Health state utility values ranges across varying stages and severity of type 2 diabetes-related complications: A systematic review.

INTRODUCTION: Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications. METHOD: A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison. RESULTS: Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes. DISCUSSION: Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies.

[Analysis of epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns].

Objective: To explore the epidemiological characteristics and risk factors of catheter-associated urinary tract infections in patients with perineal and/or hip burns. Methods: This study was a retrospective case series study. From January 2018 to December 2022, 260 patients with perineal and/or hip burns and urinary catheters indwelling who met the inclusion criteria were admitted to the Department of Burns and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine, including 192 males and 68 females, aged 20-93 years. The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns, the detection of pathogenic bacteria, and the resistance of major Gram-negative and Gram-positive bacteria to commonly used antimicrobial drugs in clinic were recorded. According to whether catheter-associated urinary tract infection occurred or not, the patients were divided into infection group (43 cases) and non-infection group (217 cases). The basic conditions including gender, age, total burn area, depth of perineal burn, depth of hip burn, and burn site on admission, complications of diabetes mellitus, inhalation injury, and hypoproteinaemia, invasive operations including tracheotomy and non-perineal/hip debridement/skin transplantation surgery, duration of catheter retention, number of urethral catheterization, and bladder irrigation of patients between the two groups were compared, and the independent risk factors influencing the occurrence of catheter-associated urinary tract infections in patients with perineal and/or hip burns were screened. Results: The total incidence of catheter-associated urinary tract infections in patients with perineal and/or hip burns in this study was 16.5% (43/260). The pathogens detected were predominantly Gram-negative, followed by fungi; the main Gram-negative bacterium was Klebsiella pneumoniae, and the main Gram-positive bacterium was Enterococcus faecalis. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid, amitraz, amikacin, ciprofloxacin, ceftriaxone, and levofloxacin were higher than 70.0%, the resistance rates of Klebsiella pneumoniae to cefoxitin, cefoperazone/sulbactam, cefepime, meropenem, imipenem, and piperacillin/tazobactam ranged from 56.3% to 68.8%, and the resistance rates of Klebsiella pneumoniae to ceftazidime and tigecycline were lower than 50.0%. The resistance rates of Enterococcus faecalis to ciprofloxacin and penicillin were both 85.7%, the resistance rates of Enterococcus faecalis to erythromycin, clindamycin, moxifloxacin, and tetracycline ranged from 14.3% to 57.1%, and the resistance rates of Enterococcus faecalis to linezolid, tigecycline, and vancomycin were all 0. The differences were statistically significant between the two groups in terms of gender, status of complication of hypoproteinaemia, depth of perineal burn, status of non-perineal/hip debridement/skin transplantation surgery, status of bladder irrigation, number of urethral catheterization, and duration of catheter retention of patients (with χ2 values of 7.80, 4.85, 10.68, 9.11, and 16.48, respectively, and Z values of -4.88 and -5.42, respectively, P<0.05). There were no statistically significant differences in the age, total burn area, complications of diabetes mellitus and inhalation injury, burn site, depth of hip burns, and status of tracheotomy of patients between the two groups (P>0.05). Multifactorial logistic regression analysis showed that gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention were the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns (with odds ratios of 2.86, 2.63, 2.79, 2.34, and 1.04, respectively, with 95% confidence intervals of 1.21-6.73, 1.03-6.71, 1.03-7.59, 1.05-5.22, and 1.02-1.06, respectively, P<0.05). Conclusions: The incidence of catheter-associated urinary tract infections is high in patients with perineal and/or hip burns, with Klebsiella pneumoniae as the predominant pathogenic bacteria having a high resistance rate to commonly used antimicrobial drugs in clinic. Gender, deep partial-thickness perineal burns, non-perineal/hip debridement/skin transplantation surgery, bladder irrigation, and duration of catheter retention are the independent risk factors for catheter-associated urinary tract infections in patients with perineal and/or hip burns.

Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients. DESIGN: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively. RESULTS: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7. CONCLUSION: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

A multi-state analysis of disease trajectories and mental health transitions in patients with type 2 diabetes: A population-based retrospective cohort study utilizing health administrative data.

AIMS: To investigate the risk of major depression and dementia in patients with type 2 diabetes, including dementia resulting from depression, and their impact on diabetes-related complications and mortality. METHODS: We conducted a population-based retrospective cohort study including 11,441 incident cases of diabetes in 2015-2017, with follow-up until 2022. A multi-state survival analysis was performed on a seven-state model with 15 transitions to capture disease progression and onset of mental disorders. RESULTS: Eight-year probabilities of depression, dementia, diabetes-related complications, and death were 9.7% (95% CI 8.7-10.7), 0.9% (95% CI 0.5-1.3), 10.4% (95% CI 9.5-11.4), and 14.8% (95% CI 13.9-15.7), respectively. Depression increased the risk of dementia up to 3.7% (95% CI 2.0-5.4), and up to 10.3% (95% CI 0.3-20.4) if coupled with diabetes complications. Eight-year mortality was 37.5% (95% CI 33.1-42.0) after depression, 74.1% (95% CI 63.7-84.5) after depression plus complications, 76.4% (95% CI 68.8-83.9) after dementia, and 98.6% (95% CI 96.1-100.0) after dementia plus complications. CONCLUSIONS: The interconnections observed across depression, dementia, complications, and mortality underscore the necessity for comprehensive and integrated approaches in managing diabetes. Early screening for depression, followed by timely and targeted interventions, may mitigate the risk of dementia and improve diabetes prognosis.

Use of machine learning to identify characteristics associated with severe hypoglycemia in older adults with type 1 diabetes: a post-hoc analysis of a case-control study.

INTRODUCTION: Severe hypoglycemia (SH) in older adults (OAs) with type 1 diabetes is associated with profound morbidity and mortality, yet its etiology can be complex and multifactorial. Enhanced tools to identify OAs who are at high risk for SH are needed. This study used machine learning to identify characteristics that distinguish those with and without recent SH, selecting from a range of demographic and clinical, behavioral and lifestyle, and neurocognitive characteristics, along with continuous glucose monitoring (CGM) measures. RESEARCH DESIGN AND METHODS: Data from a case-control study involving OAs recruited from the T1D Exchange Clinical Network were analyzed. The random forest machine learning algorithm was used to elucidate the characteristics associated with case versus control status and their relative importance. Models with successively rich characteristic sets were examined to systematically incorporate each domain of possible risk characteristics. RESULTS: Data from 191 OAs with type 1 diabetes (47.1% female, 92.1% non-Hispanic white) were analyzed. Across models, hypoglycemia unawareness was the top characteristic associated with SH history. For the model with the richest input data, the most important characteristics, in descending order, were hypoglycemia unawareness, hypoglycemia fear, coefficient of variation from CGM, % time blood glucose below 70 mg/dL, and trail making test B score. CONCLUSIONS: Machine learning may augment risk stratification for OAs by identifying key characteristics associated with SH. Prospective studies are needed to identify the predictive performance of these risk characteristics.

Initial Combination Therapy in Type 2 Diabetes.

Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved ß-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. METHODS: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. RESULTS: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. CONCLUSIONS: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.

Genetics and epigenetics of diabetes and its complications in India.

Diabetes mellitus (DM) has become a significant health concern with an increasing rate of morbidity and mortality worldwide. India ranks second in the number of diabetes cases in the world. The increasing burden of DM can be explained by genetic predisposition of Indians to type 2 diabetes mellitus (T2DM) coupled with rapid urbanization and socio-economic development in the last 3 decades leading to drastic changes in lifestyle. Environment and lifestyle changes contribute to T2DM development by altering epigenetic processes such as DNA methylation, histone post-translational modifications, and long non-coding RNAs, all of which regulate chromatin structure and gene expression. Although the genetic predisposition of Indians to T2DM is well established, how environmental and genetic factors interact and lead to T2DM is not well understood. In this review, we discuss the prevalence of diabetes and its complications across different states in India and how various risk factors contribute to its pathogenesis. The review also highlights the role of genetic predisposition among the Indian population and epigenetic factors involved in the etiology of diabetes. Lastly, we review current treatments and emphasize the knowledge gap with respect to genetic and epigenetic factors in the Indian context. Further understanding of the genetic and epigenetic determinants will help in risk prediction and prevention as well as therapeutic interventions, which will improve the clinical management of diabetes and associated macro- and micro-vascular complications.

Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study.

AIMS/HYPOTHESIS: While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN. METHODS: The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up. RESULTS: At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03). CONCLUSIONS/INTERPRETATION: In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.

Impact of diabetes and glycated hemoglobin level on the clinical manifestations of Parkinson's disease.

BACKGROUND: The coexistence of diabetes mellitus (DM) has been suggested to accelerate the progression of Parkinson's disease (PD) and make the phenotype more severe. In this study, we investigated whether DM or glycated hemoglobin (HbA1c) levels affect the differences in motor and nonmotor symptoms. METHODS: We conducted a cross-sectional study including 140 consecutive Japanese patients with PD for whom medical history and serum HbA1c records were available. The PD patients with a DM diagnosis were classified into the diabetes-complicated group (PD-DM) and the nondiabetes-complicated group (PD-no DM). Next, patients were classified based on a median HbA1c value of 5.7, and clinical parameters were compared. The correlations between HbA1c levels and other clinical variables were analyzed. RESULTS: Of 140 patients, 23 patients (16%) had DM. Compared to PD-no DM patients, PD-DM patients showed lower MMSE scores. Compared to the lower HbA1c group, the higher HbA1c group showed a higher MDS-UPDRS part III score and a lower metaiodobenzylguanidine (MIBG) scintigraphy heart-to-mediastinum (H/M) ratio. HbA1c levels were positively correlated with age and the MDS-UPDRS part III score and negatively correlated with the MMSE score and H/M ratio on cardiac MIBG scintigraphy. Binary logistic regression analysis, which included age, sex, disease duration, and MMSE and MDS-UPDRS part III scores as independent variables, revealed that a lower MMSE score was an independent contributor to PD-DM and PD with high HbA1c levels. CONCLUSIONS: DM complications and high HbA1c levels may affect cognitive function in patients with PD.

Factors Associated with Diabetic Complication Index among Type 2 Diabetes Patients: Focusing on Regular Outpatient Follow-up and HbA1c Variability.

PURPOSE: Preventing diabetic complications involves regular outpatient follow-up and maintaining low variability in hemoglobin A1c (HbA1c) levels. This study investigated the factors associated with diabetic complications, with a specific focus on the impact of regular outpatient follow-up and HbA1c variability, among patients with type 2 diabetes. METHODS: The study design was secondary data analysis of electronic medical records from a university hospital in Korea. It included patients aged 40-79 with type 2 diabetes who were prescribed diabetes medication within three months of their first HbA1c test by an endocrinologist and were followed up for at least five years. Follow-up regularity, adjusted standard deviation of HbA1c levels, and diabetic complication indices were collected. Data were analyzed using the Chi-square test, independent t-test, repeated measures analysis of variance, and multiple regression analysis. RESULTS: The study included 1566 patients. Lower follow-up regularity was observed in patients of older age, with comorbidities, diabetic complications, insulin treatment, a history of hospitalization, lower baseline estimated glomerular filtration rate (eGFR) and total cholesterol (TC), and higher HbA1c variability. Higher HbA1c variability was observed in younger patients without comorbidity but with insulin treatment, a history of hospitalization, higher baseline blood glucose (BG), HbA1c, TC, and triglyceride levels. HbA1c variability had the strongest influence on BG and HbA1c levels at the five-year follow-up. Baseline eGFR and TC were the most influential factors for their respective levels at the five-year follow-up. Follow-up regularity significantly affected BG, HbA1c, eGFR, and TC at five-year follow-up. CONCLUSIONS: It has been shown that several variables besides regular follow-up and HbA1c variability have an influence. However, these are the two that can be corrected through nursing intervention and are important, so intervention on these is important.

Urinary symptoms and female sexual dysfunction in women with type 1 diabetes: the role of depression.

BACKGROUND: Some reports suggest that women with type 1 diabetes (T1D) have a greater burden of female sexual dysfunction (FSD) than women without T1D, but the etiology of this elevated risk is poorly understood. AIM: To examine the associations between FSD and urinary incontinence/lower urinary tract symptoms (UI/LUTS) in women with T1D and to evaluate how depression may mediate these relationships. METHODS: LUTS and UI symptoms were assessed in women with T1D who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Multivariable logistic regression models estimated associations between FSD and UI/LUTS (overall and specific domains) and the impact of depression on these associations. OUTCOMES: FSD was measured with the Female Sexual Function Index-Reduced. RESULTS: In total, 499 self-reported sexually active women completed validated assessments of sexual and urinary function (mean ± SD age, 47.7 ± 7.6 years; T1D duration, 23.4 ± 5.15 years). FSD was reported in 232 (46%) responders. The frequency of UI and LUTS was 125 (25.1%) and 96 (19.2%), respectively. Neither UI nor its subcategories (urge, stress) were associated with FSD. Although LUTS (odds ratio [OR], 1.75; 95% CI, 1.09-2.77) and its symptoms of urgency (OR, 1.99; 95% CI, 1.09-3.61) and incomplete emptying (OR, 2.44; 95% CI, 1.23-4.85) were associated with FSD, these associations were attenuated following adjustment for depression and antidepressant medication use. Depression indicators were independently associated with FSD overall and across domains. CLINICAL IMPLICATIONS: The complex interplay of voiding dysfunction, mental health, and sexual function warrants further investigation to understand the potential implications for patient assessment, goal setting, treatment, and care planning. STRENGTHS AND LIMITATIONS: Data are from a prospective study of individuals with T1D. These results are unable to explore cause-and-effect relationships among LUTS, UI, depression, and FSD. The sample may not be representative of the general population of women with T1D. Because participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study are mostly White, generalizing the findings to other races and to type 2 diabetes may not be appropriate. While exclusion of sexually inactive women likely biases our findings toward the null, this design element permitted study of LUTS and UI in relation to aspects of FSD, the primary objective of this study. CONCLUSIONS: The significant associations between LUTS/UI and FSD among middle-aged women with T1D were greatly attenuated when depression was considered a mediating factor.

Early rhythm control on diabetes-related complications and mortality in patients with type 2 diabetes mellitus and atrial fibrillation.

AIMS: We evaluated the impact of early rhythm control (ERC) on diabetes-related complications and mortality in subjects with type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF). METHODS: This observational cohort study based on the Korean National Health Insurance Service claims database from 2009 to 2016, divided newly diagnosed AF patients with T2DM into ERC or usual care groups based on receiving rhythm control treatment within 1 year of AF diagnosis. The primary outcome was ischemic stroke, and the secondary outcomes were macro/microvascular complications, and all-cause death. RESULTS: Among 47,509 subjects (mean age 66.7 ± 10.5 years; 61.8 % men; mean CHA2DS2-VASc score 4.6 ± 1.8; mean follow-up 4.3 ± 2.3 years; mean DM duration 5.6 ± 4.7 years), 23.1 % received ERC, and 76.9 % did not (usual care group). ERC was associated with lower risks of ischemic stroke, macrovascular and microvascular complications, and all-cause death compared to usual care (adjusted hazard ratios [95 % confidence interval]: 0.77 [0.70-0.85], 0.79 [0.73-0.86], 0.86 [0.82-0.90], and 0.92 [0.87-0.98], p < 0.001, <0.001, <0.001, and 0.012, respectively). CONCLUSIONS: Early rhythm control was associated with reduced risks of diabetes-related complications and mortality in subjects with T2DM and AF. Rhythm control within 1 year of AF diagnosis with proper anticoagulation should be considered to prevent adverse outcomes.

Quantification of joint mobility limitation in adult type 1 diabetes.

Aims: Diabetic cheiroarthropathies limit hand mobility due to fibrosis and could be markers of a global profibrotic trajectory. Heterogeneity in definitions and lack of a method to measure it complicate studying associations with organ involvement and treatment outcomes. We measured metacarpophalangeal (MCP) joint extension as a metric and describe magnetic resonance (MR) imaging determinants of MCP restriction. Methods: Adults with type 1 diabetes were screened for hand manifestations using a symptom questionnaire, clinical examination, and function [Duruoz hand index (DHI) and grip strength]. Patients were segregated by mean MCP extension (<20°, 20°-40°, 40°-60°, and >60°) for MR imaging (MRI) scanning. Patients in the four groups were compared using ANOVA for clinical features and MRI tissue measurements (tenosynovial, skin, and fascia thickness). We performed multiple linear regression for determinants of MCP extension. Results: Of the 237 patients (90 men), 79 (33.8%) with cheiroarthropathy had MCP extension limitation (39° versus 61°, p < 0.01). Groups with limited MCP extension had higher DHI (1.9 vs. 0.2) but few (7%) had pain. Height, systolic blood pressure, and nephropathy were associated with mean MCP extension. Hand MRI (n = 61) showed flexor tenosynovitis in four patients and median neuritis in one patient. Groups with MCP mobility restriction had the thickest palmar skin; tendon thickness or median nerve area did not differ. Only mean palmar skin thickness was associated with MCP extension angle on multiple linear regression. Conclusion: Joint mobility limitation was quantified by restricted mean MCP extension and had structural correlates on MRI. These can serve as quantitative measures for future associative and interventional studies.

Prediction of clinical events by liver stiffness and chronic kidney disease by NAFLD in patients with type-2 diabetes / Predicción de eventos clínicos por elasticidad hepática y enfermedad renal crónica por EHMet en pacientes con diabetes tipo 2

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with poorer glycemic control and a higher risk of type-2 diabetes (T2D) complications, extrahepatic and cardiovascular disease (CVD). Our study aim was to evaluate the association between NAFLD, T2D complications, and the development of overall clinical events (OCE) (CV, liver-related, and mortality) in patients with T2D. Methods: Prospective single-center study comprising T2D subjects with no history of CVD and non-T2D matched controls. Patients were selected from the Outpatient Diabetes Clinic of Vall d’Hebron Hospital and related primary care centers. Results: 186 diabetics and 57 controls were included. Amongst T2D, 124/186 subjects had NAFLD (66.6%). T2D-NAFLD subjects showed a heavier metabolic burden and higher median liver stiffness (5.6kPa [4.5–7.3] vs 4.8 [4.2–5.8]; p=0.004) compared to non-NAFLD diabetics. During a median follow-up of 5.6 years, 33 (17.7%) T2D patients developed OCE vs 4 (7.0%) controls (p=0.049). No differences were found for OCE between NAFLD and non-NAFLD diabetics (16.9% vs 19.4%; p=0.68). CV was the most reported outcome and only one liver event occurred. NAFLD diabetics showed more often chronic kidney disease (CKD), whereas T2D complications and subclinical CVD rates were similar. A higher liver stiffness, older age, and male gender were independently associated with OCE amongst the entire T2D population and NAFLD diabetics. Conclusions: NAFLD and liver stiffness were associated with CKD and clinical outcomes in diabetics, respectively. A hepatic evaluation is recommended to identify high-risk T2D patients that would benefit from early referral to specialized care. (AU)

Antecedentes y objetivos: La esteatosis hepática metabólica (EHMet) se asocia con un peor control glucémico y un mayor riesgo de complicaciones de la diabetes tipo 2 (DM2), enfermedad extrahepática y cardiovascular (CV). El objetivo fue evaluar la asociación entre EHMet, complicaciones microvasculares y el desarrollo de eventos clínicos globales (ECG) (CV, hepáticos y mortalidad) en diabéticos. Métodos: Estudio unicéntrico prospectivo que incluye diabéticos sin historia de CV y controles sin DM2. Se seleccionaron pacientes de la consulta de Diabetes del Hospital Vall d’Hebron y centros de atención primaria asociados. Resultados: Se incluyeron 186 diabéticos y 57 controles. Entre los diabéticos, 124/186 presentaron EHMet (66,6%). Los pacientes DM2 con EHMet presentaron mayor carga metabólica y una elasticidad hepática superior (5,6kPa [4,5-7,3] vs. 4,8 [4,2-5,8]; p=0,004) a los diabéticos sin EHMet. Durante una mediana de seguimiento de 5,6 años, 33 (17,7%) diabéticos desarrollaron ECG vs. 4 (7,0%) controles (p=0,049). No hubo diferencias en ECG entre diabéticos con y sin EHMet (16,9% vs. 19,4%; p=0,68). El evento más reportado fue CV y solamente se produjo un evento hepático. La enfermedad renal crónica (ERC) fue más frecuente en diabéticos con EHMet, mientras que los ratios de complicaciones microvasculares y enfermedad CV silente fueron similares. El género masculino, una mayor edad y elasticidad hepática se asociaron de forma independiente a ECG para el total de diabéticos y para aquellos con EHMet. Conclusiones: La EHMet y la elasticidad hepática se asociaron a ERC y eventos clínicos en diabéticos. Se recomienda una evaluación hepática para identificar pacientes diabéticos de riesgo que se beneficiarían de una derivación precoz al especialista. (AU)

Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.

This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome ß-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

Risk of rapid progression to dialysis in patients with type 2 diabetes mellitus with and without diabetes-related complications at diagnosis.

Many adults with diabetes mellitus are unaware worldwide. The study objectives aimed to evaluate the risk of dialysis within 5 years of diagnosis between patients with newly diagnosed diabetes with and without diabetes-related complications. A retrospective longitudinal nationwide cohort study was conducted. Patients diagnosed with diabetes between 2005 and 2013 were followed up until 2018. They were categorized based on the presence or absence of complications, the number of complications, and the diabetes complications severity index (DCSI) scores. Dialysis outcomes were determined through the Registry of Catastrophic Illness from the National Health Insurance Research Database. Among the analyzed patients, 25.38% had complications at diagnosis. Patients with complications at diagnosis had a significantly higher risk of dialysis within 5 years (adjusted hazard ratio: 9.55, 95% confidence interval CI 9.02-10.11). Increasing DCSI scores and the number of complications were associated with higher dialysis risks. Patients with one complication had a 7.26-times higher risk (95% CI 6.83-7.71), while those with ≥ 3 complications had a 36.12-times higher risk (95% CI 32.28-40.41). In conclusion, newly diagnosed diabetes patients with complications face an increased risk of dialysis within 5 years. The severity and number of complications are directly linked to the risk of dialysis within this timeframe.

Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.

Diabetes affects millions of people worldwide and is mainly associated with impaired insulin function. To date, various oral anti-diabetic drugs have been developed, of which, the sodium glucose transporter-2 inhibitors (SGLT2Is) are of the most recent classes that have been introduced. They differ from other classes in terms of their novel mechanism of actions and unique beneficial effects rather than just lowering glucose levels. SGLT2Is can protect body against cardiovascular events and kidney diseases even in non-diabetic individuals. SGLT2Is participate in immune cell activation, oxidative stress reduction, and inflammation mediation, thereby, moderating diabetic complications. In addition, toll like receptors (TLRs) are the intermediators of the immune system and inflammatory process, thus it's believed to play crucial roles in diabetic complications, particularly the ones that are related to inflammatory reactions. SGLT2Is are also effective against diabetic complications via their anti-inflammatory and oxidative properties. Given the anti-inflammatory properties of TLRs and SGLT2Is, this review investigates how SGLT2Is can affect the TLR pathway, and whether this could be favorable toward diabetes.

Educational attainment affects the diagnostic time in type 2 diabetes mellitus and the mortality risk of those enrolled in the diabetes pay-for-performance program.

Most patients are diagnosed as having diabetes only after experiencing diabetes complications. Educational attainment might have a positive relationship with diabetes prognosis. The diabetes pay-for-performance (P4P) program-providing comprehensive, continuous medical care-has improved diabetes prognosis in Taiwan. This retrospective cohort study investigated how educational attainment affects the presence of diabetes complications at diabetes diagnosis and mortality risk in patients with diabetes enrolled in the P4P program. From the National Health Insurance Research Database, we identified patients aged >45 years who had received a new diagnosis of type 2 diabetes during 2002-2015; they were followed up until the end of 2017. We next used logistic regression analysis to explore whether the patients with different educational attainments had varied diabetic complication risks at diabetes diagnosis. The Cox proportional hazard model was employed to examine the association of different educational attainments in people with diabetes with mortality risk after their enrollment in the P4P program. The results indicated that as educational attainment increased, the risk of diabetes complications at type 2 diabetes diagnosis decreased gradually. When type 2 diabetes with different educational attainments joined the P4P program, high school education had the highest effect on reducing mortality risk; however, those with ≤ 6th grade education had the lowest impact.