Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena.

Neprilysin (NEP) is a transmembrane zinc-dependent metalloproteinase that inactivates various peptide hormones including glucagon-like peptide 1 (GLP-1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing the circulating level of GLP-1. However, acute-effect NEP inhibitors may lead to detrimental effects by increasing blood glucose independent of GLP-1. These findings suggest a controversial point regarding the potential role of NEP inhibitors on glucose homeostasis in T2DM patients. Therefore, this perspective aimed to clarify the controversial points concerning the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may lead to beneficial effects by inhibition of NEP, which is involved in the impairment of glucose homeostasis through modulation of insulin resistance. NEP increases dipeptidyl peptidase-4 (DPP4) activity and contributes to increasing active GLP-1 proteolysis so NEP inhibitors may improve glycemic control through increasing endogenous GLP-1 activity and reduction of DPP4 activity. Thus, NEP inhibitors could be effective alone or in combination with antidiabetic agents in treating T2DM patients. However, long-term and short-term effects of NEP inhibitors may lead to a detrimental effect on insulin sensitivity and glucose homeostasis through different mechanisms including augmentation of substrates and pancreatic amyloid deposition. These findings are confirmed in animal but not in humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental effects on glucose homeostasis and insulin sensitivity in humans though most of the detrimental effects of NEP inhibitors are confirmed in animal studies.

A Review of micro RNAs changes in T2DM in animals and humans.

Type 2 diabetes mellitus (T2DM) and its associated complications have become a crucial public health concern in the world. According to the literature, chronic inflammation and the progression of T2DM have a close relationship. Accumulated evidence suggests that inflammation enhances the insulin secretion lost by islets of Langerhans and the resistance of target tissues to insulin action, which are two critical features in T2DM development. Based on recently highlighted research that plasma concentration of inflammatory mediators such as tumor necrosis factor α and interleukin-6 are elevated in insulin-resistant and T2DM, and it raises novel question marks about the processes causing inflammation in both situations. Over the past few decades, microRNAs (miRNAs), a class of short, noncoding RNA molecules, have been discovered to be involved in the regulation of inflammation, insulin resistance, and T2DM pathology. These noncoding RNAs are specifically comprised of RNA-induced silencing complexes and regulate the expression of specific protein-coding genes through various mechanisms. There is extending evidence that describes the expression profile of a special class of miRNA molecules altered during T2DM development. These modifications can be observed as potential biomarkers for the diagnosis of T2DM and related diseases. In this review study, after reviewing the possible mechanisms involved in T2DM pathophysiology, we update recent information on the miRNA roles in T2DM, inflammation, and insulin resistance.

Developing a prediction model for all-cause mortality risk among patients with type 2 diabetes mellitus in Shanghai, China.

BACKGROUND: All-cause mortality risk prediction models for patients with type 2 diabetes mellitus (T2DM) in mainland China have not been established. This study aimed to fill this gap. METHODS: Based on the Shanghai Link Healthcare Database, patients diagnosed with T2DM and aged 40-99 years were identified between January 1, 2013 and December 31, 2016 and followed until December 31, 2021. All the patients were randomly allocated into training and validation sets at a 2:1 ratio. Cox proportional hazards models were used to develop the all-cause mortality risk prediction model. The model performance was evaluated by discrimination (Harrell C-index) and calibration (calibration plots). RESULTS: A total of 399 784 patients with T2DM were eventually enrolled, with 68 318 deaths over a median follow-up of 6.93 years. The final prediction model included age, sex, heart failure, cerebrovascular disease, moderate or severe kidney disease, moderate or severe liver disease, cancer, insulin use, glycosylated hemoglobin, and high-density lipoprotein cholesterol. The model showed good discrimination and calibration in the validation sets: the mean C-index value was 0.8113 (range 0.8110-0.8115) and the predicted risks closely matched the observed risks in the calibration plots. CONCLUSIONS: This study constructed the first 5-year all-cause mortality risk prediction model for patients with T2DM in south China, with good predictive performance.

Blood pressure targets for prevention of cognitive decline in patients with diabetes and hypertension: Design of the Blood Pressure Control Target in Diabetes (BPROAD) Cognitive Study.

BACKGROUND: Both hypertension and diabetes are risk factors of dementia. Proper management of blood pressure (BP) and blood glucose is critical in delaying cognitive decline in the elderly. However, little is known regarding the optimal BP target in type 2 diabetes (T2DM) for the management of cognitive decline. METHODS: The Blood Pressure Control Target in Diabetes (BPROAD) study is a nationwide, multicenter, randomized controlled trial that will enroll 12 702 T2DM patients with elevated systolic BP and increased cardiovascular risk from approximately 150 study centers across mainland China to undergo randomly antihypertensive treatment achieving systolic BP <120 mm Hg or systolic BP <140 mm Hg for up to 5 years. All BPROAD participants will take part in the BPROAD Cognitive Study for the assessment of cognitive function at baseline and annual visits by blinded outcome assessors to determine whether intensive BP treatment reduces risk of dementia and mild cognitive impairment (MCI) compared with standard BP treatment in patients with T2DM. In addition, approximately 1000 BPROAD participants will be enrolled in the magnetic resonance imaging (MRI) substudy to receive brain MRI at baseline and at closeout. The primary outcome of BPROAD Cognitive Study is a composite of all-cause dementia and MCI. CONCLUSIONS: The BPROAD Cognitive Study will provide crucial clinical trial data on the possible benefit of an intensive systolic BP lowering strategy in reducing dementia and MCI in patients with T2DM.

Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study.

BACKGROUND: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function. RESULTS: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function. CONCLUSIONS: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

BACKGROUND: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. METHODS: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. RESULTS: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. CONCLUSIONS: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Transparent machine learning suggests a key driver in the decision to start insulin therapy in individuals with type 2 diabetes.

AIMS: The objective of this study is to establish a predictive model using transparent machine learning (ML) to identify any drivers that characterize therapeutic inertia. METHODS: Data in the form of both descriptive and dynamic variables collected from electronic records of 1.5 million patients seen at clinics within the Italian Association of Medical Diabetologists between 2005-2019 were analyzed using logic learning machine (LLM), a "clear box" ML technique. Data were subjected to a first stage of modeling to allow ML to automatically select the most relevant factors related to inertia, and then four further modeling steps individuated key variables that discriminated the presence or absence of inertia. RESULTS: The LLM model revealed a key role for average glycated hemoglobin (HbA1c) threshold values correlated with the presence or absence of insulin therapeutic inertia with an accuracy of 0.79. The model indicated that a patient's dynamic rather than static glycemic profile has a greater effect on therapeutic inertia. Specifically, the difference in HbA1c between two consecutive visits, what we call the HbA1c gap, plays a crucial role. Namely, insulin therapeutic inertia is correlated with an HbA1c gap of <6.6 mmol/mol (0.6%), but not with an HbA1c gap of >11 mmol/mol (1.0%). CONCLUSIONS: The results reveal, for the first time, the interrelationship between a patient's glycemic trend defined by sequential HbA1c measurements and timely or delayed initiation of insulin therapy. The results further demonstrate that LLM can provide insight in support of evidence-based medicine using real world data.

Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes.

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

The impact of health literacy interventions on glycemic control and self-management outcomes among type 2 diabetes mellitus: A systematic review.

Diabetes imposes an increasing health and economic burden on individuals living with it and their societies worldwide. Glycemic control is necessary to reduce morbidity and mortality of type 2 diabetes mellitus (T2DM). Self-management is the primary tool for managing diabetes. Health literacy (HL) is the primary driver of self-management activities. The aim of this review is to evaluate the impact of HL interventions on glycemic control and self-management outcomes among T2DM. MEDLINE, CINAHL, PubMed, Cochrane, Scopus, and Web of Science were searched for eligible papers. Fifteen randomized controlled trials published in English between 1997 and 2021, used HL-driven intervention, and measured the level of glycohemoglobin A1c (HbA1c) and self-management of T2DM patients were included in this review. The findings showed that HL-driven intervention had a positive impact on glycemic control and improved self-management behaviors. The level of glycemic control and self-management skills were improved through individual and telephone-based intervention respectively. Community worker-led interventions were effective in improvements in diabetes knowledge and self-care behaviors; however, nurse-led interventions were effective in glycemic control. Better glycemic control is achieved in hospital settings compared to outpatient settings. HL interventions yielded better improvement in self-management among people with longer diabetes duration (more than 7 years). It was possible to achieve a large reduction in HbA1c level after a 3-month intervention in hospital settings. HL-driven interventions are effective in glycemic and diabetes self-management outcomes.

The serum creatinine to cystatin C to waist circumference ratios predicts risk for type 2 diabetes: A Chinese cohort study.

BACKGROUND: There is a lack of research regarding the relationship between creatinine to cystatin C to waist circumference ratio (CCR/WC ratios) and the development of type 2 diabetes mellitus (T2DM). We aimed to evaluate the association between CCR/WC ratios and incident T2DM in Chinese adults. METHODS: This prospective study was from the China Health and Retirement Longitudinal Study (2011, 2013, 2015, and 2018). The participants were divided into three groups by tertiaries of the CCR/WC ratios. Cox proportional-hazards models were used to identify the relationship between CCR/WC and T2DM. RESULTS: Overall, 5938 participants were included for analysis, 766 of whom developed T2DM between 2011 and 2018. Risk of incident T2DM was decreased with tertiaries 2, 3 versus tertiary 1 of the CCR/WC index (adjusted hazard ratio [HR] 0.772 [95% confidence interval 0.647-0.921] and 0.724 [0.596-0.880], p for trend = .001 across tertiaries of the CCR/WC index). The results were consistent excluding participants with T2DM in the first 2 years. CONCLUSIONS: This study demonstrated that CCR/WC was negatively correlated with the risk of T2DM in Chinese adults. Early detection is necessary to control the development of T2DM in Chinese with low CCR/WC levels.

The association between daytime napping and risk of type 2 diabetes is modulated by inflammation and adiposity: Evidence from 435 342 UK-Biobank participants.

BACKGROUND: Existing evidence concerning the relationship between daytime napping and type 2 diabetes (T2D) is inconsistent, and whether the effects of napping differ by body fat percentage (BFP) and C-reactive protein (CRP) is unclear. We aimed to investigate the association between daytime napping frequency and T2D risk and whether such an association was modified by BFP and CRP. METHODS: We included 435 342 participants free of diabetes from the UK Biobank. Participants were categorized as nonnappers, occasional nappers, and frequent nappers based on napping frequency, and BFP/CRP was divided into quartiles. Cox proportional hazards models were used. RESULTS: During a median follow-up of 9.2 years, 17 592 T2D cases occurred. Higher frequency of daytime napping was significantly associated with an increased risk of T2D. Compared with nonnappers, the adjusted hazard ratios (HRs) for occasional nappers and habitual nappers were 1.28 (95% confidence interval [CI]: 1.24-1.32) and 1.49 (95% CI: 1.41-1.57), respectively. There was a significant additive and multiplicative interaction (relative excess risk due to interaction [RERI] = 0.490, 95% CI 0.307-0.673; p for multiplicative interaction <.001) between napping and BFP, whereby a higher hazard of T2D associated with more frequent napping was greatest among participants in the highest BFP quartile (HR = 4.45, 95% CI: 3.92-5.06). The results for CRP were similar (RERI = 0.266, 95% CI: 0.094-0.439; p for multiplicative interaction <.001). CONCLUSIONS: Higher daytime napping frequency is associated with an increased T2D risk, and such relationships are modified by BFP and CRP. These findings underscore the importance of adiposity and inflammation control to mitigate diabetes risk.

The use of nomogram for detecting mild cognitive impairment in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram-based model to detect mild cognitive impairment (MCI) in T2DM patients. METHODS: Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well-qualified investigators conducted face-to-face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM-related information, and history of depression and anxiety. Cognitive function was assessed using the Mini-Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively. RESULTS: A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%-38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815-0.883), and the threshold probability ranged from 35.0% to 85.0%. CONCLUSIONS: Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.

Rationale and design for the Blood Pressure Control Target in Diabetes (BPROAD) study.

BACKGROUND: Diabetes and hypertension are major modifiable risk factors for cardiovascular disease. Previous clinical trials have demonstrated that intensive blood pressure reduction lowers the risk of cardiovascular disease and all-cause mortality compared to standard blood pressure reduction among patients without diabetes. However, optimal levels of blood pressure control in patients with diabetes remain uncertain. METHODS: The Blood Pressure Control Target in Diabetes (BPROAD) study is a multicenter, randomized controlled trial conducted in mainland China. We plan to enroll 12 702 participants aged ≥50 years with type 2 diabetes, an increased cardiovascular risk, and systolic blood pressure ≥130 mm Hg from 150 study centers. Participants are randomly assigned to intensive (a systolic target of <120 mm Hg) or standard (a systolic target of <140 mm Hg) blood pressure treatment group. Participants will be followed monthly for blood pressure management in the first 3 months and then every 3 months afterward. The primary study outcome is a composite of major cardiovascular events including nonfatal myocardial infarction, nonfatal stroke, treated or hospitalized heart failure, and cardiovascular death. Data will be collected every 3 months for up to 5 years and a blinded outcome committee will adjudicate all clinical outcomes. The BPROAD study is designed to have 90% statistical power to detect a 20% reduction in the primary study outcome at a two-sided significance level of 0.05. CONCLUSIONS: The BPROAD study will provide important evidence as to whether intensive blood pressure management has additional benefits on cardiovascular disease and all-cause mortality among patients with type 2 diabetes.

The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study.

AIMS: To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). MATERIALS AND METHODS: In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN. RESULTS: The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. CONCLUSIONS: High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.

Antibody response to inactivated COVID-19 vaccine in patients with type 2 diabetes mellitus after the booster immunization.

BACKGROUND: The immunogenicity of booster inactivated COVID-19 vaccines in patients with type 2 diabetes mellitus (T2DM) has remained unclear. Our study aims to investigate the antibody response to inactivated COVID-19 vaccine following booster vaccination in patients with T2DM. METHODS: A total of 201 patients with T2DM and 102 healthy controls (HCs) were enrolled. The levels of anti-SARS-CoV-2 total antibodies, anti-receptor-binding domain (RBD)-specific IgG, neutralizing antibody (NAb) toward SARS-CoV-2 wild type (WT), and NAb toward SARS-CoV-2 Omicron BA.4/5 subvariant were measured to evaluate the vaccine-induced immunological responses. RESULTS: The titers of anti-RBD-specific IgG (p = 0.018) and inhibition rates of NAb toward WT (p = 0.007) were significantly decreased in patients with T2DM compared to HCs after booster vaccination for more than 6 months. Both HCs and patients with T2DM showed poor resistance against BA.4/5 due to the detected inhibition rates being lower than the positive threshold. The levels of anti-RBD-specific IgG were positively associated with the proportions of CD3+ CD4- CD8- T cells (p = 0.045), and patients with T2DM who had anti-RBD-specific IgG positivity showed higher proportions of CD3+ CD4- CD8- T cells compared to those negative (p = 0.005). CONCLUSIONS: Patients with T2DM showed impaired antibody responses after booster vaccination for more than 6 months. Decreased anti-BA.4/5 responses give rise to the possibility of breakthrough infections for both patients with T2DM and HCs.

Interventional metabology: A review of bariatric arterial embolization and endovascular denervation for treating metabolic disorders.

The rising prevalence of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM) poses a major challenge to global health. Existing therapeutic approaches have limitations, and there is a need for new, safe, and less invasive treatments. Interventional metabolic therapy is a new addition to the treatment arsenal for metabolic disorders. This review focuses on two interventional techniques: bariatric arterial embolization (BAE) and endovascular denervation (EDN). BAE involves embolizing specific arteries feeding ghrelin-producing cells to suppress appetite and promote weight loss. EDN targets nerves that regulate metabolic organs to improve glycemic control in T2DM patients. We describe the current state of these techniques, their mechanisms of action, and the available safety and effectiveness data. We also propose a new territory called "Interventional Metabology" to encompass these and other interventional approaches to treating metabolic disorders.

Osteoarthritis and risk of type 2 diabetes: A two-sample Mendelian randomization analysis.

BACKGROUND: Physical inactivity is an independent risk factor for type 2 diabetes (T2D). Osteoarthritis (OA) is a common joint disease that limits patients' physical activity, which may increase risk of other chronic diseases including T2D. However, studies evaluating the effect of OA on T2D are scarce. This study aimed to investigate the causal effect of knee and hip OA on risk of T2D from a genetic perspective. METHODS: We performed two-sample Mendelian randomization (MR) analyses to obtain nonconfounding estimates of the effect of OA on T2D risk. Single nucleotide polymorphisms (SNPs) from genome-wide association studies were selected as genetic instruments for radiographic knee and hip OA (ie, Kellgren-Lawrence grade ≥2). The associations of these SNPs with T2D were evaluated in participants from the UK Biobank. Sensitivity analyses were conducted to test the robustness of the MR results. RESULTS: Genetic predisposition of knee but not hip OA was significantly associated with an increased risk of T2D (knee OA: odds ratio [OR] 1.18, 95% confidence interval (CI) 1.09-1.27, p <.001; hip OA: OR 1.04, 95% CI 0.94-1.16, p = .425). Sensitivity analyses showed that the main findings are robust. CONCLUSION: The current study provides genetic evidence supporting that knee OA is a potential risk factor for T2D.

Association between depression and risk of type 2 diabetes and its sociodemographic factors modifications: A prospective cohort study in southwest China.

BACKGROUND: Depression may be associated with the risk of developing type 2 diabetes. The goal of this study was to explore the association of severe of depression with the risk of type 2 diabetes in adults in Guizhou, China. METHODS: A 10-year prospective cohort study of 7158 nondiabetes adults aged 18 years or older was conducted in Guizhou, southwest China from 2010 to 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to measure the prevalence of depression. Cox proportional hazard models were used to estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of depression and incident type 2 diabetes. A quantile regression (QR) analytical approach were applied to evaluate the associations of PHQ-9 score with plasma glucose values. RESULTS: A total of 739 type 2 diabetes cases were identified during a median follow-up of 6.59 years. The HR (95% CI) per 1-SD increase for baseline PHQ-9 score was 1.051 (1.021, 1.082) after multivariable adjustment. Compared with participants without depression, those with mild or more advanced depression had a higher risk of incident type 2 diabetes (HR:1.440 [95% CI, 1.095, 1.894]). Associations between depression with type 2 diabetes were suggested to be even stronger among women or participants aged ≥45 years (p < .05). There are significant positive associations of PHQ-9 score with 2-h oral glucose tolerance test blood glucose levels. CONCLUSION: Depression significantly increased the risk of incident type 2 diabetes, especially in women, participants aged ≥45 years, Han ethnicity, and urban residents. These findings highlighted the importance and urgency of depression health care.

The role of miRNAs carried by extracellular vesicles in type 2 diabetes and its complications.

Diabetes poses severe global public health problems and places heavy burdens on the medical and economic systems of society. Type 2 diabetes (T2D) accounts for 90% of these cases. Diabetes also often accompanies serious complications that threaten multiple organs such as the brain, eyes, kidneys, and the cardiovascular system. MicroRNAs (miRNAs) carried by extracellular vesicles (EV-miRNAs) are considered to mediate cross-organ and cross-cellular communication and have a vital role in the pathophysiology of T2D. They also offer promising sources of diabetes-related biomarkers and serve as effective therapeutic targets. Here, we briefly reviewed studies of EV-miRNAs in T2D and related complications. Specially, we innovatively explore the targeting nature of miRNA action due to the target specificity of vesicle binding, aiding mechanism understanding as well as the detection and treatment of diseases.

Thiazolidinedione use is associated with reduced risk of dementia in patients with type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose-lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. METHODS: A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. RESULTS: A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person-years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38-0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. CONCLUSIONS: Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM.