Clinical practice guidelines of foot care practice for patients with type 2 diabetes: A scoping review using self-care model.

BACKGROUND: Type 2 diabetes can lead to severe foot complications, making self-care education, guided by clinical guidelines, crucial. However, fragmented and dispersed recommendations challenge effective implementation of these guidelines. Bringing together recommendations and presenting them according to a self-care model can provide a solid framework and facilitate the interpretation of results. AIMS: to map the international guidelines that provide recommendations to nurses to enable people with type 2 diabetes for foot self-care and synthesize the recommendations according to the key concepts of the middle-range theory of self-care for chronic diseases. DESIGN: A scoping review was undertaken, using the methodological guidance of the Joanna Briggs Institute. DATA SOURCES: Databases were searched between September 2022 and June 2023, including PubMed, CINAHL, PsycINFO, Scopus, Web of Science Core Collection, ProQuest Dissertations and Theses Global, guideline websites and related professional association websites. The databases were chosen for their comprehensive coverage of the area. METHODS: Eligible articles included guidance documents providing foot care recommendations for diabetes, published or updated between 2013 and 2023. Two reviewers summarized the recommendations presented in at least two guidelines according to the key concepts of the self-care model. The PRISMA-ScR checklist was used. RESULTS: Seventeen guidelines were included. In total, we synthesized 175 recommendations. The recommendations were framed in three dimensions and their respective categories: Self-care maintenance (education for prevention, control of risk factors, daily foot care, footwear, and socks), Self-care monitoring (foot inspection, detection of signs of infection, and detection of other diabetes-related foot disease complications), and Self-care management (responses to signs and symptoms, foot wound care, follow-up with health professionals, and health services). CONCLUSIONS: The main aspect of foot care revolves around daily care, including cleaning, moisturizing, nail care, selecting appropriate footwear, and regular inspection of both feet and footwear.

Identifying subtypes of type 2 diabetes mellitus with machine learning: development, internal validation, prognostic validation and medication burden in linked electronic health records in 420 448 individuals.

INTRODUCTION: None of the studies of type 2 diabetes (T2D) subtyping to date have used linked population-level data for incident and prevalent T2D, incorporating a diverse set of variables, explainable methods for cluster characterization, or adhered to an established framework. We aimed to develop and validate machine learning (ML)-informed subtypes for type 2 diabetes mellitus (T2D) using nationally representative data. RESEARCH DESIGN AND METHODS: In population-based electronic health records (2006-2020; Clinical Practice Research Datalink) in individuals ≥18 years with incident T2D (n=420 448), we included factors (n=3787), including demography, history, examination, biomarkers and medications. Using a published framework, we identified subtypes through nine unsupervised ML methods (K-means, K-means++, K-mode, K-prototype, mini-batch, agglomerative hierarchical clustering, Birch, Gaussian mixture models, and consensus clustering). We characterized clusters using intracluster distributions and explainable artificial intelligence (AI) techniques. We evaluated subtypes for (1) internal validity (within dataset; across methods); (2) prognostic validity (prediction for 5-year all-cause mortality, hospitalization and new chronic diseases); and (3) medication burden. RESULTS: Development: We identified four T2D subtypes: metabolic, early onset, late onset and cardiometabolic. Internal validity: Subtypes were predicted with high accuracy (F1 score >0.98). Prognostic validity: 5-year all-cause mortality, hospitalization, new chronic disease incidence and medication burden differed across T2D subtypes. Compared with the metabolic subtype, 5-year risks of mortality and hospitalization in incident T2D were highest in late-onset subtype (HR 1.95, 1.85-2.05 and 1.66, 1.58-1.75) and lowest in early-onset subtype (1.18, 1.11-1.27 and 0.85, 0.80-0.90). Incidence of chronic diseases was highest in late-onset subtype and lowest in early-onset subtype. Medications: Compared with the metabolic subtype, after adjusting for age, sex, and pre-T2D medications, late-onset subtype (1.31, 1.28-1.35) and early-onset subtype (0.83, 0.81-0.85) were most and least likely, respectively, to be prescribed medications within 5 years following T2D onset. CONCLUSIONS: In the largest study using ML to date in incident T2D, we identified four distinct subtypes, with potential future implications for etiology, therapeutics, and risk prediction.

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.

A Comprehensive Analysis of Clinical, Biochemical, and Polysomnographic Characteristics in Patients With Type 2 Diabetes Mellitus With and Without Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been a significant contributor to mortality all across the globe. The most attributing factors to pathogenesis are metabolic syndrome, obesity, diabetes, and so on, but the indicators of its early detection are still elusive. OBJECTIVE: The study aimed to compare the clinical, biochemical, and polysomnographic characteristics of type 2 diabetes patients with and without OSA. DESIGN AND METHODS: This cross-sectional study was conducted at the Department of Medicine and Endocrinology Unit of Dayanand Medical College and Hospital, Ludhiana. A total of 584 patients with type 2 diabetes were assessed using the Berlin questionnaire, with 302 fulfilling the criteria for a high risk of OSA. Out of 302 patients who met the criteria for the high-risk category, 110 patients underwent a sleep study. RESULTS:  Three hundred and two patients satisfying the inclusion and exclusion criteria were enrolled in the study. A total of 110 patients underwent a sleep study, of which 68 (61.8%) had evidence of OSA. The waist-to-hip ratio was considerably higher in the OSA patients than in the non-OSA group (1.09 vs 0.930, p = 0.001). HbA1c >7% was found in 58.8% of OSA patients contrary to 38.1% of non-OSA patients. Fasting plasma glucose levels (>126 mg/dl) were identified in a substantially larger proportion of OSA patients than the non-OSA patients (64.7% vs 45.2%, p = 0.04). Similarly, peripheral neuropathy was found more commonly in the OSA patients than in the non-OSA patients (47% vs. 26.1%, p = 0.02). Prevalence of retinopathy, nephropathy, coronary artery disease, stroke, heart failure, and peripheral vascular disease did not differ significantly between the two groups. CONCLUSIONS: OSA frequently occurs among individuals diagnosed with type 2 diabetes mellitus. The prompt identification of OSA within this demographic is imperative to pinpoint those at an elevated risk of succumbing to conditions such as peripheral neuropathy, the exacerbation of glycemic control, and the onset of unmanaged hypertension. Moreover, there exists a positive correlation between the waist-to-hip ratio and the prevalence of OSA in persons with type 2 diabetes mellitus, highlighting the critical role of waist-to-hip ratio assessments in this patient population.

Relationship of neutrophil-to-lymphocyte ratio, in addition to C-reactive protein, with cardiovascular events in patients with type 2 diabetes.

AIM: To quantify the relationship of neutrophil-to-lymphocyte ratio (NLR) with cardiovascular events and all-cause mortality in patients with type 2 diabetes(T2D), independent of C-reactive protein(CRP). METHODS: Patients with T2D from the UCC-SMART-cohort were studied using multivariable-adjusted Cox regression. The relationship of NLR and CRP with vascular events (cerebrovascular events, myocardial infarction and vascular death) and all-cause mortality was quantified. RESULTS: During 10,833 person-years, 232 vascular events and 302 deaths occurred in 1,239 patients with T2D. Risk of vascular events and all-cause mortality increased per standard deviation(SD) in NLR (hazard ratio(HR) 1.27;95 % confidence interval (CI);1.11-1.46) and 1.15;95 %CI:1.02-1.30) after adjustment for CRP. CRP was not associated with vascular events after adjustment for NLR, (HR per SD 1.03; 95 %CI:0.90-1.19), but was associated with all-cause mortality (HR per SD 1.18; 95 %CI:1.04-1.33). Notably, NLR was related to vascular events in patients with CRP < 2 mg/L (HR per unit 1.45; 95 %CI: 1.19-1.77). CONCLUSION: In patients with T2D, NLR is related to higher risk of CVD and all-cause mortality, independently from CRP. NLR is related to CVD even when CRP is low, indicating that NLR is a marker of CVD-risk in addition to CRP. Both NLR and CRP are independently related to all-cause mortality in T2D patients.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Incidence of Type 2 Diabetes Mellitus in Transgender Individuals Undergoing Gender Affirming Hormonal Therapy: A Systematic Review.

Gender-affirming hormonal therapy (GAHT), which includes estrogen, testosterone, androgen agonists, is commonly used in transgender individuals to change their secondary sexual characteristics to align with their gender identity. However, this treatment could result in metabolic side effects that could increase the chances of acquiring type 2 diabetes mellitus. Thus, this study aims to compare differences in body mass index (BMI), insulin resistance, and the incidence of type 2 diabetes mellitus between cisgender and transgender individuals undergoing GAHT. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review searching through PubMed, Google Scholar, Medline (Medical Literature Analysis and Retrieval System Online), and ResearchGate for articles published between 2014 and 2024. The final search was conducted in February 2024. Out of the 3,934 articles reviewed, 11 were selected, focusing on insulin sensitivity/resistance, diabetes incidence, and BMI changes with GAHT. Although our result findings did not show clear evidence of increased diabetes incidence among GAHT patients, it was observed that GAHT does increase BMI and insulin resistance in transgender individuals. Notably, compared to transgender men, transgender women on GAHT were found to be more prone to insulin resistance. We recommend regularly monitoring insulin sensitivity parameters and HbA1c during GAHT to monitor metabolic side effects. Further research and more clinical trials are needed to confirm the GAHT's impact on insulin resistance and to evaluate its role in the onset of type 2 diabetes mellitus.

Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.

Budget impact analysis of continuous glucose monitoring in individuals with type 2 diabetes on insulin treatment in England.

INTRODUCTION: In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose monitoring (CGM). In this budget impact analysis, the cost impact of CGM was compared with traditional self-monitoring of blood glucose (SMBG) in adults with T2DM over 1 year from the commissioner perspective in England. RESEARCH DESIGN AND METHODS: The NICE-eligible T2DM cohort was split into 4 subgroups to enable nuanced costing by insulin administration frequency: basal human insulin, premixed insulin, basal-bolus insulin and bolus insulin. The model's cost components comprised mild and severe hypoglycaemia (SH), diabetic ketoacidosis (DKA), consumables and healthcare resource utilisation in primary and secondary care. RESULTS: The introduction of CGM is estimated to be cost additive by approximately £4.6 million in the basecase, driven by increased spending on the CGM device. Overall, healthcare activity was reduced by approximately 20,000 attendances, due to fewer SH and DKA episodes in the CGM arm. General Practitioner (GP) practice-based activity is expected to drop after the first year as patients requiring CGM training is reduced. The budget impact could be neutralised if the CGM sensor was discounted by 13.2% (£29.76 to £25.83). CONCLUSIONS: CGM may result in increased spending in the NICE-eligible T2DM cohort but is expected to reduce demand on secondary care services and GP time. These findings may be of interest to local decision-makers who wish to resolve the COVID-19 backlog with transformational investment in primary care to reduce secondary care activity.

Association of Body Composition Changes with the Development of Diabetes Mellitus: A Nation-Wide Population Study.

Background: We investigated the association between body composition changes and new-onset diabetes mellitus (DM) development according to the body mass index (BMI) in a longitudinal setting in the general Korean population. Methods: From 2010 to 2011 (1st) and 2012 to 2013 (2nd), we included 1,607,508 stratified random sample participants without DM from the National Health Insurance Service-Health Screening dataset of Korean. The predicted appendicular skeletal muscle mass index (pASMMI), body fat mass index (pBFMI), and lean body mass index (pLBMI) were calculated using pre-validated anthropometric prediction equations. A prediction equation was constructed by combining age, weight, height, waist circumference, serum creatinine levels, alcohol consumption status, physical activity, and smoking history as variables affecting body composition. Results: Decreased pASMMI (men: hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.830 to 0.903; P<0.001; women: HR, 0.748; 95% CI, 0.635 to 0.881; P<0.001), decreased pLBMI (men: HR, 0.931; 95% CI, 0.912 to 0.952; P<0.001; women: HR, 0.906; 95% CI, 0.856 to 0.959; P=0.007), and increased pBFMI (men: HR, 1.073; 95% CI, 1.050 to 1.096; P<0.001; women: HR, 1.114; 95% CI, 1.047 to 1.186; P=0.007) correlated with the development of new-onset DM. Notably, only in the overweight and obese BMI categories, decreases in pASMMI and pLBMI and increases in pBFMI associated with new-onset DM, regardless of gender. Conclusion: Decreased pASMMI and pLBMI, and increased pBFMI with excess fat accumulation may enhance the risk of newonset DM. Therefore, appropriate changes in body composition can help prevent new-onset DM.

Serum Magnesium Levels Are Negatively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Mellitus: A Real-World Study.

Background: There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM. Methods: This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893). Results: After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P<0.001 for trend; abdominal obesity: 71.5%, 70.5%, 68.2%, 66.4%, and 64.5%, respectively, P=0.001 for trend). After controlling for confounders, there were clearly negative associations of serum magnesium levels and quintiles with obesity and abdominal obesity in T2DM. Moreover, C-reactive protein partly mediates the effect of serum magnesium on obesity and abdominal obesity (P=0.016 and P=0.004, respectively). Conclusion: The significantly negative relationship between serum magnesium and the risk of obesity and abdominal obesity was observed in T2DM. Furthermore, the independently negative association of serum magnesium with obesity may be explained by its anti-inflammatory functions. Serum magnesium levels may be applied to assess the risk of obesity and abdominal obesity in T2DM.

Apolipoprotein-CIII O-Glycosylation Is Associated with Micro- and Macrovascular Complications of Type 2 Diabetes.

Apolipoprotein-CIII (apo-CIII) inhibits the clearance of triglycerides from circulation and is associated with an increased risk of diabetes complications. It exists in four main proteoforms: O-glycosylated variants containing either zero, one, or two sialic acids and a non-glycosylated variant. O-glycosylation may affect the metabolic functions of apo-CIII. We investigated the associations of apo-CIII glycosylation in blood plasma, measured by mass spectrometry of the intact protein, and genetic variants with micro- and macrovascular complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) of type 2 diabetes in a DiaGene study (n = 1571) and the Hoorn DCS cohort (n = 5409). Mono-sialylated apolipoprotein-CIII (apo-CIII1) was associated with a reduced risk of retinopathy (ß = -7.215, 95% CI -11.137 to -3.294) whereas disialylated apolipoprotein-CIII (apo-CIII2) was associated with an increased risk (ß = 5.309, 95% CI 2.279 to 8.339). A variant of the GALNT2-gene (rs4846913), previously linked to lower apo-CIII0a, was associated with a decreased prevalence of retinopathy (OR = 0.739, 95% CI 0.575 to 0.951). Higher apo-CIII1 levels were associated with neuropathy (ß = 7.706, 95% CI 2.317 to 13.095) and lower apo-CIII0a with macrovascular complications (ß = -9.195, 95% CI -15.847 to -2.543). In conclusion, apo-CIII glycosylation was associated with the prevalence of micro- and macrovascular complications of diabetes. Moreover, a variant in the GALNT2-gene was associated with apo-CIII glycosylation and retinopathy, suggesting a causal effect. The findings facilitate a molecular understanding of the pathophysiology of diabetes complications and warrant consideration of apo-CIII glycosylation as a potential target in the prevention of diabetes complications.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

Eight-year nationwide study of the bidirectional association between type 2 diabetes and depression in nearly 8 million German outpatients.

INTRODUCTION: Research linking type 2 diabetes and depression mostly relied on hospital-based diagnoses or prescription data, overlooking many outpatient diagnoses. We aimed to quantify the risks of depression in individuals newly diagnosed with type 2 diabetes, and type 2 diabetes in those newly diagnosed with depression, while exploring potential risk differences depending on age, sex, and follow-up time. RESEARCH DESIGN AND METHODS: We conducted a matched cohort study using German nationwide outpatient claims data from 2012 to 2022. Participants were individuals newly diagnosed with type 2 diabetes (N=294 642) or depression (N=1 271 537) in 2015, matched in a 1:4 ratio to controls without these conditions by age, sex, and region. The bidirectional risk was evaluated over an 8-year period using mixed-effects Cox proportional hazards models, adjusting for the Charlson Comorbidity Index, urbanicity, and area-level deprivation. RESULTS: New type 2 diabetes diagnosis was associated with higher depression risk over 8 years (N=54 561 with depression, HR=1.23, 99% CI=1.21 to 1.24). Similarly, depression diagnosis was linked to an increased type 2 diabetes risk (N=71 848 with type 2 diabetes, HR=1.15, 99% CI=1.14 to 1.17). The association between depression and type 2 diabetes was stronger in younger age groups, especially under 34 years. Findings held across sex-stratified analyses. Time stratification showed a more pronounced association between type 2 diabetes and depression risk during the earlier follow-up quarters, whereas the risk of developing type 2 diabetes after depression diagnosis remained constant throughout the follow-up period. CONCLUSIONS: Our findings confirm a bidirectional link between type 2 diabetes and depression, particularly in younger individuals. As type 2 diabetes and depression are frequent, future research needs to study whether preventive approaches can reduce the risk of developing this comorbidity.

Effects of metformin, saxagliptin and repaglinide on gut microbiota in high-fat diet/streptozocin-induced type 2 diabetic mice.

INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.

Unveiling potential therapeutic targets for diabetes-induced frozen shoulder through Mendelian randomization analysis of the human plasma proteome.

INTRODUCTION: This study aimed to assess the causal relationship between diabetes and frozen shoulder by investigating the target proteins associated with diabetes and frozen shoulder in the human plasma proteome through Mendelian randomization (MR) and to reveal the corresponding pathological mechanisms. RESEARCH DESIGN AND METHODS: We employed the MR approach for the purposes of establishing: (1) the causal link between diabetes and frozen shoulder; (2) the plasma causal proteins associated with frozen shoulder; (3) the plasma target proteins associated with diabetes; and (4) the causal relationship between diabetes target proteins and frozen shoulder causal proteins. The MR results were validated and consolidated through colocalization analysis and protein-protein interaction network. RESULTS: Our MR analysis demonstrated a significant causal relationship between diabetes and frozen shoulder. We found that the plasma levels of four proteins were correlated with frozen shoulder at the Bonferroni significance level (p<3.03E-5). According to colocalization analysis, parathyroid hormone-related protein (PTHLH) was moderately correlated with the genetic variance of frozen shoulder (posterior probability=0.68), while secreted frizzled-related protein 4 was highly correlated with the genetic variance of frozen shoulder (posterior probability=0.97). Additionally, nine plasma proteins were activated during diabetes-associated pathologies. Subsequent MR analysis of nine diabetic target proteins with four frozen shoulder causal proteins indicated that insulin receptor subunit alpha, interleukin-6 receptor subunit alpha, interleukin-1 receptor accessory protein, glutathione peroxidase 7, and PTHLH might contribute to the onset and progression of frozen shoulder induced by diabetes. CONCLUSIONS: Our study identified a causal relationship between diabetes and frozen shoulder, highlighting the pathological pathways through which diabetes influences frozen shoulder.

Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study.

INTRODUCTION: We hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: We conducted an efficacy-implementation pilot study of MPE for T2D and CKD for primary care provider (PCP)-patient dyads at an academic health system. MPE included (1) a dashboard to identify patients without a prescription for sodium-glucose cotransporter-2 inhibitors (SGLT2i) and without a maximum dose prescription for renin-angiotensin-aldosterone system inhibitors (RAASi), (2) a multidisciplinary team of specialists to provide recommendations using e-consult templates, and (3) a workflow to deliver timely e-consult recommendations to PCPs. In-depth interviews were conducted with PCPs and specialists to assess feasibility, acceptability, and appropriateness of MPE and were analyzed using an iterative qualitative analysis approach to identify major themes. Prescription data were extracted from the electronic health record to assess preliminary effectiveness to increase GDMT. RESULTS: 20 PCPs agreed to participate, 18 PCPs received MPEs for one of their patients with T2D and CKD, and 16 PCPs and 2 specialists were interviewed. Major themes were as follows: appropriateness of prioritization of GDMT for T2D and CKD, acceptability of the content of the recommendations, PCP characteristics impact experience with MPE, acceptability and appropriateness of multidisciplinary collaboration, feasibility of MPE to overcome patient-specific barriers to GDMT, and appropriateness of workflow. At 6 months postbaseline, 7/18 (39%) patients were newly prescribed an SGLT2i, and 7/18 (39%) patients were either newly prescribed or had increased dose of RAASi. CONCLUSIONS: MPE was an acceptable and appropriate health system strategy to identify and address gaps in GDMT among patients with T2D and CKD. Adopting MPE could enhance GDMT, though PCPs raised feasibility concerns which could be improved with program enhancements, including follow-up e-consults for reinforcement, and administrative support for navigating system-level barriers.

Person-Centred Diabetes Care: Examining Patient Empowerment and Diabetes-Specific Quality of Life in Slovenian Adults with Type 2 Diabetes.

Patient empowerment is crucial for promoting and strengthening health. We aimed to assess patient empowerment and diabetes-specific health-related quality of life (HRQoL) in adults with type 2 diabetes (T2D). A multi-centre, cross-sectional survey was conducted among adults with T2D in urban and rural primary care settings in Slovenia between April and September 2023. The survey utilised convenience sampling and included sociodemographic and clinical data, the Diabetes Empowerment Scale (DES), and the Audit of Diabetes-Dependent QoL (ADDQoL). The study included 289 people with T2D and a mean age of 67.2 years (SD 9.2). The mean overall DES score was 3.9/5 (SD 0.4). In a multivariable linear regression model, higher empowerment was significantly associated with residing in a rural region (p = 0.034), higher education (p = 0.028), and a lack of comorbid AH (p = 0.016). The median overall ADDQoL score was -1.2 (IQR [-2.5, -0.6]). The greatest negative influence of diabetes on HRQoL was observed in the domain 'Freedom to eat', followed by 'Freedom to drink', 'Leisure activities', and 'Holidays'. Despite high empowerment among adults with T2D, the condition still imposes a personal burden. Integrated primary care models should prioritise the importance of implementing targeted interventions to enhance diabetes empowerment, address comorbidities, and improve specific aspects of QoL among individuals with T2D.

Validation of Nutritional Approaches to Modulate Cardiovascular and Diabetic Risk Factors in Patients with Hypertriglyceridemia or Prediabetes-The MoKaRi II Randomized Controlled Study.

Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of both clinical pictures. For the 10-week randomized, controlled, intervention study, 67 subjects with elevated plasma triglyceride (TG) concentrations (≥1.7 mmol/L) and 69 subjects with elevated fasting glucose concentrations (≥5.6 < 7.0 mmol/L) were recruited. The intervention groups received specially developed, individualized menu plans and regular counseling sessions to lower (A) TG or (B) fasting glucose and glycated hemoglobin A1c as well as other cardiovascular and diabetic risk factors. The hypertriglyceridemia intervention group was further supplemented with fish oil (3.5 g/d eicosapentaenoic acid + docosahexaenoic acid). The two control groups maintained a typical Western diet. Blood samples were taken every 2 weeks, and anthropometric data were collected. A follow-up examination was conducted after another 10 weeks. In both intervention groups, there were comparable significant reductions in blood lipids, glucose metabolism, and anthropometric parameters. These results were, with a few exceptions, significantly more pronounced in the intervention groups than in the corresponding control groups (comparison of percentage change from baseline). In particular, body weight was reduced by 7.4% (6.4 kg) and 7.5% (5.9 kg), low-density lipoprotein cholesterol concentrations by 19.8% (0.8 mmol/L) and 13.0% (0.5 mmol/L), TG concentrations by 18.2% (0.3 mmol/L) and 13.0% (0.2 mmol/L), and homeostatic model assessment for insulin resistance by 31.8% (1.1) and 26.4% (0.9) (p < 0.05) in the hypertriglyceridemia and prediabetes intervention groups, respectively. Some of these changes were maintained until follow-up. In patients with elevated TG or fasting glucose, implementing individualized menu plans in combination with regular counseling sessions over 10 weeks led to a significant improvement in cardiovascular and diabetic risk factors.