Type 2 Diabetes Patients Research Articles

6521 Continuation of Continuous Glucose Monitors in Hospitalized Diabetic Patients Decreased the Incidence of Hypoglycemia

Abstract Disclosure: C.E. DeClue: None. S. Bao: None. Objective: Glycemic control improves patient outcomes in hospitalized patients, and this is generally achieved by monitoring point-of-care (POC) capillary glucose levels. In the outpatient setting, continuous glucose monitoring (CGM) devices have shown improved glycemic control in diabetic patients, but their evidence in hospitalized patients is lacking. Methods: To evaluate CGM accuracy and safety of use in the inpatient setting, 567 consults were analyzed in a single-center inpatient diabetes service between November 2022 and January 2023. Patients were included if managed with multiple daily injections or insulin pump therapy and separated into four groups based on CGM continuation and type of diabetes. POC glucose and incidence of hypoglycemia were recorded over 72 hours from the time of consultation. Results: Forty-six Type-1 (T1DM) and 72 Type-2 (T2DM) diabetic patients were included in this study, with average hemoglobin A1c of 8.6% and 9.0%, respectively. Both diabetic groups showed an average POC glucose that was not statistically different based on CGM continuation (185 mg/dL for T1DM and 187 mg/dL for T2DM continued on CGM versus 183 mg/dL for T1DM and 188 mg/dL for T2DM not using CGM). However, only 2 of the 18 T1DM patients continued on CGM experienced hypoglycemia, whereas 17 of the 28 T1DM patients not using CGM experienced at least 1 hypoglycemic event. Similarly, only 2 of the 20 T2DM patients continued on CGM experienced hypoglycemia, whereas 13 of the 52 patients not using CGM experienced at least 1 hypoglycemic event. Additionally, less glucose variability was observed in both T1DM and T2DM patients continued on CGM (average standard deviation of 64 mg/dL and 55 mg/dL, respectively) compared to those not using CGM (average standard deviation of 84 mg/dL and 62 mg/dL, respectively). Conclusion: CGM has great potential to improve patient care and nursing workload in the hospital, but the safety and accuracy are not yet well-established. In this study, there seemed to be a statistically insignificant trend to less glycemic variability for CGM users despite no glycemic difference on average POC testing. Importantly, significantly fewer hypoglycemic events were observed in patients continued on CGM devices regardless of type of diabetes or baseline glycemic control. This study adds further evidence to the growing body of work supporting improved safety of CGM utilization in hospitalized diabetic patients. Presentation: 6/1/2024

12524 Predictive Factors For Type 2 Diabetes Remission: Insights From A Digital Twin Intervention Program At 18 Months

Abstract Disclosure: P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Balasubramanian: None. S.R. Joshi: None. Background and aims: Digital twin (DT) platform uses Artificial Intelligence (AI) and Internet of Things, to integrate multi-dimensional data for precision nutrition and health recommendations via the mobile app. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Evidence suggests that remission is more likely in individuals with early type 2 diabetes (T2D) who are not using insulin therapy and who can engage in significant weight loss. We evaluated the predictive value of baseline parameters on T2D remission, including duration of diabetes, HbA1c levels, diabetic medications as drug count, and CGM metrics, with the objective to improvise the patient selection strategies for remission Methods We analyzed T2D patients (n=209) who completed 18 months of digital twin intervention. Potential predictors were examined by logistic regression analyses, with model performance evaluated by accuracy, precision, recall, and Area under the Receiver Operating Characteristic Curve (AUC-ROC) metrics. Results The model achieved an accuracy of 78.57%, precision of 79.41%, recall of 93.10%, and AUC-ROC of 0.745. Significant inverse associations with remission were observed for the duration of diabetes (OR: 0.74), baseline HbA1c (OR: 0.76), and the number of anti-diabetic medications as oral drugs (OR: 0.77), indicating decreased odds of remission with increasing values. Conversely, positive associations were found for Time Below Range 2 at baseline (OR: 1.22) and HOMA2IR at baseline (OR: 1.24), suggesting increased odds of remission with higher values in these metrics. We describe the Receiver Operating Characteristic (ROC) curve for the diabetes remission prediction model, with the area under the curve (AUC) indicating the model's discriminatory ability. The duration of diabetes emerged as the most significant negative predictor, followed by baseline HbA1c and the number of diabetic drugs, while counterintuitive findings like the positive association of baseline HOMA2IR with remission suggest areas for further investigation. Conclusion We identified baseline parameters significantly influencing the likelihood of T2D remission in people undergoing digital twin intervention. The odds ratios indicate the effect sizes of these predictors, highlighting the importance of personalized, data-driven treatment approaches that potentially enhance remission outcomes. Further validation of these findings in larger external cohorts would be useful. Presentation: 6/1/2024

7366 Experience and perspectives of healthcare professionals regarding exercise directed guidance in pediatric type 1 diabetes

Abstract Disclosure: H. Reznik: None. A. Brener: None. F. Levy-Khademi: None. J. Yeshayahu: None. D. Pivko-Levy: None. I. Koren: None. O. Pinhas-Hamiel: None. M. Sharkia: None. L. Carmon: None. M. Rachmiel: None. M. Muller: None. L. de Vries: None. M. Cohen: None. Objective: Regular exercise can promote various aspects of health in pediatric type-1-diabetes (T1D). However, the management of exercise can be extremely challenging for the child, their family and the healthcare team involved. Studies suggest that children with T1D perform less than the recommended daily activity and that exercise does not always improve glycemic control. Multiple factors should be accounted for, including among others, the nature of the activity and individual child, as well as the treatment regimen. Proper guidance in preparation for exercise is crucial. We conducted a national study aimed at identifying strengths and limitations of exercise directed guidance (EDG) provided by staff in pediatric T1D clinics in Israel. Methods: Healthcare professionals from 8 pediatric diabetes clinics, including physicians, nurses and dietitians, were recruited. Participants completed an anonimized electronic questionnaire assessing: i) Demographics ii) Timing and content of the guidance provided to pediatric patients with T1D iii) Perceived challenges. Results: Ninety-nine professionals took part in this study, 53 physicians, 24 nurses and 23 dietitians. All reported providing EDG to pediatric T1D patients, 90 (90.9%) include EDG both during the initial post-diagnosis visits and periodically thereafter. However, while 83 (83.8%) reported offering guidance to all patients, 16 (16.1%) indicated guiding only specific children: either those that exercise, those that do not exercise or only those that asked for information. Only 64 (64.6%) reported to have specialized educational materials available in clinic, this varied even within the same clinic. The 3 most prevalent topics reported by participants as “usually included” in EDG, were: immediate effects on glucose (94.9%), adjusting carbohydrates (88.8%) and the equipment required during exercise (86.8%). The 3 least frequently addressed subjects were: addressing principals in planning exercise (28.2%) and involving family and friends (29.2% and 17.1% respectively). Challenges by order of prevalence were insufficient teaching aids, the complexity of the topic, lack of knowledge and insufficient time (reported by 44.4%, 39.4%, 34.3% and 34.3% respectively). The knowledge gap most commonly reported centered on understanding the impact of different types of exercise on blood glucose. Conclusions: Healthcare professionals recognize the importance of exercise in T1D management and all of them incorporate EDG in their routine practice. Interestingly, there is considerable variability in both timing and content of the EDG provided, even within the same clinic. We have identified important areas for improvement, with particular attention needed in increasing the availability of educational tools and enhancing staff knowledge. Our findings can assist in creating educational aids for both staff and patients. Presentation: 6/2/2024

Use of a PK/PD Model to Select Cetagliptin Dosages for Patients with Type 2 Diabetes in Phase 3 Trials.

Cetagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of patients with type 2 diabetes (T2D). Several phase 1 studies have been conducted in China. Modelling and simulation were used to obtain cetagliptin dose for phase 3 trials in T2D patients. A pharmacokinetic (PK)/pharmacodynamic (PD) model and model-based analysis of the relationship between hemoglobin A1c (HbA1c) and dosage was explored to guide dose selection of cetagliptin for phase 3 trials. The PK/PD data were derived from four phase 1 clinical studies, and sitagliptin 100 mg was employed as a positive control in studies 1, 3, and 4. The PK profiles of cetagliptin were well described by a two-compartment model with first-order absorption, saturated efflux, and first-order elimination. The final PD model was a sigmoid maximum inhibitory efficacy (Emax) model with the Hill coefficient. The final model accurately captured cetagliptin PK/PD, demonstrated by goodness-of-fit plots. Based on weighted average inhibition (WAI), the relationship between HbA1c and dose was well displayed. Cetagliptin 50 mg once daily or above as monotherapy or as add-on therapy appeared more effective in HbA1c reduction than sitagliptin 100 mg. Cetagliptin 50 mg or 100 mg once daily was selected as the dose for phase 3 trials of cetagliptin in T2D patients. The PK/PD model supports dose selection of cetagliptin for phase 3 trials. A model‑informed approach can be used to replace a dose-finding trial and accelerate cetagliptin's development.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] μIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.

Gut microbiota, serum metabolites, and lipids related to blood glucose control and type 1 diabetes.

The composition and function of gut microbiota, lipids, and metabolites in patients with type 1 diabetes (T1D) or its association with glycemic control remains unknown. We aimed to use multi-omics sequencing technology and machine learning (ML) approaches to investigate potential function and relationships among the gut microbiota, lipids, and metabolites in T1D patients at varied glycemic levels. We conducted a multi-omics analysis of the gut microbiome from fecal samples, metabolites, and lipids obtained from serum samples, collected from a cohort of 72 T1D patients. The patients were divided into two groups based on their hemoglobin A1c (HbA1c) levels. 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in composition and function of gut microbiota, metabolites, and lipids. The linear discriminant analysis, Shapley additive explanations (SHAP) algorithm, and ML algorithms revealed the enrichment of Bacteroides_nordii, Bacteroides_cellulosilyticus in the glycemic control (GC) group, while Bacteroides_coprocola and Sutterella_wadsworthensis were enriched in the poor glycemic control (PGC) group. Several metabolic enrichment sets like fatty acid biosynthesis and glycerol phosphate shuttle metabolism were different between two groups. Bacteroides_nordii exhibited a negative association with D-fructose, a component involved in the starch and sucrose metabolism pathway, as well as with monoglycerides (16:0) involved in the glycerolipid metabolism pathway. We identified distinct characteristics of gut microbiota, metabolites, and lipids in T1D patients exhibiting different levels of glycemic control. Through comprehensive analysis, microbiota (Bacteroides_nordii, Bacteroides_coprocola), metabolites (D-fructose), and lipids (Monoglycerides) may serve as potential mediators that communicated the interaction between the gut, circulatory systems, and glucose fluctuations in T1D patients.

Association Between Type 1 Diabetes Mellitus and Incident Gastrointestinal Cancer in Korean Population: A Nationwide Retrospective Cohort Study.

The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex. This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers. Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age. The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care.

Exploring CCR5 + T regulatory cell subset dysfunction in type 1 diabetes patients: implications for immune regulation.

T regulatory lymphocytes (Treg) expressing CCR5 exhibit strong suppression activity in various autoimmune disorders. However, there remains a lack of comprehensive understanding regarding their involvement in the development of type 1 diabetes (T1D). In this study, we examined the role of the CCR5/CCL5 axis in regulating inflammatory response and its impact on regulatory T cells in type 1 diabetes (T1D). We hypothesize that dysregulation of the CCR5/CCL5 axis contributes to the development and progression of T1D through modulation of Treg-dependent immune responses. We analyzed the expression levels of CCR5 on Tregs isolated from individuals with T1D, as well as the plasma concentration of its main ligands. We found that Tregs from T1D patients exhibited decreased expression of CCR5 compared to healthy controls. Additionally, we observed a correlation between the expression levels of CCR5 on Tregs and their immunosuppressive function in T1D patients. Our results indicate the impaired migratory capacity of CCR5 + Tregs, suggesting a possible link between the dysregulation of the CCR5/CCL5 axis and impaired immune regulation in T1D. In line with previous studies, our findings support the notion that dysregulation of the CCR5/CCL5 axis contributes to the development and progression of type 1 diabetes (T1D) by modulating Treg-dependent immune responses. The decreased expression of CCR5 on Tregs in T1D patients suggests a potential impairment in the migratory capacity of these cells, which could compromise their ability to suppress autoreactive T cells and maintain immune homeostasis. Furthermore, our study highlights the importance of CCR5 as a biomarker for identifying dysfunctional Tregs in T1D.

The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agoniston patients with type 2 diabetes: A population-based study.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (≥12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations.

Trends in type 2 diabetes medication use and guideline adherence in Belgian primary care (2019–2023)

AimsTo assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) in Belgium. To analyze trends in medication use and adherence to guidelines from 2019 to 2023. MethodsWe conducted a retrospective cross-sectional analysis using data from the Intego primary care database, encompassing records from 431 general practitioners. We identified adults with T2D through diagnostic codes and glycated hemoglobin levels and analyzed subgroups with ASCVD, HF, and CKD for trends in medication use, particularly SGLT2 inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP-1). ResultsThe T2D population increased from 20,766 in 2019 to 21,764 in 2023. The prevalence of ASCVD, HF, and CKD among T2D patients slightly increased to 27 %, 6.7 %, and 23.7 % by 2023 (from 25.2 %, 4.9 % and 21.5 % respectively). Medication prescription trends showed a tripling of SGLT2-i and GLP-1 prescribing in the study period to 6.2 % and 11.5 % respectively. Despite these increases, only 7.5 % of eligible patients received these medications as of 2023. ConclusionThe study highlights a growing burden of ASCVD, HF, and CKD among T2D patients in Belgium and an increase in the use of guideline-recommended medications. However, there remains a substantial gap in the optimal use of these therapies, indicating a need for improved implementation of clinical guidelines in primary care.

The Possible Association of IL-6R Gene Polymorphisms in the Development of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN. This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients. Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05). The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.

Effects of Camel Milk on Glycemic Indices and Lipid Profiles of Type-1 and Type-2 Diabetic and Metabolic Syndrome Patients: A Systematic Review

Effects of Camel Milk on Glycemic Indices and Lipid Profiles of Type-1 and Type-2 Diabetic and Metabolic Syndrome Patients: A Systematic Review

Gut microbiota composition and type 2 diabetes: Are these subjects linked Together?

PurposeEvidence suggests that changes in the composition of gut microbiota may be linked to metabolic disorders including type 2 diabetes (T2D). The present study aims to evaluate the compositional changes of the intestinal microbiota in patients with T2D as compared to healthy individuals. MethodsIn this case-control study, there were 18 T2D patients and 18 healthy individuals who served as controls. To profile the gut microbiota in both groups, bacterial DNA was extracted from fecal samples and analyzed using quantitative real-time polymerase chain reaction (qPCR). ResultsThe study discovered that diabetics had significantly greater frequencies of the genus Bacteroides and the phylum Bacteroidetes than did controls (P = 0.03 and P < 0.001, respectively). Conversely, the Actinobacteria and Firmicutes phyla were significantly more abundant in the controls (P=0.01 for both). No significant differences were observed in the fecal populations of the genus Enterococcus, Clostridium clusters IV and XIVa, phylum Proteobacteria, and all bacteria between the studied groups (P=0.88, P=0.56, P=0.8, P=0.99, and P=0.7, respectively). ConclusionsOur findings confirm that T2D may be associated with the gut microbiota fluctuations. These findings may be valuable for developing strategies to control or treatment T2D by restoring the intestinal microbiota through the strategic administration of specific probiotics/prebiotics and lifestyle and dietary modifications.

Interactions of the Osteokines, Glucose/Insulin System and Vascular Risk Networks in Patients With Newly Diagnosed Type 2 Diabetes (VNDS 15).

Bone as an endocrine organ regulates metabolic processes independently of mineral metabolism through the production/release of proteins collectively named 'osteokines'. Relevant connections were reported between the insulin/glucose system, calcification of the atherosclerotic plaque, and several osteokines. We aimed to test the hypothesis that the osteokine network could be involved in beta-cell function, insulin sensitivity, and vascular damage in a cohort of people with newly diagnosed type 2 diabetes (T2D). In 794 drug-naive, GADA-negative, newly-diagnosed T2D patients (mean±SD age: 59±9.8years; BMI: 29.3±5.3kg/m2; HbA1c: 6.6±1.3%) we assessed: plasma concentration of osteocalcin (OCN), osteopontin (OPN),RANKL, and its putative decoy receptor osteoprotegerin (OPG); insulin sensitivity (SI) by hyperinsulinemic euglycemic clamp; beta cell function (BCF), estimated by OGTT minimal modelling and expressed as derivative (DC) and proportional (PC) control. Echo-doppler of carotid and lower limb arteries were also performed in 708 and 701 subjects, respectively. OCN, RANKL and OPG were significantly associated with PC (p<0.02); OCN was positively related to DC (p=0.018). OPG was associated with lower IS (p<0.001). Finally, the higher RANKL levels, the greater was the severity of atherosclerosis in common carotid artery (p<0.001). Increased OPG and OPN concentrations were related to subclinical atherosclerosis in peripheral arteries of lower limbs (p=0.023 and p=0.047, respectively). These data suggest that, in patients with newly diagnosed T2D, the osteokine network crosstalks with the glucose/insulin system and may play a role in modulating the atherosclerotic process.

Improving Medication Adherence in Geriatric T2DM Patients: A Factorial Randomized Controlled Trial

Abstract Background: The complexity of managing type 2 diabetes (T2D) in the elderly is compounded by the need to balance over-prescription, under-prescription, and appropriate prescription. Managing hyperglycemia and its complications, along with geriatric syndromes such as cognitive impairment and falls, often leads to use of an increased number of medications. Quality improvement measures, while aimed at better management, can inadvertently contribute to the burden of polypharmacy. Addressing medication non-adherence is crucial, as it is a significant contributor to poor clinical outcomes, increased hospitalizations, and healthcare costs. Objectives: This study thus aimed to evaluate the effectiveness of interventions to improve medication adherence among elderly patients with T2D. It assessed the impact of a medication adherence device, clinical pharmacological intervention, and their combination compared to standard of care (SOC) alone on adherence rates, adverse drug reactions (ADRs), and glycemic control. Materials and Methods: This pilot study was a factorial randomized controlled trial. A total of 120 elderly T2D patients with a medication adherence rate of less than 80% over the past year were randomized into four groups: (1) medication adherence device + SOC, (2) clinical pharmacological intervention + SOC, (3) combined intervention + SOC, and (4) SOC alone. The primary outcome was medication adherence, assessed through pill counting. ADRs were evaluated using the Naranjo ADR causality assessment scale, and glycemic control was monitored through HbA1c levels. Statistical analyses included chi-square tests and ANOVA, with significance set at P &lt; 0.05. Results: Interim analysis showed the highest adherence rate in the combined intervention group (82.1%), followed by the clinical pharmacological intervention + SOC group (75.3%), the medication adherence device + SOC group (73.1%), and the SOC alone group (70.0%). The combined intervention group also recorded the lowest ADR rate (6.6%). Regarding glycemic control, 81% of the combined intervention group achieved an HbA1c level of less than 7%, compared to 80% in the clinical pharmacological intervention + SOC group, 78% in the medication adherence device + SOC group, and 69% in the SOC alone group. Differences in glycemic control were not statistically significant (P = 0.950). Conclusions: The study indicates that combined interventions including medication adherence devices along with SOC significantly improve medication adherence and reduce ADRs in elderly T2D patients. Future research should focus on diverse populations and long-term sustainability of these interventions.

MicroRNA-34a and promoter methylation contribute to peroxisome proliferator-activated receptor gamma gene expression in patients with type 2 diabetes

AimsThis study aimed to investigate the roles of DNA methylation and miR-34a in the regulation of peroxisome proliferator-activated receptor gamma (PPARγ) in patients with type 2 diabetes (T2D). MethodsWe investigated the methylation status of four regions of the PPARγ promoter and PPARγ expression in a panel of 84 T2D patients using methylation-specific PCR (MSP) and RT-qPCR, respectively. Moreover, we quantified DNA methyltransferases (DNMTs) expression and global DNA methylation levels by RT-qPCR and ELISA, respectively. We measured the expression levels of miR-34a and protein expression of PPARγ by stem-loop RT-qPCR and ELISA, respectively. ResultsWe found significant DNA hypermethylation in the R2 and R3 regions of the PPARγ promoter in people with diabetes. Functionally, this was associated with a significant reduction in PPARγ expression. In addition, we observed a significant increase in 5-methylcytosine levels in people with diabetes. A marked increase in circulating miR-34a in the early stages of T2D (up to 10 years) and a significant decrease in circulating miR-34a with increasing diabetes duration from 10 years after the onset of diabetes. Interestingly, upregulation of DNA methyltransferases 1 (DNMT1), DNMT3A, and DNMT3B was observed in people with diabetes, and the average expression of DNMTs was negatively correlated with circulating miR-34a levels. In contrast, the serum protein level of PPARγ, a direct target of miR-34a, increased considerably with diabetes duration and showed a negative correlation with circulating miR-34a, cholesterol, triglyceride, and low-density lipoprotein. ConclusionPPARγ promoter hypermethylation and miR-34a upregulation are associated with T2D pathogenesis through PPARγ dysregulation.

Women Suffered More Than Men Both During and After the COVID-19 Pandemic-A Cross-Sectional Study Among 29,079 Patients With Type 2 Diabetes.

To investigate the gender differences and the disparities between infected and noninfected patients with type 2 diabetes (T2D) regarding patient-reported experiences during the COVID-19 pandemic in Norway. Register study using questionnaires sent electronically to patients with T2D, June 2022. The questionnaire included 82 questions covering COVID-19 disease, symptoms, medications, comorbidities, hospital care, possibility of working from home and information received from health authorities. Clinical and demographic data were collected from the Norwegian diabetes registry for adults. A total of 29,079 T2D patients participated, of whom 38.1% were women. Patients infected with COVID-19 were younger, had shorter diabetes duration and less comorbidities than noninfected (p < 0.01). Women reported significantly more anxiety, depression and fear of not getting their diabetes medication than men did. Most patients were vaccinated against COVID-19 (98.3%), whereas approximately 60% had received seasonal flu vaccine, and only 27.2% the pneumococcal vaccine. Women described more vaccine adverse effects and long Covid symptoms. Overall, 14% experienced vaccine complications and 27.3% of infected individuals reported long Covid symptoms. 2.4% of the infected patients needed hospital admission. Patients were satisfied with the follow-up of their diabetes, and with information from the government during the pandemic. Female patients were more likely to experience a prolonged Covid course, and higher degree of adverse effects from the COVID-19 vaccine than male patients. Also, long Covid symptoms were significantly more often reported among female patients, while men were more prone to be hospitalised when infected. Hospitalised patients, both men and women, had significantly higher HbA1C than those who were not hospitalised. T2D patients had a surprisingly low pneumococcal vaccination coverage, despite recommendations in national guidelines.

Glucose-lowering drugs and liver-related outcomes among individuals with type 2 diabetes: A systematic review of longitudinal population-based studies.

While randomized controlled trials data on the long-term effect of glucose-lowering drugs (GLDs) on liver-related outcomes are lacking, population-based studies have evaluated the associations of GLDs with liver-related outcomes in individuals with type 2 diabetes (T2D). we aimed to conduct a systematic review of population-based studies evaluating the effects of GLDs on liver-related outcomes in people with T2D. PubMed, Web of Science, and Embase databases were systematically searched for population-based studies testing the associations of GLDs with liver-related outcomes in individuals with T2D and no liver disease other than non-alcoholic fatty liver disease (NAFLD) from inception to 23 February 2024. GLDs included SGLT2is, TZDs, insulin, GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP4Is). Ten cohort studies, comprising 1,274,641 participants, met the inclusion criteria. The median follow-up period ranged from 8.9 to 76 months. Of all the GLDs under investigation, SGLT2is were associated with the strongest reduction in NAFLD incidence, cirrhosis, and composite liver-related events compared to other medications. TZDs were associated with a reduced risk of developing NAFLD and cirrhosis but were not significantly associated with a lower incidence of hepatocellular carcinoma. GLP-1 RAs demonstrated a significant association with reduced liver-related mortality. Observational data from population-based studies suggest that GLDs such as SGLT2is are associated with beneficial long-term liver-related outcomes in T2D patients with NAFLD. Additional studies, including randomized controlled trials with long-term follow-up, are needed to confirm these findings. PROSPERO CRD442024536872.

The value of concomitant testing of cutaneous silent period with sympathetic skin response and heart rate variability in Type-2 diabetes patients: An electrophysiological study.

To explore the association among cutaneous silent period, sympathetic skin response and heart rate variability in diabetes patients. The case-control study was conducted at the Department of Physiology, College of Medicine, Al- Mustansiriyah University, Baghdad, Iraq, from November 1, 2020, to May 20, 2021, and comprised 24 healthy controls in Group I and 49 patients of type 2 diabetes in Group II who were recruited from the neuroelectrophysiological unit of Al-Imamain Al-Kadhmean Teaching Hospital, Baghdad, Iraq. Both groups were subjected to cutaneous silent period, sympathetic skin response and heart rate variability testing. Data was analysed using SPSS 24. Of the 73 subjects, 24(32.9%) were in Group I and 49(67.1%) were in Group II. Cutaneous silent period mean latency values were significantly increased in Group II compared to Group I (p<0.05), and a negative sympathetic skin response in the right lower limb was significantly different between the groups (p<0.001). There was no significant correlation between Cutaneous silent period and sympathetic skin response values (p>0.05). Heart rate variability was significantly increased in diabetic patients with negative sympathetic skin response compared to those with positive sympathetic skin response (p<0.05). Simultaneous measurement of cutaneous silent period, sympathetic skin response and heart rate variability should be done as there were no strong correlation among the tests in diabetic patients.

A PHARMACOECONOMIC EVALUATION OF TYPE 2 DIABETES DRUGS IN CENTRAL PHARMACIES IN SİVAS PROVINCE

Type 2 diabetes is characterized by insulin resistance in tissues such as the liver, muscle, and fat, resulting from detectable damage to pancreatic beta cells. The disease is also related to genetics, environmental factors, and lifestyle. In our country, 22.6% of the health budget is allocated to treating diabetes and its complications. Due to the increasing incidence of patients with type 2 diabetes, effective and rational treatments to reduce the burden of the disease on the healthcare budget have become an important issue for both payers and policymakers. In this study, prescriptions of 391 Type-2 diabetic patients were analyzed from pharmacies selected by mass sampling method in Sivas center, and the pharmacoeconomic suitability of these drugs was investigated, taking into account chronic complications related to diabetes. According to the data obtained, the drugs prescribed to diabetic patients with chronic diseases were found to be appropriate. However, when all diabetic patients were examined, it was determined that the prescribed amount of insulin preparations was high and not pharmaceutically appropriate. It was revealed that the cost of type 2 diabetes medications for 391 patients was 77,852,79 TRY, and the prescription price was 199.11 TRY.