scholarly journals Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial

2020 ◽  
Author(s):  
Antonio Ceriello ◽  
Anne Pernille Ofstad ◽  
Isabella Zwiener ◽  
Stefan Kaspers ◽  
Jyothis George ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cox Regression ◽  
Glucose Variability ◽  
Cardiovascular Death ◽  
Baseline Risk ◽  
Increased Risk ◽  
Outcome Trial ◽  
Deviation Coefficient ◽  
Hba1c Variability

Abstract Background: Glucose variability has been associated with cardiovascular (CV) outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and CV death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of CV death by 38%. We explore post-hoc the association between HbA1c variability and CV death, and the potential mediating effects of HbA1c variability on empagliflozin’s CV death reductions.Methods: In total, 7,020 patients with type 2 diabetes and established CV disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between CV death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.Results: HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for CV death in both treatment arms with no interaction with treatment.Conclusions: HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of CV death. Empagliflozin’s reduction in CV death did not appear to be mediated by reductions in HbA1c variability.ClinicalTrials.gov number, NCT01131676. Registered May 27 2010. https://clinicaltrials.gov/ct2/show/NCT01131676

scholarly journals Empagliflozin reduced long-term HbA1c variability and cardiovascular death: insights from the EMPA-REG OUTCOME trial

2020 ◽  
Author(s):  
Antonio Ceriello ◽  
Anne Pernille Ofstad ◽  
Isabella Zwiener ◽  
Stefan Kaspers ◽  
Jyothis George ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Standard Deviation ◽  
Cox Regression ◽  
Glucose Variability ◽  
Cardiovascular Death ◽  
Baseline Risk ◽  
Increased Risk ◽  
Outcome Trial ◽  
Hba1c Variability

Abstract Background: Glucose variability has been associated with cardiovascular outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and cardiovascular death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of cardiovascular death by 38%. We explore post-hoc the association between HbA1c variability and cardiovascular death, and the potential mediating effects of HbA1c variability on empagliflozin’s cardiovascular death reductions.Methods: In total, 7,020 patients with type 2 diabetes and established cardiovascular disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between cardiovascular death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.Results: HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for cardiovascular death in both treatment arms with no interaction with treatment: e.g.an increase in HbA1c variability of one unit for the standard deviation at week 28 was associated with a subsequent increased risk of CV death with HRs of 1.97 (95% CI 1.36, 2.84) and 1.53 (1.01, 2.31) in the placebo and empagliflozin groups, separately, interaction p-value 0.3615.Conclusions: HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of cardiovascular death. Empagliflozin’s reduction in cardiovascular death did not appear to be mediated by reductions in HbA1c variability.ClinicalTrials.gov number, NCT01131676

scholarly journals Empagliflozin reduced long-term HbA1c variability and cardiovascular death: insights from the EMPA-REG OUTCOME trial

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Ceriello ◽  
Anne Pernille Ofstad ◽  
Isabella Zwiener ◽  
Stefan Kaspers ◽  
Jyothis George ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Standard Deviation ◽  
Cox Regression ◽  
Glucose Variability ◽  
Cardiovascular Death ◽  
Baseline Risk ◽  
Increased Risk ◽  
Outcome Trial ◽  
Hba1c Variability

Abstract Background Glucose variability has been associated with cardiovascular outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and cardiovascular death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of cardiovascular death by 38%. We explore post-hoc the association between HbA1c variability and cardiovascular death, and the potential mediating effects of HbA1c variability on empagliflozin’s cardiovascular death reductions. Methods In total, 7,020 patients with type 2 diabetes and established cardiovascular disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between cardiovascular death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment. Results HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for cardiovascular death in both treatment arms with no interaction with treatment: e.g. an increase in HbA1c variability of one unit for the standard deviation at week 28 was associated with a subsequent increased risk of CV death with HRs of 1.97 (95% CI 1.36, 2.84) and 1.53 (1.01, 2.31) in the placebo and empagliflozin groups, separately, interaction p-value 0.3615. Conclusions HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of cardiovascular death. Empagliflozin’s reduction in cardiovascular death did not appear to be mediated by reductions in HbA1c variability. ClinicalTrials.gov number, NCT01131676

scholarly journals Cardiovascular Benefit of Empagliflozin Across the Spectrum of Cardiovascular Risk Factor Control in the EMPA-REG OUTCOME Trial

2020 ◽  
Vol 105 (9) ◽  
pp. 3025-3035
Author(s):  
Silvio E Inzucchi ◽  
Kamlesh Khunti ◽  
David H Fitchett ◽  
Christoph Wanner ◽  
Michaela Mattheus ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Density Lipoprotein ◽  
Baseline Risk ◽  
Risk Factor Control ◽  
Increased Risk ◽  
Outcome Trial

Abstract Context Control of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes. Objective To investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor. Design Post hoc analysis. Setting Randomized CV outcome trial (EMPA-REG OUTCOME). Participants Type 2 diabetes patients with established CV disease. Intervention Empagliflozin or placebo. Main Outcome Measures Risk of CV outcomes—including the treatment effect of empagliflozin—by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin <7.5%, (2) low-density lipoprotein cholesterol <100 mg/dL or statin use, (3) systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg, (4) pharmacological renin-angiotensin-aldosterone system blockade, (5) normoalbuminuria, (6) aspirin use, (7) nonsmoking. Results In the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26–7.11) and 2.48 (95% CI, 1.52–4.06) for patients achieving only 0–3 or 4–5 risk factor goals at baseline, respectively, compared with those achieving 6–7 goals. Participants achieving 0–3 or 4–5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53–3.19] and 1.42 [1.06–1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P > 0.05 for treatment-by-subgroup interactions). Conclusions Cardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin’s cardioprotective effect was consistent regardless of multiple baseline risk factor control.

scholarly journals Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

Diabetes Care ◽  
2022 ◽  
Author(s):  
Avivit Cahn ◽  
Stephen D. Wiviott ◽  
Ofri Mosenzon ◽  
Erica L. Goodrich ◽  
Sabina A. Murphy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Baseline Hba1c ◽  
Renal Outcomes ◽  
Increased Risk ◽  
Hba1c Levels

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction > 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c <7%.

P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pellicori ◽  
A Pernille Ofstad ◽  
D Fitchett ◽  
C Zeller ◽  
C Wanner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Adverse Events ◽  
Repeated Measures ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Safety Data ◽  
Increased Risk ◽  
Outcome Trial

Abstract Background The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years. Purpose To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline. Methods We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model. Results A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA. Conclusions In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.

Abstract 14962: Empagliflozin’s Cardiovascular Impact in High-Risk Patients With Type 2 Diabetes and Obstructive Pulmonary Disease: An Inquiry From EMPA-REG OUTCOME

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Stefan D Anker ◽  
David H Fitchett ◽  
Bernard Zinman ◽  
Anne Pernille Ofstad ◽  
Christoph Wanner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pulmonary Disease ◽  
Cox Regression ◽  
Baseline Risk ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Similar Treatment ◽  
Increased Risk

Introduction: Type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD) often co-exist yielding increased risk of cardiovascular (CV) complications, including heart failure (HF). In the EMPA-REG OUTCOME trial, empagliflozin (EMPA) reduced the risk of CV death and hospitalization for HF (HHF) in patients with T2D and CV disease (CVD). We hypothesized that patients with COPD had a higher risk of CV outcomes than those without COPD, but similar treatment benefits on CV outcomes from EMPA as the overall population. Methods: In total, 7020 patients were treated with EMPA 10mg, 25mg, or placebo (PBO) with median follow-up of 3.1 years. We defined COPD at baseline (BL) by investigator reported presence of COPD or emphysema, or the use of medications for obstructive airways disease. We explored the effect of pooled EMPA groups vs. PBO within the subgroups of patients with vs. without COPD on CV death, HHF, HHF or CV death (excluding fatal stroke), all-cause death and 3-point-MACE by Cox regression adjusted for baseline risk factors. Results: The 707 (10.1%) patients with COPD at BL were slightly older (65±8 vs. 63±9 yrs), had more often HF at BL (17 vs. 9%) and coronary artery disease (84 vs. 75%), used insulin (56 vs. 47%) and diuretics (57 vs. 42%,) more frequently, but had similar beta-blocker use (64 vs. 65%) as compared to those without COPD. During follow-up, those with COPD in the placebo group had increased risk of HHF (HR 2.15 [95%CI 1.32-3.49], p=0.002), HHF or CV death (HR 1.60 [1.10-2.33], p<0.015), and all-cause death (HR 1.60 [1.09-2.35], p<0.02). EMPA consistently reduced all CV outcomes irrespective of COPD status (Fig). Conclusions: In EMPA-REG OUTCOME, 10% of patients had concomitant COPD. COPD patients were at increased risk of HHF, HHF or CV death, as well as all-cause death. EMPA consistently reduced these outcomes vs PBO among patients with and without COPD. These data suggest that EMPA’s benefits in patients with T2D and CVD are not attenuated by presence of COPD.

scholarly journals Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the CARMELINA randomized trial

2020 ◽  
Author(s):  
Vlado Perkovic ◽  
Robert Toto ◽  
Mark E Cooper ◽  
Johannes FE Mann ◽  
Julio Rosenstock ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Secondary Analysis ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
First Occurrence ◽  
Outcome Trial ◽  
End Stage ◽  
Reduced Kidney Function

<b>Objective</b> <p>Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular and kidney outcomes across baseline eGFR categories (≥ 60, 45-<60, 30-<45 and < 30 ml/min/1.73 m<sup>2</sup>) in CARMELINA, a cardio-renal placebo-controlled outcome trial of the DPP-4 inhibitor linagliptin (NCT01897532).</p> <p><b>Research Design and Methods</b></p> <p>Participants with cardiovascular disease (CVD) and/or CKD were included. The primary outcome was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with a secondary outcome renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other endpoints included progression of albuminuria, change in HbA1c and adverse events (AEs) including hypoglycemia. </p> <p><b>Results</b></p> <p>6979 subjects (mean age 65.9 years, eGFR 54.6 ml/min/1.73m<sup>2</sup>, 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared to placebo did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction p-values > 0.05). Regardless of eGFR, albuminuria-progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced between groups overall and across eGFR categories. </p> <p><b>Conclusions </b></p> <p>Across all GFR categories, in participants with type 2 diabetes and CKD and/or CVD, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c, and no difference in AEs was observed.</p>

scholarly journals Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population

2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Serum Creatinine ◽  
Cox Regression ◽  
Tertiary Care ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
New Onset

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE

2019 ◽  
Vol 105 (1) ◽  
pp. 152-162 ◽  
Author(s):  
Alexandra K Lee ◽  
Mark Woodward ◽  
Dan Wang ◽  
Toshiaki Ohkuma ◽  
Bethany Warren ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Weight Change ◽  
Cox Regression ◽  
Lifestyle Changes ◽  
Baseline Body Mass Index ◽  
Diabetes Medication ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Context Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. Objective To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. Design and Setting The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: &gt;10% loss, 4% to 10% loss, stable (±&lt;4%), 4% to 10% gain, and &gt;10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. Results Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had &gt;10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had &gt;10% weight gain. Over the following 3 years of the trial, &gt;10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. Conclusions In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.

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