Bone remodeling in men with type 2 diabetes: is it just the same thing as in women?

Poster (download) Olga Fazullina1, Vadim Klimontov2, Maksim Dashkin31RICEL – Branch of IC&G SB RAS, fazullina@ngs.ru2RICEL – Branch of IC&G SB RAS, klimontov@mail.ru3RICEL – Branch of IC&G SB RAS, mdashkin@invitro.ru Background and aim: The mechanisms of reducing the bone mineral density (BMD) in men with type 2 diabetes are poorly understood. The aim of our study was to determine the relationships between the markers of bone remodeling and BMD in men with type 2 diabetes. Materials and Methods: The study included 59 men with type 2 diabetes, from 50 to 75 years of age. BMD and T-score were determined by dual-energy X-ray absorptiometry. A serum levels of parathyroid hormone (PTH), free testosterone, osteocalcin, osteoprotegerin, sclerostin, and urinary excretion of C-terminal telopeptides of type I collagen (CTX-I) were determined by ELISA. Control group comprised of 21 healthy subjects with normal BMD, matched by sex and age. Results: A reduced BMD was revealed in 29 patients, including 4 individuals with osteoporosis and 25 subjects with osteopenia. The levels of osteocalcin were decreased and the levels of osteoprotegerin and sclerostin were increased in observed diabetic subjects as compared to control (p=0.02, p<0.001 and p=0.02 respectively). The excretion of CTX-1 was reduced in patients with diabetes (p<0.001). There were no differences in PTH and free testosterone concentrations between control and diabetic subjects. In stepwise multivariate regression analysis, sclerostin was the most significant predictor for lumbar spine T-score (ОІ=0.496, R2=0.23, p=0.00007), the level of PTH influenced the femoral neck T-score (ОІ=-0.29, R2=0.26, p=0.005). Conclusions: The obtained results suggest that the bone remodeling in men with type 2 diabetes is reduced due to the inhibition of osteoblastogenesis and decrease in the bone formation and resorption.

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The prevalence and the risk factors for low-energy fractures in women with type 2 diabetes

Poster (download) Olga Fazullina1, Vadim Klimontov21RICEL – Branch of IC&G SB RAS, fazullina@ngs.ru2RICEL – Branch of IC&G SB RAS, klimontov@mail.ru Background and aim: The modeling of the risk of osteoporosis-related fractures in women with type 2 diabetes is important issue for medicine. The aim of our study was to determine the prevalence and the risk factors for low-energy fractures in postmenopausal women with type 2 diabetes. Materials and Methods: The study included 236 postmenopausal women with type 2 diabetes, from 50 to 75 years of age. Bone mineral density (BMD), T-score and total body composition were determined by dual-energy X-ray absorptiometry. Results: A reduced BMD was revealed in 150 women, including 45 individuals with osteoporosis and 105 subjects with osteopenia. A history of fractures occurred in 72 patients (30.5%). Low-energy fractures were observed in the groups of osteopenia (n=8) and osteoporosis (n=14). The most common localization of low-energy fractures was the radius (57.9% of all low-energy fractures), and proximal femur (36.8%). Women with low-energy fractures were older (p<0.001), had a lower body mass index (p<0.001), longer duration of insulin therapy and duration of postmenopause (p=0.01 and p<0.001 respectively). When analyzing the total body composition women with low-energy fractures had less total fat mass, abdominal and hip fat mass, and less lean mass (all p<0.001). In discriminant analysis, the duration of type 2 diabetes was the most reliable factor associated with low-energy fractures (model parameters: p=0.01; F=6.2; recognition accuracy 87%). Conclusions: The age, duration of diabetes, postmenopause and insulin treatment, as well as body composition parameters (fat mass and lean mass), should be taken into consideration when modeling the risk of low-grade fractures in postmenopausal women with type 2 diabetes.

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The prevalence and risk factors of carotid artery stenosis in type 2 diabetic patients.

Poster (download) Elena Koroleva1, Rustam Khapaev2, Alexandr Lykov3, Vadim Klimontov41Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, ekoro@bk.ru2Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, khapaevrs@bionet.nsc.ru3Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, aplykov2@mail.ru4Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, klimontov@mail.ru Abstract Background and aim: Diabetic patients with carotid artery stenosis have an exceptional high risk for all-cause and cardiovascular death. This study aimed to determine the prevalence and risk factors of carotid stenosis in patients with type 2 diabetes (T2D). Materials and Methods: 390 patients with T2D were examined. Duplex ultrasound of the extracranial carotid arteries was performed and the intima-media thickness of the common carotid arteries (IMT) was determined. A study of serum concentrations of NO, calponin-1, relaxin, and L-citrulline was performed in 152 patients. Results: the signs of carotid arteriosclerosis were revealed in 338 patients (86%). 134 patients (33%) had carotid stenosis. The patients with carotid artery stenosis (group 2, n = 134), as compared to those without (group 1, n = 204) were older, had a larger waist circumference, a longer diabetes duration, higher urinary albumin/creatinine ratio, and lower eGFR, all p<0.05. There were no differences in sex distribution, smoking rate and other laboratory parameters between the groups. In group 2 NO and citrulline concentrations were significantly higher than in group 1 (p=0.005 and p=0.003 respectively). According to ROC analysis, the age ≥65 years, T2D duration ≥15 years and high serum NO concentration were determined as the risk factors for carotid stenosis. The decrease in eGFR <60 ml/min*1.73 m2, diabetic retinopathy, myocardial infarction in medical history increased the risk of stenosis (HR 2.24; p=0.0006, HR 1.88; p=0.006, and HR 2.64; p=0.002, respectively). Conclusions: the study shows a high prevalence of carotid artery stenosis in patients with T2D. The age ≥65 years, T2D duration ≥15 years, GFR <60 ml/min*1.73 m2, diabetic retinopathy and myocardial infarction are risk factors for the carotid artery stenosis in patients with T2D.   Введите абстрактную аннотацию ТОЛЬКО здесь

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Transcriptome (RNA-seq) analysis of human salivary gland cells with exogenous expression of human pancreas beta cells transcription factors PDX1, MAFA, NGN3.

Poster (download) Olga Brovkina1, Alexander Artyuhov2, Yulia Kolesova3, Erdem Dashinimaev4, Mikhail Borisov5, Ekaterina Vorotelyak6, Andrey Vasiliev71Federal Research and Clinical Center, FMBA of Russia, brov.olia@gmail.com2Center for Precision Genome Editing and Genetic Technologies, Pirogov Russian National Research Medical University, alexanderartyuhov@gmail.com3Sechenov First Moscow State Medical University, Institute of Molecular Medicine, vasilenko-yuliya@mail.ru41. Center for Precision Genome Editing and Genetic Technologies, Pirogov Russian National Research Medical University; 2. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, dashinimaev@gmail.com5Koltzov Institute of Developmental Biology, Russian Academy of Sciences, borisov.mikhail2011@yandex.ru6Koltzov Institute of Developmental Biology, Russian Academy of Sciences, vorotelyak@idbras.ru7Koltzov Institute of Developmental Biology, Russian Academy of Sciences, vasiliev@idbras.ru Treatment of diabetes patients with exogenously administered insulin linked with burdensome for patients and the possibility of fallible doses. The development of cell technologies providing new sources of beta-cells represents an attractive therapeutic strategy to treat patients with diabetes.В One of the promising technologies is reprogramming the cells by target changes in transcript factors regulating beta-cells development and differentiation. In this study, we used transduction with lentivirus particles carrying a cassette for PDX1, MAFA and NGN3 expression (or all three at once) and GFP cassette as a control. We have chosen salivary gland (SGC) and HuTu80 as initial cell lines for reprogramming into beta-cells. The results were analyzed by RNAseq (Illumina HiSeq 4000). A total of 195 and 385 mRNA genes appeared to be differentially expressed in SGC and HuTu80, accordingly. The analysis of significant pathways revealed changes in the regulation of the actin cytoskeleton, which can play a crucial role in reprogramming into beta-cells.

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Continuous glucose monitoring parameters in insulin-treated type 2 diabetic patients: relationships with obesity and body composition

Poster (download) Julia F. Semenova1, Olga N. Fazullina21Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences(RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, ekmxtyjr@yandex.ru2Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, fazullina@ngs.ru Background and aim: Obesity and associated insulin resistance can modify daily blood glucose fluctuations in patients with diabetes. The aim of our study was to determine the relationships between obesity, body composition and daily dynamics of glucose, assessed by continuous glucose monitoring (CGM), in patients with type 2 diabetes treated with insulin. Materials and Methods: One hundred and thirty six insulin-treated patients with type 2 diabetes were examined. Real-time or blinded CGM was performed using Medtronic CGM devices in hospital settings. Time in ranges and a panel of GV parameters were derived from CGM recordings. Results: Patients with obesity, as compared to those without, demonstrated significantly reduced Time Below Range (p<0.001), Low Blood Glucose Index (p<0.001), Lability Index (p=0.04), Men Absolute Glucose (p=0.03) and a tendency to lower Mean Amplidude of Glucose Excursions (p=0.08) and higher glycated hemoglobin HbA1c (p=0.07). There were negative correlations between total fat mass and Standard Deviation (r=-0.53, p=0.0008), Mean Amplitude of Glucose Excursions (r=-0.38, p=0.02), Lability Index (r=-0.51, p=0.0008), High Blood Glucose Index (r=-0.33, p=0.04) and MAG (r=-0.57, p=0.0001). Truncal fat mass, android and gynoid fat mass demonstrated negative correlations with these GV parameters also. Conclusions: These data demonstrate the association between obesity, body composition and CGM parameters in insulin-treated type 2 diabetic subjects. The presence of obesity and accumulation of adipose tissue is associated with reduced GV and diminished risk of hypoglycemia.

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Clinical and metabolic parameters associated with time in ranges and glucose variability in patients with type 2 diabetes treated with insulin

Poster (download) Julia F. Semenova1, Maksim V. Dashkin2, Olga N. Fazullina31Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences(RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, ekmxtyjr@yandex.ru2Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, mdashkin@invitro.ru3Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences(RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, fazullina@ngs.ru Background and aim: Continuous glucose monitoring (CGM) provides an excellent opportunity for in-depth assessment of glycemic control and glucose variability (GV) in diabetic subjects. The aim of our study was to determine the clinical and metabolic parameters associated with non-targeted time in range (TIR) increased GV in patients with type 2 diabetes (T2D) treated with insulin.В Materials and Methods: One hundred and thirty six insulin-treated patients with T2D were included. Real-time or blinded CGM was performed using Medtronic CGM devices. The TIR and Mean Amplitude of Glucose Excursion (MAGE) were estimated. The advance glycation end-products (AGEs) levels were measured in blood serum by ELISA.В Results: Patients with non-targeted TIR (>70%) had higher glycated hemoglobin HbA1c, triglycerides and proteinuria as compared to those with targeted TIR. Urinary albumin-to-creatinine ratio tended to be higher in patients with non-targeted TIR also. Patients with higher MAGE (>4.5 mmol/l) demonstrated lower levels of triglycerides and uric acid and increased AGEs levels as compared to those with MAGE <4.5 mmol/l.В Conclusions: In T2D subjects, non-targeted TIR is associated with hypertriglyceridemia and proteinuria, meantime, increased MAGE is related to lower serum levels of triglycerides and uric acid and higher levels of AGEs.  

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Glucose variability in subjects with type 1 diabetes: the relationships with non-enzymatic glycation, albuminuria and renal function

Poster (download) Vadim V Klimontov1, Julia Рђ Semenova2, Alla K. Vigel31Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), klimontov@mail.ru2Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), ekmxtyjr@yandex.ru3Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), endo-kray@mail.ru Background and aim: Recent studies recognized increased glucose variability (GV) as an independent risk factor for chronic kidney disease (CKD) in diabetes. We aimed to assess the relationships between GV parameters, serum levels of glycation products, albuminuria and renal function in subjects with type 1 diabetes (T1D) at early and advanced stages of CKD. Materials and Methods: We observed 148 T1D patients, including 95 individuals with CKD C1-C2 and 53 subjects had CKD C3-5. Time in range (TIR: 70-180 mg/dl), time below range (TBR), time above range (TAR) and a panel of GV parameters were derived from continuous glucose monitoring (CGM). Serum levels of 1,5-anhydroglucitol (1,5-AG), glycated albumin (GA) and advanced glycation end products (AGEs) were determined by ELISA and compared to control (20 healthy subjects). Results: In patients with CKD C1-C2, HbA1c levels correlated positively with mean monitored glucose, TAR, MAGE, LI, HBGI, CONGA, MAG and M-value. In patients with more advanced CKD stages these relationships were lost. Concentrations of GA and AGEs were elevated significantly in subjects with diabetes as compared to control (p=0.004 and p<0.0001, respectively). The levels of 1,5-AG were reduced (p<0.0001), reflecting increase in GV. The levels of GA, but not AGEs, were associated negatively with 1,5-AG concentration. In CKD C1-C2 group, the estimated glomerular filtration rate (eGFR) showed inverse relationships with TBR and LBGI. Oppositely, in CKD C3-C5 patients eGFR correlated negatively with mean glucose, TAR, MAGE, CONGA, HBGI and M-value and some GV parameters. In both groups albuminuria was associated positively with AGEs, GA, HbA1c, mean glucose, TAR, and GV indices. Conclusions: The results demonstrate different patterns of relationships between eGFR and GV parameters in patients with T1D at early and advanced CKD stages. In these patients, enhanced GV may contribute to albuminuria […]

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Diabetes Type 2 as a Risk Factor of Neurodegeneration Development and Cognitive Impairment in db/db Mice

Poster (download) Tatyana A. Korolenko1, Nina I. Dubrovina2, Marina V. Ovsyukova3, Natalya P. Bgatova4, Chih-Li Lin5, Alexander B. Pupyshev6, Evgeniy L. Zavjalov7, Elena V. Anufrienko Scientific Research Institute81Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, t.a.korolenko@physiol.ru2Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, dubrov@physiol.ru3Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, ovsyukovamv@physiol.ru4Federal Research Center “ICG SB RAS”, Novosibirsk, Russia, n.bgatova@ngs.ru5Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, dll@csmu.edu.tw6Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, apupyshev@physiol.ru7Federal Research Center “ICG SB RAS”, Novosibirsk, Russia, zavjalov@bionet.nsc.ru8Scientific Research Institute of Physiology and Basic Medicine Novosibirsk, Russia, anufrienko@ngs.ru Diabetes T2 with insulin resistance is a serious disease all over the world with a tendency to steady increase the number of cases and a risk factor of neurodegenerative diseases development, among them firstly Alzheimer’s disease. The aim of this study was to investigate behavior and general characteristic of genetic model of diabetes T2 mice db/db, trying to reveal beginning of development early symptoms of neurodegeneration development and characteristic of symptoms of diabetes T2 during treatment by liraglutide or autophagy inducer trehalose. Mice age was 3 and 5 months. Db/db mice had an increase in body weight, which progressed with age, a decrease in brain mass. Blood glucose levels were increased in db/db mice. Treatment with trehalose or liraglutide reduces its level. Db/db mice were characterized by decrease of overall orientation-exploratory and locomotor activities, increase in anxiety in the open field test. Liraglutide treatment showed positive change in open field test in db/db mice. Passive avoidance test revealed significant decrease in motivation, locomotor and exploratory activity, decreased learning in db/db mice. Db/db mice of both ages were characterized by an increase in the relative number of PMN and monocytes and a decrease in the number of lymphocytes, indicating an inflammatory response. Treatment with trehalose or liraglutide restored these indicators. Thus, the identified behavioral changes in db/db mice reflected the development of neurodegeneration signs. Some positive effects of liraglutide on behavioral processes have been shown. Trehalose and liraglutide reduced blood glucose levels and the severity of the inflammatory response.

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