Visit-to-visit HbA1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes

Sheyu Li, Imola Nemeth, Louise Donnelly, Simona Hapca, Kaixin Zhou, Ewan Pearson (Lead / Corresponding author)

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Abstract

Objective: To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes.

Research Design and Methods: This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information-Diabetes Collaboration (SCIDC), who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes being evaluated. We used the previously reported HbA1c variability score (HVS) calculated as the percentage of the number of changes in HbA1c over 0.5% (5.5 mmol/mol) among all HbA1c measurement within an individual. The association between HVS and ten outcomes was assessed using Cox proportional-hazards models.

Results: We included 13,111 to 19,883 patients in the analyses of each outcome. The patients with HVS over 60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95% confidence intervals [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61~3.53] for major adverse cardiovascular events [MACE]; 2.4 [1.72~3.33] for all-cause mortality; 2.4 [1.13~5.11] for atherosclerotic cardiovascular [ASCV] death; 2.63 [1.81~3.84] for coronary artery disease; 2.04 [1.12~3.73] for ischemic stroke; 3.23 [1.76~5.93] for heart failure; 7.4 [3.84~14.27] for diabetic retinopathy; 3.07 [2.23~4.22] for diabetic peripheral neuropathy; 5.24 [2.61~10.49] for diabetic foot ulcer; 3.49 [2.47~4.95] for the newonset chronic kidney disease). Four sensitivity analyses, including adjustment for timeweighted average HbA1c confirmed the robustness of the results.

Conclusions: Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events and microvascular complication of diabetes independently of high HbA1c.
Original languageEnglish
Pages (from-to)426-432
Number of pages7
JournalDiabetes Care
Volume42
Issue number11
Early online date14 Nov 2019
DOIs
Publication statusPublished - 20 Jan 2020

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Type 2 Diabetes Mellitus
Cardiovascular Diseases
Diabetic Foot
Mortality
Diabetic Neuropathies
Peripheral Nervous System Diseases
Diabetic Retinopathy
Diabetes Complications
Chronic Renal Insufficiency
Proportional Hazards Models
Coronary Artery Disease
Cohort Studies
Research Design
Heart Failure
Retrospective Studies
Stroke
Confidence Intervals

Keywords

  • HbA1c variability
  • cardiovascular event
  • all-cause mortality
  • heart failure
  • diabetic retinopathy
  • diabetic peripheral neuropathy
  • diabetic foot ulcer
  • chronic kidney disease

Cite this

@article{22d2c9e2b5c349869cb6bda465085caf,
title = "Visit-to-visit HbA1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes",
abstract = "Objective: To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes.Research Design and Methods: This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information-Diabetes Collaboration (SCIDC), who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes being evaluated. We used the previously reported HbA1c variability score (HVS) calculated as the percentage of the number of changes in HbA1c over 0.5{\%} (5.5 mmol/mol) among all HbA1c measurement within an individual. The association between HVS and ten outcomes was assessed using Cox proportional-hazards models.Results: We included 13,111 to 19,883 patients in the analyses of each outcome. The patients with HVS over 60{\%} were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95{\%} confidence intervals [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61~3.53] for major adverse cardiovascular events [MACE]; 2.4 [1.72~3.33] for all-cause mortality; 2.4 [1.13~5.11] for atherosclerotic cardiovascular [ASCV] death; 2.63 [1.81~3.84] for coronary artery disease; 2.04 [1.12~3.73] for ischemic stroke; 3.23 [1.76~5.93] for heart failure; 7.4 [3.84~14.27] for diabetic retinopathy; 3.07 [2.23~4.22] for diabetic peripheral neuropathy; 5.24 [2.61~10.49] for diabetic foot ulcer; 3.49 [2.47~4.95] for the newonset chronic kidney disease). Four sensitivity analyses, including adjustment for timeweighted average HbA1c confirmed the robustness of the results.Conclusions: Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events and microvascular complication of diabetes independently of high HbA1c.",
keywords = "HbA1c variability, cardiovascular event, all-cause mortality, heart failure, diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot ulcer, chronic kidney disease",
author = "Sheyu Li and Imola Nemeth and Louise Donnelly and Simona Hapca and Kaixin Zhou and Ewan Pearson",
year = "2020",
month = "1",
day = "20",
doi = "10.2337/dc19-0823",
language = "English",
volume = "42",
pages = "426--432",
journal = "Diabetes Care",
issn = "0149-5992",
publisher = "American Diabetes Association",
number = "11",

}

TY - JOUR

T1 - Visit-to-visit HbA1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes

AU - Li, Sheyu

AU - Nemeth, Imola

AU - Donnelly, Louise

AU - Hapca, Simona

AU - Zhou, Kaixin

AU - Pearson, Ewan

PY - 2020/1/20

Y1 - 2020/1/20

N2 - Objective: To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes.Research Design and Methods: This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information-Diabetes Collaboration (SCIDC), who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes being evaluated. We used the previously reported HbA1c variability score (HVS) calculated as the percentage of the number of changes in HbA1c over 0.5% (5.5 mmol/mol) among all HbA1c measurement within an individual. The association between HVS and ten outcomes was assessed using Cox proportional-hazards models.Results: We included 13,111 to 19,883 patients in the analyses of each outcome. The patients with HVS over 60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95% confidence intervals [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61~3.53] for major adverse cardiovascular events [MACE]; 2.4 [1.72~3.33] for all-cause mortality; 2.4 [1.13~5.11] for atherosclerotic cardiovascular [ASCV] death; 2.63 [1.81~3.84] for coronary artery disease; 2.04 [1.12~3.73] for ischemic stroke; 3.23 [1.76~5.93] for heart failure; 7.4 [3.84~14.27] for diabetic retinopathy; 3.07 [2.23~4.22] for diabetic peripheral neuropathy; 5.24 [2.61~10.49] for diabetic foot ulcer; 3.49 [2.47~4.95] for the newonset chronic kidney disease). Four sensitivity analyses, including adjustment for timeweighted average HbA1c confirmed the robustness of the results.Conclusions: Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events and microvascular complication of diabetes independently of high HbA1c.

AB - Objective: To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes.Research Design and Methods: This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information-Diabetes Collaboration (SCIDC), who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes being evaluated. We used the previously reported HbA1c variability score (HVS) calculated as the percentage of the number of changes in HbA1c over 0.5% (5.5 mmol/mol) among all HbA1c measurement within an individual. The association between HVS and ten outcomes was assessed using Cox proportional-hazards models.Results: We included 13,111 to 19,883 patients in the analyses of each outcome. The patients with HVS over 60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95% confidence intervals [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61~3.53] for major adverse cardiovascular events [MACE]; 2.4 [1.72~3.33] for all-cause mortality; 2.4 [1.13~5.11] for atherosclerotic cardiovascular [ASCV] death; 2.63 [1.81~3.84] for coronary artery disease; 2.04 [1.12~3.73] for ischemic stroke; 3.23 [1.76~5.93] for heart failure; 7.4 [3.84~14.27] for diabetic retinopathy; 3.07 [2.23~4.22] for diabetic peripheral neuropathy; 5.24 [2.61~10.49] for diabetic foot ulcer; 3.49 [2.47~4.95] for the newonset chronic kidney disease). Four sensitivity analyses, including adjustment for timeweighted average HbA1c confirmed the robustness of the results.Conclusions: Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events and microvascular complication of diabetes independently of high HbA1c.

KW - HbA1c variability

KW - cardiovascular event

KW - all-cause mortality

KW - heart failure

KW - diabetic retinopathy

KW - diabetic peripheral neuropathy

KW - diabetic foot ulcer

KW - chronic kidney disease

U2 - 10.2337/dc19-0823

DO - 10.2337/dc19-0823

M3 - Article

C2 - 31727686

VL - 42

SP - 426

EP - 432

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 11

ER -