BMJ Open Diabetes Research & Care最新文献

Introduction: The metal-chelating activity of metformin, which has long been known but of unclear clinical relevance, has recently been implicated in the pleiotropic effects, including antitumorigenic and anti-inflammatory actions, of the drug. However, whether metformin actually influences metal dynamics in humans has remained unknown. We here investigate whether metformin influences serum metal levels in individuals with type 2 diabetes.

Research design and methods: In this cross-sectional study, individuals with type 2 diabetes treated or not treated with metformin for at least 6 months were recruited. The primary outcome was the difference in serum copper concentration between metformin users and non-users. Secondary outcomes included differences in serum levels of iron, zinc, and vitamin B₁₂ as well as in copper-related and iron-related parameters between the two groups.

Results: A total of 189 individuals (93 metformin users and 96 non-users) were analyzed. Metformin users showed significantly lower serum copper (16.0 vs 17.8 µmol/L, p<0.001) and iron levels (16.3 vs 17.3 µmol/L, p=0.02) and higher zinc levels (13.3 vs 12.5 µmol/L, p=0.01) compared with non-users. Copper-related and iron-related parameters for metformin users were consistent with latent deficiencies of these metals. Serum homocysteine levels (12.2 vs 11.2 µmol/L, p=0.03) were significantly higher, whereas vitamin B₁₂ levels (338.7 vs 412.8 pmol/L, p<0.001) were significantly lower, in metformin users. Multiple regression analysis including variables that potentially influence metal dynamics identified metformin use as an independent predictor of serum copper (B = -1.54 µmol/L, p<0.001) and iron levels (B = -2.49 µmol/L, p=0.004).

Conclusions: Metformin use was associated with reduced serum levels of copper and iron, as well as with increased serum zinc levels. These changes in metal dynamics may be related to the pharmacological effects of this widely administered drug.

Introduction: Early birth is often recommended for "poorly controlled" diabetes; however, no guidelines define the glycemic threshold that necessitates delivery. We use natural language processing (NLP) of electronic health records to identify individuals described by healthcare professionals as having "poor glucose control" and to examine the factors and outcomes associated with this categorization RESEARCH DESIGN AND METHODS: We completed a retrospective cohort study of pregnant individuals with pre-existing and gestational diabetes mellitus from 2018 to 2019. NLP identified prespecified terms indicating "poor glucose control" in clinical notes, and a cohort analysis compared those with and without "poor glucose control" language. Clinical characteristics, objective glucose measures, and neonatal and maternal outcomes were statistically compared.

Results: 1433 individuals met inclusion criteria, and 143 (10%) were described as having "poor glycemic control." After adjusting for diabetes type, pregnant individuals of color (adjusted OR (aOR) 2.4, 95% CI 1.63 to 3.57, p<0.001), individuals on public insurance (aOR 3.22, 95% CI 2.2 to 4.74, p<0.001), and non-English/non-Spanish speaking individuals (aOR 2.07, 95% CI 1.22 to 3.4, p=0.005) had higher odds of being categorized as having "poor glucose control" than control groups. This designation was often applied in the absence of objective markers of glycemia. While some individuals categorized with "poor glucose control" experienced earlier births and higher rates of neonatal complications, these differences were less pronounced when comparing individuals with A1c≤6.5%.

Conclusions: Pregnant individuals of color, those on public insurance, and non-English/non-Spanish speakers are more likely to be categorized as having "poor glycemic control." Little objective data supported this categorization.

Introduction: People with type 2 diabetes (T2DM) have an elevated risk of adverse outcomes from COVID-19. Dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 receptor agonists (GLP1RAs) might have favorable effects on COVID-19 outcomes.

Research design and methods: We conducted a population-based cohort study in Ontario, Canada. We compared the risk of both COVID-19 infection as well as adverse outcomes between users of DPP4i or GLP1RA and users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or sulfonylureas (SUs). The study population was persons ≥66 years with T2DM taking metformin who had ≥1 COVID-19 PCR test between January 2020 and July 2021. We compared (1) COVID-19 infection and (2) adverse outcomes at 30 days among COVID-19 positive patients (major cardiovascular (CV) events, hospitalizations, intensive care unit admission, all-cause mortality, venous thromboembolism, mechanical ventilation). We reported weighted risk differences (RDs) and relative risks (RRs).

Results: There were 26,485 DPP4i/GLP1RA users (mean age 76, 47% female, 91% DPP4i users) and 14,487 SGLT2i/SU users (mean age 75, 39% female, 65% SGLT2i users). The weighted rate of COVID-19 infection in DPP4i/GLP1RA users was 10.3% compared with 10.4% among SGLT2i/SU users (weighted RD -0.06, 95% CI -0.79 to 0.66; RR 0.99, 95% CI 0.93 to 1.07). Among COVID-19 positive patients, the weighted RD for all-cause hospitalization for DPP4i/GLP1RA users versus SGLT2i/SU users was -6.72% (95% CI -3.02 to -10.4) and the adjusted weighted RR was 0.79 (95% CI 0.70 to 0.89). For major CV events, the weighted RD was -1.91% (95% CI -4.00 to 0.18) and RR 0.73 (95% CI 0.54 to 1.00).

Conclusions: DPP4i/GLP1RA use was not associated with reduced risk of COVID-19 infection compared with SGLT2i/SU use. DPP4i/GLP1RA use was associated with reduced risk of 30-day hospitalization among COVID-19 positive older adults and a possible trend towards a lower associated risk of CV events.

Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended as first-line cardiorenal protective therapy in type 2 diabetes. Because SGLT2is cause glycosuria and increase urine volume, they may exacerbate incontinence symptoms among patients with pre-existing urinary incontinence. Our objective was to determine how many adults meeting guideline indications for SGLT2i have frequent urinary incontinence.

Research design and methods: We conducted a cross-sectional analysis of National Health And Nutrition Examination Survey (NHANES) participants aged ≥55 with type 2 diabetes in 2013-2020. We determined whether participants met American Diabetes Association guideline indications for an SGLT2i due to heart failure or chronic kidney disease, or due to atherosclerotic cardiovascular disease or high cardiovascular risk (for the latter two cardiovascular indications, GLP-1RAs are guideline-recommended alternative medications). Frequent urinary incontinence was defined by self-report of leaking urine daily/nightly or a few times per week.

Results: There were 1726 NHANES participants aged ≥55 with type 2 diabetes, representing 16.0 million US adults; 19.6% (95% CI 17.3% to 22.2%) (3.1 million) met indications for an SGLT2i specifically and 50.9% (95% CI 47.2% to 54.7%) (8.2 million) met indications for either an SGLT2i or a GLP-1RA. Among those with indications for an SGLT2i specifically, 32.4% (95% CI 25.9% to 39.8%) had frequent urinary incontinence, representing 333 000 men and 685 000 women. Among those with indications for either an SGLT2i or GLP-1RA, 25.5% (95% CI 20.8% to 30.8%) had frequent urinary incontinence, representing 630 000 men and 1413 000 women.

Conclusions: Frequent urinary incontinence affects >15% of men and >40% of women aged ≥55 years with guideline indications for SGLT2i. Studies are needed to determine if incontinence increases risk of genital infections when initiating SGLT2is.

Introduction: The mechanisms of estrogen in glucose metabolism are well established; however, the role of this hormone in glucose absorption remains unclear. In this study, we investigated the effects of estrogen on glucose absorption in humans, mice, and the human intestinal epithelium cell line SCBN.

Research design and methods: The ovariectomized (OVX) animal model was established. Radioimmunoassay was used to detect the serum estradiol level. Blood insulin, glucose, and homeostatic model assessment of insulin resistance index were determined. Oral glucose tolerance test was used to detect the glucose tolerance of OVX mice and women aged 20-30 years. Ussing chamber experiments were performed to measure glucose absorption ex vivo in the duodenum of the mice. Western blot and immunohistochemistry were used to detect the expressions of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), sodium/glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), phosphorylated protein kinase C (PKC), p75 neurotrophin receptor and cluster of differentiation 36.

Results: In women aged 20-30 years, we first observed a correlation between estrogen and blood glucose, with lower glucose tolerance in the premenstrual phase compared with the preovulatory phase. Similarly, compared with the controls, OVX mice showed increased body weight and abdominal fat, decreased levels of serum estradiol, and reduced duodenal (1) expression ERα and ERβ, (2) expression of SGLT1 and GLUT2, and (3) glucose absorption. In SCBN cells, estrogen upregulated SGLT1 and GLUT2 expression; silencing of ERα, but not ERβ, reversed this trend, suggesting that ERα is a key regulator. Mechanistically, estrogen modulates PKC signaling downstream.

Conclusions: Our findings suggest that, at least in premenopausal women and female mice, glucose absorption is in part regulated by estrogen via an ERα-dependent modulation of the functional expression of SGLT1 and GLUT2 in the duodenum.

Introduction: Emerging adults with chronic conditions, such as type 1 diabetes (T1D), face vulnerability during transition to adulthood and transfer to adult care. Facilitating transition preparation, disease-related knowledge acquisition, self-management, and follow-up has proved to improve transition readiness and experiences. Few studies exist on conditions related to emerging adults' transition and transfer, and how these associate with other relevant variables. The purpose of this study was to describe experiences of emerging adults with T1D regarding transitional care before transfer, and to explore potential correlates of these experiences.

Research design and methods: A cross-sectional study including 162 emerging adults with T1D was performed at eight Swedish adult diabetes clinics. The primary outcome was transition and transfer experiences measured by TEXP-Q (Transitional care EXPeriences Questionnaire)-a novel PREM (patient-reported experience measure). Correlations between TEXP-Q and sex, glycated hemoglobin, time to follow-up, empowerment, the healthcare climate in adult care, and diabetes self-efficacy were investigated.

Results: The mean average score of TEXP-Q (range 1-5) was 3.6±0.7 for the total scale, and for subscales: Healthcare-provider communication 4.5±0.7, autonomy and participation 3.5±0.9, and transition and transfer preparation 3.0±1.1. Sex proved to be significant only for transition and transfer preparation (p=0.004), demonstrating better perceived preparation among men compared with women. Positive experiences from transition and transfer were associated with higher level of empowerment (rho 0.34, p<0.001), diabetes self-efficacy (rho 0.32, p<0.001) and satisfaction with the healthcare climate in adult care (rho 0.36, p<0.001).

Conclusion: In this study we used a novel measure, TEXP-Q, to explore experiences of transitional care preparation among emerging adults with T1D. While most participants reported high satisfaction with the healthcare-provider communication, fewer reported feeling sufficiently prepared for the transition and transfer processes. The potential correlates investigated could not with conviction be regarded as important for the transition and transfer experiences. Using TEXP-Q in clinical practice may provide vital information when evaluating existing healthcare practices for emerging adults with T1D, and when planning for improvement of care offered to emerging adults in preparation for transition and transfer.

Introduction: Limited research has focused on the prospective influence of insulin resistance (IR) on new-onset chronic kidney disease (CKD) in healthy screening populations. Therefore, we aimed to investigate how IR, assessed via the estimated glucose disposal rate (eGDR), and metabolism-related comorbidities influence new-onset CKD.

Research design and methods: This two-stage retrospective cohort study (cross-sectional and longitudinal analyses) used data from health check-up participants at the Chinese People's Liberation Army General Hospital (2009-2021). The cross-sectional analysis included 83 346 participants with or without CKD; the longitudinal analyses included 13 738 participants without prior CKD who visited the hospital at least two times. The cross-sectional phase of this study analyzed the relationship between IR and CKD; the longitudinal phase analyzed the relationship between IR and new-onset CKD. The mediating role of metabolism-related comorbidities was also explored.

Results: In the cross-sectional analysis, 6.77% (n=5643) of patients had prior CKD. The eGDR was significantly higher in the non-CKD group than in the CKD group (9.16±2.11 vs 7.19±2.32, p<0.001). Higher eGDR was associated with lower CKD prevalence (OR: 0.91, 95% CI: 0.89 to 0.93, P for trend<0.001). In the cohort analysis, the average time to trigger endpoint events was 2.95±2.02 years, with 403 (2.93%) new-onset CKD cases reported. A linear correlation was observed between eGDR and new-onset CKD (p<0.001), with higher eGDR linked to reduced CKD risk (HR: 0.88, 95% CI: 0.82 to 0.96, P for trend=0.002). Mediation analysis revealed significant indirect effects of diabetes mellitus (17.1%), systolic blood pressure (22.0%), glycated hemoglobin (11.1%), and brachial-ankle pulse wave velocity (9.7%) (all p<0.05).

Conclusions: IR is independently linked to new-onset CKD, with blood glucose, blood pressure, and arterial stiffness mediating this relationship. These findings underscore the importance of managing IR and metabolic comorbidities to prevent CKD onset in at-risk populations.

Introduction: Social determinants of health (SDoH) are key risk factors impacting diabetes outcomes. The American Diabetes Association has identified five principal SDoH categories influencing diabetes outcomes: socioeconomic status, neighborhood and physical environment, food environment, healthcare, and social context. Currently, no concise and valid instruments exist to measure the burden of SDoH factors for individuals with diabetes. To fill this gap, we developed the Diabetes Index for Social Determinants of Health (DISDOH).

Research design and methods: Participants with type 1 and type 2 diabetes were recruited from the regional Health Extension for Diabetes (HED) programme and a national crowdsourcing platform. Item development through a diabetes expert stakeholder group yielded a pool of 16 items, which were further refined through piloting with individuals living with diabetes. Principal component analysis was conducted with a sample of 440 HED participants, identifying a 5-factor solution. Confirmatory factor analysis supported this 5-factor solution using 215 individuals with type 1 and type 2 diabetes. Reliability and validity of DISDOH were also assessed.

Results: The five DISDOH domains demonstrated acceptable internal consistency estimates: Domain 1, socioeconomic status (a=0.660); Domain 2, neighborhood and physical environment (a=0.812); Domain 3, food environment (a=0.801); Domain 4, health context (a=0.812); and Domain 5, social context (a=0.708). DISDOH showed strong convergent validity with related SDoH measures, and divergent validity was supported by weak or non-significant correlations with distinct constructs.

Conclusions: DISDOH is the first validated, diabetes-specific SDoH assessment designed for brief, practical use in clinical and community settings. Unlike existing instruments, which are often lengthy and not tailored to diabetes management, DISDOH offers a concise yet comprehensive approach to identifying social risk factors that impact diabetes self-care and outcomes.

Introduction: No direct comparisons have evaluated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus metformin as first-line antidiabetic therapy for preventing dementia in patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the comparative effectiveness of GLP-1 RAs and metformin in reducing dementia risk.

Research design and methods: This retrospective cohort study used data from a global health research network between 2004 and 2024. Patients with T2DM initiating GLP-1 RAs or metformin as first-line monotherapy were included. Propensity score matching was employed to balance baseline characteristics. Dementia incidence was analyzed using Cox proportional hazards models, with sensitivity analyses to confirm robustness.

Results: Among 87,229 matched patients per cohort, GLP-1 RA use was associated with a significantly lower risk of overall dementia (adjusted HR (AHR) 0.90; 95% CI 0.85 to 0.95), Alzheimer's disease (AD) (AHR 0.88; 95% CI 0.83 to 0.94), and non-vascular dementias (non-VaDs) (AHR 0.75; 95% CI 0.70 to 0.81) compared with metformin. No significant difference was observed for VaD. Subgroup analyses showed consistent benefit across age and sex, with the strongest effect among older adults and females.

Conclusions: GLP-1 RAs were more effective than metformin in reducing the risk of dementia-especially AD and non-vascular types-highlighting their potential as a preferred first-line treatment in T2DM. Further randomized trials are warranted to validate these findings.

Introduction: Lower extremity arterial disease (LEAD) represents a significant atherosclerotic complication in patients with type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and metformin are commonly prescribed glucose-lowering agents that have demonstrated potential benefits in attenuating atherosclerosis progression. This study examined the impact of SGLT2is and metformin on the risk of developing severe LEAD in elderly patients with T2D.

Research design and methods: This retrospective cohort study analyzed insurance data for individuals aged 65 years and older with advanced-age health insurance coverage, using health insurance claims and self-reported health check-up data. The observation start date was the initial prescription date of SGLT2is or metformin. Severe LEAD was defined as cases requiring revascularization after a LEAD diagnosis. We conducted a 3-year analysis using propensity score matching to compare the distinct effects of each drug on LEAD risk using a claims database.

Results: The final population comprised 31,732 new SGLT2i and metformin users, divided into two groups (n=15,866 patients each). LEAD incidence rates were 2.10 and 2.69 per 1,000 person-years for metformin and SGLT2is, respectively. Compared with metformin, SGLT2is showed a higher HR for severe LEAD, especially in patients with a diastolic blood pressure (dBP) below 80 mm Hg (HR: 2.11; 95% CI: 1.01 to 2.30) and an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m² (HR: 2.32; 95% CI: 1.09 to 2.94).

Conclusion: The endothelial benefits of metformin, achieved without affecting hemodynamics, may be particularly effective in elderly patients with T2D and low dBP or impaired renal function. However, the presence of cardiovascular disease may often lead to the selection of SGLT2is. Nevertheless, prioritizing the use of metformin may be prudent when considering LEAD status.