribution of the different body components. The prenatal and early postnatal period are considered critical- 1000 days-,as well as the adiposity rebound at 6-7 years of age, and puberty.

Iris, the patient presented here, had all the risk factors for developing prediabetes.

Since the studies by Barker as well as studies on epigenetics, a history of low weight and mainly IUGR are considered risk factors of type 2 diabetes, obesity, and death due to cardiovascular disease, especially when this low weight is followed by a rapid recovery with a visceral distribution of the adiposity. The metabolic adaptations for survival described in the IUGR are characterized by increased peripheral glucose consumption associated with free fatty acids, β hydroxybutyrate and IGFBP1, decreased β cell mass, and low insulin secretion. When these changes persist in postnatal life, enhanced by obesity and increased visceral fat, insulin sensitivity gradually changing to insulin resistance (IR)) and leptin resistance occur, which together increase the risk of developing type-2 diabetes. In addition to IR, an increase in fasting levels of proinsulin has been demonstrated suggesting that β-cell function may be an early marker in the cascade of events that determine the risk for the development of type-2 diabetes.

The effects of obesity on the pathogenesis of glucose metabolism have been extensively studied and manifest early. A high BMI is associated with insulin resistance, the presence of inflammatory factors, a family history of diabetes, and the presence of acanthosis. In the Argentine population with obesity, at age of 11 the prevalence for impaired glucose tolerance was found 7% and type-2 diabetes in 1.7%.

Adolescence is another critical period for the development of obesity or prediabetes. Clamp studies have shown that in adolescence insulin sensitivity decreases physiologically by 20-30%. When other determining factors for IR are added, this normal physiological condition enhances the risk for comorbidities. In an adolescent population with overweight or obesity studied in Argentina, the prevalence of IR measured by HOMA was 53%. During adolescence, patients with PCOS have a high rate of variables of the metabolic syndrome and abnormalities in insulin secretion. In different series, intolerance is described in 25-31% and type-2 diabetes in 7-16%

In conclusion, since alteration of human growth patterns affect adult health, a preventive approach should be emphasized.

Risk factors for the development of prediabetes and diabetes should be taken into account to identify the population in which interventions are required. Critical or vulnerable periods in life are windows of opportunity for the implementation of preventive measures.