[Effect of femtosecond laser-assisted phacoemulsification on corneal endothelium and prognosis of diabetic patients with cataract with different nuclear hardness].

Objective: To assess the impact of femtosecond laser-assisted phacoemulsification on corneal endothelial characteristics and prognosis among patients with type 2 diabetes and age-related cataracts, considering varying nuclear hardness. Methods: This non-randomized controlled trial involved 161 patients (161 eyes) with type 2 diabetes undergoing cataract extraction at Weifang Eye Hospital between March 2020 and December 2022. The cohort comprised 73 males and 88 females, with an average age of (65.9±5.23) years. Based on patient preference, 101 individuals underwent conventional phacoemulsification (group A), while 60 chose femtosecond laser-assisted phacoemulsification (group B). Patients were further stratified based on Emery-Little grade of lens nuclei into A1/B1 (grade Ⅰ and Ⅱ), A2/B2 (grade Ⅲ), and A3/B3 (grade Ⅳ) subgroups. The study compared effective phacoemulsification time (EPT), cumulative energy release of phacoemulsification (CDE), central corneal thickness (CCT), endothelial cell density (ECD), coefficient of variation (CV), and hexagon cell ratio (HEX) before and after surgery at 1 day, 1 week, 1 month, and 3 months. Results: The intraoperative EPT of patients in groups A and B were (6.52±4.93) and (5.63±4.31)s, respectively, and the CDE were 11.57%±5.21% and 10.68%±6.02%, respectively. The differences between them were not statistically significant (all P>0.05).There were no significant differences in EPT and CDE between groups A1 and B1 (all P>0.05), and there were statistically significant differences between groups A2 and B2, A3 and B3 (all P<0.05).The postoperative CCT was increased in both groups.There were no statistically significant differences in CCT between A1 and B1 groups at different time after surgery (all P>0.05), and there were statistically significant differences in CCT between A2 and B2, A3 and B3 groups at 1 day and 1 week after surgery (all P<0.05), and group B was significantly lower than group A.There was no significant difference between 1 month and 3 months after surgery (P>0.05).ECD was reduced in both groups.There was no statistically significant difference in ECD at different time of operation between A1 and B1 groups (all P>0.05), while there was statistically significant difference in ECD at 1 day, 1 week, 1 month and 3 months after operation in A2 and B2, A3 and B3 groups (all P<0.05). Group B was significantly better than group A. There was no significant difference in coefficient of variation and HEX between the two groups at different time after surgery (P>0.05). Conclusion: Femtosecond laser-assisted phacoemulsification demonstrates benefits in preserving corneal endothelial cells, reducing early postoperative corneal edema, and minimizing corneal injury in type 2 diabetes patients with cataracts of high nuclear hardness.

MARRIAGE: A Randomized Trial of Moxonidine Versus Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

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

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

Summary and Panel Discussion.

In this video, Javed Butler, MD, Jonathan Rich, MD, Rachel Pessah-Pollack, MD, and John E. Anderson, MD, summarize the key points of the enhanced publication "Role of SGLT2 Inhibitors in the Management of Heart Failure With and Without Type 2 Diabetes." The panel then delves deeper into some of the topics raised.

Use of SGLT2 Inhibitors in Patients With HF With and Without Type 2 Diabetes: An Endocrinologist's Perspective.

In this video, Javed Butler, MD, and Rachel Pessah-Pollack, MD, discuss the use of SGLT2 inhibitors in patients with and without type 2 diabetes.

Multicentre, retrospective cohort study protocol to identify racial and ethnic differences in acute kidney injuries in children and adolescents with diabetic ketoacidosis.

INTRODUCTION: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA. METHODS AND ANALYSIS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is 'sustained' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering. ETHICS AND DISSEMINATION: The Institutional Review Board of Children's Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

Associations between metabolic dysfunction-associated fatty liver disease, chronic kidney disease, and abdominal obesity: a national retrospective cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) present notable health challenges, however, abdominal obesity has received scant attention despite its potential role in exacerbating these conditions. Thus, we conducted a retrospective cohort study using the National Health and Nutrition Examination Surveys III (NHANES III) of the United States from 1988 to 1994 including 9161 participants, and mortality follow-up survey in 2019. Statistical analyze including univariable and multivariable Logistic and Cox regression models, and Mediation effect analyze were applied in study after adjustment for covariates. Our findings revealed that individuals with both abdominal obesity and MAFLD were more likely to be female, older and exhibit higher prevalence of advanced liver fibrosis (7.421% vs. 2.363%, p < 0.001), type 2 diabetes mellitus (T2DM) (21.484% vs. 8.318%, p < 0.001) and CKD(30.306% vs. 16.068%, p < 0.001) compared to those with MAFLD alone. MAFLD (adjusted OR: 1.392, 95% CI 1.013-1.913, p = 0.041), abdominal obesity (adjusted OR 1.456, 95% CI 1.127-1.880, p = 0.004), abdominal obesity with MAFLD (adjusted OR 1.839, 95% CI 1.377-2.456, p < 0.001), advanced fibrosis(adjusted OR 1.756, 95% CI 1.178-2.619, p = 0.006) and T2DM (adjusted OR 2.365, 95% CI 1.758-3.183, p < 0.001) were independent risk factors of CKD. The abdominal obese MAFLD group had the highest all-cause mortality as well as mortality categorized by disease during the 30-year follow-up period. Indices for measuring abdominal obesity, such as waist circumference (WC), waist-hip ratio (WHR), and lipid accumulation product (LAP), elucidated a greater mediation effect of MAFLD on CKD compared to BMI on CKD (proportion mediation 65.23%,70.68%, 71.98%, respectively vs. 32.63%). In conclusion, the coexistence of abdominal obesity and MAFLD increases the prevalence and mortality of CKD, and abdominal obesity serves as a mediator in the association between MAFLD and CKD.

The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark.

Background: Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We assessed the impact of different types of surgical cancer resections and oncological treatment on risk of T2D development in CRC patients. Methods: We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001 and 2018. Using nationwide register data, we identified and followed patients from date of surgery and until new onset of T2D, death, or end of follow-up. Results: In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5257 Left-Chemo (11%), 9618 Rectal-No-Chemo (21%), and 6136 Rectal-Chemo (13%). During 245,466 person-years of follow-up, 2556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95% CI: 10.4-12.2) per 1000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95% CI: 8.8-10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower T2D risk (HR 0.86 [95% CI 0.75-0.98]) compared to Right-No-Chemo.For all six groups, an increased level of body mass index (BMI) resulted in a nearly twofold increased risk of developing T2D. Conclusions: This study suggests that postoperative T2D screening should be prioritised in CRC survivors with overweight/obesity regardless of type of CRC treatment applied. Funding: The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).

The role of small dense LDL-C/large buoyant LDL-C ratio as an independent risk factor in patients with type 2 diabetes mellitus and metabolic syndrome

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC > 0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Prevalence and risk factors for diabetic retinopathy at diagnosis of type 2 diabetes: an observational study of 77 681 patients from the Swedish National Diabetes Registry.

INTRODUCTION: To assess the prevalence of diabetic retinopathy (DR) in persons with newly diagnosed type 2 diabetes (T2D) to understand the potential need for intensified screening for early detection of T2D. RESEARCH DESIGN AND METHODS: Individuals from the Swedish National Diabetes Registry with a retinal photo <2 years after diagnosis of T2D were included. The proportion of patients with retinopathy (simplex or worse) was assessed. Patient characteristics and risk factors at diagnosis were analyzed in relation to DR with logistic regression. RESULTS: In total, 77 681 individuals with newly diagnosed T2D, mean age 62.6 years, 41.1% females were included. Of these, 13 329 (17.2%) had DR.DR was more common in older persons (adjusted OR 1.03 per 10-year increase, 95% CI 1.01 to 1.05) and men compared with women, OR 1.10 (1.05 to 1.14). Other variables associated with DR were OR (95% CI): lower education 1.08 (1.02 to 1.14); previous stroke 1.18 (1.07 to 1.30); chronic kidney disease 1.29 (1.07 to 1.56); treatment with acetylsalicylic acid 1.14 (1.07 to 1.21); ACE inhibitors 1.12 (1.05 to 1.19); and alpha blockers 1.41 (1.15 to 1.73). DR was more common in individuals born in Asia (OR 1.16, 95% CI 1.08 to 1.25) and European countries other than those born in Sweden (OR 1.11, 95% CI 1.05 to 1.18). CONCLUSIONS: Intensified focus on screening of T2D may be needed in Sweden in clinical practice since nearly one-fifth of persons have retinopathy at diagnosis of T2D. The prevalence of DR was higher in men, birthplace outside of Sweden, and those with a history of stroke, kidney disease, and hypertension.

Are soluble E-selectin, ICAM-1, and VCAM-1 potential predictors for the development of diabetic retinopathy in young adults, 15-34 years of age? A Swedish prospective cohort study.

The aim of this study was to determine plasma levels of three adhesion molecules that may contribute to the development of diabetic retinopathy; soluble endothelial selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), in young adults, aged 15-34 years at diagnosis of diabetes, to find potential predictors for development of retinopathy, and to evaluate their relation to diabetes associated autoantibodies. Participants with type 1 (n = 169) and type 2 diabetes (n = 83) were selected from the complications trial of the Diabetes Incidence Study in Sweden and classified in two subgroups according to presence (n = 80) or absence (n = 172) of retinopathy as determined by retinal photography at follow-up 8-10 years after diagnosis of diabetes. Blood samples were collected at diagnosis in 1987-88. The levels of sE-selectin, sICAM-1, and sVCAM-1 were analysed by enzyme-linked immunosorbent assay and islet cell antibodies by a prolonged two-colour immunofluorescent assay. Mean HbA1c (p<0.001) and clinical characteristics: mean body mass index (p = 0.019), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.003), male gender (p = 0.026), and young age at diagnosis of diabetes (p = 0.015) remained associated with development of retinopathy in type 1 diabetes. However, in a multivariate analysis only HbA1c remained as a risk factor. sE-selectin was significantly higher in the group with type 2 diabetes and retinopathy, compared to the group with type 2 diabetes without retinopathy (p = 0.04). Regarding sE-selectin, sICAM-1, and sVCAM-1 in participants with type 1 diabetes, no differences were observed between the groups with or without retinopathy. This trial confirmed the role of HbA1c and clinical characteristics as predictors for development of retinopathy in type 1 diabetes. sE-selectin stands out as a potential predictor for development of retinopathy in type 2 diabetes, whereas a predictive role for sICAM-1 and sVCAM-1 could not be identified neither for type 1 nor type 2 diabetes.

Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.

Diabetes and Infectious Diseases with a Focus on Melioidosis.

Diabetes mellitus (DM) leads to impaired innate and adaptive immune responses. This renders individuals with DM highly susceptible to microbial infections such as COVID-19, tuberculosis and melioidosis. Melioidosis is a tropical disease caused by the bacterial pathogen Burkholderia pseudomallei, where diabetes is consistently reported as the most significant risk factor associated with the disease. Type-2 diabetes is observed in 39% of melioidosis patients where the risk of infection is 13-fold higher than non-diabetic individuals. B. pseudomallei is found in the environment and is an opportunistic pathogen in humans, often exhibiting severe clinical manifestations in immunocompromised patients. The pathophysiology of diabetes significantly affects the host immune responses that play a critical role in fighting the infection, such as leukocyte and neutrophil impairment, macrophage and monocyte inhibition and natural killer cell dysfunction. These defects result in delayed recruitment as well as activation of immune cells to target the invading B. pseudomallei. This provides an advantage for the pathogen to survive and adapt within the immunocompromised diabetic patients. Nevertheless, knowledge gaps on diabetes-infectious disease comorbidity, in particular, melioidosis-diabetes comorbidity, need to be filled to fully understand the dysfunctional host immune responses and adaptation of the pathogen under diabetic conditions to guide therapeutic options.

Potential role of serum copeptin among smoker T2DM patients with emphasis to ACE I/D gene polymorphism predicting DN.

Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p < 0.044 and for Kim-1 was 0.54, p = 0.13 while for uPb was 0.71, p < 0.033. Serum copeptin and UPb might be a prognostic biomarker for renal function decline in smoker T2DM patients while KIM-1 was potent marker in non-smoker T2DM with association with D allele of ACE I/D gene polymorphism.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011-2018.

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis.

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.

Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes.

BACKGROUND: Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D. METHODS: This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non - specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease. RESULTS: Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non-specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD. CONCLUSION: While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.

The predictive value of lesion-specific pericoronary fat attenuation index for major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to explore the prognostic significance of the lesion-specific pericoronary fat attenuation index (FAI) in forecasting major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). METHODS: This study conducted a retrospective analysis of 304 patients diagnosed with T2DM who underwent coronary computed tomography angiography (CCTA) in our hospital from December 2011 to October 2021. All participants were followed for a period exceeding three years. Detailed clinical data and CCTA imaging features were carefully recorded, encompassing lesion-specific pericoronary FAI, FAI of the three prime coronary arteries, features of high-risk plaques, and the coronary artery calcium score (CACS). The MACE included in the study comprised cardiac death, acute coronary syndrome (which encompasses unstable angina pectoris and myocardial infarction), late-phase coronary revascularization procedures, and hospital admissions prompted by heart failure. RESULTS: Within the three-year follow-up, 76 patients with T2DM suffered from MACE. The lesion-specific pericoronary FAI in patients who experienced MACE was notably higher compared to those without MACE (-84.87 ± 11.36 Hounsfield Units (HU) vs. -88.65 ± 11.89 HU, p = 0.016). Multivariate Cox regression analysis revealed that CACS ≥ 100 (hazard ratio [HR] = 4.071, 95% confidence interval [CI] 2.157-7.683, p < 0.001) and lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.400, 95% CI 1.399-4.120, p = 0.001) were independently associated with heightened risk of MACE in patients with T2DM over a three-year period. Kaplan-Meier analysis showed that patients with higher lesion-specific pericoronary FAI were more likely to develop MACE (p = 0.0023). Additionally, lesions characterized by higher lesion-specific pericoronary FAI values were found to have a greater proportion of high-risk plaques (p = 0.015). Subgroup analysis indicated that lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.017, 95% CI 1.143-3.559, p = 0.015) was independently correlated with MACE in patients with T2DM who have moderate to severe coronary calcification. Moreover, the combination of CACS ≥ 100 and lesion-specific pericoronary FAI>-83.5 HU significantly enhanced the predictive value of MACE in patients with T2DM within 3 years. CONCLUSIONS: The elevated lesion-specific pericoronary FAI emerged as an independent prognostic factor for MACE in patients with T2DM, inclusive of those with moderate to severe coronary artery calcification. Incorporating lesion-specific pericoronary FAI with the CACS provided incremental predictive power for MACE in patients with T2DM.

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus.

Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses a significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly in histone modifications, DNA methylation, and microRNAs, play a pivotal role in unraveling the complex molecular underpinnings of blood pressure regulation. This review emphasizes the crucial interplay between epigenetic attributes and hypertension, shedding light on the prominence of DNA methylation, both globally and at the gene-specific level, in essential hypertension. Additionally, histone modifications, including acetylation and methylation, emerge as essential epigenetic markers linked to hypertension. Furthermore, microRNAs exert regulatory influence on blood pressure homeostasis, targeting key genes within the aldosterone and renin-angiotensin pathways. Understanding the intricate crosstalk between genetics and epigenetics in hypertension is particularly pertinent in the context of its interaction with T2DM, where hypertension serves as a notable risk factor for the development of CAD. These findings not only contribute to the comprehensive elucidation of essential hypertension but also offer promising avenues for innovative strategies in the prevention and treatment of cardiovascular complications, especially in the context of T2DM.