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Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial
Open accessAbstract
OBJECTIVE: There is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. RESEARCH DESIGN AND METHODS: ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3–24 months after randomization. Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group. RESULTS: Among 4,399 patients in the intensive group, an increase in VVV of HbA1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05–2.55) and 3.31 (1.57–6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 [1.65–4.42]). HbA1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro- and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results. CONCLUSIONS: Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.
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“Other studies have demonstrated that fluctuations in blood glucose levels may contribute more to outcomes than constant high blood glucose concentrations.31–35”
From Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen (2020) · cites this paper as [33]
In the citing paper
“Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level.”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [21]
In the citing paper
“and that HbA1c variability was positively associated with risk of macrovascular events.21”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [21]
In the citing paper
“Increased HbA1c visit-to-visit variation was associated with increased risk of vascular events (p=0.01, HR 1.64, 1.05–2.55), macrovascular events (p=0.02), and mortality (p<0.001, HR 3.31, 1.57–6.98).”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [21]
In the citing paper
“FG visit-to-visit variation was associated with increased risk of CV events (p<0.001, HR 2.70, 1.65–4.42) and macrovascular (p=0.005) and microvascular (p<0.001) events.”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [21]
In the citing paper
“They found that fasting GV was associated with both macrovascular and microvascular events”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [21]
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Metadata
- Authors
- Hirakawa, Y., Arima, H., Zoungas, S., Ninomiya, T., Cooper, M., Hamet, P., Mancia, G., Poulter, N., Harrap, S., Woodward, M., & Chalmers, J.
- Affiliations
- The University of Sydney (AU)
- Baker Heart and Diabetes Institute (AU)
- Centre Hospitalier de l’Université de Montréal (CA)
- IRCCS Istituto Auxologico Italiano (IT)
- St Mary's Hospital (GB)
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Chalmers, John
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2014-07-12
- Volume
- 37
- Issue
- 8
- Pages
- 2359-2365
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2122273643
- Cited by
- 363
- References
- 36
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 32 · 2023: 33 · 2022: 44 · 2021: 47 · 2020: 51 · 2019: 35 · 2018: 25 · 2017: 25 · 2016: 18 · 2015: 18 · 2014: 5
- FWCI
- 17.69
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, HbA1c variability, macrovascular events, all-cause mortality, tight glycemic control, blood pressure reduction, ADVANCE trial
- MeSH terms
- Aged, Aged, 80 and over, Blood Glucose, Cause of Death, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Drug Combinations, Female, Follow-Up Studies, Gliclazide, Humans, Hypoglycemic Agents, Indapamide, Male, Middle Aged, Office Visits, Risk Factors, Perindopril
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