RESUMO
BACKGROUND: It is important to determine the influence of traditional risk factors on the development of type 2 diabetes mellitus (T2DM) in young adults. Goal of the research: To study the incidence of T2DM and factors that increase the risk of its occurrence during the observation of a cohort of young adults. MATERIALS AND METHODS: 1341 people aged 25-44 were included in the study from 2013 to 2017, of whom 622 were men (46.4%). The examination included anamnesis, anthropometric data, and a blood test. Cases of developed T2DM were identified by comparing the Diabetes Mellitus Register, medical records of patients, and the database of examined individuals from 2019 to 2023. T2DM Results: In the examined population, 11 participants (0.82%) developed T2DM. The prevalence of T2DM was 0.96% in men and 0.69% in women. Patients with T2DM had a higher waist circumference, BMI, SBP, TG, and lower HDL than patients without T2DM, and were also less likely to have a higher education. The risk of developing T2DM increases 6.5 times at a BMI of ≥30 kg/m2, and 5.2 times at a TG level of ≥1.7 mmol/L, regardless of other risk factors. In the absence of a higher education, the risk of developing T2DM is increased by 5.6 times. CONCLUSION: In young people, high triglyceride levels, obesity, and a low level of education are associated with the risk of developing type 2 diabetes, regardless of other factors.
RESUMO
The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45-69 years old) was examined at baseline in 2003-2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006-2008 and 2015-2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m2; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM.
RESUMO
Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-ß-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 -1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A.
RESUMO
The APPL1 gene encodes a protein mediating the cross-talk between adiponectin and insulin signaling. Recently, it was found that APPL1 mutations can cause maturity onset diabetes of the young, type 14. Here, an analysis of APPL1 was performed in patients with a maturity-onset diabetes of the young (MODY) phenotype, and prevalence of these mutations was estimated in a Russian population, among type 2 diabetes mellitus (T2DM) and MODY patients. Whole-exome sequencing or targeted sequencing was performed on 151 probands with a MODY phenotype, with subsequent association analysis of one of identified variants, rs11544593, in a white population of Western Siberia (276 control subjects and 169 T2DM patients). Thirteen variants were found in APPL1, three of which (rs79282761, rs138485817, and rs11544593) are located in exons. There were no statistically significant differences in the frequencies of rs11544593 alleles and genotypes between T2DM patients and the general population. In the MODY group, AG rs11544593 genotype carriers were significantly more frequent (AG vs. AA + GG: odds ratio 1.83, confidence interval 1.15-2.90, p = 0.011) compared with the control group. An association of rs11544593 with blood glucose concentration was revealed in the MODY group. The genotyping data suggest that rs11544593 may contribute to carbohydrate metabolism disturbances.
RESUMO
Maturity-onset diabetes of the young (MODY) is a heterogeneous group of diseases associated with gene mutations leading to dysfunction of pancreatic ß-cells. Thirteen identified MODY variants differ from each other by the clinical course and treatment requirement. Currently, MODY subtypes 1-5 are best-studied, descriptions of the other forms are sporadic. This article reports a MODY12 clinical case, caused by a mutation in the gene of the ATP-binding cassette transporter sub-family C member 8 (ABCC8), encoding sulfonylurea receptor 1. Diabetes manifested in a 27-year-old non-obese man with epilepsy in anamnesis. No evidence of ketosis was present, pancreatic antibodies were undetectable, and C-peptide remained within the reference range. During the initial investigation, non-proliferative diabetic retinopathy and elevated albumin excretion rate was revealed. After 4 months, diabetes was complicated by pre-proliferative retinopathy and diabetic macular edema. Recurrent hypoglycemia and an increase in body weight was observed on moderate and even small insulin doses. Taking into account the clinical features and the presence of diabetes in four generations on the maternal side, screening for all MODY subtypes was performed. A mutation in the ABCC8 gene was found in proband and in his mother. After the insulin discontinuation, gliclazide modified release combined with sodium/glucose cotransporter 2 (SGLT2) inhibitors was started. This treatment eliminated hypoglycemia and improved glycemic variability parameters. A decrease in the amplitude of glucose excursions was documented by continuous glucose monitoring. After 3 months of treatment, glycemic control was still optimal, and no hypoglycemic episodes were observed. The case report demonstrates the clinical features of ABCC8-associated MODY and the therapeutic potential of a combination of sulfonylurea with SGLT2 inhibitor in this disease.
