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Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial.

ABSTRACT: Diabetes is associated with substantially increased mortality. Classic risk factors explain a portion of the excess of mortality in type 2 diabetes. The aim of this study was to examine whether visit-to-visit variation in fasting glucose and haemoglobin A1c values in the Veteran Affairs Diabetes Trial were associated with all-cause mortality in patients with type 2 diabetes in addition to other comorbidity conditions, hypoglycaemic events and adverse lifestyle behaviours. The Veteran Affairs Diabetes Trial was a randomized trial that enrolled 1791 military veterans who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. During the Veteran Affairs Diabetes Trial, fasting glucose and haemoglobin A1c were measured quarterly for up to 84?months. Variability measures included coefficient of variation and average real variability. We found that variability measures (coefficient of variation and average real variability) of fasting glucose were predictors of all-cause mortality, even after adjusting for comorbidity index, mean fasting glucose and adverse lifestyle behaviour during the study. Accounting for severe hypoglycaemia did not weaken this association. Our analysis indicates that in the Veteran Affairs Diabetes Trial, longitudinal variation in fasting glucose was associated with all-cause mortality, even when accounting for standard measures of glucose control as well as comorbidity and lifestyle factors.

SUBMITTER: Zhou JJ

PROVIDER: S-EPMC7380497 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial.

Zhou Jin J JJ Koska Juraj J Bahn Gideon G Reaven Peter P

Diabetes & vascular disease research 20190301 2

Diabetes is associated with substantially increased mortality. Classic risk factors explain a portion of the excess of mortality in type 2 diabetes. The aim of this study was to examine whether visit-to-visit variation in fasting glucose and haemoglobin A1c values in the Veteran Affairs Diabetes Trial were associated with all-cause mortality in patients with type 2 diabetes in addition to other comorbidity conditions, hypoglycaemic events and adverse lifestyle behaviours. The Veteran Affairs Dia ...[more]

PMID: 31014099

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Project description:AIMS/HYPOTHESIS:We conducted an analysis of data collected during the Veterans Affairs Diabetes Trial (VADT) and the follow-up study (VADT-F) to determine whether intensive (INT) compared with standard (STD) glycaemic control during the VADT resulted in better long-term kidney outcomes. METHODS:VADT randomly assigned 1791 veterans from 20 Veterans Affairs (VA) medical centres who had type 2 diabetes mellitus and a mean HbA1c of 9.4 ± 2% (79.2 mmol/mol) at baseline to receive either INT or STD glucose control for a median of 5.6 years (randomisation December 2000 to May 2003; intervention ending in May 2008). After the trial, participants received routine care through their own physicians within the VA. This is an interim analysis of the VADT-F (June 2008 to December 2013). We collected data using VA and National databases and report renal outcomes based on serum creatinine, eGFR and urine albumin to creatinine ratio (ACR) in 1033 people who provided informed consent to participate in the VADT-F. RESULTS:By the end of the VADT-F, significantly more people who received INT treatment during the VADT maintained an eGFR >60 ml min-1 1.73 m-2 (OR 1.34 [95% CI 1.05, 1.71], p = 0.02). This benefit was most evident in those who were classified as at moderate risk (INT vs STD, RR 1.3, p = 0.03) or high risk (RR 2.3, p = 0.04) of chronic kidney disease on the Kidney Disease Improving Global Outcomes (KDIGO-CKD) at the beginning of VADT. At the end of VADT-F, significantly more people from the INT group improved to a low KDIGO risk category (RR 6.1, p = 0.002). During the VADT-F there were no significant differences between INT and STD for average HbA1c, blood pressure or lipid levels. CONCLUSIONS/INTERPRETATION:After just over 11 years of follow-up, there was a 34% greater odds of maintaining an eGFR of >60 ml min-1 1.73 m-2 and of improving the KDIGO category in individuals with type 2 diabetes who had received INT for a median of 5.6 years. VADT clinical trials.gov number: NCT 00032487.

Project description:Aims/hypothesisThere is controversy regarding the performance of HbA1c in old age. We evaluated the prognostic value of HbA1c and other glycaemic markers (fructosamine, glycated albumin, fasting glucose) with mortality risk in older adults (66-90 years).MethodsThis was a prospective analysis of 5636 participants (31% with diagnosed diabetes, mean age 76, 58% female, 21% black) in the Atherosclerosis Risk in Communities (ARIC) study, baseline 2011-2013. We used Cox regression to examine associations of glycaemic markers (modelled in categories) with mortality risk, stratified by diagnosed diabetes status.ResultsDuring a median of 6 years of follow-up, 983 deaths occurred. Among older adults with diabetes, 30% had low HbA1c (<42 mmol/mol [<6.0%]) and 10% had high HbA1c (≥64 mmol/mol [≥8.0%]); low (HR 1.32 [95% CI 1.04, 1.68]) and high (HR 1.86 [95% CI 1.32, 2.62]) HbA1c were associated with mortality risk vs HbA1c 42-52 mmol/mol (6.0-6.9%) after demographic adjustment. Low fructosamine and glycated albumin were not associated with mortality risk. Both low and high fasting glucose were associated with mortality risk. After further adjustment for lifestyle and clinical risk factors, high HbA1c (HR 1.81 [95% CI 1.28, 2.56]), fructosamine (HR 1.96 [95% CI 1.43-2.69]), glycated albumin (HR 1.81 [95% CI 1.33-2.47]) and fasting glucose (HR 1.81 [95% CI 1.24, 2.66]) were associated with mortality risk. Low HbA1c and fasting glucose were no longer significantly associated with mortality risk. Among participants without diabetes, associations of glycaemic markers with mortality risk were less robust.Conclusions/interpretationElevated HbA1c, fructosamine, glycated albumin and fasting glucose were associated with risk of mortality in older adults with diabetes. Low HbA1c and fasting glucose may be markers of poor prognosis but are possibly confounded by health status. Our findings support the clinical use of HbA1c in older adults with diabetes. Graphical abstract.

Project description:INTRODUCTION:Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. METHODS AND ANALYSIS:Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. ETHICS AND DISSEMINATION:This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication. PROSPERO REGISTRATION NUMBER:CRD42017079500.

Project description:BackgroundDiabetes is a cause of at least a third of all deaths in Mexican adults aged 35-74 years, with the excess mortality due mainly to vascular disease, renal disease, infection, and acute diabetic crises. We aimed to analyse the effect of diabetes duration and glycaemic control on death rate ratios (RRs) for these causes and to assess the relevance to cause-specific mortality of undiagnosed diabetes.MethodsAbout 100 000 women and 50 000 men aged 35 years or older from Mexico City were recruited into a blood-based prospective study between April 14, 1998, and Sept 28, 2004, and followed up until Jan 1, 2016, for cause-specific mortality. Participants who, at recruitment, reported any chronic disease other than diabetes and those who had missing data for HbA1c or diabetes duration were excluded. We used Cox models to estimate the associations of undiagnosed or previously diagnosed diabetes (almost all type 2) with risk of mortality from vascular disease, renal disease, and infection, exploring among those with previously diagnosed diabetes the independent relevance of diabetes duration (<5 years, ≥5 to <10 years, or ≥10 years) and HbA1c (<9%, ≥9% to <11%, or ≥11%). We also estimated the association of HbA1c with mortality in participants without diabetes at recruitment.Findings133 662 participants were aged 35-74 years and had complete data and no other chronic disease. 16 940 (13%) had previously diagnosed diabetes, 6541 (5%) had undiagnosed diabetes, and 110 181 (82%) had no diabetes. Among participants with previously diagnosed diabetes, glycaemic control was poor (median HbA1c 8·9% [IQR 7·0-10·9]), and was worse in those with longer duration of disease at recruitment. Compared with participants without diabetes, the death RRs at ages 35-74 years for the combination of vascular, renal, or infectious causes were 3·0 (95% CI 2·7-3·4) in those with undiagnosed diabetes, 4·5 (4·0-5·0) for the 5042 participants with a diabetes duration of less than 5 years, 6·6 (6·1-7·1) for the 7713 participants with a duration of 5 years to less than 10 years, and 11·7 (10·7-12·7) for the 4185 participants with a duration of at least 10 years. Similarly, the death RRs were 5·2 (4·8-5·7) for those with HbA1c less than 9%, 6·8 (6·2-7·4) for those with HbA1c of 9% to less than 11%, and 10·5 (9·7-11·5) for those with HbA1c of at least 11%. Diabetes was not strongly associated with the combination of deaths from other causes apart from acute glycaemic crises. Among participants without diabetes, higher HbA1c was not positively related to mortality.InterpretationIn Mexico, the rates of death from causes strongly associated with diabetes increased steeply with duration of diabetes and were higher still among people with poor glycaemic control. Delaying the onset of type 2 diabetes, as well as improving its treatment, is essential to reduce premature adult mortality in Mexico.FundingWellcome Trust, the Mexican Health Ministry, the Mexican National Council of Science and Technology, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.

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Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial.

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Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial.

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