BMJ Open Diabetes Research & Care最新文献

Depression is associated with diabetes, but the underlying causes remain unclear. To better understand depression in diabetes, this study investigated associations between 135 inflammatory and neurological protein biomarkers and depressive symptoms in individuals with diabetes.This cross-sectional study included 430 adults with a known diabetes duration <1 year from the German Diabetes Study (GDS), in whom biomarkers were measured in serum and depressive symptoms were evaluated at baseline and annually over 5 years using the Center for Epidemiological Studies Depression Scale (CES-D). Based on the information on depressive symptoms from the baseline and follow-up visits (n=305, ≥3 time points), we subdivided the sample into individuals with persistent or recurrent and transient or never depressive symptoms. We assessed the associations of each biomarker with baseline CES-D score (continuous) and persistent/recurrent depressive symptoms using multiple linear and logistic regression models, respectively.After adjustment for covariates, we identified a three-protein signature associated with baseline CES-D score and persistent/recurrent depressive symptoms. CUB domain-containing protein 1 (CDCP1) and NAD-dependent protein deacetylase sirtuin-2 (SIRT2) were positively associated with baseline (β 1.24 (95% CI 0.19 to 2.29); β 0.89 (95% CI 0.06 to 1.72)), respectively) and persistent/recurrent depressive symptoms (OR 1.58 (95% CI 1.08 to 2.31); OR 1.32 (95% CI 1.03 to 1.71), respectively), whereas leptin receptor (LEPR) was inversely associated with baseline (β -0.99 (95% CI -1.87 to -0.11)) and persistent/recurrent depressive symptoms (OR 0.70 (95% CI 0.49 to 0.99)). However, results were not significant after adjustment for multiple testing.In conclusion, the three-protein signature identified may provide insights into mechanisms underlying depressive symptoms in diabetes and might open new therapeutic avenues.The trial registration number of the study is NCT01055093.

Introduction: The risk of cardiovascular disease is increased in individuals with type 1 diabetes, despite good glycemic control. This study aims to evaluate early signs of atherosclerosis and predisposing factors in individuals with childhood-onset type 1 diabetes compared with healthy controls.

Research design and methods: The Atherosclerosis and Childhood Diabetes study is a prospective population-based cohort study with follow-up every fifth year. The cohort consists of 329 subjects with type 1 diabetes and 173 controls. Carotid intima-media thickness (cIMT) was measured at baseline and 5 and 10 years of follow-up. Data from the Norwegian Childhood Diabetes Registry were used in assessment of traditional risk factors.

Results: Mean cIMT in young women with type 1 diabetes increased significantly over a 10-year period compared with healthy controls (∆0.019 mm (0.001-0.035), p=0.035). At the 10-year follow-up the group with type 1 diabetes had a mean age of 24.2±2.9 years (13.7±2.8 years at baseline), diabetes duration of 15.6±3.4 years (5.4±3.3 years at baseline) and HbA1c of 8.2±3.6% (66±16 mmol/mol) (8.4±3.4% (68±13 mmol/mol) at baseline). Women with type 1 diabetes had significantly higher mean weight, body mass index, waist circumference, diastolic blood pressure (DBP), serum low-density lipoprotein (LDL)-cholesterol and apolipoprotein B, while men with type 1 diabetes had significantly higher mean DBP and urinary albumin-creatinine ratio compared with the control group. Mean cIMT change over time was not associated with long-term HbA1c or LDL-cholesterol burden in childhood and adolescence.

Conclusion: Young women with childhood-onset type 1 diabetes of relatively short diabetes duration had a higher mean cIMT over a 10-year period compared with their healthy female controls, with values similar to males.

Introduction: Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear.

Objective: Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).

Research design and methods: We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30-180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control.

Results: Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to <10% (OR 1.20, 95% CI 1.02 to 1.41) and ≥10% (OR 1.40, 95% CI 1.14 to 1.72) compared with those with HbA1c 6.5% to <8%. This association was not seen in the COVID-negative group. Higher HbA1c levels were associated with increased risk of Long COVID symptoms, especially respiratory and brain fog. There was no association between HbA1c levels and risk of death within 30-180 days following COVID-19. NLP identified more patients with Long COVID symptoms compared with diagnosis codes.

Conclusion: Poor glycemic control (HbA1c≥8%) in people with T2D was associated with higher risk of Long COVID symptoms 30-180 days following COVID-19. Notably, this risk increased as HbA1c levels rose. However, this association was not observed in patients with T2D without a history of COVID-19. An NLP-based definition of Long COVID identified more patients than diagnosis codes and should be considered in future studies.

Introduction: The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables.

Research design and methods: A retrospective analysis of participants who received structured education in continuous glucose monitoring (CGM) use was conducted at a tertiary center. HbA1c was paired with glucose metrics from 90-day CGM data. The influence of ethnicity, SES determined by Index of Multiple Deprivation (IMD), MBG and other covariates on HbA1c was evaluated using multiple variable regression analysis. Occurrence of hypoglycemia was evaluated.

Results: A total of 168 (79 White, 61 South Asian, 28 Black) CYP with T1D were included. There were no differences between groups for age, MBG, time in range (3.9-10.0 mmol/L), diabetes duration, gender, insulin delivery method (multiple daily injections vs continuous subcutaneous insulin infusion), or percent sensor use (PSU). In multiple variable analysis, MBG (p<0.0001), ethnicity (p<0.0001), age (p<0.001), duration of diabetes (p<0.01) and PSU (p<0.05) accounted for 81% of the variability in HbA1c. Adjusted HbA1c in the Black group (67 mmol/mol) was higher than both South Asian (63 mmol/mol) and White groups (62 mmol/mol) (p<0.001). Despite significant IMD differences between groups, it did not influence HbA1c. Multiple variable analysis showed that the Black group experienced more hypoglycemia than South Asian and White groups (<3.9 and <3.0 mmol/L, p<0.05).

Conclusions: CYP from Black ethnic backgrounds have a higher HbA1c compared with their South Asian and White counterparts which is clinically significant and independent of MBG, potentially contributing to increased complications risk. Additionally, the Black group experienced a higher incidence of hypoglycemia, possibly due to a treat-to-HbA1c target approach.

Objectives: To assess the association between sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use and the risk of incident dementia compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) use among individuals with type 2 diabetes.

Design: A population-based retrospective cohort study.

Setting: The Clinical Practice Research Datalink (CPRD) Aurum database from the UK.

Participants: Individuals with type 2 diabetes, aged 40 years or older, newly prescribed SGLT-2i or DPP-4i on or after 2013-2021, registered in the CPRD Aurum database.

Main outcome measure: The primary outcome was incident dementia, and the secondary outcome was incident mild cognitive impairment (MCI). Cox proportional hazard models were used to estimate the HR and corresponding 95% CI for the primary and secondary outcomes. Propensity score fine stratification weights were used to adjust for confounding.

Results: Among a cohort of 118 006 individuals, the incident rate (IR) of dementia was 0.56/1000 person-years over a median follow-up period of 1.54 years among SGLT-2i users compared with 2.67/1000 person-years in DPP-4i users, over a median follow-up period of 1.79 years. The adjusted HR for SGLT-2i use compared with DPP-4i use for dementia was 0.78 (95% CI 0.55 to 1.12), while for MCI was 0.86 (95% CI 0.80 to 0.92). The age-specific stratified analysis demonstrated the adjusted HR for SGLT-2i use compared with DPP-4i use for the risk of incident dementia among elderly, aged ≥65 years, was 0.50 (95% CI 0.31 to 0.80).

Conclusion: Primary findings did not yield conclusive evidence to infer an association between SGLT-2i use and the risk of incident dementia.

Introduction: Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency of insulin. This study aims to explore the mechanism of TGFB-induced factor homeobox 1 (TGIF1) in the glycolipid metabolism of mice with T2D.

Research design and methods: Mice with T2D were induced by high-fat diet and low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed in mice with T2D, the weight was monitored. The levels of fasting plasma glucose, fasting serum insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. Staining assays were performed to observe liver tissue pathology and lipid accumulation. Liver function and oxidative stress were measured. Palmitic acid (PA)-induced primary hepatocytes were used to establish cell models. After TGIF1 was overexpressed in the cells, cell viability, cellular glucose uptake and consumption, and intracellular glycogen content were detected. The expression of TGIF1, miR-106b-5p, and early growth response 2 (EGR2) was detected and their binding relationships were analyzed. Combined experiments were conducted to validate the mechanism.

Results: TGIF1 was downregulated in mice with T2D. TGIF1 overexpression reduced hyperglycemia and hyperlipidemia, improved insulin resistance, increased liver glycogen content, and attenuated lipid accumulation and glycolipid metabolism disorders in mice with T2D. TGIF1 was enriched on the miR-106b-5p promoter and promoted miR-106b-5p expression. miR-106b-5p inhibited EGR2 expression. miR-106b-5p inhibition or EGR2 overexpression partially reversed the alleviative effect of TGIF1 overexpression on glycolipid metabolism disorders.

Conclusion: TGIF1 reduces glycolipid metabolism disorders in mice with T2D through the miR-106b-5p/EGR2 axis.

Introduction: This study aimed to investigate if individuals with childhood-onset type 1 diabetes having a parent with the same condition (parental diabetes) had worse metabolic control and an increased risk of death and renal failure compared with those with parents without type 1 diabetes (sporadic diabetes).

Research design and methods: We conducted a population-based cohort study using data from the Swedish Childhood Diabetes Register, including cases with onset of type 1 diabetes before the age of 15 and recorded between 1977 and 2010. The cohort was linked to national registers to compare mortality, renal failure, and glycated hemoglobin (HBA1c) levels.

Results: We identified 16 572 incident cases of childhood-onset type 1 diabetes. Of these, 15 701 had data on parental diabetes status, with 1390 (8.9%) having at least one parent with this condition. HbA1c data were available in 9105 individuals at 20-30 years of age, with the parental group showing higher levels compared with the sporadic diabetes group (8.4% (68 mmol/mol) vs 8.2% (66 mmol/mol), p=0.004). The Cox proportional HR for death in parental diabetes was 1.33 (95% CI 1.00 to 1.75), and the competing risk HR for renal failure was 1.27 (95% CI 1.08 to 1.50). Women in the parental diabetes group had a higher risk of early death (HR 1.79, 95% CI 1.17 to 2.72) compared with the sporadic diabetes group.

Conclusions: Individuals with parental diabetes had slightly higher HbA1c and elevated risks of renal failure and death compared with those with sporadic diabetes, especially pronounced in women. Although the exact mechanisms behind these differences are unclear, we suggest that individualized care may benefit individuals with parental type 1 diabetes.

Introduction: To compare the clinical outcomes and healthcare utilization of patients enrolled in the multidisciplinary Diabetic Foot in Primary and Tertiary (DEFINITE) Care program with a matched historical cohort and estimate the program's long-term cost-effectiveness using simulation.

Research design and methods: This study consisted of two components: a 1-year observational outcome evaluation and a long-term simulation-based cost-effectiveness analysis (CEA). We conducted an observational study to analyze 2798 patients with diabetic foot ulcers (DFUs) enrolled in the program between June 2020 and June 2021 (DEFINITE Care group) and 5462 patients with DFUs from June 2016 to December 2017 as historical controls. One-to-one propensity score matching (PSM) with replacement was conducted to estimate the treatment effect of the program on clinical outcomes and healthcare utilization over 1 year. For the simulation component, a long-term CEA was performed using a Markov state transition model on a simulated cohort of 10 000 patients with DFUs over a 20-year period, assessing transitions between health states, including minor and major amputations and death. The incremental cost-effectiveness ratio (ICER) was calculated for the DEFINITE Care program relative to routine care.

Results: The estimation of average treatment effects based on propensity scores showed that the DEFINITE Care group exhibited a 9% lower mortality, 5% higher lower extremity amputation (LEA)-free survival, yet a 5% higher minor LEA rate compared with the matched historical controls. Additionally, they experienced fewer inpatient admissions (0.98 fewer episodes) and shorter hospital stays (5.5 fewer days) within 1 year (p-value <0.001). The ICER was US$22 707 (SE: 430) per quality-adjusted life year gained, indicating long-term cost-effectiveness. Probabilistic sensitivity analysis supported these findings.

Conclusions: The integrated multidisciplinary DEFINITE Care program improved LEA-free survival, reduced inpatient admissions and length of stay within 1 year and demonstrated long-term cost-effectiveness managing DFUs.

Introduction: Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in predicting AAb/T1D status.

Research design and methods: Cross-sectional serum samples (n=154 T1D, n=56 1AAb+, n=77 ≥2AAb+, n=256 AAb-) were assessed for IGF1, IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen (n=543, age range 2.7-30.0 years) using random forest modeling.

Results: GRS2, age, lipase, trypsinogen, and AAb against ZnT8, GAD65, and insulin were the most informative markers. Notably, these variables were differentially informative according to AAb/T1D status. Higher GRS2 (p<0.001) and lower lipase levels (p=0.002) favored ≥2AAb+ versus AAb- classification. AAb against ZnT8 (p<0.01), GAD65 (p=0.021), or insulin (p=0.01) each independently favored ≥2AAb+ versus 1AAb+ classification. Reduced trypsinogen (p<0.001) and increased lipase levels (p<0.001) favored recent-onset T1D versus ≥2AAb+ classification.

Conclusions: Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups, with the utility of each enzyme varying according to GRS2 and AAb/T1D status. These data support exocrine pancreas enzymes as candidates for longitudinal follow-up.