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

Bethany Warren, James S. Pankow, Kunihiro Matsushita, Naresh M. Punjabi, Natalie R. Daya, Morgan Grams, Mark Woodward, Elizabeth Selvin

Research output: Contribution to journalArticle

Abstract

Background 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. Methods 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). Findings 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. Interpretation 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. Funding US National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)34-42
Number of pages9
JournalThe Lancet Diabetes and Endocrinology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Prediabetic State
Glucose
Fasting
Chronic Renal Insufficiency
Atherosclerosis
Mortality
Peripheral Arterial Disease
Cardiovascular Diseases

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{5de5f43cab734d93bf946da3aac15561,
title = "Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study",
abstract = "Background 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. Methods 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). Findings 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. Interpretation 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. Funding US National Institutes of Health.",
author = "Bethany Warren and Pankow, {James S.} and Kunihiro Matsushita and Punjabi, {Naresh M.} and Daya, {Natalie R.} and Morgan Grams and Mark Woodward and Elizabeth Selvin",
year = "2017",
month = "1",
doi = "10.1016/S2213-8587(16)30321-7",
volume = "5",
pages = "34--42",
journal = "The Lancet Diabetes and Endocrinology",
issn = "2213-8587",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Comparative prognostic performance of definitions of prediabetes

T2 - The Lancet Diabetes and Endocrinology

AU - Warren,Bethany

AU - Pankow,James S.

AU - Matsushita,Kunihiro

AU - Punjabi,Naresh M.

AU - Daya,Natalie R.

AU - Grams,Morgan

AU - Woodward,Mark

AU - Selvin,Elizabeth

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background 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. Methods 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). Findings 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. Interpretation 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. Funding US National Institutes of Health.

AB - Background 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. Methods 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). Findings 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. Interpretation 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. Funding US National Institutes of Health.

UR - http://www.scopus.com/inward/record.url?scp=85006766654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006766654&partnerID=8YFLogxK

U2 - 10.1016/S2213-8587(16)30321-7

DO - 10.1016/S2213-8587(16)30321-7

M3 - Article

VL - 5

SP - 34

EP - 42

JO - The Lancet Diabetes and Endocrinology

JF - The Lancet Diabetes and Endocrinology

SN - 2213-8587

IS - 1

ER -