Insulin resistance and its role in the pathogenesis of pre-diabetes development in obese adolescents

Background. The prevalence of childhood obesity has increased significantly over the past three decades worldwide, and in this regard, the frequency of diseases associated with obesity, including disorders of carbohydrate metabolism, has increased. The involvement of insulin resistance and insulin deficiency in the development of prediabetes in obesity has been established. However, the significance of each pathological mechanism in the development of prediabetes in childhood and adolescence has not been established. In this regard, in children's practice, there is no reliable data on methods of prevention and treatment of prediabetes in obesity.

Aim. To study the role of insulin resistance in the development of prediabetes in obese adolescents.

Materials and methods. The study involved 95 adolescents with obesity. Inclusion criteria: SDS BMI≥2.0, Tanner stage ≥II, age <18.0 years, exclusion criteria: diabetes mellitus. The sample was divided into prediabetics (n=40, mean age 14.0±1.53 years; SDS BMI 3.09±0.54, boys n=23) and non-prediabetics (n=55, mean age 14.6±1.67 years; SDS BMI 3.11±0.54; boys n=32). Both groups were matched on age, SDS BMI, sex (p=0.082, p=0.975, p=0.947, respectively). The research consisted of estimates of BMI, insulin, C-peptide, fasting venous blood glucose, HbA1c, cholesterol, low-density lipoprotein, high Density Lipoprotein, triglycerides, alanine aminotransferase, aspartat aminotransferase, HOMA-IR and TyG indices, results of oral glucose tolerance test at 0 and 2 hours after glucose load, ultrasound of the hepatobiliary system. Prediabetes in adolescents was diagnosed using American Diabetes Association criteria. Data was analyzed by using SPSS Statistics for Windows, Version 26.0.

Results. Prediabetes was diagnosed in 42.1% (40/95) of cases. There were statistically significant differences between the indices of groups with prediabetes and normal glucose metabolism: fasting plasma glucose – FPG (mean 5.63±0.49; 95% confidence interval – CI 5.48–5.79 vs 5.03±0.42; 4.92–5.15 mmol/L; p<0.001); 2hPG (mean 7.04±0.93; 95% CI 6.74–7.34 vs 6.23±0.82; 6.01–6.46 mmol/l; p<0.001); HbA_1c (mean 5.5±0.31; 95% CI 5.39–5.59% vs 5.2±0.25; 5.15–5.29%; p<0.001); cholesterol (4.47±0.73; 95% CI 4.23–4.72 vs 3.96±0.92; 3.73–4.24 mmol/l; p=0.004), low-density lipoprotein (2.89±0.96, 95% CI 2.55–3.20 vs 2.46±0.89, 2.21–2.71 mmol/l; p=0.036). There were no significant differences in fasting insulin, C-peptide, triglycerides, high density lipoprotein, aspartat aminotransferase, alanine aminotransferase, HOMA-IR index and TyG, were also no significant differences in the frequency of hepatic steatosis (47.5% vs 52.7%; p=0.532).

Conclusion. Teenagers with obesity, with prediabetes, and without disorders of carbohydrate metabolism had a similar level of peripheral tissue sensitivity to the action of insulin. There are additional factors leading to the formation of prediabetes with obesity in the child population that have to be learned in future researches.