Patient-reported outcomes and treatment adherence in type 2 diabetes using natural language processing: Wave 8 of the Observational International Diabetes Management Practices Study.

AIMS/INTRODUCTION: We analyzed patient-reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence. MATERIALS AND METHODS: In the ongoing International Diabetes Management Practices Study, we collected patient-reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self-Management Questionnaire) and free-text answers to open-ended questions to assess perceptions of treatment value and side-effects, as well as barriers to, and enablers for, adherence and self-management. Free-text answers were analyzed by natural language processing. RESULTS: In 2018-2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin-treated, glycated hemoglobin (HbA1c) 8.0 ± 1.8%; 30.9% with HbA1c <7%) from 13 countries across Africa, the Middle East, Europe, Latin America and Asia. Mean ± standard deviation scores of chronic treatment acceptance questionnaire (acceptance of medication, rated out of 100) and Diabetes Self-Management Questionnaire (self-management, rated out of 10) were 87.8 ± 24.5 and 3.3 ± 0.9, respectively. Based on free-text analysis and coded responses, one in three patients reported treatment non-adherence. Overall, although most patients accepted treatment values and side-effects, self-management was suboptimal. Treatment duration, regimen complexity and disruption of daily routines were major barriers to adherence, whereas habit formation was a key enabler. Treatment-adherent patients were older (60 ± 11.6 vs 55 ± 11.7 years, P < 0.001), and more likely to have longer disease duration (12 ± 8.6 vs 10 ± 7.7 years, P < 0.001), exposure to diabetes education (73.1% vs 67.8%, P < 0.05), lower HbA1c (7.9 ± 1.8% vs 8.3 ± 1.9%, P < 0.001) and attainment of HbA1c <7% (29.7% vs 23.3%, P < 0.01). CONCLUSIONS: Patient perceptions/experiences influence treatment adherence and self-management. Patient-centered education and support programs that consider patient-reported outcomes aimed at promoting empowerment and developing new routines might improve glycemic control.

Application of Clinical Blood Metabogram to Type 2 Diabetes Mellitus.

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual's metabolic status in diabetes mellitus for diagnostic and treatment purposes.

Shear Stress and the AMP-Activated Protein Kinase Independently Protect the Vascular Endothelium from Palmitate Lipotoxicity.

Saturated free fatty acids are thought to play a critical role in metabolic disorders associated with obesity, insulin resistance, type 2 diabetes (T2D), and their vascular complications via effects on the vascular endothelium. The most abundant saturated free fatty acid, palmitate, exerts lipotoxic effects on the vascular endothelium, eventually leading to cell death. Shear stress activates the endothelial AMP-activated protein kinase (AMPK), a cellular energy sensor, and protects endothelial cells from lipotoxicity, however their relationship is uncertain. Here, we used isoform-specific shRNA-mediated silencing of AMPK to explore its involvement in the long-term protection of macrovascular human umbilical vein endothelial cells (HUVECs) against palmitate lipotoxicity and to relate it to the effects of shear stress. We demonstrated that it is the α1 catalytic subunit of AMPK that is critical for HUVEC protection under static conditions, whereas AMPK-α2 autocompensated a substantial loss of AMPK-α1, but failed to protect the cells from palmitate. Shear stress equally protected the wild type HUVECs and those lacking either α1, or α2, or both AMPK-α isoforms; however, the protective effect of AMPK reappeared after returning to static conditions. Moreover, in human adipose microvascular endothelial cells isolated from obese diabetic individuals, shear stress was a strong protector from palmitate lipotoxicity, thus highlighting the importance of circulation that is often obstructed in obesity/T2D. Altogether, these results indicate that AMPK is important for vascular endothelial cell protection against lipotoxicity in the static environment, however it may be dispensable for persistent and more effective protection exerted by shear stress.

Dysregulation of early gene response to a mixed meal in skeletal muscle in obesity and type 2 diabetes.

Obesity- and type 2 diabetes mellitus-induced changes in the expression of protein-coding genes in human skeletal muscle were extensively examined at baseline (after an overnight fast). We aimed to compare the early transcriptomic response to a typical single meal in skeletal muscle of metabolically healthy subjects and obese individuals without and with type 2 diabetes. Transcriptomic response (RNA-seq) to a mixed meal (nutritional drink, ∼25 kJ/kg of body mass) was examined in the vastus lateralis muscle (1 h after a meal) in 7 healthy subjects and 14 obese individuals without or with type 2 diabetes. In all obese individuals, the transcriptome response to a meal was dysregulated (suppressed and altered) and associated with different biological processes compared with healthy control. To search for potential transcription factors regulating transcriptomic response to a meal, the enrichment of transcription factor-binding sites in individual promoters of the human skeletal muscle was examined. In obese individuals, the transcriptomic response is associated with a different set of transcription factors than that in healthy subjects. In conclusion, metabolic disorders are associated with a defect in the regulation of mixed meal/insulin-mediated gene expression-insulin resistance in terms of gene expression. Importantly, this dysregulation occurs in obese individuals without type 2 diabetes, i.e., at the first stage of the development of metabolic disorders.NEW & NOTEWORTHY In skeletal muscle of metabolically healthy subjects, a typical single meal normalized to body mass induces activation of various transcription factors, expression of numerous receptor tyrosine kinases associated with the insulin signaling cascade, and transcription regulators. In skeletal muscle of obese individuals without and with type 2 diabetes, this signaling network is poorly regulated at the transcriptional level, indicating dysregulation of the early gene response to a mixed meal.

Efficacy and safety of luseogliflozin in Caucasian patients with type 2 diabetes: results from a phase III, randomized, placebo-controlled, clinical trial.

INTRODUCTION: Most data demonstrating the efficacy and safety of luseogliflozin (luseo) in people with type 2 diabetes mellitus (T2DM) originate from the Japanese population. This study evaluated luseo versus placebo (PCB) as add-on to metformin in a Caucasian population with inadequately controlled T2DM. RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, PCB-controlled, parallel-group study. Patients aged 18-75 years with inadequately controlled T2DM (glycated hemoglobin (HbA1c) ≥7% to ≤10% (≥53 to ≤86 mmol/mol)) despite a diet and exercise program and on a stable metformin regimen were eligible. Patients were randomized to one of three luseo groups (2.5, 5.0 and 10.0 mg) or PCB for 12 weeks (W12). The primary endpoint was change in HbA1c expressed as least-square means from baseline (W0) to W12. RESULTS: A total of 328 patients were randomized: PCB (n=83) and luseo 2.5 mg (n=80), 5.0 mg (n=86), and 10.0 mg (n=79). Mean age (±SD) was 58.5±8.8 years; 64.6% were women; body mass index was 31.5±3.4 kg/m2; and HbA1c was 8.54±0.70. At W12, mean reductions in HbA1c from W0 were -0.98%, -1.09%, -1.18%, and -0.73% in the luseo 2.5, 5.0 and 10.0 mg, and PCB groups, respectively, all of which were statistically significant. Compared with PCB, HbA1c levels were significantly decreased by 0.25% (p=0.045), 0.36% (p=0.006), and 0.45% (p=0.001) in the luseo 2.5, 5.0, and 10.0 mg groups, respectively. In all luseo dose groups, reductions in body weight were statistically significant compared with PCB. Data from the safety analysis were consistent with the known luseo safety profile. CONCLUSIONS: All doses of luseo as add-on to metformin in Caucasian patients with uncontrolled T2DM demonstrated significant efficacy in decreasing HbA1c after W12 of treatment. TRIAL REGISTRATION NUMBER: ISRCTN39549850.

Continuous Glucose Monitoring in Patients Following Simultaneous Pancreas-Kidney Transplantation: Time in Range and Glucose Variability.

Simultaneous pancreas-kidney transplantation (SPKT) can improve long-term patient survival and restore endogenous insulin secretion in recipients with type 1 diabetes (T1D). There are currently few data on glucose fluctuations assessed by continuous glucose monitoring (CGM) after SPKT. Aim: to evaluate CGM-derived time in range (TIR) and glucose variability (GV) in patients with T1D and functioning pancreatic grafts after SPKT. Fifty-four CGM recordings from 43 patients, 15 men and 28 women, aged 34 (31; 39) years were analyzed. Time since SKPT was up to 1 year (group 1, n = 13), from 1 to 5 years (group 2, n = 15), and from 5 to 12 years (group 3, n = 26). TIR (3.9-10 mmol/L), Time Above Range (TAR), Time Below Range (TBR), and GV parameters were estimated. There were no differences in mean glucose (5.5 [5.1; 6.2], 5.9 [5.4; 6.2], and 5.9 [5.6; 6.7] mmol/L), TIR (97.6 [92.8-99.1], 97.2 [93.2; 99.1], and 97.5 [93.4; 99]%); TAR (0, 1.8 [1.3; 3.7], and 2.5 [2; 5]%), TBR (5 [3.3; 12.7], 4.1 [2.2; 10.1], and 3.5 [1.3; 6.5]%) and GV parameters between three groups (all p > 0.05). Thus, recipients with functioning pancreatic grafts demonstrate remarkably high TIR and low GV after SPKT.

Visceral mesenchymal stem cells from type 2 diabetes donors activate triglycerides synthesis in healthy adipocytes via metabolites exchange and cytokines secretion.

BACKGROUND: In recent years, there has been an increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM). Development of visceral instead of subcutaneous adipose tissue is pathogenic and increases the risk of metabolic abnormalities. We hypothesize that visceral adipocytes and stromal cells are able to deteriorate other fat depots metabolism via secretory mechanisms. METHODS: We study the regulatory role of visceral adipose-derived stem cells (vADSC) from donors with obesity and T2DM or normal glucose tolerance (NGT) on healthy subcutaneous ADSC (sADSC) in the Transwell system. Lipid droplets formation during adipogenesis was assessed by confocal microscopy. Cell metabolism was evaluated by 14C-glucose incorporation analysis and western blotting. vADSC secretome was assessed by Milliplex assay. RESULTS: We showed that both NGT and T2DM vADSC had mesenchymal phenotype, but expression of CD29 was enhanced, whereas expressions of CD90, CD140b and IGF1R were suppressed in both NGT and T2DM vADSC. Co-differentiation with T2DM vADSC increased lipid droplet size and stimulated accumulation of fatty acids in adipocytes from healthy sADSC. In mature adipocytes T2DM vADSC stimulated triglyceride formation, whereas NGT vADSC activated oxidative metabolism. Secretome of NGT vADSC was pro-inflammatory and pro-angiogenic in comparison with T2DM vADSC. CONCLUSIONS: The present study has demonstrated the critical role of secretory interactions between visceral and subcutaneous fat depots both in the level of progenitor and mature cells. Mechanisms of these interactions are related to direct exchange of metabolites and cytokines secretion.

HbA1c trajectories over 3 years in people with type 2 diabetes starting second-line glucose-lowering therapy: The prospective global DISCOVER study.

AIM: To identify distinct HbA1c trajectories in people with type 2 diabetes (T2D) starting second-line glucose-lowering therapy. MATERIALS AND METHODS: DISCOVER was a 3-year observational study of individuals with T2D beginning second-line glucose-lowering therapy. Data were collected at initiation of second-line treatment (baseline) and at 6, 12, 24 and 36 months. Latent class growth modelling was used to identify groups with distinct HbA1c trajectories. RESULTS: After exclusions, 9295 participants were assessed. Four distinct HbA1c trajectories were identified. Mean HbA1c levels decreased between baseline and 6 months in all groups; 72.4% of participants showed stable good levels of glycaemic control over the remainder of follow-up, 18.0% showed stable moderate levels of glycaemic control and 2.9% showed stable poor levels of glycaemic control. Only 6.7% of participants showed highly improved glycaemic control at month 6 and stable control over the rest of follow-up. For all groups, dual oral therapy use decreased over time, compensated for by the increasing use of other treatment regimens. Use of injectable agents increased over time in groups with moderate and poor glycaemic control. Logistic regression models suggested that participants from high-income countries were more probable to be in the stable good trajectory group. CONCLUSIONS: Most people receiving second-line glucose-lowering treatment in this global cohort achieved stable good or highly improved long-term glycaemic control. One-fifth of participants showed moderate or poor glycaemic control during follow-up. Further large-scale studies are required to characterize possible factors associated with patterns of glycaemic control to inform personalized diabetes treatment.

Treatment patterns and glycated haemoglobin levels over 36 months in individuals with type 2 diabetes initiating second-line glucose-lowering therapy: The global DISCOVER study.

AIMS: To describe glucose-lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow-up from the start of second-line therapy. MATERIALS AND METHODS: This data analysis from the 3-year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second-line glucose-lowering therapy. Treatment and HbA1c data were collected at baseline (start of second-line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow-up were analysed using the McNemar test, with carry-forward imputation for intermediate missing values. RESULTS: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow-up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. CONCLUSIONS: Dual oral therapy was the most common treatment regimen at the start of second-line treatment, and over half of the participants remained on the same treatment during follow-up.

Dynamic Evaluation of Vitamin D Metabolism in Post-Bariatric Patients.

BACKGROUND: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate understanding of the subject. METHODS: we evaluated serum parameters of vitamin D and mineral metabolism (vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3), vitamin D-binding protein (DBP), free 25(OH)D, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), total calcium, albumin, phosphorus, creatinine, magnesium) in 30 patients referred for bariatric surgery in comparison with 30 healthy volunteers of similar age, sex and baseline 25(OH)D3. Patients were also followed up with repeated laboratory assessments 3 months and 6 months after surgery. During the first 3 months, patients were prescribed high-dose cholecalciferol therapy (50,000 IU per week), with subsequent correction based on the results of the 3-month visit examination. RESULTS: Preoperatively, patients with morbid obesity were characterized by a high prevalence of vitamin D deficiency (median 25(OH)D3 level 11.9 (6.8; 22.2) ng/mL), significantly lower levels of active vitamin D metabolite 1,25(OH)2D3 (20 (10; 37) vs. 39 (33; 50) pg/mL, p < 0.001), lower serum albumin-adjusted calcium levels (2.24 (2.20; 2.32) vs. 2.31 (2.25; 2.35) mmol/L, p = 0.009) and magnesium levels (0.79 (0.72; 0.82) vs. 0.82 (0.78; 0.85) mmol/L, p = 0.043) with simultaneous similar PTH levels (p = 0.912), and higher DBP levels (328 (288; 401) vs. 248 (217; 284) mg/L, p < 0.001). The 25(OH)D3 levels remained suboptimal (24.5 (14.7; 29.5) ng/mL at the 3-month visit and 17.9 (12.4; 21.0) ng/mL at the 6-month visit, p = 0.052) despite recommended high-dose cholecalciferol supplementation. Patients also demonstrated an increase in 1,25(OH)2D3 levels (38 (31; 52) pg/mL at the 3-month visit and 49 (29; 59) pg/mL at the 6-month visit, p < 0.001) without a change in PTH or calcium levels during the follow-up. CONCLUSION: our results of a comprehensive laboratory evaluation of vitamin D status and mineral metabolism in patients undergoing bariatric surgery highlight the importance of improving current clinical guidelines, as well as careful monitoring and education of patients.

Glycated hemoglobin level dynamics in COVID-19 survivors: 12 months follow-up study after discharge from hospital.

INTRODUCTION: One of the stages of reproduction of SARS-CoV-2 is the S-protein glycosylation to facilitate penetration into target cells. It has been suggested that SARS-CoV-2 is able to enter erythrocytes, interact with heme and porphyrin, which could influence HbA1c levels. Assessment of HbA1c levels in individuals with acute COVID-19 and after recovery may show clinical relevance of this hypothesis. AIM: To assess HbA1c levels in patients with COVID-19 in the acute phase and in early (6-8 weeks) and late (52±2 weeks) periods after recovery. MATERIALS AND METHODS: We conducted a multicenter prospective study, which included patients hospitalized in Endocrinology Research Centre and the City Clinical Hospital № 52" diagnosed with COVID-19, virus identified/ not identified. Patients were divided into three groups according to baseline HbA1c level and the presence or absence of previous history of diabetes previous history of diabetes mellitus (DM): HbA1c ≤ 6.0%, HbA1c > 6.0% and patients with DM. Patients were examined during the acute COVID-19 phase and in early (6-8 weeks) and late (52±2 weeks) periods after recovery. Oral glucose tolerance test was performed in the group with initial HbA1c > 6.0% to clarify the diagnosis. RESULTS: We included 194 patients in the study. During the follow-up, 52 patients were examined in 6-8 week period: 7 with HbA1c ≤ 6.0%, 34 with HbA1c > 6.0%, 11-with previously diagnosed DM. Carbohydrate metabolism assessment in the later stages (52±2 weeks) after recovery was performed in 78 patients: 33 patients with HbA1c ≤ 6.0%, 36 patients with HbA1c > 6.0% and 9 patients with previously established diabetes. HbA1c median in patients with HbA1c ≤ 6.0% was 5.7% [5.3;5.8], with HbA1c>6.0% -6.4% [6.2; 6.6], with previously diagnosed DM-7.7% [7.2; 8.9]. Statistically significant decrease in HbA1c over time 6-8 weeks after extracts were obtained in both groups of individuals without a history of DM (Wilcoxon test, p<0.05). After 52±2 weeks we observed HbA1c decrease in all three groups (Fridman test, p<0.05): in patients with HbA1c ≤ 6.0% median HbA1c was 5.5[5.3;5.7], with HbA1c>6.0% - 6.1[6.15;6.54], with previously diagnosed DM-7.8 [5.83; 8.08]. Development of DM after 52±2 weeks was recorded in 7.24% of all examined patients without a history of DM, which is 16.6% of the total number of patients examined in dynamics with HbA1c > 6.0%. CONCLUSION: HbA1c elevation during the acute phase of COVID-19 may be false due to the effect of SARS-CoV-2 on hemoglobin kinetics and/or detection on the surface of the SARS-CoV-2 virion highly glycosylated S-proteins by high performance liquid chromatography determinations. Upon detection HbA1c > 6.0% in patients with COVID-19 in the active phase of the disease without concomitant hyperglycemia re-determine the level of HbA1c after recovery is recommended.

Association of country economy and socioeconomic factors on risk factor control for primary prevention of cardiovascular disease in patients with diabetes mellitus: Insights from the DISCOVER study.

BACKGROUND: We sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control. METHODS: The DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin <7%, blood pressure <140/90 mmHg, prescription of a statin) at 3 years among those without optimal control at baseline. Countries were stratified by gross national income (GNI)/capita, from 2017). We examined the impact of country GNI/capita with achievement of risk factor control. FINDINGS: Our cohort included 9613 patients with T2D and without baseline cardiovascular disease (mean age 57.2 ± 8.7 years, 47.9% women). At baseline, 6354/7646 patients (83.1%) had suboptimal glucose control, 3449/9200 patients (37.5%) had suboptimal BP control, and 2800/4221 patients (66.7%) were not on an appropriate statin (sample sizes differed due to missing covariate data). Optimal control at 3 years of follow-up was achieved in 41% (glucose), 56% (blood pressure), and 29% (statins) of patients. There was significant variability in achievement of risk factor control across countries but no association between country GNI/capita with achievement of risk factor control (p > 0.08 for all). INTERPRETATION: In a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding.

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity.

OBJECTIVE: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions. METHODS: In the study, ADSCs from donors with obesity were used. After clinical characterization, all patients underwent bariatric surgery and ADSCs were isolated from subcutaneous fat biopsies. ADSCs were subjected to osteogenic differentiation, stained with Alizarin Red S, and harvested for real-time PCR and Western blotting. Cell senescence was evaluated with a ß-galactosidase-activity-based assay. RESULTS: Our results demonstrated the significantly increased calcification of ADSC on day 28 of osteogenesis in the T2DM group. These data were confirmed by the statistically significant enhancement of RUNX2 gene expression, which is a master regulator of osteogenesis. Protein expression analysis showed the increased expression of syndecan 1 and collagen I before and during osteogenesis, respectively. Moreover, T2DM ADSCs demonstrated an increased level of cellular senescence. CONCLUSION: We suggest that T2DM-associated cellular senescence can cause ADSC differentiation to shift toward osteogenesis, the impaired formation of new fat depots in adipose tissue, and the development of insulin resistance. The balance between ADSC adipo- and osteogenesis commitment is crucial for the determination of the metabolic fate of patients and their adipose tissue.

Socioeconomic Factors Associated With Glycemic Measurement and Poor HbA1c Control in People With Type 2 Diabetes: The Global DISCOVER Study.

DISCOVER is a 3-year observational study program of 15,983 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. We investigated the association between socioeconomic status and both the availability of a baseline glycated hemoglobin (HbA1c) measurement and poor glycemic control (HbA1c level ≥ 9.0%) in participants enrolled in DISCOVER. Factors associated with a lack of baseline HbA1c measurement or an HbA1c level ≥ 9.0% were assessed using three-level hierarchical logistic models. Overall, 19.1% of participants did not have a baseline HbA1c measurement recorded. Lower-middle country income (vs. high) and primary/no formal education (vs. university education) were independently associated with a reduced likelihood of having a baseline HbA1c measurement (odds ratio [95% confidence interval]: 0.11 [0.03-0.49] and 0.81 [0.66-0.98], respectively. Of the participants with an available HbA1c measurement, 26.9% had an HbA1c level ≥ 9.0%; 68.7% of these individuals were from lower- or upper-middle-income countries. Factors associated with an increased likelihood of poor glycemic control included low country income, treatment at a site with public and/or governmental funding (vs. private funding) and having public or no health insurance (vs. private). A substantial proportion of DISCOVER participants did not have an HbA1c measurement; more than one-quarter of these participants had poorly controlled type 2 diabetes. Both individual- and country-level socioeconomic factors are associated with the quality of care regarding glycemic control. Awareness of these factors could help improve the management of patients with type 2 diabetes.

Factors associated with weight loss in people with overweight or obesity living with type 2 diabetes mellitus: Insights from the global DISCOVER study.

AIMS: To estimate real-world change in weight over 3 years and the factors influencing it in participants who are overweight and live with type 2 diabetes. MATERIALS AND METHODS: DISCOVER is a multinational prospective observational study that enrolled participants with type 2 diabetes between December 2014 and June 2016 at the time of initiation of a second-line glucose-lowering medication (GLM). Demographic, anthropometric, and quality-of-life data were collected at baseline, and after 6, 12, 24 and 36 months of follow-up. Using a hierarchical, repeated-measures linear regression model, we examined factors associated with weight change over time. RESULTS: Of 10 675 participants with type 2 diabetes who were overweight/obese (mean age 57.1 ± 11.1 years, 46% women), 21% lost ≥5% weight over 3 years, which was associated with modestly improved physical and mental health. Advancing age, female sex, and higher baseline weight were associated with weight loss. Most importantly, the type of GLM prescribed at previous visit had the strongest impact on weight change over time independent of participant factors, with use of a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist associated with 1.0% weight loss versus a 0.6% weight gain with sulphonylureas, thiazolidinediones, meglitinides or insulin. CONCLUSION: In this large contemporary prospective study, approximately one in five participants with early-stage type 2 diabetes and overweight/obesity lost ≥5% weight over 3 years. The type of GLM has the most impact on weight loss over time, highlighting the need for a careful selection of agents that takes baseline weight into consideration.

Three-year progress report of Bone Health TeleECHO Moscow: a strategy to improve the care of patients with osteoporosis and other metabolic skeletal diseases in underserved communities of Russia.

Bone Health TeleECHO Moscow is the first Russian-speaking Project ECHO (Extension for Community Healthcare Outcomes) program that is modeled after the original Bone Health TeleECHO created in the USA. Bone Health TeleECHO Moscow was effective (effect size of 0.87 p < 0.001) at improving clinicians' skills in the management of osteoporosis based on self-evaluation over 3 years. INTRODUCTION: Bone Health TeleECHO (Extension for Community Healthcare Outcomes) Moscow is the first Russian-speaking ECHO program, modeled after Bone Health TeleECHO at the University of New Mexico, USA. The bone ECHO programs are designed to expand the capacity to deliver best practice skeletal healthcare worldwide through ongoing technology-enabled case-based collaborative learning. To evaluate the impact of the first 3 years of Bone Health TeleECHO Moscow on physicians' knowledge in the management of bone diseases. METHODS: Demographic data were obtained, and outcomes were assessed through an electronic blinded self-efficacy questionnaire focusing on competence and skills in 20 domains of osteoporosis care before and after each year of participation in the Bone Health TeleECHO Moscow. RESULTS: Over 3 years, a total of 296 participants completed the questionnaire. Average attendance for each monthly session increased from 64 in 2019 to 73 in 2020 and to 96 in 2021. Participants were from all regions of Russia and Russian-speaking countries. The mean age of respondents was 43 years with the youngest being 23 and the eldest 74. The most common participants' primary specialties were endocrinology (n = 263), gynecology (n = 20), orthopedics (n = 3), and other (n = 10). All of our participants were physicians, including 73 MD PhDs. This educational intervention was associated with a statistically significant improvement in each of the 20 domains of osteoporosis care, with an effect size of 0.87 (p < 0.001). CONCLUSION: Bone Health TeleECHO is effective at improving clinicians' skills in the management of osteoporosis based on self-evaluation over 3 years.

In hospital risk factors for acute kidney injury and its burden in patients with Sars-Cov-2 infection: a longitudinal multinational study.

Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8-5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.

Quality of life in people with type 2 diabetes in the 3 years following initiation of second-line therapy: The DISCOVER study.

AIMS: To assess changes in health-related quality of life (HRQoL) in DISCOVER, a 3-year, longitudinal, observational study of patients with type 2 diabetes initiating a second-line glucose-lowering therapy. METHODS: HRQoL was assessed using the physical and mental component summary (PCS and MCS) scores of the 36-item Short-Form Health Survey version 2 (score ranges: 0-100; higher denotes better HRQoL) and the Hypoglycaemia Fear Survey II (HFS-II; score range: 0-132 scale; higher indicates greater fear of hypoglycaemia). Latent class growth modelling (LCGM) was used to identify patients with similar score trajectories. RESULTS: Mean baseline PCS (n = 7428), MCS (n = 7453), and HFS-II (n = 5005) scores were 48.0, 45.4, and 15.4, respectively, and remained stable during follow-up. LCGM revealed subgroups with low or decreasing HRQoL. Patients in these subgroups tended to be older, had more comorbidities, and a lower socioeconomic status than in other subgroups. Use of insulin and sulfonylureas was highest in the subgroup with the highest fear of hypoglycaemia. CONCLUSIONS: Overall, HRQoL remained stable in DISCOVER patients during follow-up. However, LCGM suggests that some patient characteristics and use of sulfonylureas or insulin are associated with low or decreasing HRQoL, potentially warranting the use of alternative therapies.

Impact of micro- and macrovascular complications of type 2 diabetes on quality of life: Insights from the DISCOVER prospective cohort study.

BACKGROUND: The key goals of management in patients with type 2 diabetes (T2D) are to prolong life and improve quality of life. Micro- and macrovascular complications of T2D not only increase the risk of morbidity and mortality, but cross-sectional studies indicate they may also worsen quality of life. We prospectively examined the association of complications that developed during the follow-up with concurrent changes in quality of life. MATERIALS AND METHODS: DISCOVER is a multinational, prospective, observational cohort study of T2D patients enrolled at initiation of second-line glucose-lowering therapy. Quality of life was assessed with the SF-36 Physical (PCS) and Mental Components Summary (MCS) scores at baseline, 6 months, and 1, 2 and 3 years. Hierarchical repeated measures regression models for PCS and MCS were constructed with complications included as time-dependent covariates; first each complication was modelled alone and then second including all interval complications (to account for different complications occurring in the same patient). RESULTS: Among 7830 patients with T2D from 30 countries (mean age 56.6 years, 47.6% women, mean duration of T2D 5.6 years), baseline mean SF-36 PCS was 48.0 ± 7.8 and SF-36 MCS was 45.5 ± 10.4. At baseline, 1422 (18.2%) patients had a known microvascular complication, and 966 (12.3%) had a macrovascular complication. Over the 3 years of the study, 641 (12.0%) developed a new microvascular complication (most commonly neuropathy) and 372 (5.8%) developed a new macrovascular complication (most commonly coronary disease). New diagnoses of coronary disease, peripheral artery disease, heart failure and neuropathy were each associated with subsequent moderate reductions in SF-36 PCS (range 0.7 to 1.6 points) and new cerebrovascular disease was associated with a reduction in SF-36 MCS (2.6 points). Results were consistent when all interval complications were considered in the same model. CONCLUSION: In a prospective, multinational study of patients with T2D, the development of macrovascular complications and neuropathy was associated with decreases in both physical and mental quality of life. Our results provide additional support for clinicians to focus on the prevention, detection and management of the complications of T2D.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.