Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Effectiveness of date seed on glycemia and advanced glycation end-products in type 2 diabetes: a randomized placebo-controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients. METHODS: In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively. RESULTS: The results showed that supplementation with DSP significantly decreased HbA1c (-0.30 ± 0.48%), insulin (-1.70 ± 2.21 µU/ml), HOMA-IR (-1.05 ± 0.21), HOMA-B (-0.76 ± 21.21), lipopolysaccharide (LPS) (-3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P < 0.05, ANCOVA adjusted for baseline and confounding factors). On the other hand, DSP supplementation significantly increased total antioxidant capacity (TAC) (0.50 ± 0.26 mmol/L), superoxide dismutase (SOD) (0.69 ± 0.32 U/ml), and s-RAGE (240.13 ± 54.25 pg/mL) compared to the placebo group. FPG, hs-CRP, GPx, CML, and uric acid had no significant within- or between-group changes. CONCLUSION: Supplementation of DSP could be considered an effective strategy to improve glycemic control and oxidative stress in T2DM patients (Registration ID at www.irct.ir : IRCT20150205020965N10).

Treatment intensification and therapeutic inertia of antihypertensive therapy among patients with type 2 diabetes and hypertension with uncontrolled blood pressure.

Treatment intensification is essential to ensure guideline targets are attained in diabetes patients. The failure to intensify treatment when the targets are not achieved is therapeutic inertia. This study aimed to determine the proportions and factors associated with treatment intensification and therapeutic inertia of antihypertensive therapy in type 2 diabetes patients with uncontrolled hypertension in Malaysia. A retrospective cohort analysis was conducted utilising registry data. Diabetes hypertensive patients with uncontrolled baseline systolic or diastolic blood pressure were included. Treatment intensification was the increase in the number of antihypertensive agents from the index treatment. Therapeutic inertia was the absence of treatment intensification when the second blood pressure reading was still uncontrolled. About 6956 patients were followed up over 2.5 ± 1.1 person-years. Treatment intensification was observed in 29.8% of patients, while 38.6% had therapeutic inertia. Chinese, Indian, and 'others' ethnic groups, retinopathy, more antihypertensive agents, and higher systolic blood pressure were associated with therapeutic inertia. Underweight, overweight patients and those with dyslipidaemia had lower risks for therapeutic inertia. The results indicate suboptimal quality of care in public health clinics in Malaysia. Further studies are needed to determine the underlying causes to formulate precise interventions to tackle the problem in Malaysia.

Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Association of GRK5 variant rs10886471 with the therapeutic effect of repaglinide in patients of type 2 diabetes mellitus in Peshawar, Pakistan.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a rising global prevalence. The primary objective of this study was to explore the relationship between the GRK5 variant (rs10886471) and the therapeutic effect of repaglinide in patients of T2DM in Peshawar, Pakistan. A quasi-experimental study was designed. The study group consisted of patients with Type 2 Diabetes Mellitus (T2DM) categorized into responders and non-responders based on their HbA1c level reduction in response to repaglinide treatment. After ethical approval, and consent from the participants, sociodemographic and clinical data was collected from 60 T2DM patients. Blood samples were collected followed by DNA extraction and quantification with UV-Vis Spectroscopy. Genotyping for the GRK5 variant rs10886471 was done using the PCR-based method. Among socio-demographic factors family history and BMI showed significant association (P<0.05) with the therapeutic response to repaglinide. The Statistical analyses, including chi-square tests and logistic regression of GRK5 variant rs10886471 exhibited a significant association with the therapeutic response. Variant allele exhibited significant association (OR: 1.2, p=0.049) with the therapeutic response to repaglinide. The study demonstrated a significant relationship between the GRK5 variant (rs10886471) and the therapeutic response to repaglinide in patients of T2DM of Peshawar, Pakistan.

Therapeutic effect of ginger garlic powder in rats with induced diabetes.

The purpose of this study was to examine the potential hypoglycemic effects of administering ginger (Zingiber officinale) and garlic (Allium sativum) to rats with induced type 2 diabetes. A total of forty-five male adult albino rats were randomly assigned to five groups. The groups were named Normal Control, Diabetic Control, Ginger group, Garlic group and a combination group of ginger and garlic. Diabetes was produced in all groups, except the normal control group, using an intraperitoneal injection of streptozotocin at a dosage of 60 mg/body weight. During the course of two months, rats were administered varying amounts of ginger and garlic powders as part of their treatment After the experiment concluded, measurements were taken for glycated hemoglobin, serum glucose, insulin, cholesterol, high density protein, low density protein and liver glycogen levels. These groups exhibited considerably greater serum insulin and high-density lipoprotein concentrations (P<0.05) compared to the diabetic control group. Conversely, body weight, fasting blood glucose, total cholesterol, low density lipoprotein, and glycated hemoglobin levels were significantly lower (P<0.05) in all groups compared to the diabetic control group. A statistically significant increase (P<0.05) increase shown in liver glycogen levels. This study proposes that the utilization of ginger and garlic powders improve the condition of type 2 diabetes and maybe reduce the risk of subsequent diabetic complications.

Coprevalence and associations of diabetes mellitus and hypertension among people living with HIV/AIDS in Cameroon.

BACKGROUND: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon. METHODS: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking. RESULTS: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25th-75th percentiles: 35-51) years. Age > 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19-29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p < 0.02). However, BMI did not mediate the relationship between ART use and diabetes. CONCLUSIONS: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted.

Mogroside Alleviates Diabetes Mellitus and Modulates Intestinal Microflora in Type 2 Diabetic Mice.

Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.

The mitochondrial tRNA-derived fragment, mt-tRF-LeuTAA, couples mitochondrial metabolism to insulin secretion.

OBJECTIVE: The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-LeuTAA) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-LeuTAA, on mitochondrial metabolism and pancreatic islet functions. METHODS: We used antisense oligonucleotides to reduce mt-tRF-LeuTAA levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-LeuTAA inhibition. Additionally, we employed pull-down assays followed by mass spectrometry to identify direct interactors of the fragment. Finally, we characterized the impact of mt-tRF-LeuTAA silencing on the coupling between mitochondrial metabolism and insulin secretion using high-resolution respirometry and insulin secretion assays. RESULTS: Our study unveils a modulation of mt-tRF-LeuTAA levels in pancreatic islets in different Type 2 diabetes models and in response to changes in nutritional status. The level of the fragment is finely tuned by the mechanistic target of rapamycin complex 1. Located within mitochondria, mt-tRF-LeuTAA interacts with core subunits and assembly factors of respiratory complexes of the electron transfer system. Silencing of mt-tRF-LeuTAA in islet cells limits the inner mitochondrial membrane potential and impairs mitochondrial oxidative phosphorylation, predominantly by affecting the Succinate (via Complex II)-linked electron transfer pathway. Lowering mt-tRF-LeuTAA impairs insulin secretion of rat and human pancreatic ß-cells. CONCLUSIONS: Our findings indicate that mt-tRF-LeuTAA interacts with electron transfer system complexes and is a pivotal regulator of mitochondrial oxidative phosphorylation and its coupling to insulin secretion.

Association between Interleukin-6 Gene Polymorphism (rs1800795 and rs1800796) and Type 2 Diabetes Mellitus in a Ghanaian Population: A Case-Control Study in the Ho Municipality.

Background: There is no conclusive evidence on the association between interleukin- (IL-) 6 gene polymorphism and type 2 diabetes mellitus (type 2 DM). Thus, this study is aimed at evaluating the role of rs1800795 and rs1800796 polymorphisms in the pathogenesis of type 2 DM among Ghanaians in the Ho Municipality. Materials and Methods: We recruited into this hospital-based case-control study 174 patients with type 2 DM (75 DM alone and 99 with DM+HTN) and 149 healthy individuals between 2018 and 2020. Demographic, lifestyle, clinical, anthropometric, and haemodynamic variables were obtained. Fasting blood samples were collected for haematological, biochemical, and molecular analyses. Genomic DNA was extracted, amplified using Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique, and genotyped for IL-6 gene polymorphism. Logistic regression analyses were performed to assess the association between IL-6 gene polymorphism and type 2 DM. Results: The minor allele frequency (MAF) of the rs1800795 and rs1800796 polymorphisms was higher in DM alone (57.5%, 62.0%) and DM with HTN groups (58.3%, 65.3%) than controls (33.1%, 20.0%). Carriers of the rs1800795GC genotype (aOR = 2.35, 95% CI: 1.13-4.90, p = 0.022) and mutant C allele (aOR = 2.41, 95% CI: 1.16-5.00, p = 0.019) as well as those who carried the rs1800796GC (aOR = 8.67, 95% CI: 4.00-18.90, p < 0.001) and mutant C allele (aOR = 8.84, 95% CI: 4.06-19.26, p = 0.001) had increased odds of type 2 DM. For both polymorphisms, carriers of the GC genotype had comparable levels of insulin, HOMA-IR, and fasting blood glucose (FBG) with those who carried the GG genotype. IL-6 levels were higher among carriers of the rs1800796GC variant compared to carriers of the rs1800796GG variant (p = 0.023). The rs1800796 polymorphism, dietary sugar intake, and exercise status, respectively, explained approximately 3% (p = 0.046), 3.2% (p = 0.038, coefficient = 1.456), and 6.2% (p = 0.004, coefficient = -2.754) of the variability in IL-6 levels, suggesting weak effect sizes. Conclusion: The GC genotype and mutant C allele are risk genetic variants associated with type 2 DM in the Ghanaian population. The rs1800796 GC variant, dietary sugar intake, and exercise status appear to contribute significantly to the variations in circulating IL-6 levels but with weak effect sizes.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Monogenic diabetes in a Chinese population with young-onset diabetes: A 17-year prospective follow-up study in Hong Kong.

AIMS: Asians have a high prevalence of young-onset diabetes, but the pattern of monogenic diabetes is unknown. We aimed to determine the prevalence of monogenic diabetes in Chinese patients with young-onset diabetes and compare the clinical characteristics and outcome between patients with and without monogenic diabetes. MATERIALS AND METHODS: We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non-type 1 diabetes diagnosed at age ≤40 years. Incident complications including cardiovascular disease (CVD), end-stage kidney disease (ESKD) and all-cause death were captured since enrolment (1995-2012) until 2019. RESULTS: In this cohort (mean ± SD age at diagnosis: 33.0 ± 6.0 years, median[IQR] diabetes duration 7.0[1.0-15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%-3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK (n = 6), HNF1A (n = 9), HNF4A (n = 1), PLIN1 (n = 1) and PPARG (n = 2), together with copy number variations in HNF1B (n = 3). Over a median follow-up of 17.1 years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1-29.4] per 1000 person-years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8-18.9] per 1000 person-years) developed the composite outcome of CVD, ESKD and/or death (p = 0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups. CONCLUSIONS: In Chinese with young-onset non-type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.

BACKGROUND: Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. OBJECTIVES: This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. MAIN RESULTS: Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I2 = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I2 = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I2 = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I2 = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I2 = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I2 = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I2 = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I2 = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I2 = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I2 = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I2 = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. AUTHORS' CONCLUSIONS: SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.

Participatory Development of an Integrated, eHealth-Supported, Educational Care Pathway (Diabetes Box) for People With Type 2 Diabetes: Development and Usability Study.

BACKGROUND: Type 2 diabetes (T2D) tremendously affects patient health and health care globally. Changing lifestyle behaviors can help curb the burden of T2D. However, health behavior change is a complex interplay of medical, behavioral, and psychological factors. Personalized lifestyle advice and promotion of self-management can help patients change their health behavior and improve glucose regulation. Digital tools are effective in areas of self-management and have great potential to support patient self-management due to low costs, 24/7 availability, and the option of dynamic automated feedback. To develop successful eHealth solutions, it is important to include stakeholders throughout the development and use a structured approach to guide the development team in planning, coordinating, and executing the development process. OBJECTIVE: The aim of this study is to develop an integrated, eHealth-supported, educational care pathway for patients with T2D. METHODS: The educational care pathway was developed using the first 3 phases of the Center for eHealth and Wellbeing Research roadmap: the contextual inquiry, the value specification, and the design phase. Following this roadmap, we used a scoping review about diabetes self-management education and eHealth, past experiences of eHealth practices in our hospital, focus groups with health care professionals (HCPs), and a patient panel to develop a prototype of an educational care pathway. This care pathway is called the Diabetes Box (Leiden University Medical Center) and consists of personalized education, digital educational material, self-measurements of glucose, blood pressure, activity, and sleep, and a smartphone app to bring it all together. RESULTS: The scoping review highlights the importance of self-management education and the potential of telemonitoring and mobile apps for blood glucose regulation in patients with T2D. Focus groups with HCPs revealed the importance of including all relevant lifestyle factors, using a tailored approach, and using digital consultations. The contextual inquiry led to a set of values that stakeholders found important to include in the educational care pathway. All values were specified in biweekly meetings with key stakeholders, and a prototype was designed. This prototype was evaluated in a patient panel that revealed an overall positive impression of the care pathway but stressed that the number of apps should be restricted to one, that there should be no delay in glucose value visualization, and that insulin use should be incorporated into the app. Both patients and HCPs stressed the importance of direct automated feedback in the Diabetes Box. CONCLUSIONS: After developing the Diabetes Box prototype using the Center for eHealth and Wellbeing Research roadmap, all stakeholders believe that the concept of the Diabetes Box is useful and feasible and that direct automated feedback and education on stress and sleep are essential. A pilot study is planned to assess feasibility, acceptability, and usefulness in more detail.

Impact of Skills for Change Program on metabolic control, diet and physical activity levels in adults with type 2 diabetes: A cluster randomized trial.

BACKGROUND: Type 2 diabetes mellitus is highly prevalent in the Arab Gulf countries. Despite this, limited culturally-adapted lifestyle intervention studies have been conducted in this region. METHODS: In this culturally adapted 12-month cluster randomized trial, 382 patients with type 2 diabetes, aged 20-70 years were recruited from 6 public healthcare centers (3 interventions and 3 controls) in Al Ain, United Arab Emirates. The primary outcome of this study was a change in hemoglobin A1c (HbA1c). The secondary outcomes were Body Mass Index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, dietary intake, and physical activity levels. A diet and physical activity intervention, guided by the social cognitive theory, was delivered individually and in group format to the intervention group. The control group continued receiving only their usual diabetes management care. The data were collected at baseline and 1 year after participation. RESULTS: The mean baseline HbA1c levels of the control and the intervention groups were 7.45 ± 0.11% and 7.81 ± 0.11%, respectively. At the end of the 12-month intervention, there was no significant difference in the changes of mean HbA1c between the intervention and the control groups. On the other hand, BMI and daily caloric intake were significantly decreased in the intervention compared to the control group by 1.18 kg/m2 (95% CI: -1.78 - -0.60) and 246 kcal (95% CI: -419.52 - -77.21), respectively, after controlling for age, gender, education, marital status, duration since diabetes diagnosis, diabetes treatment, treatment clinic, and baseline values. Sitting time during the week-end was significantly lower, difference 52.53 minutes (95% CI: 93.93 - -11.14). CONCLUSIONS: This community-based lifestyle intervention for patients with baseline HbA1c <8% did not result in a significant decrease of HbA1c but reduced caloric intake, body weight, and weekend inactivity after controlling for the covariates. TRIAL REGISTRATION: This trial was registered on February 11, 2020 with Clinicaltrials.gov (NCT04264793).

Perception of Type 2 Diabetes Mellitus (T2DM) patients on diabetes self-care management in Fiji.

INTRODUCTION: The prevalence of diabetes has increased globally where Type 2 Diabetes Mellitus (T2DM) is more common than any other type of diabetes. Self- care management education of diabetes provides skills and information for diabetic patients to effectively perform their own self diabetic self-care for optimum glycemic index control. As T2DM is a growing health issue in Fiji, promoting diabetes self manages among patients is a need, however there is lack of evidence in this regard. Therefore, the aim of this study is to explore the perception of T2DM patients on diabetic self-care management. METHOD: This study used a qualitative method among T2DM patients regarding diabetic self-care management in Central Division, Fiji in 2022. This study was conducted in SOPD (Special Out Patient Department) clinics in the three chosen governmental health centers in the central division of Fiji. The study sample inclusion criteria were only T2DM patients, and no other types of diabetes, patients who are 18years and above, patients who are attending clinic at least for more than 6 months, self-identified as Fijian participants of any ethnicity or gender. The study settings were also purposively selected but the study sample was selected using purposive sampling. In depth interview using semi-structured open-ended questionnaires was used to collect data. Thematic analysis was done, followed by reviewing themes, defining and naming them. RESULTS: Thirty patients participated in this study. Five major themes emerged from the in-depth interview including; patient factors that affect diabetes self-care management, behavior and attitude towards T2DM self-care management, health services delivery, challenges and barriers faced by patients to perform diabetes self-care management, and recommendations to improve patient self-care management. Patients in this study have good knowledge about T2DM and the self-care management they have to perform. It is the patients' attitude and behavior towards T2DM self-care management that affects patients to perform self-care management. The study also showed patients have gained good knowledge from Health Care Workers (HCW). Socio-economic and psychological status also played a vital part in patients' self-care management. Apart from challenges, there were opportunities to learn the difficulties patients face in order to perform self-care management. CONCLUSION: The results of this study revealed a combination of individual, cultural, and health systematic related factors as the mots influencer of diabetes self-management among patients in Fiji. Patients have to take ownership of their own health in order to improve their blood sugar reading and reduce complication of diabetes. Tailored interventions that consider patients' belief and address potential challenges would be useful. A lot is needed in terms of upgrading facilities for the comfort of patients and need to collaborate more with other multidisciplinary team and stakeholders.

Informal caregiving among people supporting a person with type 2 diabetes in rural communities of Northern Vietnam: A cross-sectional study of caregiver burdens.

OBJECTIVE: The prevalence of type 2 diabetes mellitus (T2DM) in Vietnam has doubled from 3% to 6% over the last decades, with potential consequences for persons with diabetes and their caregivers. This study aimed to assess caregiver burdens and factors associated with caregiver burden. METHOD: A cross-sectional study was conducted in 2019, using data from 1,241 informal caregivers (ICGs). Caregiver burden was scored from 0-32 using 8 questions from the Zarit Burden Interview (ZBI). Quantile regression analysis was used to identify factors associated with caregiver burden. RESULTS: The median score of the ZBI was 7.0 (Q1-Q3: 2.0-10.0), indicating that the burden among caregiver of persons with T2DM is not high. Quantile regression showed that the higher the monthly income, the lower the burden among caregivers (50% quantile and 75% quantile of burden: -0.004). Lower educational level (25%Q: 4.0, 50%Q; 3.0, 75%Q: 2.16), being a farmer (25%Q: 2.0) and providing care to other people besides the person with T2DM (25%Q: 2.0, 50%Q; 2.54, 75%Q: 1.66) were associated with higher burden on caregivers. CONCLUSION: The study found that caregivers facing additional life stressors, such as low income or other caregiving responsibilities, reported higher levels of burden. These findings could inform the development of interventions targeted at supporting informal caregivers in rural areas in low- and middle-income countries.

Measuring the effectiveness of hybrid diabetes care over 90 days through continuous data monitoring in type 2 diabetic patients.

Background: Diabetes Mellitus, a global health challenge, affects 537 million individuals. Traditional management relies on periodic clinic visits, but technological advancements, including remote monitoring, offer transformative changes. Telemedicine enhances access, convenience, adherence, and glycemic control. Challenges include trust-building and limitations in face-to-face interactions. Integrating remote monitoring with in-person healthcare creates a hybrid approach. This study evaluates the impact on Type 2 Diabetes patients over 3 months. Methods: A retrospective case-control observational study. Inclusion criteria involved previous Type 2 Diabetes diagnosis and a minimum 3-month GluCare model period with two physical visits. Patients in the case group had in-clinic visits, bi-weekly app engagement, and monthly body weight readings. Control group had in-clinic visits only. Outcomes measured included HbA1c, lipid profile, CV risk, eGFR, urine Albumin/Creatinine Ratio, Uric Acid, and CRP. Results: Case group showed significant HbA1c improvements (-2.19%), especially in higher baseline levels. Weight, BMI, LDL, total cholesterol, and CVD risk also improved. Controls showed smaller improvements. Higher digital interactions correlated with better outcomes. Patients with ≥11 interactions showed significant reductions in HbA1c (-2.38%) and weight (-6.00 kg). Conclusion: The GluCare.Health hybrid model demonstrates promising outcomes in Type 2 diabetes management. The integration of in-clinic consultations with continuous remote monitoring leads to substantial improvements in glycemic control and clinical parameters. The study highlights the importance of patient engagement in achieving positive outcomes, with higher digital interactions associated with greater reductions in HbA1c and weight. The hybrid approach proves more effective than digital-only interventions, emphasizing the need for comprehensive, end-to-end solutions in diabetes care.

Metabolomic analysis of retinopathy stages and amputation in type 2 diabetes.

BACKGROUND: Diabetic retinopathy (DR) and limb amputation are frequent complications of diabetes that cannot always be explained by blood glucose control. Metabolomics is a science that is currently being explored in the search for biomarkers or profiles that identify clinical conditions of interest. OBJECTIVE: This study aimed to analyze, using a metabolomic approach, peripheral blood samples from type 2 diabetes mellitus (DM2) individuals, compared with those with diabetic retinopathy and limb amputation. METHODS: The sample consisted of 128 participants, divided into groups: control, DM2 without DR (DM2), non-proliferative DR (DRNP), proliferative DR (DRP), and DM2 amputated (AMP). Metabolites from blood plasma were classified by spectra using nuclear magnetic resonance (NMR), and the metabolic routes of each group using metaboanalyst. RESULTS: We identified that the metabolism of phenylalanine, tyrosine, and tryptophan was discriminant for the DRP group. Histidine biosynthesis, on the other hand, was statistically associated with the AMP group. The results of this work consolidate metabolites such as glutamine and citrulline as discriminating for DRP, and the branched-chain amino acids as important for DR. CONCLUSIONS: The results demonstrate the relationship between the metabolism of ketone bodies, with acetoacetate metabolite being discriminating for the DRP group and histidine being a significant metabolite in the AMP group, when compared to the DM2 group.

Type II diabetes mellitus increases the risk of inflammatory bowel disease in a prospective cohort study.

BACKGROUND: Inflammatory bowel disease is a common digestive disorder and diabetes can lead to intestinal dysfunction. Patients with inflammatory bowel disease in combination with diabetes present a higher rate of hospitalization and consumption of medical resources, yet the association between type 2 diabetes and Inflammatory bowel disease remains unknown. METHODS: We studied 313,008 participants from the UK Biobank, including 5891 patients with type 2 diabetes at baseline. Multivariate Cox proportional risk models were constructed to examine the risks associated with type 2 diabetes and inflammatory bowel disease and its subtypes (Crohn's disease, ulcerative colitis). Potential confounders including sociodemographic, lifestyle, physical body indicators, psychological state, hypertension, and thyroid-related disorders were adjusted. Propensity score matching was also performed to analyze their sensitivity. RESULTS: Of a total of 313,008 participants included in the study, 5891 (1.88 %) were diagnosed with type 2 diabetes mellitus at baseline and 1829 (0.58 %) of the entire cohort developed inflammatory bowel disease during follow-up, with a median follow-up time of 13.72 years. Patients with type 2 diabetes had a higher cumulative risk of inflammatory bowel disease compared to the non-type 2 diabetes population (inflammatory bowel disease: 1.24% vs. 0.57%, p < 0.001; Crohn's disease: 0.46% vs. 0.15%, p < 0.001; ulcerative colitis: 0.73% vs. 0.35%, p < 0.001). Multivariate Cox regression analysis showed that type 2 diabetes was independently associated with inflammatory bowel disease (Hazard Ratio: 1.61 [95% Confidence Interval: 1.26-2.06], p < 0.001), Crohn's disease (Hazard Ratio: 2.10 [95% Confidence Interval: 1.39-3.17], p < 0.001) and ulcerative colitis (Hazard Ratio: 1.58 [95% Confidence Interval: 1.15-2.18], p = 0.005). In a propensity-matched analysis, type 2 diabetes still showed its ability to predict the risk of inflammatory bowel disease (Hazard Ratio: 2.09 [95% Confidence Interval: 1.55-2.83], p < 0.001), Crohn's disease (Hazard Ratio: 3.49 [95% Confidence Interval: 2.00 to 6.09], p < 0.001), and ulcerative colitis (Hazard Ratio: 1.76 [95% Confidence Interval: 1.20 to 2.56], p = 0.003) of robustness. CONCLUSION: In patients with type 2 diabetes mellitus, the risk of inflammatory bowel disease is higher, and the presence of gastrointestinal symptoms in patients with type 2 diabetes requires vigilance for the possibility of inflammatory bowel disease in clinical practice.