BMJ Open Diabetes Research & Care最新文献

Introduction: This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research design and methods: In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial. Linear mixed models were conducted, using restricted maximum likelihood estimation, unadjusted and adjusted (for covariates: age, sex, diabetes duration, glycated hemoglobin, recent severe hypoglycemia, pre-trial insulin delivery modality, enrollment and mid-study scores).

Results: 120 participants (mean age 44±12 years) were randomized to intervention (n=61) or standard therapy (n=59). At 13 weeks, the HCL group had better diabetes-specific positive well-being than the standard therapy group (unadjusted: Δ=1.0, p=0.025; adjusted: Δ=1.1, p=0.01), which was maintained at 26 weeks (unadjusted: Δ=0.9, p=0.042; adjusted: Δ=1.0, p=0.023). At 26 weeks, the HCL group also had less diabetes distress (adjusted: Δ=-6.4, p=0.039), fear of hypoglycemia ("maintain high": adjusted: Δ=-0.8, p=0.034; and "worry": adjusted: Δ=-1.8, p=0.048), and perceived "unacceptably high glucose levels" (unadjusted: Δ=-1.1, p<0.001; adjusted: Δ=-1.1, p<0.001). HCL did not improve diabetes treatment satisfaction, diabetes-specific QoL, hypoglycemia awareness, or perceived frequency of unacceptably low glucose levels.

Conclusions: These findings imply that HCL offers important psychological benefits. In particular, improvement in diabetes-specific positive well-being was observed 13 weeks after HCL initiation and maintained at 26 weeks. Reduction in the perceived frequency of hyperglycemia was also apparent by 26 weeks. Adjusted analyses showed significant reductions in diabetes distress and fear of hypoglycemia at 26 weeks, suggesting these benefits were apparent for people with particular characteristics.

Trial registration number: Australian New Zealand Clinical Trials Registry: ACTRN12617000520336.

Introduction: The balance of trace elements plays an important role in diabetic kidney disease (DKD) patients. However, studies on the differences in urinary trace elements across different DKD stages are scarce. This study aimed to explore the associations between nine essential trace elements and DKD.

Research design and methods: This cross-sectional analysis included 830 diabetic patients. Participants were classified into non-DKD (NDKD) and DKD, the latter was further grouped into mid and end DKD based on estimated glomerular filtration rate (eGFR), and the case and control were matched based on age and sex. The concentration of urinary trace elements was measured with inductively coupled plasma mass spectrometry.

Results: Urinary concentrations of copper (Cu) and manganese (Mn) in DKD patients were significantly higher than that of NDKD patients, whereas that of iron (Fe), cobalt, selenium, and nickel (Ni) of DKD were lower. Positive correlations between urinary Mn/Cu and the risk of mid-stage and end-stage DKD were revealed by conditional logistic regression, while Fe and Ni were negatively associated with the risk of DKD. In mixed effect analyses, no significant trend was found for joint trace element exposure and risk of mid DKD, while negative associations between combined effects of trace elements and the risk of end DKD were observed.

Conclusions: This study revealed different associations between trace elements and the risk of mid and end DKD using both single and mixture effect modeling. The results suggested that the urinary trace element profile might be associated with the progression of DKD, which provides important insights for understanding the pathogenesis of DKD and developing individualized nutritive management strategies.

Introduction: Previous studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.

Research design and methods: Twenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m²) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m²) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP >233 dB/m.

Results: A CAP >233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A "cut-off" value of 15,620 uIU/mL^-1*180 min^-1 provided a 75% sensitivity and 75% specificity for CAP >233 dB/m.

Conclusions: Our results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.

Background: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

Research design and methods: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) type 2 with prior ketosis and (4) type 1 DM. A ß-hydroxybutyrate >20 mg/dL defined diabetic ketoacidosis (DKA). A directed acyclic graph was constructed to diagram a causal pathway.

Results: Of 450 patients, 326 were non-type I and 37% of these had DKA. Concentrations of ß-hydroxybutyrate, glucose, bicarbonate were not different between non-type1 versus type 1 DM patients. Admission rates to the ICU and hospital lengths of stay were similar between the four phenotypes with DKA. We found no association with sex, race or body mass index. Unadjusted odds for DKA were significant for non-adherence (odds=1.74, 95% CI 1.08 to 2.21) arrival by Emergency Medical Services (odds=0.54, 95% CI 0.33 to 0.86) and private or Medicare insurance (odds=6.80, 95% CI 4.00 to 11.60). The median HbA1C was statistically higher in patients with DKA (median 11.3%) versus those without DKA (median 9.5%, Mann-Whitney U p<0.001) and was also higher in patients with a history of non-adherence. In multivariable analysis, non-adherence was found to be a mediator of DKA with T2KPDM.

Conclusions: in Detroit, MI, prior ketosis and private or Medicare health insurance were significantly associated with new or recurrent DKA in T2KPDM. Medication non-adherence had a mediating role.

Introduction: Maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM) are the most prevalent causes of monogenic diabetes. MODY is an autosomal dominant condition with onset in childhood and young adulthood, while NDM is defined with diabetes onset within 6 months of age and can be caused by dominant, recessive, X-linked genes or by chromosomal abnormalities. Here, we describe a rare case of monogenic diabetes in a patient who is homozygous for an INS gene variant.

Research design and methods: The index patient, a male diagnosed with type 2 diabetes, was treated with low-dose insulin and metformin. Blood plasma was collected under fasting conditions for analysis. MODY screening was performed using a next-generation sequencing panel. In silico analysis of the insulin variant's three-dimensional structure and its interaction with the insulin receptor was conducted. Insulin receptor affinity and downstream signaling potency were evaluated in vitro.

Results: Auto-immune diabetes was excluded. A homozygous missense variant of the INS gene (c.130G>A, p.Gly44Arg) was identified in the patient. The combination of three different insulin assays showed that the biosynthesis of proinsulin into insulin was intact. In silico analysis of the mutant insulin 3D structure revealed that the INS variant is likely to affect insulin receptor binding and subsequent in vitro analysis suggested reduced potency in downstream signaling.

Conclusions: The homozygous c.130G>A variant in the INS gene results in reduced insulin receptor binding and signaling potency. This, combined with pancreatic β-cell apoptosis or dedifferentiation supposedly, has contributed in the late-onset of monogenic diabetes in the index patient.

Introduction: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.

Research design and methods: This was a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration Adverse Event Reporting System between January 1997 through December 2023. We analyzed cases that mentioned atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin in aggregate as well as cases reporting atorvastatin, pravastatin, rosuvastatin, simvastatin individually. DM events were identified using the Medical Dictionary for Regulatory Activities. We used the proportional reporting ratio to identify increased rates of statin-associated DM events in women and men compared with all other medications, and the reporting OR to compare reporting rates in women versus men.

Results: A total of 18,294,814 ADEs were reported during the study period. Among statin-associated ADEs, 14,874/519,209 (2.9%) reports mentioned DM in women compared with 7,411/489,453 (1.5%) in men, which were both significantly higher than background (0.6%). Statins were the primary-suspected or secondary-suspected cause of the ADE significantly more often in women than men (60 vs 30%), and reporting rates were disproportionately higher in women than in men for all statins. (reporting OR 1.9 (95% CI 1.9 to 2.0)). The largest difference in reporting of statin-associated DM between women and women was observed with atorvastatin.

Conclusions: Analysis of post-marketing spontaneous ADE reports demonstrated a higher reporting rate of DM-associated with statin use compared with other medications with a significantly higher reporting rate in women compared with men. Future studies should consider mechanisms of statin-associated DM moderated by sex.

Introduction: To evaluate the long-term risk of developing type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM) compared with those with impaired glucose tolerance (IGT).

Research design and methods: Using data from a primary care dataset linked with multiple health registries, this longitudinal study analyzed demographics, clinical data, and lifestyle factors of women diagnosed with GDM or IGT, assessing T2D incidence over 25 years, using Cox regression models.

Results: Women with GDM, especially those over 35 years of Māori ethnicity, or socioeconomic deprivation, exhibited an elevated risk of T2D compared with those with IGT. The first 5 years post partum emerged as a critical window for intervention.

Conclusions: This study underscores the importance of early, targeted post-GDM interventions to mitigate T2D risk. It highlights the necessity of personalized post-GDM interventions to reduce T2D incidence which consider age, ethnicity, and socioeconomic status to maximize effectiveness.

Introduction: The aim of this study was to evaluate the effects of flexor tendon tenotomy treatment of the diabetic hammertoe deformity on plantar pressure.

Research design and methods: The study was a substudy including participants from a randomized study on tenotomy treatment of diabetic hammertoes. This study was conducted between December 20, 2019 and June 22, 2021. Participants were randomized to tenotomy and standard non-surgical treatment or standard non-surgical treatment alone. Barefoot plantar pressure measurement was performed pre-intervention and 3 months post-intervention. Primary outcome was change in peak plantar pressure post tenotomy treatment.

Results: Of the 95 participants screened in the original study, 45 (57.8% male) were included andcompleted this substudy. Of the 45 participants, 22 were randomized to intervention. The average age of participants was 65.6 ((SD±) 9.5) years and 30 (66.7%) had type 2 diabetes.The average peak plantar pressure (PPP) in toe regions of the participants in the intervention group was significantly (p<0.0001) reduced from 205.6 kPa ((Q1-Q3) 152.0-289.1) pre-intervention to 61.3 kPa (39.1-100.5) post-intervention. The average reduction in PPP of toe regions for participants in the intervention group (-145.3 kPa (-225.9 to -56.2)) was significantly (p=0.00017) higher than what was observed for participants in the control group (-1.6 kPa (-30.2 to 27.9)).

Conclusion: This study found that tenotomies of the diabetic hammertoe reduces plantar pressure affecting the treated toes. This likely explains the positive effects of tenotomy treatment on diabetic foot ulcers.

This study aimed to investigate the effects of concurrent aerobic and strength training (CT) in patients with type 2 diabetes and determine the most effective dose of CT. From the inception of the databases to March 2024, we conducted a systematic search of four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) to identify randomized controlled trials (RCTs) on CT intervention in patients with type 2 diabetes. Two independent authors assessed the risk of bias of the study using the Cochrane Risk of Bias Assessment Tools. Results analyzed included glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), body mass index, body fat percentage, blood pressure, and VO₂max. Pairwise and dose-response meta-analyses using Bayesian hierarchical random-effects modeling were performed to analyze the effects of CT in patients with type 2 diabetes. From the inception of the databases to March 2024, we conducted a systematic search of four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) to identify randomized controlled trials (RCTs) on CT intervention in patients with type 2 diabetes. Two independent authors assessed the risk of bias of the study using the Cochrane Risk of Bias Assessment Tools. Results analyzed included glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), body mass index, body fat percentage, blood pressure, and VO₂max. Pairwise and dose-response meta-analyses using Bayesian hierarchical random-effects modeling were performed to analyze the effects of CT in patients with type 2 diabetes. A total of 1948 participants (935 males) were included in 23 RCTs. The male/female ratio of participants was 52/48; the mean age range was 50-65 years. The results show that CT significantly reduced HbA1c levels (MD=-0.48%, 95% CrI: -0.55 to -0.40), with some heterogeneity among different levels (SD=0.31, 95% CrI: 0.17 to 0.51), and the model converged well. Similarly, FBG levels were also significantly improved (MD=-0.48 mmol/L, 95% CrI: -0.55 to -0.40), with greater heterogeneity (SD=17.73, 95% CrI: 11.23 to 28.09). Additionally, we found a non-linear dose-response relationship between CT and HbA1c levels, with an optimal dose of 1030 METs-min/week (MD=-0.47%, 95% CrI: -0.68 to -0.26, SE=0.11). CT significantly improves several health indicators in patients with type 2 diabetes. A non-linear dose-response relationship was observed between the training dose of CT and HbA1c, and it is recommended that 270 min of moderate-intensity CT or 160 min of vigorous-intensity CT be performed weekly.PROSPERO registration number: CRD42024547119.Keywords: meta-analysis; concurrent aerobic and strength training.