BMJ Open Diabetes Research & Care最新文献

Objective: Using national claims databases, we sought to emulate the design of the ongoing SEPRA trial and predict its findings, comparing the effects of once weekly semaglutide to SoC medications on glycemic control (A1C <7%) in type-2 diabetes mellitus (T2D).

Research design and methods: Using Optum Clinformatics (July 2017 - May 2022), we identified a 1:1 propensity score-matched (PSM) cohort of adults with T2D on metformin monotherapy, who had recorded A1C and initiated either injectable semaglutide or SoC medications (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, SUs, or glucagon-like peptide-1 agonists) and met eligibility criteria adapted from the SEPRA trial. The primary outcome was the proportion of patients achieving A1C <7%. The study protocol was preregistered (NCT05577728, ClinicalTrials.gov) before any etiologic analyses. Risk ratios and corresponding 95% CIs were estimated.

Results: We identified 1,144 PSM pairs of injectable semaglutide and SoC initiators with balance in pre-exposure covariates. Semaglutide initiators were 30% (risk ratio (95% CI), 1.30 (1.16 to 1.45)) more likely to achieve glycemic control (A1C <7%) than those initiating SoC. Additionally, semaglutide initiators had a 1.3% reduction in A1C, compared with a 1.1% reduction in the SoC group. These results were consistent with interim results of the SEPRA trial, which were released after the protocol for our database study was preregistered.

Conclusion: This claims database study, designed to predict the results of the SEPRA trial, found results consistent with interim trial results. Our findings support the notion that well-designed non-randomized studies using fit-for-purpose data can effectively complement pragmatic randomized controlled trials.

Introduction: This study aims to investigate the association between change in urine albumin-to-creatinine ratio (UACR) and clinical outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes.

Research design and methods: Adult patients with elevated UACR (≥30 mg/g in initial testing) after the diagnosis of type 2 diabetes and CKD were identified from the Optum electronic health records database (01/2007-09/2021). UACR change from initial to last test (6-24 months) was categorized as >30% decrease, stable (-30% to 30%), or >30% increase. Risk of all-cause mortality, composite cardiovascular (CV) outcome (CV death, myocardial infarction, stroke, and hospitalization for heart failure), and CKD progression (≥40% decline in estimated glomerular filtration rate or kidney failure) were estimated with Cox proportional hazard models adjusted for baseline characteristics.

Results: Compared with patients with a stable UACR (n=35 117), those with a >30% UACR decrease (n=89 562) had lower risk of all-cause mortality (adjusted HR (aHR)=0.93, 95% CI 0.90 to 0.96), composite CV outcomes (aHR=0.93, 95% CI 0.90 to 0.95), and CKD progression (aHR=0.84, 95% CI 0.81 to 0.86) (all p<0.001), and patients with a >30% UACR increase (n=35 703) had higher risk of each endpoint (aHR=1.24, 95% CI 1.19 to 1.28; aHR=1.24, 95% CI 1.20 to 1.28; and aHR=1.41, 95% CI 1.36 to 1.46, respectively; all p<0.001).

Conclusions: In patients with CKD and type 2 diabetes, a >30% UACR decrease was associated with lower risk of mortality, CV events, and CKD progression, whereas a >30% UACR increase was associated with higher risk of these clinical outcomes. These findings highlight the importance of albuminuria monitoring and potential clinical benefits of targeted UACR reductions in this population.

Introduction: This study evaluated the long-term effectiveness of once-weekly subcutaneous semaglutide versus alternative treatment in adults with type 2 diabetes (T2D) in routine clinical practice.

Research design and methods: The SEmaglutide PRAgmatic (SEPRA) was a 2-year, randomized, open-label, pragmatic clinical trial (NCT03596450). Adults with T2D and inadequate glycemic control on one or two oral antidiabetic medications were randomized to receive once-weekly subcutaneous semaglutide or alternative treatment (chosen by the treating physician) as add-on therapy. Endpoints included proportion of participants achieving glycated hemoglobin (HbA_1c)<7.0% at year 1 (primary endpoint) and year 2; changes in HbA_1c (percentage point), body weight, and patient-reported outcomes (PROs) at years 1 and 2; and treatment changes (baseline to year 2). Missing data were imputed for some analyses.

Results: Participants were randomized to semaglutide (n=644) or alternative treatment (n=634). Proportions of participants achieving HbA_1c <7.0% were significantly higher with semaglutide versus alternative treatment at years 1 (53.1% vs 45.5%; OR (95% CI): 1.36 (1.03 to 1.79); p=0.033) and 2 (49.9% vs 38.9%; OR (95% CI): 1.56 (1.13 to 2.16); p=0.007). Mean HbA_1c decreases were larger with semaglutide versus alternative treatment at year 1 (-1.35% vs -1.16%; estimated treatment difference (ETD) (95% CI): -0.20% (-0.39% to 0.00%); p=0.046) and year 2 (-1.27% vs -0.96%; ETD (95% CI): -0.31% (-0.57% to -0.05%); p=0.018). Semaglutide was associated with larger reductions in body weight at year 1 (-3.57% vs -1.91%; ETD (95% CI): -1.65% (-2.92% to -0.39%); p=0.010) but not year 2 (p=0.175). Treatment changes occurred less frequently with semaglutide than with alternative treatments. Some PROs indicated greater improvement with semaglutide versus alternative treatment. No new safety concerns were identified.

Conclusions: SEPRA demonstrates that semaglutide is an appropriate choice for treatment intensification among individuals with T2D in the USA who are receiving 1-2 antidiabetic medications. Findings support semaglutide as an effective and well-tolerated option in clinical practice.

Trial registration number: NCT03596450.

Introduction: This study investigated the incidence of diabetic retinopathy (DR) and sight-threatening DR (STDR) through 2021 in patients diagnosed with type 2 diabetes (T2DM) in 1996-2004. The study also investigated risk factors associated with DR.

Research design and methods: The cohort comprised patients in the Swedish Skaraborg Diabetes Register in 1996-2004 who were ≤70 years at T2DM diagnosis and without DR at first-eye examination. Clinical data at diagnosis included age, smoking habits, body mass index, blood pressure, HbA1c, high-density lipoprotein cholesterol, triglycerides, c-peptide and antihypertensive drugs as a proxy for hypertension. The level of DR at first eye examination after diagnosis through 31 December 2021 was extracted from medical records at the Department of Ophthalmology, Skaraborg Hospital. The cumulative incidence of DR was estimated by the Kaplan-Meier method, and multivariate Cox regression models were used to estimate the risk of DR.

Results: The study included 2267 patients; over the course of 24 years of follow-up (mean 12.8±5.8 years), 926 developed DR and 101 developed STDR. The cumulative incidence after 10 and 20 years was 29.0% and 67.6% for DR and 1.4% and 11.4% for STDR. Higher HbA1c (HR 1.02 per 1 mmol/mol, 95% CI 1.01 to 1.02) and antihypertensive treatment at diagnosis (HR 1.26, 95% CI 1.08 to 1.47) were associated with increased risk of DR. Higher age (HR 0.98 per year, 95% CI 0.97 to 0.98) and diagnosis in 1999-2004 versus 1996-1998 (HR 0.58, 95% CI 0.51 to 0.66) were associated with a lower risk of DR.

Conclusion: During follow-up, 926 patients developed DR, whereas 101 developed STDR. Higher HbA1c and antihypertensive treatment were associated with a higher risk of developing DR and STDR, while higher age at diagnosis and diagnosis in 1999-2004 versus 1996-1998 were associated with lower risk.

Introduction: Preclinical studies suggest a potential link between glucagon-like peptide 1 receptor agonists (GLP-1RA) and thyroid cancer (TC), yet it is unclear if this risk translates to humans.

Research design and methods: We estimated the comparative effect of incretin-based therapies (GLP-1RA and dipeptidyl-peptidase-4 inhibitors (DPP-4i)) versus sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on TC incidence among US older adults with type 2 diabetes. We defined TC as a thyroidectomy followed by ≥2 separate diagnoses codes for malignant neoplasm of thyroid gland within 90 days. We estimated adjusted 3-year cumulative risk differences of TC (aRDs) with 95% CIs using weighted Kaplan-Meier survival functions, and adjusted HRs using weighted Cox models.

Results: We included 73 388 new users in the GLP-1RA versus SGLT-2i cohort (mean age 72.4 years, men: 48.3%) and 106 274 in the DPP-4i versus SGLT-2i cohort (mean age 74.6 years, men: 44.9%). At 3 years and a median duration of treatment of 0.82-1.15 years, the aRD for GLP-1RA versus SGLT-2i for TC was -23 per 10 000 (95% CI: -51 to 4) and the aRD for DPP-4i versus SGLT-2i was -2 per 10 000 (95% CI: -17 to 13). Secondary and sensitivity analyses were consistent.

Conclusions: Our study of US Medicare beneficiaries with type 2 diabetes suggests that the initiation of incretin-based therapies may not increase the 3-year risk of TC compared with initiation of SGLT-2i. This finding offers reassurance for short-term use but does not eliminate the possibility of increased long-term or subtype-specific risks.

Introduction: Gestational diabetes mellitus (GDM) is associated with metabolic risks and adverse maternal and fetal perinatal outcomes. This study aimed to compare pregnancy outcomes, postpartum glucose intolerance and insulin secretion capacity in women with early-onset GDM (EGDM, diagnosed<24 weeks) and late GDM (LGDM, diagnosed≥24 weeks) in Japan.

Research design and methods: This single-center, retrospective study included 107 women with EGDM and 109 with LGDM. GDM was diagnosed through the 75 g oral glucose tolerance test. Postpartum glucose tolerance was assessed 4-16 weeks post partum. Maternal and neonatal outcomes, insulin secretion, and postpartum glucose tolerance were analyzed and compared. Subgroup analyses were performed for women with and without obesity.

Results: Although gestational weight gain was significantly lower in women with EGDM than in those with LGDM, pregnancy outcomes, including neonatal birth weight, small for gestational age and large for gestational age, were comparable between the two groups. However, postpartum glucose intolerance was more prevalent in women with EGDM, particularly in those without obesity who also had significantly lower initial insulin secretion capacity. Insulin resistance was comparable between the groups, suggesting that reduced insulin secretion, rather than insulin resistance, contributes to postpartum glucose intolerance in EGDM.

Conclusions: EGDM in women without obesity is associated with a high risk for postpartum glucose intolerance. This could be related to impaired insulin secretion rather than insulin resistance. These findings highlight the need for close monitoring and tailored interventions for patients with EGDM. More research is required to improve diagnostic and management strategies, considering ethnic variations in insulin secretion and glucose tolerance.

Introduction: Type 2 diabetes (T2D) is closely associated with excess adiposity, particularly visceral fat. The body roundness index (BRI), calculated from height and waist circumference, provides a refined estimate of visceral adiposity. This study aimed to investigate the associations of baseline BRI and longitudinal changes in BRI with the risk of incident T2D.

Research design and methods: We used UK Biobank data, a cohort involving adults aged 37-73 years. Both baseline and last follow-up BRI values were classified according to the tertiles of baseline BRI, and long-term BRI changes were categorized by baseline and follow-up grades. The annual average rate of change (AARC) of BRI was also calculated. Cox regression models were employed to evaluate HRs and 95% CIs, while restricted cubic splines explored non-linear relationships.

Results: Among 485 509 participants, 32 956 developed T2D during the follow-up period. Elevated baseline BRI was correlated with a greater risk of T2D, with adjusted HRs of 2.39 (95% CI: 2.28 to 2.51) and 6.23 (95% CI: 5.96 to 6.50) for the second and third tertiles of BRI, respectively. In the longitudinal analysis of 65 684 participants (1153 T2D cases), low baseline BRI with grade increase was linked to higher risk of T2D (HR: 1.49, 95% CI: 1.05 to 2.13). Among participants with middle baseline BRI, grade decrease and increase showed HRs of 0.65 (95% CI: 0.45 to 0.93) and 1.66 (95% CI: 1.32 to 2.10) versus stable middle. Grade decrease with high baseline BRI was associated with lower T2D risk (HR: 0.50, 95% CI: 0.40 to 0.62) compared with stable high. Non-linear associations between AARC of BRI and T2D risk were identified (p <0.05).

Conclusions: This study shows that both baseline BRI and long-term BRI changes are linked to T2D risk, emphasizing the significance of monitoring BRI trends for T2D prevention and control.

Introduction: This study aimed to identify factors associated with pancreatic abnormal findings on imaging (PAI) suggesting precancerous potential between slowly progressive type 1 diabetes and acute-onset type 1 diabetes.

Research design and methods: The study was designed to identify factors associated with PAI using data from a nationwide cohort, the Japanese Type 1 Diabetes Database. Clinical factors, including sex, age, type of diabetes onset, diabetes duration, body mass index, and human leucocyte antigen genotypes associated with type 1 diabetes, were evaluated.

Results: Among 279 patients with type 1 diabetes, 95 patients who had not undergone imaging evaluations, two patients with pancreatic lipomatosis, and 15 patients with missing data were excluded. Finally, a total of 167 patients with type 1 diabetes were analyzed. Among 13 patients who were identified as PAI positive, female sex (92.3% vs 53.2%, p=0.007), slowly progressive type 1 diabetes (69.2% vs 36.4%, p=0.034), and older age were more common compared with PAI-negative cases. The multivariable logistic regression analysis revealed that female sex (OR 13.87; 95% CI 1.6 to 120.1; p=0.017), slowly progressive type 1 diabetes (OR 5.70; 95% CI 1.46 to 22.19; p=0.012), and age (OR 1.05; 95% CI 1.002 to 1.103; p=0.043) were independently associated with PAI positivity.

Conclusions: The findings indicate that slowly progressive type 1 diabetes and female sex are closely associated with PAI, along with age. These results suggest the need for increased clinical vigilance for pancreatic pathology in patients with slowly progressive type 1 diabetes.

Introduction: Poorly controlled type 1 diabetes (T1D) has been associated with impaired bone health, but the mechanisms remain unclear. We aimed to investigate whether changes in glycemic control and glucose variability are associated with skeletal health and to evaluate the roles of insulin-like growth factor I (IGF-I) and advanced glycation end-products (AGEs) in bone mineral accrual.

Research design and methods: This longitudinal study included adolescents with poorly controlled T1D (HbA1c >9%/75 mmol/mol), who underwent dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months. Glycemic control was assessed using glycohemoglobin (HbA1c), continuous glucose monitoring (CGM) parameters, and glycemic load. Serum IGF-I and AGEs, specifically methyl-glyoxal-hydro-imidazolone (MG-HI), were measured. Correlation analyses and linear regression models were used to evaluate the associations between glycemic markers, IGF-I, AGEs and bone parameters.

Results: Altogether, 37 adolescents (48.6 % female) with T1D, with mean HbA1c 9.9% (85 mmol/mol), were followed up from mean age of 14.3 for 12 months. DXA-derived bone mineral density (BMD) z-scores at lumbar spine, proximal femur, and total body less head were approximately 0.5 SDS lower than reference values (p=0.005-0.04). The only significant change in BMD z-scores during the 12-month follow-up was an increase in proximal femur in girls. In the whole group, an increase in IGF-1 was associated with BMD accrual, while changes in HbA1c, time in range, or MG-HI were not. No vertebral fractures were detected.

Conclusions: Despite lower BMD in adolescents with poorly controlled T1D, neither changes in glycemic control nor MG-HI levels correlated significantly with bone health measures, while increase of IGF-1 was associated with BMD accrual. Future studies should explore alternative AGEs and use advanced bone imaging techniques to better understand skeletal fragility in T1D.