A Target HbA1c Between 7 and 7.7% Reduces Microvascular and Macrovascular Events in T2D Regardless of Duration of Diabetes: a Meta-Analysis of Randomized Controlled Trials.
Ontology highlight
ABSTRACT: Introduction
The target glycated haemoglobin (HbA1c) at which micro- and macrovascular benefits may be derived in type 2 diabetes (T2D) has never been clearly outlined. This meta-analysis was conducted on 15 randomized controlled trials to highlight the association of HbA1c range with outcomes.Methods
The association of different HbA1c cluster (intention-to-treat (ITT) and end-of-study [EOS]) ranges (≤ 6.5%, 6.6-7.0%, 7.1-7.7%) with micro- and macrovascular complications and also the combined effect of T2D duration (< 10 years or ≥ 10 years) and HbA1c levels was assessed.Results
An intensive glucose-lowering strategy resulted in a significant 17% (95% CI: 0.73-0.93, P < 0.01) reduction in retinopathy, 18% reduction in macroalbuminuria (95% CI 0.62-0.83, P < 0.01), 32% reduction in end-stage renal disease (ESRD) (95% CI 0.36-0.92, P = 0.02) and 13% reduction in non-fatal myocardial infarction (NFMI) (95% CI 0.78-0.96, P < 0.01). Based on HbA1c achieved at EOS, a significant 46% reduction in retinopathy, 52% reduction in macroalbuminuria, 36% reduction in (NFS) non-fatal stroke and a 22% reduction in all-cause mortality (ACM) were observed in the group with HbA1c in the 7.1-7.7% range. In the cohort, with diabetes duration ≥ 10 years, reduction of HbA1c to ≤ 7.0% and significant improvements in new-onset retinopathy (24%) and macroalbuminuria (30%) were offset by an increase in ACM (21%) and NFMI (17%).Conclusion
Contrasting with most recommendations, this meta-analysis including recent studies suggests that the optimal HbA1c range for T2D is 7.1-7.7% regardless of diabetes duration.
SUBMITTER: Sinha B
PROVIDER: S-EPMC8179883 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This study evaluate association between glycemic variability and adverse vascular events in nondiabetic middle-aged adults. From 10,020 Ansung-Ansan cohort, Korean Genome, and Epidemiology Study (KoGES) data. 6,462 nondiabetic adults aged <65 years was analyzed. The mean and coefficient of variation (CV) of all biannually recorded HbA1c, fasting blood glucose(FBG), and post 2?hr blood glucose (PBG) were calculated and divided into 3 groups based on tertile of CV at each measurement, respectively. Primary endpoint was composite of Macro (composite of Coronary artery disease, Myocardial infarction, Congestive heart failure or Stroke) and Microvascular event (Creatine Clearance <60?ml/min/1.73?m2). The participants (mean age: 50 years, 50% men) were followed for a median of 9.9 (9.1-10.0) years. The high HbA1c-CV tertile (odds ratio 1.30; 1.01-1.66) was independent risk factor for microvascular events. In contrast, high FBG-CV tertile (2.32; 1.30-4.12) and PBG-CV (1.85; 1.05-3.26) was for macrovascular events. In this 10-year prespective cohort study, higher HbA1c-CV tertile was associated with higher composite of macro- and microvascular events and independent risk factor in non-DM middle-aged participants. In addition, higher tertile of FBG-CV and PBG-CV were risk factors for macrovascular events.
| S-EPMC6362217 | biostudies-literature
Project description:AbstractThe endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size-dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.
| S-EPMC8647695 | biostudies-literature
Project description:Aging is associated with reductions in endothelial function, observations primarily reported using brachial artery ultrasound. There is growing interest in the use of peripheral artery tonometry (PAT) of microvessels in the fingertip to assess endothelial function because it is less technically demanding and has a high sensitivity and specificity for assessing coronary endothelial function. Moreover, similar to brachial artery flow-mediated dilation (FMD), PAT predicts cardiovascular disease outcomes. However, the relationship between PAT and FMD have yet to be examined in the context of aging. To address this question, reactive hyperemic index (RHI) using EndoPAT and FMD using brachial artery ultrasound were assessed after 5 min of forearm ischemia in 20 younger (18-40 yr old; 29 ± 4 yr) and 20 older (60-75 yr old; 65 ± 4 yr) healthy adult men. Higher values of both FMD and RHI indicate better endothelial function. Endothelial function assessed via brachial artery FMD was lower in older (4.8 ± 2.1%), compared with younger (7.5 ± 1.6%) men (P < 0.001). In contrast, the RHI assessed via PAT was greater in older (2.2 ± 0.6), compared with younger (1.8 ± 0.5) men (P = 0.014). FMD and RHI were not correlated (r = -0.15; P = 0.35). We conclude that PAT may not be an appropriate measure to evaluate age-associated changes in endothelial function.NEW & NOTEWORTHY Microvessel endothelial function assessed via finger plethysmography may not reflect age-associated reductions in large artery endothelial function assessed via brachial artery flow-mediated dilation.
| S-EPMC7944925 | biostudies-literature
Project description:Understanding of the long-term clinical outcomes associated with bariatric surgery has recently been advanced. Research related to the sequelae of diabetes-in particular, long-term microvascular and macrovascular complications-in patients who undergo weight-loss surgery is imperative to this pursuit. While numerous randomized control trials have assessed glucose control with bariatric surgery compared with intensive medical therapy, bariatric surgery outcome data relating to microvascular and macrovascular complications have been limited to observational studies and nonrandomized clinical trials. As a result, whether bariatric surgery is associated with a long-term reduction in microvascular and macrovascular complications when compared with current intensive glycemic control therapy cannot be determined because the evidence is insufficient. However, the consistent salutary effects of bariatric surgery on diabetes remission and glycemic improvement support the opportunity (and need) to conduct high-quality studies of bariatric surgery versus intensive glucose control. This review provides relevant background information related to the treatment of diabetes, hyperglycemia, and long-term complications; reports clinical findings (to date) with bariatric surgery; and identifies ongoing research focusing on long-term vascular outcomes associated with bariatric surgery.
| S-EPMC5562446 | biostudies-other
Project description:AIMS:To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. METHODS:We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ? 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. RESULTS:Among people with a diabetes duration of ? 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c , BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. CONCLUSIONS:People with Type 1 diabetes who have survived ? 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
| S-EPMC5516128 | biostudies-literature
Project description:Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.
| S-EPMC9332701 | biostudies-literature
Project description:BackgroundMicrovascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.MethodsThis prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009).ResultsAt 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease.ConclusionsConsidering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.
| S-EPMC4271022 | biostudies-literature
Project description:BackgroundType 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies.MethodsThis cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications. The Illumina's Infinium Exome-24 array was used and 39,840 SNPs remained for analysis after quality control.FindingsThe analysis revealed the associations of various genes with each complication category: 1) diabetic retinopathy was associated to SHANK3 gene in locus 22q13.33 (SNP rs9616915; p=5.18 x10-4), ZSCAN5A gene in locus 19q13.43 (SNP rs7252603; p=7.55 x10-4), and DCP1B gene in locus 12p13.33 (SNPs rs715146, rs1044950, rs113147414, rs34730825; p=7.62 x10-4); 2) diabetic neuropathy was associated to ADH4 gene in locus 4q23 (SNP rs4148883; p=1.23 x10-4), SLC11A1 gene in locus 2q35 (SNP rs17235409; p=1.85 x10-4), and MATN4 gene in locus 20q13.12 (SNP rs2072788; p=2.68 x10-4); 3) diabetic nephropathy was associated to PPP1R3A gene in locus 7q31.1 (SNP rs1799999; p=1.91 x10-4), ZNF136 gene in locus 19p13.2 (SNP rs140861589; p=2.80 x10-4), and HSPA12B gene in locus 20p13 (SNP rs6076550; p=2.86 x10-4); and 4) cardiovascular complications was associated to PCNT gene in locus 21q22.3 (SNPs rs7279204, rs6518289, rs2839227, rs2839223; p=2.18 x10-4,3.04 x10-4,4.51 x10-4,5.22 x10-4 respectively), SEPT14 gene in locus 7p11.2 (SNP rs146350220; p=2.77 x10-4), and WDR73 gene in locus 15q25.2 (SNP rs72750868; p=4.47 x10-4).InterpretationWe have identified susceptibility loci associated with each category of T2DM-related complications in the Emirati population. Given that only 16% of the markers from the Illumina's Infinium Exome chip passed quality control assessment, this demonstrates that multiple variants were, either, monomorphic in the Arab population or were not genotyped due to the use of a Euro-centric EWAS array that limits the possibility of including targeted ethnic-specific SNPs. Our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci associated to T2DM complications. Further effort must be conducted to improve the representation of diverse populations in genotyping and sequencing studies.
| S-EPMC10076756 | biostudies-literature
Project description:The vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organelles involved in this process is unclear. This study reports the effect of exogenous VEGF on translocation of VEGFRs and organelles in micro- and macrovascular endothelial cells. We showed that VEGF is responsible for: a rapid and substantial nuclear translocation of VEGFRs; VEGFR1 and VEGFR2 exhibit distinct spatial, temporal and structural translocation characteristics both in vitro and in vivo and this determines the nuclear VEGFR1:VEGFR2 ratio which differs between microvascular and macrovascular cells; VEGFR2 nuclear translocation is associated with the endosomal pathway transporting the receptor from Golgi in microvascular endothelial cells; and an increase in the volume of intracellular organelles. In conclusion, the nuclear translocation of VEGFRs is both receptor and vessel (macro versus micro) dependent and the endosomal pathway plays a key role in the translocation of VEGFRs to the nucleus and the subsequent export to the lysosomal system. Modulating VEGF-mediated VEGFR1 and VEGFR2 intracellular transmigration pathways may offer an alternative for the development of new anti-angiogenic therapies.
| S-EPMC8405636 | biostudies-literature
Project description:BackgroundCardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline metformin use.MethodsA post hoc analysis was conducted using pooled SUSTAIN 6 and PIONEER 6 CVOT data in subjects with and without metformin use at baseline. Additionally, a trial-level meta-analysis was conducted using data from seven CVOTs with GLP-1RAs-SUSTAIN 6, PIONEER 6, HARMONY OUTCOMES, LEADER, REWIND, EXSCEL and AMPLITUDE-O-including adults with type 2 diabetes at high CV risk, and a primary endpoint of time to first major adverse CV event (MACE).ResultsIn the post hoc analysis, the no-metformin subgroup was older, with a higher body mass index, lower estimated glomerular filtration rate and higher CV risk at baseline vs the metformin subgroup. Hazard ratios (95% confidence intervals) for the reduction in risk of MACE with semaglutide vs placebo in the metformin and no-metformin subgroups were 0.70 (0.55;0.89) and 0.86 (0.60;1.22), respectively. No significant interaction between the treatment effect on MACE and metformin subgroup was observed. Findings for other CV endpoints were similar. In the meta-analysis, treatment effect (GLP-1RA vs placebo) on CV outcomes was no different with vs without baseline metformin (overall ratio between the hazard ratios for metformin vs no-metformin 1.09 [0.96;1.22]).ConclusionThese findings indicate that the CV outcomes for semaglutide were similar regardless of baseline metformin use, which may also apply to all GLP-1RAs. Trial registration SUSTAIN 6 (NCT01720446), PIONEER 6 (NCT02692716).
| S-EPMC9052629 | biostudies-literature