Historical HbA1c values may explain the type 2 diabetes legacy effect: UKPDS 88
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OBJECTIVE: Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycemic legacy effects have not been explained. We examined their relationships with prior individual HbA1c values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy. RESEARCH DESIGN AND METHODS: Twenty-year ACM and MI hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. Impact of HbA1c values over time was analyzed by weighting them according to their influence on downstream ACM and MI risks. RESULTS: Hazard ratios for a one percentage unit higher HbA1c for ACM were 1.08 (95% CI 1.07–1.09), 1.18 (1.15–1.21), and 1.36 (1.30–1.42) at 5, 10, and 20 years, respectively, and for MI was 1.13 (1.11–1.15) at 5 years, increasing to 1.31 (1.25–1.36) at 20 years. Imposing a one percentage unit lower HbA1c from diagnosis generated an 18.8% (95% CI 21.1–16.0) ACM risk reduction 10–15 years later, whereas delaying this reduction until 10 years after diagnosis showed a sevenfold lower 2.7% (3.1–2.3) risk reduction. Corresponding MI risk reductions were 19.7% (22.4–16.5) when lowering HbA1c at diagnosis, and threefold lower 6.5% (7.4–5.3%) when imposed 10 years later. CONCLUSIONS: The glycemic legacy effects seen in type 2 diabetes are explained largely by historical HbA1c values having a greater impact than recent values on clinical outcomes. Early detection of diabetes and intensive glucose control from the time of diagnosis is essential to maximize reduction of the long-term risk of glycemic complications.
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Early intervention is essential for reducing microvascular complications.
“and early intervention is essential (13).”
From Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022) · cites this paper as [13]
The Introduction reports that intensive glycemic control lowered microvascular complications in people with type 2 diabetes, and Conclusions > Other Studies says minimizing hyperglycemia is particularly important for these complications (page numbers unavailable). The paper advocates early glucose optimization, but its analysis of the advantage of early over delayed control concerns mortality and myocardial infarction, not microvascular complications. It therefore does not establish that early intervention specifically is essential for reducing microvascular complications. (LLM, conf=0.83)
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- Authors
- Lind, M., Imberg, H., Coleman, R. L., Nerman, O., & Holman, R. R.
- Affiliations
- NU Hospital Group (SE)
- Chalmers University of Technology (SE)
- University of Oxford (GB)
- Corresponding author
- Lind, Marcus
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2021-07-08
- Volume
- 44
- Issue
- 10
- Pages
- 2231-2237
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC8740943
- OpenAlex
- W3180546758
- Cited by
- 128
- References
- 39
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 32 · 2023: 32 · 2022: 20 · 2021: 6
- FWCI
- 16.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Eli Lilly and Company
- AstraZeneca
- Intarcia Therapeutics
- Dexcom
- National Institute for Health and Care Research
- Chalmers Tekniska Högskola
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, HbA1c, all-cause mortality, myocardial infarction, glucose-lowering therapy, tight glycemic control, early detection of diabetes, long-term risk, UK Prospective Diabetes Study
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