-
1.
Non-pharmacological interventions to improve cardiovascular risk factors in people with diabetic foot disease: A systematic review and meta-analysis.
Highton, P, Almaqhawi, A, Oroko, M, Sathanapally, H, Gray, L, Davies, M, Webb, D, Game, F, Petrie, J, Tesfaye, S, et al
Diabetes research and clinical practice. 2024;:111590
Abstract
Cardiovascular disease (CVD) risk in those with diabetic foot disease is very high. Non-pharmacological interventions may improve this risk, though no previous evidence synthesis has been completed. This systematic review aimed to investigate the impact of non-pharmacological interventions on CVD risk factors in diabetic ulcer disease. Multiple databases and trials registers were searched from inception to December 6th 2023. We included reports of randomised controlled trials investigating the impact of non-pharmacological interventions on cardiovascular risk in those with type 1 or type 2 diabetes and current or previous diabetic foot disease. Twenty studies were included. Extracted data included: study design and setting; participant sociodemographic factors; and change in cardiovascular risk factors. Data were synthesised using random effects meta-analyses and narrative syntheses. Interventions included nutritional supplementation, collaborative care, hyperbaric oxygen therapy, patient education, nurse-led intervention, self-management, family support, relaxation and exercise, over a median duration of 12 weeks. Significant post-intervention changes were observed in fasting plasma glucose, serum insulin levels, insulin sensitivity and resistance, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol and C-reactive protein. No effects were detected in very low- or high-density lipoprotein-cholesterol or body mass index. Non-pharmacological interventions show promise in improving CVD risk in diabetic foot disease.
-
2.
Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.
Kunutsor, SK, Balasubramanian, VG, Zaccardi, F, Gillies, CL, Aroda, VR, Seidu, S, Khunti, K
Diabetes, obesity & metabolism. 2024
Abstract
AIM: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. MATERIALS AND METHODS In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. RESULTS We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. CONCLUSIONS In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.
-
3.
Effect of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on time to outcome in type 2 diabetes cardiorenal outcome trials.
Rizzi, A, Kloecker, DE, Pitocco, D, Khunti, K, Davies, MJ, Zaccardi, F
Diabetes & metabolic syndrome. 2024;(2):102945
Abstract
INTRODUCTION In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials' results. METHODS Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes. RESULTS AFs were estimated from 28 Kaplan-Meier plots of 19 RCTs. Compared to placebo, most GLP1-RAs increased the time before the onset of POs (from 9 % to 59 %) and all-cause mortality (from 8 to 13 %). Similarly, SGLT2-is increased time before the onset of POs (from 19 % to 87 %) and all-cause mortality (from 13 % to 42 %). CONCLUSIONS The AFs provide a complementary and easier-to-interpret measure of treatment effect that could be useful to improve the shared decision-making.
-
4.
Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.
Kunutsor, SK, Zaccardi, F, Balasubramanian, VG, Gillies, CL, Aroda, VR, Seidu, S, Davies, MJ, Khunti, K
Diabetes, obesity & metabolism. 2024;(5):1837-1849
Abstract
AIM: Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes. MATERIALS AND METHODS Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions. RESULTS Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R2 = 14.2%), which was driven by the component of non-fatal stroke (R2 = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. CONCLUSIONS SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.
-
5.
The impact of the COVID-19 pandemic and associated disruptions in health-care provision on clinical outcomes in people with diabetes: a systematic review.
Hartmann-Boyce, J, Highton, P, Rees, K, Onakpoya, I, Suklan, J, Curtis, F, O'Mahoney, L, Morris, E, Kudlek, L, Morgan, J, et al
The lancet. Diabetes & endocrinology. 2024;(2):132-148
Abstract
The COVID-19 pandemic triggered disruptions to health care and lifestyles that could conceivably impact diabetes management. We set out to identify the impact of disruptions caused by COVID-19 on clinical outcomes in people with diabetes. We performed a systematic review of the available literature in the MEDLINE and OVID databases from Jan 1, 2020, to June 7, 2023, and included 138 studies (n>1 000 000 people). All but five studies were judged to be at some risk of bias. All studies compared prepandemic with pandemic periods. All-cause mortality (six studies) and diabetes-related mortality (13 studies) showed consistent increases, and most studies indicated increases in sight loss (six studies). In adult and mixed samples, data generally suggested no difference in diabetic ketoacidosis frequency or severity, whereas in children and adolescents most studies showed increases with some due to new-onset diabetes (69 studies). Data suggested decreases in hospital admissions in adults but increases in diabetes-related admissions to paediatric intensive care units (35 studies). Data were equivocal on diabetic foot ulcer presentations (nine studies), emergency department admissions (nine studies), and overall amputation rates (20 studies). No studies investigated renal failure. Where reported, the impact was most pronounced for females, younger people, and racial and ethnic minority groups. Further studies are needed to investigate the longer-term impact of the pandemic and the on potential differential impacts, which risk further exacerbating existing inequalities within people with diabetes.
-
6.
Translating trial results into interpretable risk estimates: Systematic analysis of cardiorenal outcome trials of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors.
Rizzi, A, Kloecker, DE, Pitocco, D, Khunti, K, Davies, MJ, Zaccardi, F
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024;(5):1129-1133
Abstract
BACKGROUND AND AIMS In a randomised controlled trial (RCT), the between-arm difference in the average probability of an event per unit of time (i.e., yearly incidence risk difference, YIRD) is an easy-to-interpret treatment effect metric. We aimed to quantify the YIRD in cardiorenal RCTs of GLP-1RAs or SGLT-2is. METHODS AND RESULTS We digitally searched for RCTs published up to March 1st, 2023, including subjects with type 2 diabetes randomised to GLP-1RAs or SGLT-2is and investigating cardiorenal outcomes or death. We extracted information from Kaplan-Meier (KM) plots to obtain time-to-event individual data and estimate within-arm yearly incidence risk and YIRD. Data from 19 RCTs (28 kM plots) were analysed: comparing treatment to placebo, in GLP-1RA RCTs the YIRD ranged from 0.2 % (95 % CI: -0.7 %, 1.1 %) to -1.9 % (-3.1, -0.7), for primary outcome; and from -0.2 % (-0.5, 0.2) to -0.4 % (-0.7 %, -0.0 %), for mortality. With the exception of SOLOIST-WHF (YIRD 11.9 % for primary outcome), corresponding estimates in SGLT-2is RCTs were: from -0.1 % (-0.4, 0.1) to -5.0 % (-7.7, -2.6), for primary outcome; and from -0.1 % (-0.2, 0.1) to -1.9 % (-4.4 %, 0.6 %), for mortality. CONCLUSION The YIRD metric complements other relative treatment effect estimates and helps quantify the absolute benefit of GLP-1RAs and SGLT-2is.
-
7.
Racial and Ethnic Disparities in Primary Prevention of Cardiovascular Disease.
Ali, MR, Nacer, H, Lawson, CA, Khunti, K
The Canadian journal of cardiology. 2024
Abstract
Cardiovascular disease (CVD) disproportionately affects ethnic-minority groups globally. Ethnic-minority groups face particularly high CVD burden and mortality, exacerbated by disparities across modifiable risk factors, wider determinants of health, and limited access to preventative interventions. This narrative review summarizes evidence on modifiable risk factors, such as physical activity, hypertension, diet, smoking, alcohol consumption, diabetes, and the polypill for the primary prevention of CVD in ethnic minorities. Across these factors, we find inequities in risk factor prevalence. The evidence underscores that inequalities in accessibility to interventions and treatments impede progress in reducing CVD risk using primary prevention interventions for ethnic-minority people. Although culturally tailored interventions show promise, further research is required across the different risk factors. Social determinants of health and structural inequities also exacerbate CVD risk for ethnic-minority people and warrant greater attention. Additionally, we find that only limited ethnicity-specific data and guidelines are available on CVD primary prevention interventions for most risk factors. To address these gaps in research, we provide recommendations that include the following: investigating the sustainability and real-world effectiveness of culturally sensitive interventions; ensuring that ethnic-minority peoples' perspectives are considered in research; longitudinal tracking of risk factors; interventions and outcomes in ethnic-minority people; and ensuring that data collection and reporting of ethnicity data are standardized.
-
8.
Effect of Conventional Lifestyle Interventions on Type 2 Diabetes Incidence by Glucose-Defined Prediabetes Phenotype: An Individual Participant Data Meta-analysis of Randomized Controlled Trials.
Sathish, T, Khunti, K, Narayan, KMV, Mohan, V, Davies, MJ, Yates, T, Oldenburg, B, Thankappan, KR, Tapp, RJ, Bajpai, R, et al
Diabetes care. 2023;(11):1903-1907
Abstract
OBJECTIVE To examine whether the effect of conventional lifestyle interventions on type 2 diabetes incidence differs by glucose-defined prediabetes phenotype. RESEARCH DESIGN AND METHODS We searched multiple databases until 1 April 2023 for randomized controlled trials that recruited people with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and impaired fasting glucose plus impaired glucose tolerance (IFG+IGT). Individual participant data were pooled from relevant trials and analyzed through random-effects models with use of the within-trial interactions approach. RESULTS Four trials with 2,794 participants (mean age 53.0 years, 60.7% men) were included: 1,240 (44.4%), 796 (28.5%), and 758 (27.1%) had i-IFG, i-IGT, and IFG+IGT, respectively. After a median of 2.5 years, the pooled hazard ratio for diabetes incidence in i-IFG was 0.97 (95% CI 0.66, 1.44), i-IGT 0.65 (0.44, 0.96), and IFG+IGT 0.51 (0.38, 0.68; Pinteraction = 0.01). CONCLUSIONS Conventional lifestyle interventions reduced diabetes incidence in people with IGT (with or without IFG) but not in those with i-IFG.
-
9.
Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19: The CORONADO, ABCD COVID-19 UK national audit and AMERICADO study groups.
Hadjadj, S, Saulnier, PJ, Ruan, Y, Zhu, X, Pekmezaris, R, Marre, M, Halimi, JM, Wargny, M, Rea, R, Gourdy, P, et al
Diabetes, obesity & metabolism. 2023;(1):78-88
-
-
Free full text
-
Abstract
AIM: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19. MATERIALS AND METHODS We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer. RESULTS Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (adj OR) 2.57 (95% CI 1.69-3.92), adj OR 1.22 (95% CI 1.00-1.52) and adj OR 1.33 (95% CI 1.15-1.53), respectively. In meta-analysis of the three studies, compared to patients free of complications, those with microvascular complications had an unadjusted OR for all-cause death during hospital stay of 2.05 (95% CI 1.42-2.97), which decreased to 1.62 (95% CI 1.19-2.119) after adjustment for age and sex, and to 1.50 (1.12-2.02) after hypertension and CVD were further added to the model. CONCLUSION Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID-19.
-
10.
Overcoming Therapeutic Inertia as the Achilles' Heel for Improving Suboptimal Diabetes Care: An Integrative Review.
Chew, BH, Mohd-Yusof, BN, Lai, PSM, Khunti, K
Endocrinology and metabolism (Seoul, Korea). 2023;(1):34-42
Abstract
The ultimate purpose of diabetes care is achieving the outcomes that patients regard as important throughout the life course. Despite advances in pharmaceuticals, nutraceuticals, psychoeducational programs, information technologies, and digital health, the levels of treatment target achievement in people with diabetes mellitus (DM) have remained suboptimal. This clinical care of people with DM is highly challenging, complex, costly, and confounded for patients, physicians, and healthcare systems. One key underlying problem is clinical inertia in general and therapeutic inertia (TI) in particular. TI refers to healthcare providers' failure to modify therapy appropriately when treatment goals are not met. TI therefore relates to the prescribing decisions made by healthcare professionals, such as doctors, nurses, and pharmacists. The known causes of TI include factors at the level of the physician (50%), patient (30%), and health system (20%). Although TI is often multifactorial, the literature suggests that 28% of strategies are targeted at multiple levels of causes, 38% at the patient level, 26% at the healthcare professional level, and only 8% at the healthcare system level. The most effective interventions against TI are shorter intervals until revisit appointments and empowering nurses, diabetes educators, and pharmacists to review treatments and modify prescriptions.