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Introduction Hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been used to predict the prognosis in several types of cancers for the last few years. We aimed to reveal whether HALP score has high sensitivity and specificity in the detection of diabetic nephropathy. Methods A cross-sectional study developed in Abant Izzet Baysal University Hospital in Bolu, Türkiye. Patients with type 2 diabetes mellitus (DM) were enrolled in the study. Study cohort included patients with diabetic nephropathy and patients without diabetic nephropathy. Pregnant women, subjects with malignancy, active infections conditions, and rheumatologic or hematologic diseases were excluded. We retrospectively analyzed and compared the HALP scores of the type 2 DM patients with and without diabetic nephropathy. Moreover, we sought correlation between HALP score and fasting glucose, glycated hemoglobin (HbA1c), and estimated glomerular filtration rate (eGFR). Results A total of 356 DM patients, 162 with nephropathy and 194 without nephropathy were included in the study. The HALP score was 44.86 (4.5–119.9) in the nephropathic group, while it was 55.14 (13.2–173.7) in the nonnephropathic group (p < 0.001). HALP score was negatively correlated with HbA1c (r = –0.66, p = 0.003) and fasting glucose (r = –0.65, p = 0.002), while positive correlation was found between HALP score and eGFR (r = 0.13, p = 0.02). HALP score lower than 45.9% have 73% sensitivity and 52% specificity in detecting diabetic nephropathy (area under the curve: 0.64, p < 0.001, 95% confidence interval: 0.59–0.70). Conclusion We suggest that HALP score can become a simple and easy to assess marker for diabetic nephropathy in addition to standard tests. [ABSTRACT FROM AUTHOR]

Konjit Eshetu,1 Lemma Demissie Regassa,2 Merga Dehresa,3 Desta Genete4 1Department of Pediatrics and Child Health, School of Medicine, College of Health and Medical Science, Haramaya University, Harar, Ethiopia; 2Department of Epidemiology and Biostatistics, School of Public Health, College of Health and Medical Science, Haramaya University, Harar, Ethiopia; 3Department of Maternal and Child Health, School of Public Health, College of Health and Medical Science, Haramaya University, Harar, Ethiopia; 4Department of Ophthalmology, School of Medicine, College of Health and Medical Science, Haramaya University, Harar, EthiopiaCorrespondence: Konjit Eshetu, Department of pediatrics and child health, school of medicine, college of health and medical science, Haramaya University, Harar, Ethiopia, Tel +251936807604, Email Konjiteshetu09@gmail.comIntroduction: Type 1 diabetes mellitus is the most common pediatric endocrine disorder. Poor glycemic control in diabetes mellitus can result in microvascular complications (retinopathy, neuropathy, and nephropathy). There is no study done in our setting either about prevalence of pediatric type 1 diabetes mellitus or chronic microvascular complication among these patients, which gap this study is expected to fill.Objective: This study aimed to assess the risk and predictors of chronic microvascular complication of type 1 diabetes mellitus among children with diabetes at Haramaya University Hiwot Fana Compressive Specialized Hospital from September 10, 2021 to January 30, 2023.Methods: A hospital-based Ambi directional cohort study was conducted. Survival data are described by follow-up time and Kaplan–Meier graph. To determine predictors associated with chronic microvascular complication we used a Poisson regression optimal model selected using the information criterion. All associations are tested at the 95% confidence level and a reported IRR P-value less than 0.05 is declared as a significant association between variables.Results: A total of 124 children with type 1 diabetes mellitus were followed with total 407.5 years risk time. The overall incidence rate of chronic microvascular complication was 83 per 1000 population per year (95% CI: 59− 116). The median time for detection of microvascular complication was 7 years after diagnosis. Being male with IRR 1.71 (95% CI: 0. 0.81– 3.56), being at pubertal age IRR 1.91 (95% CI: 1.05– 3.48), longer diabetes mellitus duration IRR 1.13 (95% CI: 1.07– 1.28), and poor glycemic control IRR 1.50 (95% CI: 0.46– 4.97) were found to be at higher risk for chronic microvascular complication.Conclusion: There was high incidence of chronic microvascular complication of diabetes mellitus. Being pubertal age group and more than 3 years duration after diagnosis had statistically significant association with complication.Keywords: pediatric diabetes mellitus, microvascular complication, Harar

In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications.

Objectives: Type 2 diabetes mellitus (T2DM) and its microvascular complications are characterized by chronic inflammation. The Controlling Nutritional Status (CONUT) score is a tool used to assess nutritional status and is often associated indirectly with inflammatory processes. We aimed to compare the CONUT scores of T2DM patients with those of healthy volunteers and to compare T2DM patients with and without microvascular complications. Methods: Patients diagnosed with T2DM and healthy volunteers (as controls) were included in the study. The CONUT score is calculated using the following formula: serum albumin score + total cholesterol score + total lymphocyte count score. CONUT scores of T2DM patients and healthy controls, as well as those of diabetics with and without microvascular complications, were compared. Results: The CONUT scores of the T2DM and control groups were (1 [0–7]) and (0 [0–2]), respectively (p < 0.001). The sensitivity and specificity of the CONUT score (<1.5 threshold) in detecting T2DM were 43% and 90%, respectively (AUC: 0.67, p < 0.001, 95% CI: 0.64–0.71). Moreover, the CONUT score was an independent risk factor for T2DM (OR: 0.34, p < 0.001, 95% CI: 0.22–0.52). The CONUT score of T2DM patients with microvascular complications (2 [0–7]) was significantly higher than that of T2DM patients without microvascular complications (0 [0–4]) and control subjects (0 [0–2]) (p < 0.001). A CONUT score higher than 1.5 had 83% sensitivity and 92% specificity in detecting T2DM with microvascular complications (AUC: 0.91, p < 0.001, 95% CI: 0.89–0.93). Conclusion: The CONUT score could be useful in detecting diabetic microvascular complications in clinical practice, as it is an inexpensive and easy-to-assess marker. [ABSTRACT FROM AUTHOR]

Background: People living with diabetes often encounter psychosocial challenges, including diabetes distress and depression. Despite this, little research has focused on the co-occurrence of these conditions. This study aimed to explore the prevalence of depressive symptoms and diabetes distress in people with type 1 diabetes in Kuwait and to identify clinical and demographic factors associated with these conditions. Methods: A total of 832 people with type 1 diabetes (females: 54.1%, mean age: 29 ± 8.5 years), were invited to participate in Dose Adjustment for Normal Eating (DAFNE) course. Diabetes distress was measured using the Problem Areas in Diabetes (PAID) scale and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Depressive symptoms were defined as PHQ-9 scores =10. Data on biomedical outcomes, lifestyle factors, and sociodemographic information were collected. Results: The prevalence rates of diabetes distress and depressive symptoms were 27.8% and 38.3%, respectively. Notably, 19.6% of people experienced both conditions. In the regression analysis, PAID scale and PHQ-9 scores were significantly associated, patients with higher score on depressive symptoms scale were more likely to suffer diabetes distress (B= 2.65, p < 0.001). Female sex (odds ratio [OR]= 2.2, 95% CI= 1.5, 3.2), higher hemoglobin A1c levels (OR= 1.6, 95% CI= 1.0, 2.5), obesity (OR= 1.7, 95% CI= 1.1, 2.8), inactivity (OR= 2.4, 95% CI= 1.6, 3.6), microvascular complications (OR= 2.8, 95% CI= 1.5, 5.4), and lipohypertrophy (OR= 1.7, 95% CI= 1.1, 2.5) were associated with greater odds for the cooccurrence of diabetes distress and depressive symptoms (p< 0.05 for all). Conclusion: The majority of people with type 1 diabetes in Kuwait experience both diabetes distress and depressive symptoms. The strong correlation between diabetes distress and depressive symptoms suggests mutual predictability. The co-occurrence of both symptoms is associated with many sociodemographic and clinical factors. [ABSTRACT FROM AUTHOR]

Abstract Background and aims The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC). Method We carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study. Result In this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline. Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort. Conclusion The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population.

Background and aims: The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC). Method: We carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study. Result: In this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline. Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort. Conclusion: The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population. [ABSTRACT FROM AUTHOR]

Objective: To find out the frequency of chronic complication among type 2 diabetic subjects in a Tertiary Care Hospital in the province of Punjab. Methodology: This retrospective study elaborates the assessment of information records from people with type 2 diabetes (T2D) who visited the Outpatient department of Nishtar Medical College, a tertiary consideration clinic in Multan, from January 2013 to December 2018. The study comprised subjects who had preexisting microvascular complications or developed diabetic complications during the study period. Entities with gestational and type 1 diabetes were barred from the study. Statistical analysis was performed using Statistical Packages for Social Sciences (SPSS) version 20. Result: The study comprised a total of 4556 participants, with 44.1% being male. The average age of the participants was 47.72 ± 10.82 years. A positive family history of diabetes was detected in 46.3% of the subjects. Furthermore, 21.2% of the participants had hypertension, and 10.3% were classified as obese. Among the subjects, 53.5% had been diagnosed with diabetes for less than 5 years. Among them 74.4% of the participants had hypertension and 58.1% were obese. Conclusion: Frequency of hypertension and obesity was found higher in subjects with T2D in the province of Punjab-Pakistan. Furthermore, these findings underscore the necessity for a multi-center study to confirm their validity. [ABSTRACT FROM AUTHOR]

Objective To explore the correlation between the prolongating PR interval of electrocardiogram and the general information and biochemical indicators of diabetes patients with microvascular complications, and the predictive value of diabetes microvascular complications. Methods A total of 217 patients with diabetes who hospitalized in Department of Endocrinology, Xi'an Third Hospital from August 2020 to November 2022 were selected retrospectively. Among them, 149 patients only with diabetes were divided into control group, while 68 diabetes patients with microvascular complications were divided into observation group. The general data and biochemical indexes of all diabetes patients were collected, and the PR interval was measured by standard 12 lead synchronous electrocardiograph. The correlation between PR interval and general data and biochemical indicators in patients with microvascular complications of diabetes were analyzed. The predictive value of PR interval on microvascular complications in diabetes was analyzed by receiver operating characteristic (ROC) curve. Results Age, duration of diabetes, body mass index (BMI), hemoglobin A1c (HbA1c), PR interval in the observation group were higher than those in the control group (P＜0.01). PR interval of diabetes patients with microvascular complications was positively correlated with age, diabetes duration, BMI, HbA1c (P＜0.01). The AUC of PR interval for predicting microvascular complications in diabetes was 0.812 (95%CI:0.752-0.872), the sensitivity was 70.6%, the specificity was 78.5%, and the cut-off value was 212.61 ms. Prolonged PR interval was an independent risk factor for microvascular complications in diabetes (OR=2.475, 95%CI: 1.472-5.120, P＜0.01). Conclusion In patients with microvascular complications of diabetes, the PR interval in electrocardiogrom is significantly prolonged. Prolonged PR interval is an independent risk factor for microvascular complications in diabetes, which is helpful to predict the occurance of diatetic microvascular complications.

Objective To explore the correlation between the prolongating PR interval of electrocardiogram and the general information and biochemical indicators of diabetes patients with microvascular complications, and the predictive value of diabetes microvascular complications. Methods A total of 217 patients with diabetes who hospitalized in Department of Endocrinology, Xi'an Third Hospital from August 2020 to November 2022 were selected retrospectively. Among them, 149 patients only with diabetes were divided into control group, while 68 diabetes patients with microvascular complications were divided into observation group. The general data and biochemical indexes of all diabetes patients were collected, and the PR interval was measured by standard 12 lead synchronous electrocardiograph. The correlation between PR interval and general data and biochemical indicators in patients with microvascular complications of diabetes were analyzed. The predictive value of PR interval on microvascular complications in diabetes was analyzed by receiver operating characteristic (ROC) curve. Results Age, duration of diabetes, body mass index (BMI), hemoglobin A1c (HbA1c), PR interval in the observation group were higher than those in the control group (P＜0.01). PR interval of diabetes patients with microvascular complications was positively correlated with age, diabetes duration, BMI, HbA1c (P＜0.01). The AUC of PR interval for predicting microvascular complications in diabetes was 0.812 (95%CI:0.752-0.872), the sensitivity was 70.6%, the specificity was 78.5%, and the cut-off value was 212.61 ms. Prolonged PR interval was an independent risk factor for microvascular complications in diabetes (OR=2.475, 95%CI: 1.472-5.120, P＜0.01). Conclusion In patients with microvascular complications of diabetes, the PR interval in electrocardiogrom is significantly prolonged. Prolonged PR interval is an independent risk factor for microvascular complications in diabetes, which is helpful to predict the occurance of diatetic microvascular complications.

This review outlines the function of oxidative stress in DR and discusses therapeutic strategies to treat DR with antioxidants. Published papers on oxidative stress in DR and therapeutic strategies to treat DR with antioxidants were collected and reviewed via database searching on PubMed. The abnormal development of DR is a complicated process. The pathogenesis of DR has been reported to involve oxidative stress, despite the fact that the mechanisms underlying this are still not fully understood. Excessive reactive oxygen species (ROS) accumulation can damage retina, eventually leading to DR. Increasing evidence have demonstrated that antioxidant therapy can alleviate the degeneration of retinal capillaries in DR. Oxidative stress can play an important contributor in the pathogenesis of DR. Furthermore, animal experiments have shown that antioxidants are a beneficial therapy for treating DR, but more clinical trial data is needed. [ABSTRACT FROM AUTHOR]

BackgroundPeople living with diabetes often encounter psychosocial challenges, including diabetes distress and depression. Despite this, little research has focused on the co-occurrence of these conditions. This study aimed to explore the prevalence of depressive symptoms and diabetes distress in people with type 1 diabetes in Kuwait and to identify clinical and demographic factors associated with these conditions.MethodsA total of 832 people with type 1 diabetes (females: 54.1%, mean age: 29 ± 8.5 years), were invited to participate in Dose Adjustment for Normal Eating (DAFNE) course. Diabetes distress was measured using the Problem Areas in Diabetes (PAID) scale and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Depressive symptoms were defined as PHQ-9 scores ≥10. Data on biomedical outcomes, lifestyle factors, and sociodemographic information were collected.ResultsThe prevalence rates of diabetes distress and depressive symptoms were 27.8% and 38.3%, respectively. Notably, 19.6% of people experienced both conditions. In the regression analysis, PAID scale and PHQ-9 scores were significantly associated, patients with higher score on depressive symptoms scale were more likely to suffer diabetes distress (B= 2.65, p < 0.001). Female sex (odds ratio [OR]= 2.2, 95% CI= 1.5, 3.2), higher hemoglobin A1c levels (OR= 1.6, 95% CI= 1.0, 2.5), obesity (OR= 1.7, 95% CI= 1.1, 2.8), inactivity (OR= 2.4, 95% CI= 1.6, 3.6), microvascular complications (OR= 2.8, 95% CI= 1.5, 5.4), and lipohypertrophy (OR= 1.7, 95% CI= 1.1, 2.5) were associated with greater odds for the co-occurrence of diabetes distress and depressive symptoms (p< 0.05 for all).ConclusionThe majority of people with type 1 diabetes in Kuwait experience both diabetes distress and depressive symptoms. The strong correlation between diabetes distress and depressive symptoms suggests mutual predictability. The co-occurrence of both symptoms is associated with many sociodemographic and clinical factors.

Abstract Objective To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications. Methods We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006–2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD. Results We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32–0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications. Conclusion HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.

Objective: To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications. Methods: We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006–2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD. Results: We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32–0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications. Conclusion: HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To estimate if newly diagnosed patients with different subphenotypes of type 2 diabetes (T2DM) or latent autoimmune diabetes of adults (LADA) differ with respect to subclinical retinal microvascular structure or diabetic retinopathy (DR). Methods: This population‐based, cross‐sectional study of 340 patients (675 eyes) classified patients with recently diagnosed T2DM in different subphenotypes according to beta cell function and insulin sensitivity in to; classical (n = 218), hyperinsulinaemic (n = 86), insulinopenic (n = 20), or LADA (n = 16). Retinal 6‐field images were graded according to the International Clinical DR Severity Scale by a retinal expert. Retinal microvascular structures were analysed in eyes by a semiautomatic software. Results: Median age and duration of diabetes were 58.1 (49.9; 65.5) and 0.9 (0.5; 2.4) years, respectively, and 56.8% were male. In a multivariate linear mixed model regression analysis of eyes without DR (n = 570), there was no statistically significant difference in retinal venular or arteriolar width between subtypes and patients with classical T2DM. In addition, eyes from different subphenotypes did not differ according to vessel density, tortuosity or fractal dimension. In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure and history of cardiovascular disease, there was a tendency towards persons with hyperinsulinaemic T2DM to be more likely to have DR (OR 1.97, 95% CI 0.95; 4.09) compared to classical T2DM. Conclusion: We found no difference in retinal microvascular structure in patients with newly diagnosed subtypes of T2DM. However, DR may be more prevalent in newly diagnosed patients with hyperinsulinaemic T2DM compared to individuals with classical T2DM. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), the most common microvascular complication that occurs in diabetes mellitus (DM), is the leading cause of vision loss in working-age adults. The prevalence of diabetic retinopathy is approximately 30% of the diabetic population and untreated DR can eventually cause blindness. For decades, diabetic retinopathy was considered a microvascular complication and clinically staged by its vascular manifestations. In recent years, emerging evidence has shown that diabetic retinopathy causes early neuronal dysfunction and neurodegeneration that may precede vascular pathology and affect retinal neurons as well as glial cells. This knowledge leads to new therapeutic strategies aiming to prevent dysfunction of retinal neurons at the early stage of DR. Early detection and timely treatment to protect retinal neurons are critical to preventing visual loss in DR. This review provides an overview of DR and the structural and functional changes associated with DR, and discusses neuronal degeneration during diabetic retinopathy, the mechanisms underlying retinal neurodegeneration and microvascular complications, and perspectives on current and future clinic therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus is a complex chronic disease characterized by chronic hyperglycemia resulting from defective insulin secretion, defective insulin action, or both. Chronic hyperglycemia related to diabetes can lead to end-organ dysfunction or failure, and changes related to diabetes involving arterioles and capillaries are responsible for long-term microvascular complications in diabetic patients. The neutrophil-to-lymphocyte ratio (NLR) is a novel, simple, and inexpensive marker of subclinical inflammation. Aim of work To evaluate the possibility that neutrophil-lymphocyte ratio (NLR) could be used as a predictor of microvascular complications during follow-up of elderly patients with type 2 diabetes. Patients and methods Sixty elderly diabetes patients ≥ 65 years old, diagnosed 16 according to ADA criteria, were collected from the endocrine clinic in Kasr El-Ainy Hospital. For every patient, full history and examination were done (including 18 neurological and fundus examinations). Labs (CBC with a differential in blood and 19 albumin/creatinine ratio in urine) were done and the neutrophil/lymphocyte ratio. Results We found that NLR has a statistically significant difference in the detection of nephropathy and retinopathy. There is a significant correlation between nephropathy and NL ratio in all patients (r = 0.44, P < 0.001). Elderly diabetic patients (with or without hypertension) with microvascular complications had a higher NLR value than those without complications. Conclusion NLR value can be used as a non-invasive simple marker for predicting microvascular complications in elderly diabetics with/without hypertension.

Background/Aim: Diabetic retinopathy is a common ailment that causes visual impairment among adults, and evidence suggests that oxidative stress plays a significant role in its pathogenesis. The objective of this study was to examine the potential association between selenium deficiency and an increased risk of diabetic retinopathy among individuals with type 2 diabetes mellitus. Methods: This study was a prospective case-control study. 115 patients with a diagnosis of type 2 diabetes mellitus were included. The patients were divided into groups with and without retinopathy. No subgroups were made according to the level of retinopathy. The aim was to compare the serum selenium level of patients between groups. Therefore, other variables that may contribute to the development of retinopathy were also recorded. The duration of diabetes, medications used, and glycosylated hemoglobin levels were recorded. The retinopathy group included 47 patients, and the non-retinopathy group included 68 patients. Selenium levels were measured in plasma samples. Results: The mean selenium level of the retinopathy group (70.11 [17.28] μg/l) was significantly lower than that of the non-retinopathy group (80.20 [19.10] μg/l) (P=0.005). The median duration of diabetes mellitus was significantly higher in the retinopathy group than in the non-retinopathy group (10 [1-25] and 6 [1-21], respectively; P=0.002). Logistic regression analyses showed that higher levels of blood selenium were independent preventive factors against the occurrence of retinopathy (OR [95% CI]: 0.965 [0.939-0. 991]). The duration of diabetes mellitus was an independent risk factor for retinopathy occurrence (OR [95% CI]: 1.131 [1.050-1.219]). One unit increase in selenium level was associated with a unit decrease in diabetic retinopathy of 0.965 (0.939-0.991). Conclusion: Our research revealed a correlation between the duration of diabetes and the incidence of diabetic retinopathy. Furthermore, a notable difference was observed in blood selenium levels between patients with diabetic retinopathy and those without it. Specifically, patients with diabetic retinopathy had lower plasma selenium levels compared to the control group. These findings have potential implications for the treatment or prevention of diabetic retinopathy, but more research is needed to determine the efficacy of selenium supplementation for diabetic patients with or without microvascular complications. Future studies should investigate the effect of selenium deficiency on different subtypes of diabetic retinopathy and the impact of selenium supplementation in this patient population. [ABSTRACT FROM AUTHOR]

Shaik Sarfaraz Nawaz,1,&ast; Khalid Siddiqui,1,&ast; Muhammad Mujammami,1– 3 Obeed Alotaibi,2 Saud Sulaiman Alanazi,1 Mohamed Rafiullah1 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.o Box: 245, Riyadh, 11411, Saudi Arabia, Tel +966 114724179 Ext.3106, Fax +966 114725682, Email ksiddiqui@ksu.edu.saBackground: Osteopontin (OPN) is a 44-kDa multifunctional protein and has a diverse role in biomineralization, tissue remodeling, and chronic inflammation. However, its role in type 2 diabetes (T2D) patients with microvascular complications is not clear. Therefore, the present study aimed to investigate the role of OPN in T2D patients with microvascular complications.Methods: A total of 324 type 2 diabetes patients in the age group of 38– 66 years were included in this study; 249 T2D patients were diagnosed with microvascular complications. OPN was measured using an enzyme-linked immunosorbent assay kit. Clinical data, such as age, gender, diabetes duration, systolic blood pressure, diastolic blood pressure, were measured. Correlation between OPN levels with different clinical parameters was evaluated.Results: In patients with microvascular complications, OPN levels were significantly higher than those without microvascular complications (p < 0.05). Moreover, OPN levels were positively associated with systolic blood pressure (SBP), C-reactive protein, and albumin creatinine ratio (ACR). Multiple linear regression analysis showed that OPN levels were independently associated with C-reactive protein (p < 0.045).Conclusion: The findings in the present study showed that OPN level was more positively associated with C-reactive protein than that with glucose metabolism in patients with microvascular complications. Thus, OPN might serve as a marker in predicting vascular disease.Keywords: osteopontin, diabetes, microvascular complication, inflammation, C-reactive protein

Background: Diabetes mellitus is a complex chronic disease characterized by chronic hyperglycemia resulting from defective insulin secretion, defective insulin action, or both. Chronic hyperglycemia related to diabetes can lead to end-organ dysfunction or failure, and changes related to diabetes involving arterioles and capillaries are responsible for long-term microvascular complications in diabetic patients. The neutrophil-to-lymphocyte ratio (NLR) is a novel, simple, and inexpensive marker of subclinical inflammation. Aim of work: To evaluate the possibility that neutrophil-lymphocyte ratio (NLR) could be used as a predictor of microvascular complications during follow-up of elderly patients with type 2 diabetes. Patients and methods: Sixty elderly diabetes patients ≥ 65 years old, diagnosed 16 according to ADA criteria, were collected from the endocrine clinic in Kasr El-Ainy Hospital. For every patient, full history and examination were done (including 18 neurological and fundus examinations). Labs (CBC with a differential in blood and 19 albumin/creatinine ratio in urine) were done and the neutrophil/lymphocyte ratio. Results: We found that NLR has a statistically significant difference in the detection of nephropathy and retinopathy. There is a significant correlation between nephropathy and NL ratio in all patients (r = 0.44, P < 0.001). Elderly diabetic patients (with or without hypertension) with microvascular complications had a higher NLR value than those without complications. Conclusion: NLR value can be used as a non-invasive simple marker for predicting microvascular complications in elderly diabetics with/without hypertension. [ABSTRACT FROM AUTHOR]

Introduction: Teleophthalmology for diabetic retinopathy seems to be a cost-effective, accurate, and reliable method for screening for diabetic retinopathy. Aims: To study the cost-effectiveness of a novel telemedicine-based digital retinal imaging teleophthalmology performed by a locally trained nurse compared to conventional ophthalmologic fundus examination of diabetic patients for early diagnosis of diabetic retinopathy. Materials and methods: We compared the cost of evaluation of diabetic retinopathy in a total of 3090 patients. These were grouped based on the conventional approach of evaluation (n = 1500) and compared with the teleophthalmology (n = 1590) approach. The diabetic patients were examined through teleophthalmology by a trained nurse using the Forbes 3nethra fundal camera, and these fundal images were transferred by iCloud to a specialized retina center. Results: In total, 18.2% (n = 562) patients were diagnosed with diabetic retinopathy (DR). Of these, 8.7% had mild non-proliferative diabetic retinopathy (NPDR), 4.8% had moderate NPDR, 3.8% had severe NPDR, and 0.9% had PDR. The total cost of conventional telemedicine-based digital retinal imaging was approximately INR 550 which in contrast was less than half to the total cost of conventional dilated fundus examination by an ophthalmologist (INR 1400). Conclusion: Our cost analysis indicates that telemedicine-based diabetic retinopathy screening is economical (INR 550 as compared to INR 1400) than conventional retinal examination. [ABSTRACT FROM AUTHOR]

Purpose: To assess the structural and functional changes among diabetics with no diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography angiography (SSOCTA) and photopic negative response (PhNR) and to find the earliest changes. Methods: This was a prospective, cross-sectional, case–control study. Participants with minimum 5 years of diabetes mellitus (DM) were recruited and classified as NDR and mild NPDR based on fundus findings. Age-matched normals with nil ocular pathology were considered as controls. SSOCTA scan acquisition (6*6 mm angiography), followed by full field photopic electroretinography (FFERG) and red on blue PhNR (R/B PhNR) were done with complete pupillary dilatation. Results: A total of 88 participants were included with 35 controls, 39 NDR and 14 mild NPDR subjects. Vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of mild NPDR were significantly reduced compared to the controls (17.12 ± 2.65 mm−1 vs. 18.75 ± 0.90 mm−1, p = 0.025 and 7.96 ± 3.92 mm−1 vs. 11.83 ± 3.05 mm−1, p = 0.001 respectively). None of the parameters of controls had significant difference compared to NDR group (p > 0.05). The amplitudes of white on white (W/W) a-wave, W/W b-wave, red on blue (R/B) PhNR baseline to trough (BT) and R/B PhNR peak to trough in controls were significantly high compared to NDR and mild NPDR. Amplitude of R/B PhNR BT had the maximum area under the curve of 75.9% with a sensitivity and specificity of 94.3and 77.4%, respectively. Conclusion: A significant decrease in functional changes as measured by ERG especially PhNR, is seen even among the NDR group compared to controls unlike SSOCTA parameters that measures very early vascular structural changes. PhNR is a sensitive test to identify early preclinical changes in DR when microvascular structural changes as determined by SSOCTA are normal. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction To examine the incidence rate of severe non‐proliferative and proliferative diabetic retinopathy (severe‐NPDR/PDR) and determine its potential risk factors. Materials and Methods The study consisted of 1,169 participants (675 women) with type 2 diabetes mellitus, aged ≥20 years. A trained interviewer collected information about the history of pan‐retinal photocoagulation as a result of diabetic retinopathy. Multivariable Cox proportional hazards regression models were applied. Results We found 187 cases (126 women) of severe‐NPDR/PDR during a median follow‐up period of 12.7 years; the corresponding incidence rate was 13.6 per 1,000 person‐years. Being overweight (hazard ratio [HR], 95% confidence interval [CI] 0.60, 0.39–0.92) and obese (HR 0.48, 95% CI 0.27–0.83) were associated with lower risk, whereas being smoker (HR 1.75, 95% CI 1.12–2.74), having fasting plasma glucose levels 7.22–10.0 mmol/L (HR 2.81, 95% CI 1.70–4.62), fasting plasma glucose ≥10 mmol/L (HR 5.87, 95% CI 3.67–9.41), taking glucose‐lowering medications (HR 2.58, 95% CI 1.87–3.56), prehypertension status (HR 1.65, 95% CI 1.05–2.58) and newly diagnosed hypertension (HR 1.96, 95% CI 1.06–3.65) increased the risk of severe‐NPDR/PDR. Among newly diagnosed diabetes patients, being male was associated with a 59% lower risk of severe‐NPDR/PDR (HR 0.41, 95% CI 0.21–0.79). Furthermore, patients who had an intermediate level of education (6–12 years) had a higher risk of developing PDR (HR 1.86, 95% CI 1.05–3.30) compared with those who had

Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), the most common microvascular complication that occurs in diabetes mellitus (DM), is the leading cause of vision loss in working-age adults. The prevalence of diabetic retinopathy is approximately 30% of the diabetic population and untreated DR can eventually cause blindness. For decades, diabetic retinopathy was considered a microvascular complication and clinically staged by its vascular manifestations. In recent years, emerging evidence has shown that diabetic retinopathy causes early neuronal dysfunction and neurodegeneration that may precede vascular pathology and affect retinal neurons as well as glial cells. This knowledge leads to new therapeutic strategies aiming to prevent dysfunction of retinal neurons at the early stage of DR. Early detection and timely treatment to protect retinal neurons are critical to preventing visual loss in DR. This review provides an overview of DR and the structural and functional changes associated with DR, and discusses neuronal degeneration during diabetic retinopathy, the mechanisms underlying retinal neurodegeneration and microvascular complications, and perspectives on current and future clinic therapies.

Introduction. Diabetes mellitus type 2 (DMT2) is a multisystem disease with significant microvascular and macrovascular complications. Chronic kidney disease (CKD) is one of the leading causes of death, and DMT2 is the root cause of end-stage CKD. A scientific paradigm is whether the occurrence of chronic complications and disturbed bone-mineral metabolism (BMM) are significantly associated. In DMT2 with eGFR45-70ml/min, fibroblast growth factor (FGF23) as part of CMM is a targeted predictive biomarker for the occurrence of micro/macrovascular complications. Because scientific knowledge is still inconsistent, more research is needed to further define the role of FGF23 in DMT2 and CKD patients. The aim of this research is to determine the association of FGF23 with ophtalmic microvascular complications, macrovascular complications as well as impaired BMM, in patients with DMT2 and eGFR45-70 ml/min/1.73m2. Methods. As a pilot study, we present a group of 5 patients. Regarding the control of hypertension, dyslipidemia, and glycoregulation, the chosen group is homogeneous. BMD was evaluated using osteodensitometry to measure bone density and assessing the levels of vitamin D, parathyroid hormone (PTH), calcium, phosphorus, and FGF23. As a marker for subclinical atherosclerosis, carotid artery intima media thickness (IMT) was assessed using ultrasound (US) color Doppler, and the existence of peripheral arterial disease (PAD) was examined in seven blood vessels in the lower limbs. Albuminuria and eGFR following CKD-EPI, were assessed to evaluate renal consequences. Diabetic retinopathy (DR) was discovered during a fundus examination. Due to the small number of patients, the gathered data cannot be statistically analysed. Results. All participants had at least one bone mineral or micro/macrovascular alteration. FGF23 has a value that is above average in three participants, or 60% of the sample. FGF23 was increased at all of the subjects with CVD and it was Inversely associated with value of eGFR. One participant had DR, another had osteoporosis, and one had albuminuria >30 mg/l, and all of them had increased FGF23. Two of the four individuals with PAB also had high FGF23. Conclusion. The findings, even in a small sample of patients, suggest to a possible association between FGF23 and micro- and macrovascular complications as well as impaired CMM in DMT2 patients with early CKD. This indicates the need for additional research using larger samples. [ABSTRACT FROM AUTHOR]

Objective - This study was conducted to evaluate the efficacy of platelet indices, namely mean platelet volume, platelet distribution width, plateletcrit and platelet count for prediction of microvascular complications of type 2 diabetes mellitus. Methods - A hospital-based, single-centre, observational, matched case-control study was conducted. A total of 120 diabetic cases and 120 non-diabetic controls were recruited and various biochemical parameters (fasting and post-prandial blood glucose, HbA1c, mean platelet volume, platelet distribution width, plateletcrit, platelet count and others) were measured. All diabetic cases were subjected for diagnosis of retinopathy, nephropathy or neuropathy. Statistical analyses were performed using unpaired t-test and Pearson's correlation test. Results - The mean (±SD) age of the diabetic cases and controls were 59.8 (±11.2) years and 53.61 (±10.66) years, respectively. The overall male:female distribution was 64.2%:35.8% and 55.8%:44.2% in diabetic cases and controls, respectively. Platelet count and plateletcrit were found to be significantly higher in diabetic cases than controls (288741 (±97447)/µL vs. 255041 (±63883)/µL, p-value = 0.002; 0.234±0.072% vs. 0.201±0.043%, p-value = 0.0002). However, mean platelet volume and platelet distribution width in diabetic cases were not found to be significantly changed when compared to controls. Plateletcrit showed positive correlation with HbA1c with Pearson's correlation coefficient of r=0.19 (p-value <0.05). Mean platelet volume and platelet distribution width were found to be not-significantly correlated with HbA1c. Among diabetics, only plateletcrit was found to be significantly raised in cases with all complications compared to cases with no complication (p-value <0.05). Conclusion - Plateletcrit and platelet count were found to be efficacious in forecasting the microvascular complications in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Retinal vessel calibre metrics were evaluated at baseline and 2 years in a FIELD substudy (n = 208). Central retinal venule calibre was significantly reduced by fenofibrate and unchanged by placebo. Arteriole metrics did not change. Larger studies relating retinal vessel calibre to future diabetes complications and response to therapy are merited. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic kidney disease (CKD) introduces an increased cardiovascular risk among patients with diabetes mellitus (DM). The risk and tempo of cardiovascular diseases may differ depending upon their type. Whether CKD differentially influences the risk of developing each cardiovascular morbidity in patients with newly diagnosed DM remains unexplored. Methods We identified patients with incident DM from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort (n = 429,616), and uncovered those developing CKD after DM and their propensity score-matched counterparts without. After follow-up, we examined the cardiovascular morbidity-free rates of patients with and without CKD after DM, followed by Cox proportional hazard regression analyses. We further evaluated the cumulative risk of developing each outcome consecutively during the study period. Results From LCDP, we identified 55,961 diabetic patients with CKD and matched controls without CKD. After 4.2 years, patients with incident DM and CKD afterward had a significantly higher risk of mortality (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.06–1.14), heart failure (HF) (HR 1.282, 95% CI 1.19–1.38), acute myocardial infarction (AMI) (HR 1.16, 95% CI 1.04–1.3), and peripheral vascular disease (PVD) (HR 1.277, 95% CI 1.08–1.52) compared to those without CKD. The CKD-associated risk of mortality, HF and AMI became significant soon after DM occurred and remained significant throughout follow-up, while the risk of PVD conferred by CKD did not emerge until 4 years later. The CKD-associated risk of ischemic, hemorrhagic stroke and atrial fibrillation remained insignificant. Conclusions The cardiovascular risk profile among incident DM patients differs depending on disease type. These findings can facilitate the selection of an optimal strategy for early cardiovascular care for newly diagnosed diabetic patients.

Mitku Mammo Taderegew,1 Gashaw Garedew Woldeamanuel,1 Mamo Solomon Emeria,2 Melkamu Tilahun,3 Getachew Yideg Yitbarek,4 Betregiorgis Zegeye5 1Department of Biomedical Sciences, College of Medicine and Health Sciences, Wolkite University, Wolkite, Ethiopia; 2Department of Nursing, College of Medicine and Health Sciences, Wolkite University, Wolkite, Ethiopia; 3Department of Biomedical Sciences (Medical Physiology), College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia; 4Department of Biomedical Sciences, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 5HaSET Maternal and Child Health Research Program, Shewarobit Field Office, Shewarobit, EthiopiaCorrespondence: Mitku Mammo TaderegewDepartment of Biomedical Sciences, School of Medicine, College of Medicine and Health Sciences, Wolkite University, PO Box 07, Wolkite, EthiopiaEmail mitkumamo@gmail.comPurpose: Platelet indices have been shown to be associated with complications of diabetes mellitus (DM). However, the clinical relevance of platelet indices for assessing the risk of being microvascular complications among patients with DM is largely overlooked. Hence this study aimed to determine the association of platelet indices with microvascular complications among type 2 DM patients.Patients and Methods: A hospital-based cross-sectional study was conducted among 352 type 2 DM patients from April 1 to May 30/2019 at Debre Berhan Referral Hospital. Data were collected by interview, physical measurements, document review, and laboratory tests. Then the data were entered into Epi-data manager-4.4.1.0 and exported into SPSS-25 for analysis. Platelet indices were compared between participants with and without microvascular complications using an independent t-test. A logistic regression model was used to assess the association between microvascular complications and platelet indices. All inferences were considered statistically significant at P< 0.05.Results: One hundred seventeen (33.2%) of participants were suffering from at least one microvascular complications. The mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR) were significantly increased in DM patients with complications as compared to without complications (13.57± 2.17fl vs. 11.76± 1.93fl), (16.57± 2.49fl vs. 14.97± 2.41fl) and (28.09± 7.58% vs. 24.19± 6.46%), respectively (all are P˂0.001). In multivariate logistic regression analysis, MPV (AOR=1.68, 95% CI: 1.37– 2.05), PDW (AOR=1.37, 95% CI: 1.15– 1.63), P-LCR (AOR=1.07, 95% CI: 1.01– 1.14), age (AOR=1.07, 95% CI: 1.01– 1.12), and duration of DM (AOR=1.31, 95% CI: 1.18– 1.46) were significantly associated with the presence of microvascular complications.Conclusion: MPV, PDW, and P-LCR were significantly higher among type 2 DM patients with microvascular complications. This indicates that platelet indices can be used as prognostic markers of vascular complications and can be used as simple and cost-effective parameters to predict microvascular complications particularly in patients with old age and long duration of DM.Keywords: platelet indices, microvascular complication, type 2 DM, Ethiopia

Aims/Introduction: To examine the incidence rate of severe non‐proliferative and proliferative diabetic retinopathy (severe‐NPDR/PDR) and determine its potential risk factors. Materials and Methods: The study consisted of 1,169 participants (675 women) with type 2 diabetes mellitus, aged ≥20 years. A trained interviewer collected information about the history of pan‐retinal photocoagulation as a result of diabetic retinopathy. Multivariable Cox proportional hazards regression models were applied. Results: We found 187 cases (126 women) of severe‐NPDR/PDR during a median follow‐up period of 12.7 years; the corresponding incidence rate was 13.6 per 1,000 person‐years. Being overweight (hazard ratio [HR], 95% confidence interval [CI] 0.60, 0.39–0.92) and obese (HR 0.48, 95% CI 0.27–0.83) were associated with lower risk, whereas being smoker (HR 1.75, 95% CI 1.12–2.74), having fasting plasma glucose levels 7.22–10.0 mmol/L (HR 2.81, 95% CI 1.70–4.62), fasting plasma glucose ≥10 mmol/L (HR 5.87, 95% CI 3.67–9.41), taking glucose‐lowering medications (HR 2.58, 95% CI 1.87–3.56), prehypertension status (HR 1.65, 95% CI 1.05–2.58) and newly diagnosed hypertension (HR 1.96, 95% CI 1.06–3.65) increased the risk of severe‐NPDR/PDR. Among newly diagnosed diabetes patients, being male was associated with a 59% lower risk of severe‐NPDR/PDR (HR 0.41, 95% CI 0.21–0.79). Furthermore, patients who had an intermediate level of education (6–12 years) had a higher risk of developing PDR (HR 1.86, 95% CI 1.05–3.30) compared with those who had <6 years of education. Conclusions: Among Iranians with type 2 diabetes mellitus, 1.36% developed severe‐NPDR/PDR annually. Normal bodyweight, being a smoker, out of target fasting plasma glucose level, prehypertension and newly diagnosed hypertension status were independent risk factors of severe‐NPDR/PDR. Regarding the sight‐threatening entity of advanced diabetic retinopathy, the multicomponent strategy to control diabetes, abstinence of smoking and tight control of blood pressure should be considered. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement. [ABSTRACT FROM AUTHOR]

Aim: Type 2 Diabetes Mellitus (T2DM) is associated with microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DNp), and diabetic peripheral neuropathy (DPN). In this study, we investigated genetic variations and Single Nucleotide Polymorphisms (SNPs) associated with DR, DNp, DPN and their combinations among T2DM patients of Arab origin from the United Arab Emirates, to establish the role of genes in the progression of microvascular diabetes complications. Methods: A total of 158 Emirati patients with T2DM were recruited in this study. The study population was divided into 8 groups based on the presence of single, dual, or all three complications. SNPs were selected for association analyses through a search of publicly available databases, specifically genome-wide association study (GWAS) catalog, infinome genome interpretation platform, and GWAS Central database. A multivariate logistic regression analysis and association test were performed to evaluate the association between 83 SNPs and DR, DNp, DPN, and their combinations. Results: Eighty-three SNPs were identified as being associated with T2DM and 18 SNPs had significant associations to one or more diabetes complications. The most strongly significant association for DR was rs3024997 SNP in the VEGFA gene. The top-ranked SNP for DPN was rs4496877 in the NOS3 gene. A trend towards association was detected at rs833068 and rs3024998 in the VEGFA gene with DR and rs743507 and rs1808593 in the NOS3 gene with DNp. For dual complications, the rs833061, rs833068 and rs3024997 in the VEGFA gene and the rs4149263 SNP in the ABCA1 gene were also with borderline association with DR/DNp and DPN/DNp, respectively. Diabetic with all of the complications was significantly associated with rs2230806 in the ABCA1 gene. In addition, the highly associated SNPs rs3024997 of the VEGFA gene and rs4496877 of the NOS3 gene were linked to DR and DPN after adjusting for the effects of other associated markers, respectively. Conclusions: The present study reports associations of different genetic polymorphisms with microvascular complications and their combinations in Emirati T2DM patients, reporting new associations, and corroborating previous findings. Of interest is that some SNPs/genes were only present if multiple comorbidities were present and not associated with any single complication. [ABSTRACT FROM AUTHOR]

Introduction: Adenosine Deaminase (ADA), a purine metabolic enzyme is suggested to contribute significantly to the modulation of bioactivity of insulin but its relation with diabetes is not yet fully understood. Aim: To assess the relation of ADA with diabetes and its complications. Materials and Methods: This study included a total of 100 diabetic patients and 100 well matched healthy non-diabetic as control subjects. Serum ADA levels of patients with Diabetes Mellitus (DM) as diagnosed by current American Diabetic Association (ADA) criteria were compared with well-matched healthy nondiabetic patients, further ADA levels were compared with micro and macrovascular complications of diabetes. The recorded data was exported to Statistical Package for the Social Sciences (SPSS) version 23.0 after being compiled in Microsoft excel. Results: The mean age of diabetic patients was 57.7±9.49 and 54.9±11.29 years for controls. Significant difference in ADA in diabetic and non-diabetics with mean ADA of 38.7±16.02 and 28.9±6.39 IU/L respectively with a p-value of 10 in 48% cases. Significant correlation was observed between serum ADA and microvascular complication and duration of diabetes. Conclusion: Serum ADA can be an addition marker of diabetes and has significant correlation with its various complications.

AimType 2 Diabetes Mellitus (T2DM) is associated with microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DNp), and diabetic peripheral neuropathy (DPN). In this study, we investigated genetic variations and Single Nucleotide Polymorphisms (SNPs) associated with DR, DNp, DPN and their combinations among T2DM patients of Arab origin from the United Arab Emirates, to establish the role of genes in the progression of microvascular diabetes complications.MethodsA total of 158 Emirati patients with T2DM were recruited in this study. The study population was divided into 8 groups based on the presence of single, dual, or all three complications. SNPs were selected for association analyses through a search of publicly available databases, specifically genome-wide association study (GWAS) catalog, infinome genome interpretation platform, and GWAS Central database. A multivariate logistic regression analysis and association test were performed to evaluate the association between 83 SNPs and DR, DNp, DPN, and their combinations.ResultsEighty-three SNPs were identified as being associated with T2DM and 18 SNPs had significant associations to one or more diabetes complications. The most strongly significant association for DR was rs3024997 SNP in the VEGFA gene. The top-ranked SNP for DPN was rs4496877 in the NOS3 gene. A trend towards association was detected at rs833068 and rs3024998 in the VEGFA gene with DR and rs743507 and rs1808593 in the NOS3 gene with DNp. For dual complications, the rs833061, rs833068 and rs3024997 in the VEGFA gene and the rs4149263 SNP in the ABCA1 gene were also with borderline association with DR/DNp and DPN/DNp, respectively. Diabetic with all of the complications was significantly associated with rs2230806 in the ABCA1 gene. In addition, the highly associated SNPs rs3024997 of the VEGFA gene and rs4496877 of the NOS3 gene were linked to DR and DPN after adjusting for the effects of other associated markers, respectively.ConclusionsThe present study reports associations of different genetic polymorphisms with microvascular complications and their combinations in Emirati T2DM patients, reporting new associations, and corroborating previous findings. Of interest is that some SNPs/genes were only present if multiple comorbidities were present and not associated with any single complication.

The search for an ideal natural drug candidate with minimal side effects has been a never-ending challenge. In diabetes, there are so many potential drug candidates; however, systematic research is necessary to put candidate molecules into effect. β-glucogallin (PubChem CID: 124021) found in Emblica officinalis is explored as a potential candidate molecule to inhibit aldose reductase activity, a key enzyme related to the microvascular complications in diabetic patients. High-resolution crystal structure of human aldose reductase (ALR2) (PDB ID: “1pwm”) from ‘Protein Data Bank’ was retrieved, and active site determination was done using “ CASTp” and blind docking strategies. “Swiss Dock” blind docking revealed a total of 13 active residues, which were found common in the five best binding modes in regard to their free binding energy. The active residues were utilized again to selectively dock β-glucogallin (PubChem CID: 124021) in “Swiss Dock” for which the average free binding energy was −8.07884 kcal/mol calculated from 5 best binding modes. Additionally, a selective docking analysis was performed in ‘Auto Dock 4.2′ using a genetic algorithm where the same binding mode was observed. The lowest binding energy calculated in Auto Dock was −17.37 kcal/mol with an inhibition constant of 186.59 fM, which is substantial to prove the efficacy of this molecule as a potential drug target. In both docking platforms, the interaction pattern stayed in the same orientation. So, this study showed the interactions pattern of β-glucogallin (PubChem CID: 124021) with tentative active sites of aldose reductase (ALR2) (PDB ID: 1pwm) in details which may open up future possibilities for treating patients with diabetic microvascular complications.

Abstract Aims/Introduction There are substantial differences in genes, diet, culture and environment between the northern and southern Chinese populations, which might influence treatment strategy and screening policy. We studied the differences in type 2 diabetes and diabetic complications between northern and southern China. Materials and Methods We carried out a cross‐sectional survey using data from the China Cardiometabolic Registries on blood pressure, blood lipids and blood glucose in 25,398 Chinese type 2 diabetes patients. Macrovascular, microvascular and other complications were collected by self‐report or medical records, and then divided into the northern and southern groups by the boundary of the Yangtze River. Results Northern patients were younger, and had heavier weight, greater body mass index and waist circumference, higher blood pressure, higher total cholesterol, higher low‐density lipoprotein cholesterol, and higher hemoglobin A1C. The prevalence of cardiovascular, cerebrovascular and macrovascular complications were 1.76‐fold, 1.24‐fold and 1.47‐fold more in northern than that in southern Chinese patients. In addition, the prevalence of diabetic nephropathy, retinopathy, neuropathy and microvascular complications in northern Chinese patients also increased. When stratified by age, the difference in both cardiovascular disease and ischemic stroke morbidity became significant, even in the 35–44 years age group. Conclusions More macrovascular and microvascular complications were found in northern compared with southern patients, and the largest difference also appeared in the younger age groups

Aims: To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a retrospective cohort study by analysing a large multi‐institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. Results: We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61‐81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4‐108.7] mL/min/1.73 m2 and urine albumin‐creatinine ratio [UACR] 26.1 [9.7‐117.6] mg/g) and 1067 new users of GLP‐1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64‐84] mmol/mol, eGFR 91.6 [68.6‐114.0] mL/min/1.73 m2 and UACR 37.6 [11.1‐153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person‐years), compared to those receiving GLP‐1RAs (10.7/1000 person‐years) with an HR of 0.75 (95% CI 0.64‐0.88). Conclusions: Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP‐1RAs. Future studies are necessary to confirm this observation. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus is characterised by hyperglycaemia. Chronic elevation of hyperglycaemia lead to generation of free radicals and Advanced Glycation End products (AGEs) which results in damage of many organs such as heart, kidney, eyes, nerves, blood vessels. Diabetic Retinopathy (DR) is the leading cause of blindness among diabetic patients. Vitamin B12 is a vital micronutrient that is essential for the proper functioning of the central nervous, cardiovascular and haemopoetic systems. It is also found that its deficiency is more prevalent in Type 2 Diabetes Mellitus (T2DM) and evident clinically. Aim: To compare the serum vitamin B12 levels and Glycated hemoglobin (HbA1c) levels in patients with and without diabetic retinopathy. Materials and Methods: This was hospital based observational case-control study conducted in Biochemistry Department in collaboration with Ophthalmology Department at the Oxford Medical College, Hospital and Research Centre, Yadavanahalli, Bengaluru, Karnataka, India, from January 2018 to June 2018 with total of 90 subjects. Among 90 patients, 30 patients were with diabetes mellitus with Retinopathy (DR), 30 were with Diabetes mellitus without retinopathy (NDR) and 30 were also recruited as control (healthy individuals). The mean and standard deviation were used to describe continuous data. Analysis of Variance (ANOVA) was used to statistically compare the mean difference between more than two sets of quantitative data. Results: The mean plasma blood glucose levels were higher in T2D patients with DR, Fasting Blood Glucose (FBG) (270.4±94.2 mg/dL) and PPBG (425.6±131.8 mg/dL) and compared to control subjects FBG (95.4±10.7 mg/dL). Among the T2D patients the plasma HbA1c concentration of DR group was found to be higher (11.0±2.3%) compared to the NDR group (p-value <0.05). While, the blood levels of vitamin B12 were comparable between the groups, serum vitamin B12 levels were significantly lower (p-value <0.001) in T2DM group with DR (200.7±201.9 pg/mL) compared to the control group (1004.8±304 pg/mL). Conclusion: The patients with diabetic retinopathy showed that low serum vitamin B12 is associated with elevated Glycated hemoglobin (HbA1c) levels, as a result of poor glycaemic control, endothelial dysfunction and oxidative stress leading to development and progression of DR. [ABSTRACT FROM AUTHOR]

Introduction: Despite an increasing incidence of diabetic nephropathy, undermining the renal production of Erythropoietin (EPO), there are significant number of studies being reported with anaemia among diabetic patients with renal insufficiency, implicating numerous theoretical pathogenesis. Its impact being ignored over the years among Indian contexts, women and men in rural Southern India are particularly vulnerable to anaemia. The associated risk factors and occurrence of anaemia in Type-2 Diabetes Mellitus (T2DM) can be seen even in the absence of renal insufficiency. Aim: To determine the prevalence of anaemia in T2DM patients with normal renal function and assessment of its association with sociodemographic characteristics, biochemical and haematological variables. Materials and Methods: A descriptive cross-sectional study was conducted for a period of six months from December 2018 to May 2019 on total of 150 patients with T2DM, attending the Outpatient Department. All the patients of either sex, aged between 18-60 years, with a duration of DM more than five years, with no renal involvement, were included in the study. All statistical analysis was done using Statistical Package for Social Sciences (SPSS) Version 20.0. The Chi-square test, Z-test was used for data analysis. Results: Among the 150 subjects, 86 (57.3%) were classified to be anaemic, with a mean age of 53 years whereas, 64 (42.6%) were classified as non anaemics with a mean age of 50 years. The mean duration of diabetes was found to be 10.5 years among anaemics and 9.7 years among non anaemics. Compared to non anaemics subjects, drug therapy with both Oral Hypoglycaemic Agents (OHA) and insulin showed a statistically significant difference among diabetic subjects with anaemia. The high prevalence of normocytic anaemia (52.3%) suggests the importance of non renal causes of anaemia in diabetic patients. Conclusion: Patients with T2DM have an independent risk for anaemia irrespective of renal insufficiency, posing a significant adverse effect on the quality of life and the progression of the underlying disease with high cardiovascular morbidity and mortality. Hence, management of diabetic patients should include mandatory routine haematological tests, with consideration of advancing age and poor glycaemic control. [ABSTRACT FROM AUTHOR]

Introduction: Despite an increasing incidence of diabetic nephropathy, undermining the renal production of Erythropoietin (EPO), there are significant number of studies being reported with anaemia among diabetic patients with renal insufficiency, implicating numerous theoretical pathogenesis. Its impact being ignored over the years among Indian contexts, women and men in rural Southern India are particularly vulnerable to anaemia. The associated risk factors and occurrence of anaemia in Type-2 Diabetes Mellitus (T2DM) can be seen even in the absence of renal insufficiency. Aim: To determine the prevalence of anaemia in T2DM patients with normal renal function and assessment of its association with sociodemographic characteristics, biochemical and haematological variables. Materials and Methods: A descriptive cross-sectional study was conducted for a period of six months from December 2018 to May 2019 on total of 150 patients with T2DM, attending the Outpatient Department, Rajarajeswari Medical College and Hospital, Bangalore, India. All the patients of either sex, aged between 18-60 years, with a duration of Diabetes Mellitus (DM) more than five years, with no renal involvement, were included in the study. All statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 20.0. The Chi-square test, Z-test was used for data analysis. Results: Among the 150 subjects, 86 (57.3%) were classified to be anaemic, with a mean age of 53 years whereas, 64 (42.6%) were classified as non anaemics with a mean age of 50 years. The mean duration of diabetes was found to be 10.5 years among anaemics and 9.7 years among non anaemics. Compared to non anaemics subjects, drug therapy with both Oral Hypoglycaemic Agents (OHA) and insulin showed a statistically significant difference among diabetic subjects with anaemia. The high prevalence of normocytic anaemia (52.3%) suggests the importance of non renal causes of anaemia in diabetic patients. Conclusion: Patients with T2DM have an independent risk for anaemia irrespective of renal insufficiency, posing a significant adverse effect on the quality of life and the progression of the underlying disease with high cardiovascular morbidity and mortality. Hence, management of diabetic patients should include mandatory routine haematological tests, with consideration of advancing age and poor glycaemic control.

Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment.

Context: Although diabetic peripheral neuropathy (DPN) is predominantly considered a disorder of the peripheral nerves, some evidence for central nervous system involvement has recently emerged. However, whether or to what extent the microstructure of central somatosensory tracts may be injured remains unknown.Objective: This work aimed to detect the microstructure of central somatosensory tracts in type 2 diabetic patients and to correlate it with the severity of DPN.Methods: A case-control study at a tertiary referral hospital took place with 57 individuals with type 2 diabetes (25 with DPN, 32 without DPN) and 33 nondiabetic controls. The fractional anisotropy (FA) values of 2 major somatosensory tracts (the spinothalamic tract and its thalamocortical [spino-thalamo-cortical, STC] pathway, the medial lemniscus and its thalamocortical [medial lemnisco-thalamo-cortical, MLTC] pathway) were assessed based on diffusion tensor tractography. Regression models were further applied to detect the association of FA values with the severity of DPN in diabetic patients.Results: The mean FA values of left STC and left MLTC pathways were significantly lower in patients with DPN than those without DPN and controls. Moreover, FA values of left STC and left MLTC pathways were significantly associated with the severity of DPN (expressed as Toronto Clinical Scoring System values) in patients after adjusting for multiple confounders.Conclusion: Our findings demonstrated the axonal degeneration of central somatosensory tracts in type 2 diabetic patients with DPN. The parallel disease progression of the intracranial and extracranial somatosensory system merits further attention to the central nerves in diabetic patients with DPN. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) introduces an increased cardiovascular risk among patients with diabetes mellitus (DM). The risk and tempo of cardiovascular diseases may differ depending upon their type. Whether CKD differentially influences the risk of developing each cardiovascular morbidity in patients with newly diagnosed DM remains unexplored. Methods: We identified patients with incident DM from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort (n = 429,616), and uncovered those developing CKD after DM and their propensity score-matched counterparts without. After follow-up, we examined the cardiovascular morbidity-free rates of patients with and without CKD after DM, followed by Cox proportional hazard regression analyses. We further evaluated the cumulative risk of developing each outcome consecutively during the study period. Results: From LCDP, we identified 55,961 diabetic patients with CKD and matched controls without CKD. After 4.2 years, patients with incident DM and CKD afterward had a significantly higher risk of mortality (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.06–1.14), heart failure (HF) (HR 1.282, 95% CI 1.19–1.38), acute myocardial infarction (AMI) (HR 1.16, 95% CI 1.04–1.3), and peripheral vascular disease (PVD) (HR 1.277, 95% CI 1.08–1.52) compared to those without CKD. The CKD-associated risk of mortality, HF and AMI became significant soon after DM occurred and remained significant throughout follow-up, while the risk of PVD conferred by CKD did not emerge until 4 years later. The CKD-associated risk of ischemic, hemorrhagic stroke and atrial fibrillation remained insignificant. Conclusions: The cardiovascular risk profile among incident DM patients differs depending on disease type. These findings can facilitate the selection of an optimal strategy for early cardiovascular care for newly diagnosed diabetic patients. [ABSTRACT FROM AUTHOR]

The continually increasing number of patients with type 2 diabetes is a worldwide health problem, and the incidence of microvascular complications is closely related to type 2 diabetes. Structural brain abnormalities are considered an important pathway through which type 2 diabetes causes brain diseases. In fact, there is considerable evidence that type 2 diabetes is associated with an increased risk of structural brain abnormalities such as lacunar infarcts (LIs), white matter hyperintensities (WMHs), and brain atrophy. WMHs are a common cerebral small-vessel disease in elderly adults, and it is characterized histologically by demyelination, loss of oligodendrocytes, and vacuolization as a result of small-vessel ischemia in the white matter. An increasing number of studies have found that diabetes is closely related to WMHs. However, the exact mechanism by which type 2 diabetes causes WMHs is not fully understood. This article reviews the mechanisms of type 2 diabetes-related WMHs to better understand the disease and provide help for better clinical treatment.

Background and objectives: This study aimed to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients. Materials and Methods: A total of 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results: The median age of study subjects was 16.2 years (2.1;26.4), diabetes duration—5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c < 7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine—63 µmol/L (6;126). The median of eGFRcys was lower than eGFRcreat (92 mL/min/1.73 m2 vs. 101 mL/min/1.73 m2, p < 0.001). A total of 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r = −0.088, p < 0.05, as well as cystatin C and HDL, r = −0.097, p < 0.01. Conclusions: This study showed that cystatin C might be used as an additional biomarker of early kidney injury in young patients with T1D.

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.