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Purpose: To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and diabetic neuropathy. Methods: This prospective noninterventional hospital-based study included 57 consecutive cases of DR of either sex, presenting to the eye OPD between January 2019 and November 2020 with minimum 5-year duration of Type 1 and 2 DM. Complete ophthalmic examination was done and DR was classified according to early treatment diabetic retinopathy study classification. Severity of diabetic nephropathy was based on urine albumin creatinine ratio and estimated glomerular filtration rate. Severity of diabetic neuropathy was based on nerve conduction velocity. Results: The study was conducted on 57 patients of whom patients 45 were males and 12 were females. Mild nonproliferative diabetic retinopathy was present in 22 patients, moderate in 14 patients, severe in 18 patients, and proliferative diabetic retinopathy in 3 patients. In our study, group 30 patients of DR presented without clinically significant macular edema (CSME) and 27 patients presented with CSME. The distribution of severity of DR according to CSME was observed to be statistically significant (P<<0.05). The association of severity of DR with severity of diabetic nephropathy was observed to be statistically significant (P<<0.05). The association of severity of DR with that of diabetic neuropathy was inconclusive. Conclusion: The association of severity of DR with severity of diabetic nephropathy and diabetic neuropathy can be used as a marker for future chronic kidney diseases progression and also to prognosticate neurological outcomes in diabetic patients.

Left ventricular hypertrophy (LVH) is an important and common pathologic change in the heart of patients with diabetes mellitus. Microvascular complications have been reported to be involved in the development and process of LVH. This study aimed to explore the association between diabetic microvascular complications and LVH in patients with type 2 diabetes mellitus (T2DM). This is a cross-sectional study. A total of 2912 patients with T2DM were enrolled, including 360 patients with LVH and 2552 patients without LVH. Demographic data, medical history and laboratory indices were collected, along with information on diabetic microvascular complications and results from cardiac ultrasonography. The study utilized multivariable logistic regression to evaluate the independent effects of microvascular complications (DR, DPN, or DKD) and the cumulative number of these complications on the presence of LVH, while adjusting for potential confounding factors. In patients with T2DM, those with LVH were older and had higher body mass index, waist circumference and hip circumference than those without LVH. Additionally, the proportion of patients with diabetic retinopathy (DR) and diabetic kidney disease (DKD) was larger among those with LVH compared to those without LVH. After adjusting for potential confounding factors, DR and DKD were associated with increased odds of LVH (odds ratio [OR] = 1.351 and OR = 1.404, respectively). The risk of LVH also increased progressively in patients with two or more diabetic microvascular conditions compared to those with only one. In subgroup analysis, the risk of LVH increased with the number of microvascular conditions in male patients with T2DM. Diabetic microvascular complications were significantly associated with LVH in T2DM. Moreover, the risk of LVH increased with the number of microvascular complications, particularly in males with T2DM. •Diabetic microvascular complications were positively and independently associated with LVH.•Patients with diabetic retinopathy and diabetic kidney disease had higher risk of LVH.•The risk of LVH significantly increased with the number of microvascular diseases in male patients with T2DM.

This study aimed to evaluate the association between total bilirubin (TBiL) and major diabetic complications among Chinese senile diabetic patients. A cross-sectional study was conducted in all the cadre sanitariums in Beijing, between May 2012 and December 2014. All the diagnoses of diabetic complications were extracted from the medical records including chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease, and ischemic stroke. The mean age of the 1839 senile diabetic patients were 87.4±4.0 (80–102years) and mean TBiL level was 13.2±6.0μmol/L. The prevalence of chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke was 13.8%, 17.8%, 5.8%, 62.5%, and 44.5%, respectively. TBiL level was negatively correlated with age, weight, SBP, TC, FBG, 2hPG, diabetic duration and positively correlated with HDL-C. Prevalence of all five diseases gradually decreased with the increase of TBiL level (p<0.05). Also, number of diabetic complications showed a decreasing trend along with TBiL tertiaries. After adjusted age, education, marital status, current smoking, current drinking, physical activity ≥0.5h/day, BMI, hypertension, dyslipidemia, treatment and control status of diabetes, patients with higher TBiL level were at significantly decreased ORs for prevalence of major diabetic complications. The ORs were 0.97 (95%CI: 0.96–0.99), 0.90 (95%CI: 0.87–0.93), 0.98 (95%CI: 0.97–0.99), 0.97 (95%CI: 0.95–.99) and 0.98 (95%CI: 0.97–0.99) for chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke (p<0.005). Similar results were obtained when TBiL was used as tertiary variable. Higher TBiL was significantly associated with lower prevalence of major diabetic complication among senile diabetic patients, and this association was graded with TBiL level and independent of age and control status of diabetes.

Cardiovascular autonomic neuropathy in diabetics is a common but often underestimated and underdiagnosed complication of diabetes mellitus. One of the most clinical apparent forms of cardiovascular autonomic neuropathy is orthostatic hypotension. To retrospectively assess the association of the orthostatic hypotension (OH) with macrovascular and microvascular complications of diabetes mellitus and to determine its effect on mortality. We retrospectively analyzed 187 patients with diabetes mellitus (60 patients with diabetes type 1 and 127 patients with diabetes type 2). Patients were divided into groups according to presence or absence of OH and type of diabetes. Association of OH with macrovascular and microvascular complications was evaluated and the effect of OH on 10-year all-cause mortality was also assessed. OH was present in 31.7% of patients with diabetes type 1 (DM1) and in 32.3% of patients with diabetes type 2 (DM2). OH was positively associated with the prevalence of myocardial infarction in DM1 (OR=10.67) and with prevalence of stroke in DM2 (OR=3.33). There was also a strong association of OH and the prevalence of peripheral artery disease in both DM1 (OR=14.18) and DM2 (OR=3.26). Patients with both types of diabetes and OH had significantly higher prevalence of nephropathy (DM1 OR=8.68, DM2 OR=3.24), retinopathy (DM1 OR=8.09, DM2 OR=4.08) and peripheral neuropathy (DM1 OR=17.14, DM2 OR=7.51) Overall 10year mortality rate was higher in diabetic patients with OH. Presence of OH in diabetics is associated with higher prevalence of macrovascular and microvascular complications of diabetes mellitus and also with higher 10-year mortality.

The association between an overall healthy lifestyle and the subsequent risk of microvascular complications among patients with diabetes remains unclear. To examine the association between adherence to a healthy lifestyle before and after diabetes diagnosis and the risk of subsequent microvascular complications among adults with diabetes. This prospective cohort study included incident patients with type 2 diabetes who were free of cardiovascular disease and cancer at the time of diabetes diagnosis and completed the diabetes supplementary questionnaires in the Nurses' Health Study (in 2000 and 2005) and the Health Professionals Follow-Up Study (in 2000, 2004, and 2008) in the US. Data were analyzed from April to August 2021. Diet and lifestyle factors before and after diabetes diagnosis were assessed by validated questionnaires. A healthy lifestyle consisted of nonsmoking, having a healthy body weight (a body mass index of ≥18.5 or <25), engaging in moderate-to-vigorous physical activity (≥150 minutes per week), consuming a high-quality diet (top 40th percentile of the Alternative Healthy Eating Index), and moderate alcohol drinking (5-15 g/d for women and 5-30 g/d for men). Physician-diagnosed microvascular complications including diabetic neuropathy, retinopathy, nephropathy, and foot disorders were self-reported at questionnaire surveys. A total of 7077 patients with type 2 diabetes were included in the cohort (4982 women in NHS and 2095 men in HPFS, mean [SD] age 61 [8.8], 94.2% White). During follow-up, 2878 patients developed microvascular complications. After multivariable adjustment, adherence to a healthy lifestyle before and after diabetes diagnosis were both associated with a lower risk of developing microvascular complications. The relative risk (RR) for participants with 4 or more low-risk lifestyle factors before diabetes diagnosis compared with zero was 0.73 (95% CI, 0.60-0.91) for any microvascular complications, 0.71 (95% CI, 0.54-0.93) for diabetic neuropathy, 0.76 (95% CI, 0.57-1.01) for diabetic retinopathy, 0.42 (95% CI, 0.23-0.79) for diabetic nephropathy, and 0.60 (95% CI, 0.35-1.00) for diabetic foot disorders. Similar results were observed for adherence to a healthy lifestyle after diabetes diagnosis, with an RR of 0.68 (95% CI, 0.55-0.83) for any microvascular complications, 0.67 (95% CI, 0.51-0.88) for diabetic neuropathy, 0.65 (95% CI, 0.48-0.86) for diabetic retinopathy, 0.57 (95% CI, 0.34-0.98) for diabetic nephropathy, and 0.62 (95% CI, 0.37-1.05) for diabetic foot disorders. In addition, greater improvement in lifestyle factors from before to after diabetes diagnosis was also significantly associated with a lower risk of neuropathy or total microvascular complications. Each increment in number of low-risk lifestyle factors was associated with a 6% (RR, 0.94; 95% CI, 0.90-0.98) lower risk for any microvascular complications and a 9% (RR, 0.91; 95% CI, 0.86-0.96) lower risk for diabetic neuropathy. Consistent results were observed when analyses were stratified by age at diabetes diagnosis, sex/cohort, or lifestyle factors before diabetes diagnosis. In this cohort study, adhering to an overall healthy lifestyle was associated with a significantly lower risk of microvascular complications among individuals with diabetes. These findings suggest substantial reduction in the burden of microvascular complications associated with adopting a healthy lifestyle among patients with type 2 diabetes.

The financial impact of intensive (blood glucose [BG] 100–140mg/dl [5.5–7.8mM] vs. conservative (141–180mg/dl (7.9–10.0mM) glucose control in the ICU in patients, with and without diabetes, undergoing coronary artery bypass graft (CABG) surgery is not known. This post-hoc cost analysis determined differences in hospitalization costs, resource utilization and perioperative complications in 288 CABG patients with diabetes (n=143) and without diabetes (n=145), randomized to intensive (n=143) and conservative (n=145) glucose control. Intensive glucose control resulted in lower BG (131.4±14mg/dl-(7.2±0.8mM) vs. 151.6±17mg/dl (8.4±0.8mM, p<0.001), a nonsignificant reduction in the median length of stay (LOS, 7.9 vs. 8.5days, p=0.17) and in a composite of perioperative complications including wound infection, bacteremia, acute renal and respiratory failure, major cardiovascular events (42% vs 52%, p=0.10) compared to conservative control. Median hospitalization costs were lower in the intensive group ($39,366 vs. $42,141, p=0.040), with a total cost savings of $3654 (95% CI: $1780–$3723), than conservative control. Resource utilization for radiology (p=0.008), laboratory (p=0.014), consultation service (p=0.013), and ICU utilization (p=0.007) were also lower in the intensive group. Compared to patients without perioperative complications, those with complications had longer hospital length of stay (10.7days vs. 6.7days, p<0.001), higher total hospitalization cost ($48,299 vs. $32,675, p<0.001), and higher resource utilization units (2745 vs. 1710, p<0.001). Intensive glycemic control [BG 100–140mg/dl (5.5–7.8mM)] in patients undergoing CABG resulted in significant reductions in hospitalization costs and resource utilization compared to patients treated with conservative [BG 141–180mg/dl (7.9–10.0mM)] glucose control.

Patients with previous diabetic foot ulcer are prone to re-ulceration and (re)amputation, to various comorbidities, have significantly impaired quality of life and increased mortality. We aimed to evaluate the risk of foot related complications and mortality in a high-risk population of patients with healed diabetic foot syndrome over a decade. 91 patients with recently healed diabetic foot ulcer were invited for follow-up at 1, 6 and 11 years after inclusion. Patient characteristics at inclusion were: 40 women, 65 ± 11 years, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 ± 4.4 kg/m 2 , and HbA1c 68 ± 17 mmol/mol. Comorbidities included neuropathy (n = 91), peripheral artery disease (PAD), history of minor (n = 25) or major (n = 5, 5.5%) amputation, nephropathy (n = 40) and retinopathy (n = 53). Ulceration recurred in 71 (65%) patients, time to first recurrence was 1.8 ± 2.4 years (mean ± SD). 21 patients had to undergo (re)amputation (minor n = 19, major n = 2), time to amputation was 3.6 ± 1.9 years. Over time, 3 further major amputations were required in patients with an initial minor amputation. Thirty-three (36%) of the initially included patients completed the follow-up period of 11.0 ± 0.6 years. 58 patients (64%) died during the observational period, time to death was 5 ± 3 years in this group. We found overall high mortality of 64% throughout the follow-up period of 11 years in high-risk patients with healed diabetic foot syndrome. Presence of PAD, prior amputation and nephropathy as well as poor glycemic control were significantly predictive for death.

In this trial in persons with chronic kidney disease and type 2 diabetes, combination therapy with finerenone and empagliflozin led to a greater reduction in the urinary albumin-to-creatinine ratio than either drug alone.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes 1 , 2 and molecular mechanisms that are often specific to cell type 3 , 4 . Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance ( P  < 5 × 10 −8 ) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores 5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care. A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

We sought to determine the predictive value of Matrix Gla Protein MGP T-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). MGP T-138C polymorphism was assessed in 40 diabetic patients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. TT homozygotes for the MGP T-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGP T-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. MGP T-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients. •No association was observed between cIMT and dp-ucMGP levels in diabetic nephropathy patients.•In this population, the TT genotype of MGP T-138C polymorphism is associated with increased cIMT.•MGP T-138C polymorphism is a strong and independent predictor of all-cause and cardiovascular mortality in diabetic nephropathy patients.