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Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

ABSTRACT: No consensus on definitions of prediabetes exists among international organisations. Analysis of associations with different definitions and clinical complications can inform the comparative value of different prediabetes definitions. We compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA1c, and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the associations of definitions with outcomes to provide a comparison of different definitions.We did a prospective cohort study of participants in the ARIC study who did not have diagnosed diabetes and who attended visit 2 (1990-92; n=10?844) and who attended visit 4 (1996-98; n=7194). ARIC participants were enrolled from four communities across the USA. Fasting glucose concentration and HbA1c were measured at visit 2 and fasting glucose concentration and 2 h glucose concentration were measured at visit 4. We compared prediabetes definitions based on fasting glucose concentration (American Diabetes Association [ADA] fasting glucose concentration cutoff 5·6-6·9 mmol/L and WHO fasting glucose concentration cutoff 6·1-6·9 mmol/L), HbA1c (ADA HbA1c cutoff 5·7-6·4% [39-46 mmol/mol] and International Expert Committee [IEC] HbA1c cutoff 6·0-6·4% [42-46 mmol/mol]), and 2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7·8-11·0 mmol/L).Prediabetes defined using the ADA fasting glucose concentration cutoff (prevalence 4112 [38%] of 10?844 people; 95% CI 37·0-38·8) was the most sensitive for major clinical outcomes, whereas using the ADA HbA1c cutoff (2027 [19%] of 10?884 people; 18·0-19·4) and IEC HbA1c cutoff (970 [9%] of 10?844 people; 8·4-9·5), and the WHO fasting glucose concentration cutoff (1213 [11%] of 10?844 people; 10·6-11·8) were more specific. After demographic adjustment, HbA1c-based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality than did fasting glucose concentration-based definitions (all p<0·05). The C-statistic for incident chronic kidney disease was 0·636 for ADA fasting glucose concentration clinical categories and 0·640 for ADA HbA1c clinical categories (difference -0·005, 95% CI -0·008 to -0·001). The C-statistics were 0·662 for ADA fasting glucose clinical concentration categories and 0·672 for ADA HbA1c clinical categories for atherosclerotic cardiovascular disease, 0·701 for ADA fasting glucose concentration clinical categories and 0·722 for ADA HbA1c clinical categories for peripheral arterial disease, and 0·683 for ADA fasting glucose concentration clinical categories and 0·688 for ADA HbA1c clinical categories for all-cause mortality. Prediabetes defined using the ADA HbA1c cutoff showed a significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared with prediabetes defined with glucose-based definitions. ADA fasting glucose concentration clinical categories, WHO fasting glucose concentration clinical categories, and ADA and WHO 2 h glucose concentrations clinical categories were not significantly different in terms of risk discrimination for chronic kidney disease, cardiovascular outcomes, or mortality outcomes.Our results suggest that prediabetes definitions using HbA1c were more specific and provided modest improvements in risk discrimination for clinical complications. The definition of prediabetes using the ADA fasting glucose concentration cutoff was more sensitive overall.US National Institutes of Health.

SUBMITTER: Warren B

PROVIDER: S-EPMC5183486 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

Warren Bethany B Pankow James S JS Matsushita Kunihiro K Punjabi Naresh M NM Daya Natalie R NR Grams Morgan M Woodward Mark M Selvin Elizabeth E

The lancet. Diabetes & endocrinology 20161116 1

<h4>Background</h4>No consensus on definitions of prediabetes exists among international organisations. Analysis of associations with different definitions and clinical complications can inform the comparative value of different prediabetes definitions. We compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA<sub>1c</sub>, and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis R ...[more]

PMID: 27863979

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Project description:ObjectiveTo examine the magnitude and types of hospitalizations among persons with prediabetes, undiagnosed diabetes, and diagnosed diabetes.Research design and methodsThis study included 13,522 participants in the Atherosclerosis Risk in Communities (ARIC) study (mean age 57 years, 56% female, 24% black, 18% with prediabetes, 4% with undiagnosed diabetes, 9% with diagnosed diabetes) with follow-up in 1990-2011 for hospitalizations. Participants were categorized by diabetes/HbA1c status: without diagnosed diabetes, HbA1c <5.7% (reference); prediabetes, 5.7 to <6.5%; undiagnosed diabetes, ?6.5%; and diagnosed diabetes, <7.0 and ?7.0%.ResultsDemographic adjusted rates per 1,000 person-years of all-cause hospitalizations were higher with increasing diabetes/HbA1c category (Ptrend < 0.001). Persons with diagnosed diabetes and HbA1c ?7.0% had the highest rates of hospitalization (3.1 times higher than those without a history of diagnosed diabetes, HbA1c <5.7%, and 1.5 times higher than those with diagnosed diabetes, HbA1c <7.0%, P < 0.001 for both comparisons). Persons with undiagnosed diabetes had 1.6 times higher rates of hospitalization and those with prediabetes had 1.3 times higher rates of hospitalization than those without diabetes and HbA1c <5.7% (P < 0.001 for both comparisons). Rates of hospitalization by diabetes/HbA1c category were different by race (Pinteraction = 0.011) and by sex (Pinteraction = 0.020). There were significantly excess rates of hospitalizations due to cardiovascular, endocrine, respiratory, gastrointestinal, iatrogenic/injury, neoplasm, genitourinary, neurologic, and infection causes among those with diagnosed diabetes compared with those without a history of diagnosed diabetes (all P < 0.05).ConclusionsPersons with diagnosed diabetes, undiagnosed diabetes, and prediabetes are at a significantly elevated risk of hospitalization compared with those without diabetes. Substantial excess rates of hospitalizations in persons with diagnosed diabetes were for endocrine, infection, and iatrogenic/injury causes, which may be preventable with improved diabetes care.

Project description:ObjectivesThe goal of the study was to determine an association of cardiac ventricular substrate with thrombotic stroke (TS), cardioembolic stroke (ES) and intracerebral haemorrhage (ICH).DesignProspective cohort study.SettingThe Atherosclerosis Risk in Communities (ARIC) study in 1987-1989 enrolled adults (45-64 years), selected as a probability sample from four US communities (Minneapolis, Minnesota; Washington, Maryland; Forsyth, North Carolina; Jackson, Mississippi). Visit 2 was in 1990-1992, visit 3 in 1993-1995, visit 4 in 1996-1998 and visit 5 in 2011-2013.ParticipantsARIC participants with analysable ECGs and no history of stroke were included (n=14 479; age 54±6 y; 55% female; 24% black). Ventricular substrate was characterised by cardiac memory, spatial QRS-T angle (QRS-Ta), sum absolute QRST integral (SAIQRST), spatial ventricular gradient magnitude (SVGmag), premature ventricular contractions (PVCs) and tachycardia-dependent intermittent bundle branch block (TD-IBBB) on 12-lead ECG at visits 1-5.OutcomeAdjudicated TS included a first definite or probable thrombotic cerebral infarction, ES-a first definite or probable non-carotid cardioembolic brain infarction. Definite ICH was included if it was the only stroke event.ResultsOver a median 24.5 years follow-up, there were 899 TS, 400 ES and 120 ICH events. Cox proportional hazard risk models were adjusted for demographics, cardiovascular disease, risk factors, atrial fibrillation, atrial substrate and left ventricular hypertrophy. After adjustment, PVCs (HR 1.72; 95% CI 1.02 to 2.92), QRS-Ta (HR 1.15; 95% CI 1.03 to 1.28), SAIQRST (HR 1.20; 95% CI 1.07 to 1.34) and time-updated SVGmag (HR 1.19; 95% CI 1.08 to 1.32) associated with ES. Similarly, PVCs (HR 1.53; 95% CI 1.03 to 2.26), QRS-Ta (HR 1.08; 95% CI 1.01 to 1.16), SAIQRST (HR 1.07; 95% CI 1.01 to 1.14) and time-updated SVGmag (HR 1.11; 95% CI 1.04 to 1.19) associated with TS. TD-IBBB (HR 3.28; 95% CI 1.03 to 10.46) and time-updated SVGmag (HR 1.23; 95% CI 1.03 to 1.47) were associated with ICH.ConclusionsPVC burden (reflected by cardiac memory) is associated with ischaemic stroke. Transient cardiac memory (likely through TD-IBBB) precedes ICH.

Project description:ObjectiveTo examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.Research design and methodsCross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ?6.5%] <7.0% vs. ?7.0%), with further stratification by diabetes duration (<10 vs. ?10 years).ResultsIn adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ?7.0% had smaller total brain volume (? -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ?7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (?10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).ConclusionsMore-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

Dataset Information

Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

Publications

Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

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