Use of alternative thresholds defining insulin resistance to predict incident type 2 diabetes mellitus and cardiovascular disease
Open accessAbstract
Background— The performance characteristics of surrogate insulin resistance (IR) measures, commonly defined as the top 25% of the measure’s distribution, used to predict incident type 2 diabetes mellitus (DM) and cardiovascular disease (CVD) have not been critically assessed in community samples. Methods and Results— Baseline IR was assessed among 2720 Framingham Offspring Study subjects by use of fasting insulin, the homeostasis model assessment of IR (HOMA-IR), and the reciprocal of the Gutt insulin sensitivity index, with 7- to 11-year follow-up for incident DM (130 cases) or CVD (235). Area under the receiver operating characteristic curve, sensitivity, specificity, and positive likelihood ratio were estimated at 12 diagnostic thresholds (quantiles) of IR measures. Positive likelihood ratios for DM or CVD increased in relation to IR quantiles; risk gradients were greater for DM than for CVD, with no 9th to 10th quantile (76th centile) threshold effects. IR had better discrimination for incident DM than for CVD (HOMA-IR area under the receiver operating characteristic curve: DM 0.80 versus CVD 0.63). The HOMA-IR ≥76th centile threshold was associated with these test-performance values: sensitivity (DM 68%, CVD 40%), specificity (DM 77%, CVD 76%), and positive likelihood ratio (DM 3.0, CVD 1.7). The HOMA-IR threshold that yielded >90% sensitivity was the 6th quantile for DM prediction and the 3rd quantile for CVD. Compared with the ≥76th centile threshold, these alternative thresholds yielded lower specificity (DM 43%, CVD 17%) and positive likelihood ratios (DM 1.6, CVD 1.1). Conclusions— Surrogate IR measures have modest performance at the 76th centile, with no threshold effects. Different centile thresholds might be selected to optimize sensitivity versus specificity for DM versus CVD prediction if surrogate IR measures are used for risk prediction.
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Measures of insulin resistance predicted risk of diabetes or CAD only moderately, with no threshold effects.
“and that measures of insulin resistance (which include insulin measurements) predicted risk of diabetes or CAD only moderately, with no threshold effects (509).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [509]
The Conclusions report modest predictive performance and no apparent threshold effects for surrogate measures of insulin resistance. However, the paper assesses diabetes and cardiovascular disease (CVD), not coronary artery disease (CAD) separately; the DM and CVD Assessment section defines CVD to include noncoronary events such as stroke and heart failure. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMeasures of insulin resistance (including insulin measurements) predict the risk of diabetes or coronary artery disease only moderately well, with no threshold effects.
“More-recent analyses suggest that insulin values do not add significantly to diabetes risk prediction carried out with more traditional clinical and laboratory measurements (366) and that measures of insulin resistance (that include insulin measurements) predict the risk of diabetes or coronary artery disease only moderately well, with no threshold effects (367).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [367]
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Self-citation
- Authors
- Rutter, M. K., Wilson, P. W. F., Sullivan, L. M., Fox, C. S., D’Agostino, R. B., & Meigs, J. B.
- Affiliations
- Boston University (US)
- ORCID
- Venue
- Circulation
- Published
- 2008-02-26
- Volume
- 117
- Issue
- 8
- Pages
- 1003-1009
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2519012
- OpenAlex
- W2010972074
- Semantic Scholar
- 96727d563dd73688f7777e3cb0fa9a01babdc756
- Cited by
- 64
- References
- 22
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 9 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (N01‐HC25195, N01-HC-025195)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK080140)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin resistance, type 2 diabetes, cardiovascular disease, HOMA-IR, fasting insulin, diagnostic thresholds, risk prediction, Framingham Offspring Study, sensitivity and specificity, positive likelihood ratio
- MeSH terms
- Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Fasting, Female, Homeostasis, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk Factors, Sensitivity and Specificity, Incidence
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