Combination of osteogenesis imperfecta and type 1 diabetes mellitus

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder accompanied by increased bone fragility. Five types of OI are distinguished on the basis of phenotypic manifestations. OI type 1 is characterized by a reduced amount of normal type 1 collagen and is the mildest form. In addition to the fractures, course of disease can be accompanied by short stature, skeletal deformity and joint hypermobility. Although fracture risk decreases with age, such patients needs regular follow-up with an assessment of bone mineral density (BMD) and, if necessary, correction of therapy to improve the quality of life. Type 1 diabetes mellitus (T1DM) is associated with a decreased BMD, which is mostly attributed to insulin deficiency and hyperglycemia, which also increase the risk of fractures. Achieving and stable maintenance of glycemic targets is often challenging, but it is necessary to exclude hyperglycemia as a factor that further worsens the quality of bone. This paper describes a clinical case of an extremely rare combination of type 1 OI and T1DM, two diseases with a pronounced negative effect on bone tissue. The combination of these pathologies requires special management tactics for such patients to reduce the risk of developing new fractures.

Immunohistochemical features of the bone tissue of the lower extremities in patients with type 2 diabetes mellitus

Background: Diabetic neuroosteoarthropathy is a serious disabling complication of diabetes mellitus, which, in the absence of timely correct treatment, can lead to high amputations of the affected limb. At present, the reasons and mechanism of the development of Charcot’s foot are not completely clear. It is extremely important to determine the pathophysiological mechanisms of DNOAP formation and to search for reliable markers-predictors of this pathology.Aim: To study the immunohistochemical characteristics of the bone tissue of the lower extremities in patients with diabetic neuroosteoarthropathy in comparison with patients with diabetes mellitus without this pathology.Materials and methods: During the foot surgery, a bone fragment of the foot was harvested for immunohistochemical study of receptor markers for PINP, PIIINP, and RAGE in the group of patients with DNOAP compared with the control group.Results: The study included 20 patients with type 2 diabetes mellitus and were divided into 2 groups: 10 patients with DNOAP made up group 1, 10 patients without DNOAP — group 2.Patients in both groups were comparable in AGE, experience with type 2 diabetes, and glycemic control.During the immunohistochemical study, a significant increase in the staining intensity of receptor markers for PINP, PIIINP, and AGE was recorded in the group of patients with DNOAP compared with the control group (p <0.05).Conclusion: For the first time, an immunohistochemical study of markers of bone resorption and AGE was carried out in persons with DNOAP. The results obtained indicate impaired collagen formation and, as a consequence, impaired bone formation and bone resorption in patients with DNOAP: in group 1, a statistically significant increase in the expression of PINP, PIIINP, and RAGE was revealed.

Quality of ejaculate of male patients with type 2 diabetes mellitus (DM), vaccinated with GamCovidVac (Sputnik V)

Background: New coronavirus infection (Covid-19) in patients with diabetes type 2 mellitus (DM) often has severe clinical course and manifestation. This comorbidity is a reasonable indication for vaccination. Male patients are often concerned about the vaccination impact on their fertility, so the current research of this issue seems to be essential and relevant.Aims: To evaluate the quality of ejaculate in type 2 diabetes mellitus (DM) patients, vaccinated by GamCovidVac (Sputnik V).Materials and Methods: The pilot observational prospective study included 30 males with type 2 diabetes mellitus (DM). The study continued from February 2021 till June 2021. The research design involved medical history analysis, glycated hemoglobin (HbA1c) tests, total testosterone level in blood measurement, semen analysis (sperm count test). Group comparison was performed by Wilcoxon Signed Ranks Test. The differences were considered statistically significant at p<0.05.Results: After vaccination 19 patients (63%) demonstrated a temperature rise which lasted for 2 days; 26 patients (87%) complained of tenderness in the injections site which lasted up to 5 days. Though a few patients reported general somatic side effects after the vaccination, there have been no statistically significant deviations in sperm count, viability, function and morphology. The levels of glycated hemoglobin and total testosterone remained unchanged.Conclusion: The study revealed no negative impact of GamCovidVac on ejaculate quality, total testosterone level and compensation of carbohydrate metabolism.

Endothelial function status in hypogonadal men

Background: Type 2 diabetes mellitus (T2DM) and hypogonadism are mutually aggravating diseases associated with the development and progression of cardiovascular pathology. The status of endothelial function in men with T2DM and hypogonadism hasn’t been studied.Aims: To assess the effect of hypogonadism on endothelial function in men with T2DM.Materials and methods: Patients underwent clinical studies, assessment of carbohydrate and lipid metabolism, the content of sex hormones (total testosterone (T), sex hormones binding globulin, free T, luteinizing hormone) and markers of endothelial function (nitric oxide (NO), endothelial nitric oxide synthase type 3 (eNOS3), endothelin, adhesion molecules ICAM-1, VCAM-1, p- and e-selectins, cadherin), ultrasound examinations of endothelium-dependent vasodilation (EDVD) of the brachial artery (BA) and carotid arteries with an assessment of the thickness of intima-media complex (TIM) were performed.Results: The study included 276 men with T2DM (age 54.0[49;60] years), who were divided into 2 groups: 1–124 patients with hypogonadism; 2–152 eugonadal patients. Reduction of the endothelial vasomotor function was detected in 32.4% of patients in the 2st group and in 55.3% of the 1nd group (χ2=6.1; p=0.01), which was associated with a decrease in EDVD by 29.8 % (p<0.001) and an increase in the time of development of maximal BA vasodilation by 30 seconds in patients with hypogonadism (p<0.001). The TIM of the carotid arteries was 10% more in group 1 compared with group 2 (p=0.03). The ­level of NO in the 1st group was reduced by 1.6 times (p=0.001), eNOS3–by 1.5 times (p=0.038) compared with the 2nd group. The concentrations of adhesion molecules were higher in group 1 compared to group 2: VCAM-1 by 32.5% (p<0.001), ICAM-1 by 43.5% (p<0.001), p-selectin–by 19.3% (p=0.004), cadherin–6 times (p<0.001).Conclusion: Hypogonadism in men with T2DM is associated with the development of endothelial dysfunction, which manifests in a weakening of the EDVD and a slowdown in its development, as well as disturbances of the secretory activity of endothelium–a decrease in NO synthesis and activation of the adhesion molecules expression, which can be regarded as an universal pathogenetic mechanism of the development of cardiovascular diseases in combination of T deficiency and T2DM.

The role of advanced glycation end products in patogenesis of diabetic nephropathy

Diabetes mellitus (DM) and chronic kidney disease are the diseases that have exceeded epidemic thresholds in terms of prevalence all over the world. That made it possible to classify them as non-communicable epidemics of the XXI century. Diabetic nephropathy (DN) is implicated with high levels of disablement and mortality. Advanced glycation end products (AGE) play a key role in the progression of DN. Increased formation of AGE occurs due to hyperglycemia under the conditions of diabetes. Moreover, there are additional factors in DN that increase the elaboration of AGE, such as high levels of oxidative stress and decreased renal clearance which slows down the AGE excretion. Both immediate effects of AGE and interaction of AGE with its cell-bound receptor (RAGE) result in a сascade of events that lead to further progression of DN. Thus, the research of the new therapeutic approaches targeted on the AGE-RAGE system is of great interest to slow progression of DN and improve the prognosis.

Ethnic characteristics of bone remodeling in female patients with type 2 diabetes mellitus

Background: Structural and metabolic disorders of bone tissue in women with T2DM have no clinical manifestations, but they are accompanied by the risk of fractures.Aim: To study the parameters of bone metabolism, BMD and microarchitectonics in female patients with T2DM in the Buryat population.Materials and methods: The observational single-center one-stage controlled study included 73 women with T2DM, which were divided into 2 groups depending on the functional state of the ovaries (reproductive and postmenopausal periods). In each group, subgroups of the Buryat and Russian populations were identified. The first group included 34 patients with T2DM of the reproductive period: 16 from the Buryat population and 18 from the Russian population. The second group consisted of 39 postmenopausal patients with T2DM: 17 from the Buryat population and 22 from the Russian population. The study of BMD in the lumbar spine (L1-L4), femoral neck (Neck), in the proximal femur (Total hip), trabecular bone score (TBS), serum osteocalcin (OC), N-terminal propeptide type 1 procollagen was carried out (P1NP), vitamin D 25 (OH), blood plasma type I collagen C-terminal telopeptide (β-Cross laps) and ionized calcium (iCa).Results: In female patients with T2DM of the reproductive age of the Buryat population, an increase in both markers of osteosynthesis P1NP (p=0.035), OC (p=0.047), and bone resorption β-Cross laps (p=0.040) was found relative to the similar group of the Russian population. In women with T2DM in the postmenopausal period of the Buryat population, there was also an increase in P1NP (p = 0.016), OC (p = 0.048), β-Cross laps (p = 0.020) compared with the group of postmenopausal women in the Russian population. Structural disorders, characterized by a decrease in TBS, were detected only in the postmenopausal period in female patients of the Buryat population compared to women in the Russian population (p = 0.029).Comparative analysis among women with T2DM of the Buryat population, depending on the functional state of the ovaries, showed that activation of bone remodeling with an increase in P1NP (p = 0.019), OC (p = 0.004) and β-Cross laps (p = 0.004) is characteristic of postmenopausal women accompanied by a decrease in BMD Neck (p = 0.006), BMD Total hip (p = 0.003), BMD L1-L4 (p = 0.049) and TBS (p = 0.020) relative to female patients with T2DM in the reproductive period.Conclusion: In women with T2DM in the Buryat population, both in the reproductive and postmenopausal periods, an increase in bone remodeling markers and BMD stability was found when compared with the corresponding groups of patients in the Russian population. The postmenopausal period was characterized by an additional decrease in TBS in patients with T2DM in the Buryat population relative to women in the Russian population.

Physical Activity Profile and Risk of Type 2 Diabetes Mellitus in Udupi (India) Population

Background: Throught the world, More than 75% of adults with type 2 diabetes mellitus (T2DM) live in low and middle-income countries. Amongst which 69.2 million of these adults live in India. Its been shown that, as level of physical activity increases, risk of developing T2DM decreases by 15-60%. Many studies are conducted to find the risk of development of T2DM in the coastal areas of Karnataka. However, the screening of people living in Udupi was not carried out.Aim: To find out the risk for the development of T2DM using IDRS and physical activity levels in Udupi population.Material and Methods: In the current study, we included participants who were asymptomatic and undiagnosed to be having T2DM. The participants age ranged between 30–65 yrs. Participants with the history of any neurological conditions and women who were pregnant at the time of screening were excluded. We recorded random blood glucose levels of the participants following which the risk score was obtained using the Indian Diabetes Risk Score (IDRS) and the participants were classified as high risk (score ≥60), moderate risk score (30–50) and low risk (score <30). The level of physical ­activity was measured using Global Physical Activity Questionnaire.Results: The study included 23,960 participants from Udupi district, Karnataka. Based on IDRS risk stratification, 1.5%, 17.9%, 27.5% of the participants with the age ange of 30–35 yrs, 36–50 yrs and more than 50 yrs respectively had higher risk of developing T2DM. According to GPAQ score 14% of the participants were following sedentary lifestyle, 27.6% of the were minimally active, 53.7% were very active, and 4.6% were highly active.Conclusion: From the current study we conclude that 46.9% of participants had a higher risk of developing T2DM in future who are living in Udupi district.

Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Inhibitors of the sodium-glucose cotransporter type 2 (SGLT2i) are a modern class of antihyperglycemic drugs with an insulin-independent mechanism of action. Due to its ability to effectively lower blood glucose levels, improve a number of other cardiometabolic parameters (body weight, blood pressure, uric acid), as well as reduce cardiovascular and renal risks, SGLT2i have become drugs of choice for many of patients with type 2 diabetes mellitus (T2DM). Meanwhile, along with the generally recognized classes-effects of this group of drugs, there are intragroup features, including those associated with their different selectivity in sodium-glucose cotransporters of types 1 and 2 (SGLT1 and SGLT 2). For example, one of the most studied SGLT2i, canagliflozin, in addition to its inhibitory activity against SGLT2, can also moderately block SGLT1 in the intestine and kidneys that could give a maximum efficiency in the control glycemia and others cardiometabolic parameters. In addition, canagliflozin improves not only cardiovascular, but also renal prognosis in patients with T2DM, which is reflected in the corresponding indications in the summary of product characteristics of the drug. This document summarize the established and new data regarding the efficacy and safety of canagliflozin, as well as its place in the treatment of T2DM.

Remote monitoring of adolescents with type 1 diabetes mellitus using a mobile application

Background: The prevalence of type 1 diabetes mellitus (T1DM) in childhood is increasing every year. Adolescence is the most challenging age for achieving optimal metabolic control of T1DM. Telemedicine has already been shown to be ­effective in children with the condition, but there are not enough studies in adolescents. The use of mobile apps may be associated with better glycemic control in patients with type 1 diabetes.Aims: To assess the effectiveness and safety of a model of medical care for adolescents with type 1 diabetes using remote counseling and a mobile application.Materials and methods: Were included adolescents aged ≥14 and 18 years with a T1DM duration> 3 months, a glycated hemoglobin level (HbA1c)> 7%. The duration of the study was 26 weeks. There were 3 face-to-face and at least 4 remote visits using a mobile application. All patients underwent standard examination and anthropometry, study of HbA1c, registration and analysis of indicators, assessment and correction of the treatment. The quality of life of adolescents was assessed at baseline and at the end of the study. Adolescents and physicians were interviewed about program evaluation.Results: 56 patients were included, 7 adolescents withdrew. HbA1c significantly decreased by the 12th week of the study (–0.3%; p = 0.005), by the end of the study the change in HbA1c was –0.5% (p <0.001). There was an increase in the percentage of glucose measurements in the target range (+5.3 pp; p = 0.016) and a decrease in blood glucose variability (-3.1 pp; p = 0.015). There was a significant improvement in both the total assessment of the quality of life by patients (+2.9 points; p = 0.008) and individual components of its indicators: attitude to diabetes (+3.0 points; p = 0.049), attitude to treatment (+4.6 points; p = 0.010) and communication with others (+4.5 points; p = 0.015). The majority of doctors and patients assessed their participation in the study positively. The incidence of adverse events did not change significantly during the study from baseline.Conclusion: Remote counseling using a mobile app is a safe and effective approach for adolescents with T1DM in terms of glycemic control and quality of life, and provides convenience and speed of interaction.

Clinical, hormonal and molecular-genetic characteristics of monogenic diabetes mellitus associated with the mutations in the INS gene

Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “­Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation.