BMJ Open Diabetes Research & Care最新文献

Introduction: Given the limited knowledge about family dynamics and well-being among pediatric patients with type 1 diabetes (T1D) in Finland, this study aimed to assess parental stress, patient well-being, and their potential associations with glycemic control at a Finnish diabetes clinic.

Research design and methods: A cross-sectional survey was conducted with 199 children (aged 1-16 years) using a background information questionnaire, the Parenting Stress Index Short Form (PSI-4-SF), and the WHO-5 Well-Being Index (WHO-5) questionnaire.

Results: The mean glycated hemoglobin (HbA1c) level was 7.7% (61 mmol/mol), and the time in range (TIR) was 55.4%. Parents reported low stress levels (PSI total stress: median=31, IQR=12-55, n=133), with no significant correlation between parental stress and children's glycemic control. However, parents of children aged <7 years reported higher stress levels, which correlated with better metabolic control in children (HbA1c: rho=-0.86; TIR: rho=0.78; n=9). The mean WHO-5 score for all children was good (70; IQR=64-80, n=180). Their WHO-5 did not correlate with HbA1c (rho=-0.08, n=180) but correlated positively with TIR (rho=0.17, p=0.038, n=156).

Conclusions: Better glycemic stability in children, as measured by TIR, correlated with well-being. Additionally, higher parental stress in young children was linked to better metabolic control in their children. These findings emphasize the importance of integrating psychosocial aspects into the care of pediatric patients with T1D.

Introduction: Frequent glycated hemoglobin A1c (HbA1c) monitoring is recommended in individuals with type 2 diabetes mellitus (T2D). We aimed to identify distinct, long-term HbA1c trajectories following a T2D diagnosis and investigate how these glycemic control trajectories were associated with health-related traits and T2D complications.

Research design and methods: A cohort of 12,435 unrelated individuals of European ancestry with T2D was extracted from the UK Biobank data linked to primary care records. Latent class growth mixture modeling was applied to identify classes with similar HbA1c trajectories over the 10 years following T2D diagnosis. Associations between HbA1c class membership and sociodemographic factors, biomarkers, polygenic scores, and T2D-related outcomes, were tested using logistic regression and Cox proportional hazards models.

Results: Six HbA1c trajectory classes were identified. The largest class (76.8%) maintained low and stable HbA1c levels over time. Five additional smaller classes with distinct, but more variable, trajectories were found and were associated with younger age at T2D diagnosis, higher fasting glucose levels, higher random glucose levels, higher body mass index polygenic score and increased healthcare use before T2D diagnosis. Relative to the low and stable class, these five showed increased risks of T2D complications, including stroke (HR=1.55 (1.31-1.84)), kidney disease (HR=1.39 (1.27-1.53)), all-cause mortality (HR=1.36 (1.23-1.51)), and progression to combination therapy (HR=3.22 (3.04-3.41)) or insulin (HR=3.21 (2.89-3.55)).

Conclusion: Individuals with T2D who show higher and more variable HbA1c trajectories are at increased risk of developing T2D-related complications. Early identification of patients at risk, based on factors such as age at diagnosis and previous healthcare utilization could improve patient outcomes.

Introduction: To examine the association of the number of controlled risk factors with the excess risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and major adverse liver outcomes (MALO) among patients with type 2 diabetes.

Research design and methods: In this cohort study, a total of 307,688 participants from the UK Biobank were included. Participants with baseline type 2 diabetes were categorized according to the number of risk factors within the guideline-recommended ranges (diet, smoking, drinking, exercise, sedentary behavior, body mass index, glycated hemoglobin, blood pressure, and low-density lipoprotein cholesterol).

Results: During a median (IQR) of 12.5 (11.8-13.2) years of follow-up, 519 (3.9%) participants with type 2 diabetes and 2718 (0.9%) participants without diabetes developed severe MASLD. Patients with type 2 diabetes had an increased risk of severe MASLD compared with participants without diabetes (HR 3.93, 95% CI 3.56 to 4.33), but the excess risk decreased stepwise with an increasing number of risk factors on target (HR (95% CI) for zero to two controlled risk factors: 5.44 (4.09 to 7.25); three controlled risk factors: 4.47 (3.59 to 5.57); four controlled risk factors: 4.16 (3.49 to 4.96); five controlled risk factors: 3.91 (3.28 to 4.66); six controlled risk factors: 3.50 (2.80 to 4.38); seven to nine controlled risk factors: 2.61 (1.92 to 3.56)). Similar patterns were observed in the analysis of MALO.

Conclusions: Patients with type 2 diabetes who had more controlled risk factors showed progressively lower excess risk of severe MASLD and MALO. Comprehensive interventions targeting multiple risk factors may be associated with reduced liver lesions in patients with type 2 diabetes.

In mammalian and human life, it is important that the immune system defends against microorganisms. Although there is a huge overlap, innate cells are good against bacteria, whereas T cells are good against viruses, mainly because of antibody production via T helper and B lymphocytes. Toll-like receptor 5 (TLR5) is a regulator; when it is highly expressed, T cells are inhibited, and innate cells are favored. In glucose-activated pancreatic islets, TLR5 gene expression has been found to be highly upregulated, and the islets may therefore be protected from T cell destruction resulting in autoimmune type 1 diabetes (T1D).

Research design and methods: We investigated mRNA from the islets of Langerhans in patients with newly diagnosed T1D for TLR5 gene expression, as well as Tlr5 and Cd3 expression in the whole pancreatic tissue of female diabetic non-obese diabetic (NOD) mice. Also, we examined for polymorphisms between TLR5, immunological parameters, and T1D.

Results: Islet mRNA for TLR5 was downregulated by one-third of patients with newly diagnosed T1D, compared with controls, and correlated inversely with T cell infiltration in the islets. Moreover, the association between TLR5 and T cells was supported by a corresponding correlation of Tlr5 and Cd3 expression in the pancreatic tissue of diabetic NOD mice. Regarding polymorphisms, two associations were found between TLR5 and monocytes. Also, a significant polymorphism was seen concerning TLR5 and T1D.

Conclusions: In the present study, we find a low expression of mRNA for TLR5 in patients with newly diagnosed T1D associated with enhanced T cell infiltration. T cells are important for autoimmune diseases, including T1D. We hope that the present findings may be influential for the understanding of how T1D develops.

Introduction: Adults with learning disabilities in the UK have a substantially higher risk of developing type 2 diabetes mellitus (T2DM) than the general population. This study aimed to assess the impact of living with learning disabilities on T2DM control, therapeutic management, vascular outcomes, and mortality in UK primary care.

Research design and methods: We conducted an observational cohort study using primary care electronic health records from the UK Clinical Practice Research Datalink. The study included adults newly diagnosed with T2DM from 2004 to 2021. The exposure was learning disability status at the time of diagnosis. Multivariable logistic regression was used to compare glycemic control at 5 years post-diagnosis between people with and without learning disabilities. Multivariable Cox regression was used to compare time to insulin initiation, macrovascular and microvascular complications, and mortality between people with and without learning disabilities.

Results: Of 280 300 adults with T2DM included in the study, 2074 (0.74%) had a learning disability at T2DM diagnosis. After adjustment, people with learning disabilities had lower odds of poor glycemic control than those without learning disabilities 5 years after diagnosis (OR=0.81, 95% CI 0.70 to 0.94) and faster insulin initiation (HR=1.20, 95% CI 1.00 to 1.45) than those without learning disabilities. The risks of all-cause and diabetes-related mortality were doubled in those with learning disabilities (all-cause HR=2.15, 95% CI 1.82 to 2.54; diabetes-related HR=1.93, 95% CI 1.32 to 2.80). We found no difference in the risk of vascular complications.

Conclusions: Individuals with learning disabilities had better glycemic control but shorter time to insulin initiation. This may be related to more frequent diabetes monitoring, or faster advancing T2DM requiring quicker treatment intensification. Despite having similar risks of vascular complications, people with learning disabilities were at higher risk of death. Future research into the mechanisms behind this could help reduce health disparities for people with T2DM and learning disabilities.

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.