Lipid profile indices in young people with different types of diabetes mellitus

Of all types of diabetes mellitus (DM), type 1 diabetes mellitus (DM1) and type 2 diabetes (DM2) are most often diagnosed in young people. However, up to 10 % of all cases of DM diagnosed at a young age are monogenic forms of DM – MODY (Maturity-Onset Diabetes of the Young), the most common forms of which are MODY2 (GCK-MODY) and MODY3 (HNF1AMODY). These genetic forms of DM are poorly understood, so the investigation of their clinical and biochemical parameters, including lipid profile, and comparison with more studied forms of DM is of high importance. The aim of this study was to analyze the characteristics of the lipid profile in patients aged 18–45 years with DM1, DM2, GCK-MODY and HNF1A-MODY. Material and methods. In 56 patients diagnosed by the molecular genetic method MODY, as well as in 82 patients with DM2 and 14 patients with DM1, matched by sex, age, a lipid profile was studied. Results. There were no statistically significant differences in total cholesterol and low-density lipoprotein cholesterol between young patients with different types of DM. In HNF1a-MODY, the highest level of triglycerides was revealed; in DM1, the level of high-density lipoprotein cholesterol was significantly higher than in other types of DM. Among the changes in the lipid profile among all types of DM, hypercholesterolemia was more often determined

Тhe prevalence of metabolically healthy obesity: data from the epidemiological survey in of Novosibirsk

Background: Obesity is associated with numerous metabolic complications, such as type 2 diabetes mellitus (DM2), dyslipidemia, arterial hypertension (AH), cardiovascular diseases and some forms of cancer. Nevertheless, the literature describes a group of obese individuals who are more resistant to the development of metabolic disorders. At present, this phenomenon is known as "Metabolically healthy obesity", "metabolically healthy obesity" (MZO). Despite the presence of excess weight or obesity, a favorable metabolic profile can be observed in this cohort of patients, characterized by preserved insulin sensitivity, absence of arterial hypertension, normal lipid, hormonal profile, absence of inflammation and unchanged hepatic transaminases. Aims: To study the prevalence of metabolically healthy obesity (MHO) and its characteristics in men and women at the age of 45–69 years in Novosibirsk. Materials and methods: To study covered 3197 persons from the base of the international project HAPPIE. They had a body mass index (BMI ≥ 30 kg/m²). «Metabolically healthy obesity» was determined as obesity (BMI ≥ 30 kg/m², with 2 and fewer components of metabolic syndrome (MS) by criteria NCEP ATP III, 2001. Statistical analisys SPSS-13. Results: The prevalence of metabolic healthy obesity (MHO) was 42% (38% for men and 43% for women). The examined people with MHO have reliably more favorable average level of TG, HDL-cholesterol, indicators of blood glucose, systolic arterial pressure and diastolic arterial pressure and less waist circumference. In the groups withMHO and MS abdominal obesity is common in men at 95 and 71%, in women at 99 and 90%; hyperTG – in men at 74 and 9%, in women at 72 and 5,5%; lower level HDL-cholesterol in 16 and 1% for men, and in 44,5% and 3% for women; AP in 96 and 77% and 94 and 71% in men and women respectively, the frequency fasting of hyperglycaemia 77 and 21% in men and 60 and 5% in women was markedly different. According to the data obtained by us, the frequency in the sample is high and amounted to 42%. In the subgroup the most commonly found is the MHO phenotype – 53%, than in the men -38%, р <0,001 Conclusions: According to our data, the frequency of metabolic healthy obesity in the sample is high and amounted to 42%. In the female subgroup, a metabolically healthy phenotype is more common 43% than in the male 38%, p <0.001. Metabolically healthy obese individuals are characterized by a significantly lower incidence of fasting hyperglycaemia and dyslipidemia

Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy

Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mutation in ABCC8, encoding the sulphonylurea receptor. Diabetes mellitus manifested in a 27-year-old man with hyperglycaemia up to 24 mmol/L, without ketosis. Non-proliferative diabetic retinopathy, microalbuminuria, dyslipidaemia and carotid atherosclerosis were revealed upon initial examination. The levels of pancreatic islet cell antibodies and glutamate decarboxylase antibodies were negative, while the level of C-peptide was within the normal range. Insulin therapy in the basal-bolus regimen was provided with a gradual dose reduction due to frequent hypoglycaemia. The preproliferative retinopathy with macular oedema was revealed after 4 months of therapy, and panretinal photocoagulation of both eyes was performed. A molecular genetics study revealed a mutation in the gene ABCC8, the same mutation was found in patient’s mother and uncle. Insulin therapy was cancelled, and the treatment of gliclazide MR 60 mg/day was initiated, which resulted in extreme glycaemic excursions. Thereby, sodium–glucose cotranporter-2 (SGLT2) inhibitor dapagliflozin 10 mg/day was added. A reduction in glucose variability parameters were observed on combination therapy. After 6 months till 1.5 years of treatment, glycaemic control was optimal, no hypoglycaemic episodes were observed. This case study demonstrates clinical features of MODY 12, and the potential of combination of sulfonylurea and SGLT2 inhibitor in the treatment of this disease

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Analysis of the actual nutrition of the female population of Novosibirsk, depending on the magnitude of the glycemic index of their diet

Background. When choosing foods rich in carbohydrates, it is important to consider not only their chemical composition, but also the ability to influence the level of postprandial blood glucose (glycemic response). A qualitative indicator of this ability is the glycemic index (GI) of a carbohydrate-containing product. Recently, there have been some evidences that control of GI nutrition can be important for prevention and nutrition therapy of metabolic disorders. Aim. To determine of the magnitude of the glycemic index (GI) of actual nutrition in women in Novosibirsk, and the study of the connection with metabolism and obesity. Material and methods. The study was designed as cross-sectional research and was carried out within the framework of the international HAPIEE project on a random representative sample of the unorganized population of Novosibirsk, 4397 women, the average age was 57.7 &plusmn; 7.1, without diabetes. For the calculation of GI nutrition, the International Table of Glycemic Index and Glycemic Load (2008) were used. The frequency method was used to evaluate the actual nutrition. Metabolic Syndrome (MS) criteria were used in accordance with the Russian National Recommendations of the GEF (2009), as well as with the international recommendations of NCEP ATP III (2001) and JIS (2009). Statistical processing of data was carried out using the SPSS 13.0 software package (Bonferroni criterion in the GLM procedure). The odds ratio (OR) was estimated using binary logistic regression in quartiles of the glycemic index. Differences were considered statistically significant at p &lt;0.05. Results. The GI of women's nutrition was on average low and amounted to 53.1 units. In the quartiles of the GI OR, the MS for all the criteria used was not significantly different. In the quartiles of the body mass index (BMI) in women with GI in the group with normal body weight (BMI = 23.3 kg/m2) was significantly higher by 0.9 units (p &lt;0.001) compared with the obese group (BMI = 37.3 kg/m2). The diet was unbalanced and did not meet the recommendation in all groups of women studied. It was noted a significant reduction in the group with obesity 1.6 times the value of total caloric intake per 1 kg of body weight. Conclusions. Nutrition of women in Novosibirsk is unbalanced, with increased consumption of fat and inadequate intake of carbohydrates. The GI value is close to the GI nutrition of the population of European countries. The presence of a connection between the GI nutrition of women with a metabolic disorder in the sample of the population was not established

Validation of the Finnish diabetes risk score (FINDRISC) for the Caucasian population of Siberia

Aim. A validation of the Finnish diabetes risk score (FINDRISC) was conducted among the Siberian population. FINDRISC was used to study the prevalence of risk factors for type 2 diabetes mellitus (T2DM) and to estimate the incidence of T2DM in high-risk groups during a 10-year observation period.  Materials and methods. A total of 9,360 subjects aged between 45 and 69 years were enrolled in this cross-sectional, population-based study. FINDRISC was used to group 8,050 people without diabetes according to their risk for T2DM. Statistical analysis was performed using SPSS.  Results. When a cutoff point of 11 was used to identify those with diabetes, sensitivity was 76. 0% and specificity was 60. 2%. The area under the receiver operating curve for diabetes was 0. 73 (0. 73 for men and 0. 70 for women). More than one-third (31. 7%) of the adult population of Novosibirsk was estimated to have medium, high or very high risk of developing T2DM in the next 10 years. Cases of T2DM estimated to occur during the 10 years of follow-up had significantly higher incidence of risk factors such as BMI ≥30 kg/m2, waist circumference 102 cm in men and 88 cm in women and a family history of T2DM and were more likely to take drugs to lower blood pressure.  Conclusion. FINDRISC provided good results in our sample, and we recommend its use in the Siberian population

Triglycerides, Obesity and Education Status Are Associated with the Risk of Developing Type 2 Diabetes in Young Adults, Cohort Study

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

Prevalence of diabetes in the adult population of Novosibirsk

Aims. To estimate the prevalence of type 2 diabetes mellitus (T2DM) in different age groups of the adult population of Novosibirsk, according to epidemiological studies in 20032005 and 20132016. Methods. We examined a representative population sample (assessed in 20032005) of men and women aged 4569 years in two administrative districts of Novosibirsk, as a part of the international HAPIEE project. According to the tables of random numbers, representative samples of men and women aged 4569 years were formed, to which letters were sent, inviting them to pass for examination. During 20132016, a second population survey was conducted on a random representative sample of a population of 2544-year-olds of both sexes. Participants were residents of one of the districts of Novosibirsk. T2DM and impaired fasting glucose (IFG) were diagnosed using fasting plasma glucose (FPG) levels (diabetes: FPG 7.0 mmol/l; IFG: FPG 6.16.9 mmol/l). Results. The prevalence of T2DM among residents aged 4569 years was 11.3%, and overall, no significant difference in prevalence was found between females and males (11.3% vs. 11.0%). However, the overall prevalence of T2DM among residents aged 2544 years was 2.2%, and prevalence was higher in men (3.5%) than in women (1.1%), p 0.05. High prevalence of IFG was found in the 4569 age group (18.2%, in 20032005), and in the younger age group of 2544 years (21.6%, in 20132016). The high rate among young individuals is particularly alarming. Less than one half (4.8 out of 11.3%) of participants aged 4569 tested positive for T2DM, and only one in the age group 2544 years knew he/she had diabetes. This indicates a lack of knowledge among Siberians about their problem with diabetes. Conclusion. Approximately one in five adults had IFG. Among the adult population aged 4569 (in 20032005), 18.2% had IFG and 11.3% had T2DM. In individuals aged 2544 years in 20132016, IFG was observed in 21.6%, and 2.2% had T2DM (p0.05)

Association of candidate gene polymorphisms for autoimmune thyroid diseases in patients with familial diffuse toxic goiter and autoimmune thyroiditis

Aim: to study the relation polymorphism of some genes of the immune response with familial autoimmune thyroid disease. Materials and methods. 100 patients from 49 families were examined. At least 2 first-degree affected relatives with autoimmune thyroiditis or diffuse toxic goiter were included from each family. 76 persons were included to control group without thyroid pathology and negative history of any thyroid disease in families. Clinical, hormonal, ultra-sound data was collected for each subject. Genotyping ofCTLA4 A49G and PTPN22 C1858T polymorphisms was performed for 70 patients (35 families) with familial autoimmune thyroid disease and for all subjects from the control group. Results. Autoimmune thyroid disease was observed among one generation (siblings) in 11 families (22.5%) and among two generations (parent-child) in 38 families (75.5%). Patients with chronic autoimmune thyroiditis with hypothyroidism in the outcome were dominated – 66%, 34% experienced diffuse toxic goiter. Autoimmune thyroiditis was observed in parent and offspring from 21 families (55%). In the group of siblings autoimmune thyroiditis was diagnosed for both relatives in 6 families (54%). Frequency of genotypes of CTLA4 A49G polymorphism is not differ between patients with familial autoimmune thyroid disease and control group. Carriage of T allele of PTPN22 C1858T polymorphism is associated with the risk of autoimmune thyroid disease developing in a group of female offspring: OR = 3.175; 95% CI 1,423–7,262. These results allow us to recommend to test this polymorphism to identify patients with the risk of autoimmune thyroid diseases in families. Conclusion. Taking into account that DNA testing is one of the most important part of personalized approach in medicine, the current results of molecular genetic study for familial cases of autoimmune thyroid disease creates prerequisites for optimizing the diagnostic pathway of these patients

Analysis of APPL1 Gene Polymorphisms in Patients with a Phenotype of Maturity Onset Diabetes of the Young

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&ndash;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