Cardiovascular Diabetology最新文献

Background: The relationship between ankle blood pressure (BP) and cardiovascular disease remains unclear. We examined the relationships between known and new ankle BP indices and major cardiovascular outcomes in people with and without type 2 diabetes.

Methods: We used data from 3 large trials with measurements of ankle systolic BP (SBP), ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). The primary outcome was a composite of cardiovascular mortality, myocardial infarction, hospitalization for heart failure, or stroke. Secondary outcomes included death from cardiovascular causes, total (fatal and non-fatal) myocardial infarction, hospitalization for heart failure, and total stroke.

Results: Among 42,929 participants (age 65.6 years, females 31.3%, type 2 diabetes 50.1%, 53 countries), the primary outcome occurred in 7230 (16.8%) participants during 5 years of follow-up (19.4% in people with diabetes, 14.3% in those without diabetes). The incidence of the outcome increased with lower ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, multivariable-adjusted hazard ratios (HRs, 95% CI) of the outcome for each lower fourth were 1.05 (0.98-1.12), 1.17 (1.08-1.25), and 1.54 (1.54-1.65) for ankle SBP; HR 1.06 (0.99-1.14), 1.26 (1.17-1.35), and 1.48 (1.38-1.58) for ABI; and HR 1.02 (0.95-1.10), 1.15 (1.07-1.23), and 1.48 (1.38-1.58) for APPD. The largest effect size was noted for ankle SBP (HRs 1.05 [0.90-1.21], 1.21 [1.05-1.40], and 1.93 [1.68-2.22]), and APPD (HRs 1.08 [0.93-1.26], 1.30 [1.12-1.50], and 1.97 [1.72-2.25]) with respect to hospitalization for heart failure, while only a marginal association was observed for stroke. The relationships were similar in people with and without diabetes (all p for interaction > 0.05).

Conclusions: Inverse and independent associations were observed between ankle BP and cardiovascular events, similarly in people with and without type 2 diabetes. The largest associations were observed for heart failure and the smallest for stroke. Including ankle BP indices in routine clinical assessments may help to identify people at highest risk of cardiovascular outcomes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement.

Methods: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission.

Results: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions.

Conclusions: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis.

Background: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI.

Methods: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI.

Results: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014).

Conclusions: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.

Background: The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated.

Methods: We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009-2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed.

Results: A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70-0.94), LEA (HR 0.76; 95% CI 0.60-0.96), and PAD (HR 0.81; 95% CI 0.68-0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles.

Conclusions: This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.

Background: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.

Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP).  RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).

Conclusions: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.

Background: The association between baseline triglyceride glucose index (TyG index) and incident non-communicable diseases, mainly in Asian populations, has been reported. In the current study, we aimed to evaluate the association between index-year, average, and visit-to-visit variability (VVV) of the TyG index with incident type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), and all-cause mortality among the Iranian population.

Methods: The study population included 5220 participants (2195 men) aged ≥ 30 years. TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). Average values of the TyG index and also VVV (assessed by the standard deviation (SD) and variability independent of mean) were derived during the exposure period from 2002 to 2011 (index-year). Multivariable Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index for incident different health outcomes.

Results: During more than 6 years of follow-up after the index year, 290, 560, 361, and 280 events of T2DM, hypertension, CVD, and all-cause mortality occurred. 1-SD increase in the TyG index values at the index-year was independently associated with the incident T2DM [HR (95% CI) 2.50 (2.13-2.93)]; the corresponding values for the average of TyG index were 2.37 (2.03-2.76), 1.12 (0.99-1.26, p_value = 0.05), 1.18 (1.01-1.36), and 1.29 (1.08-1.53) for incident T2DM, hypertension, CVD, and all-cause mortality, respectively. Compared to the first tertile, tertile 3 of VVV of the TyG index was independently associated with incident hypertension [1.33 (1.07-1.64), P_trend <0.01]. Likewise, a 1-SD increase in VVV of the TyG index was associated with an 11% excess risk of incident hypertension [1.11 (1.02-1.21)]. However, no association was found between the VVV of the TyG index and other outcomes. Moreover, the impact of index-year and average values of the TyG index was more prominent among women regarding incident CVD (P for interactions < 0.05).

Conclusion: Although the higher TyG index at index-year and its VVV were only associated with the incident T2DM and hypertension, respectively, its average value was capable of capturing the risk for all of the health outcomes.

Background: Diabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS.

Objective: Investigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA).

Methods: Systematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis.

Main outcomes: Recurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes.

Results: Of 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34-1.85, I² = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29-1.56, I² = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50-1.61, I² = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34-1.82, I² = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15-1.96, I² = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18-1.91, I² = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73-4.57, I² = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19-2.05, I² = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66-2.59, I² = 85%).

Discussion: DM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes.

Background: Continuous glucose monitoring (CGM) devices provide detailed information on daily glucose control and glycemic variability. Yet limited population-based studies have explored the association between CGM metrics and fatty liver. We aimed to investigate the associations of CGM metrics with the degree of hepatic steatosis.

Methods: This cross-sectional study included 1180 participants from the Guangzhou Nutrition and Health Study. CGM metrics, covering mean glucose level, glycemic variability, and in-range measures, were separately processed for all-day, nighttime, and daytime periods. Hepatic steatosis degree (healthy: n = 698; mild steatosis: n = 242; moderate/severe steatosis: n = 240) was determined by magnetic resonance imaging proton density fat fraction. Multivariate ordinal logistic regression models were conducted to estimate the associations between CGM metrics and steatosis degree. Machine learning models were employed to evaluate the predictive performance of CGM metrics for steatosis degree.

Results: Mean blood glucose, coefficient of variation (CV) of glucose, mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD) were positively associated with steatosis degree, with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) of 1.35 (1.17, 1.56), 1.21 (1.06, 1.39), 1.37 (1.19, 1.57), and 1.35 (1.17, 1.56) during all-day period. Notably, lower daytime time in range (TIR) and higher nighttime TIR were associated with higher steatosis degree, with ORs (95% CIs) of 0.83 (0.73, 0.95) and 1.16 (1.00, 1.33), respectively. For moderate/severe steatosis (vs. healthy) prediction, the average area under the receiver operating characteristic curves were higher for the nighttime (0.69) and daytime (0.66) metrics than that of all-day metrics (0.63, P < 0.001 for all comparisons). The model combining both nighttime and daytime metrics achieved the highest predictive capacity (0.73), with nighttime MODD emerging as the most important predictor.

Conclusions: Higher CGM-derived mean glucose and glycemic variability were linked with higher steatosis degree. CGM-derived metrics during nighttime and daytime provided distinct and complementary insights into hepatic steatosis.

Background: Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.

Methods: Independent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.

Results: Genetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = - 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = - 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = - 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).

Conclusion: Our MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

Objective: We aimed to summarize the association between gestational diabetes mellitus (GDM) and its intergenerational cardiovascular diseases (CVDs) impacts in both mothers and offspring post-delivery in existing literature.

Methods: PubMed, Embase, Web of Science, and Scopus were utilized for searching publications between January 1980 and June 2024, with data extraction and meta-analysis continuing until 31 July 2024. Based on a predefined PROSPERO protocol, studies published as full-length, English-language journal articles that reported the presence of GDM during pregnancy and its association with any CVD development post-delivery were selected. All studies were evaluated using the Newcastle-Ottawa Scale. Maximally adjusted risk estimates were pooled using random-effects meta-analysis to assess the risk ratio (RR) of GDM, and overall and subtypes of CVDs in both mothers and offspring post-delivery.

Results: The meta-analysis was based on 38 studies with a total of 77,678,684 participants. The results showed a 46% increased risk (RR 1.46, 95% CI 1.34-1.59) for mothers and a 23% increased risk (1.23, 1.05-1.45) for offspring of developing overall CVDs after delivery, following a GDM-complicated pregnancy. Our subgroup analysis revealed that mothers with a history of GDM faced various risks (20% to 2-fold) of developing different subtypes of CVDs, including cerebrovascular disease, coronary artery disease, heart failure, and venous thromboembolism.

Conclusions: These findings underscore the heightened risk of developing various CVDs for mothers and offspring affected by GDM, emphasizing the importance of preventive measures even right after birth to mitigate the burden of CVDs in these populations.