Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities?
Open accessAbstract
This review critically appraises studies examining the association of novel factors with diabetes. We show that many of the most studied novel and apparently 'independent' risk factors are correlated with each other by virtue of their common origins or pathways, and that residual confounding is likely. Available studies also have other limitations, including differences in methodology or inadequate statistical analyses. Furthermore, although most relevant work in this area has focused on improving our understanding of the pathogenesis of diabetes, association studies in isolation cannot prove causality; intervention studies with specific agents (if available) are required, and genetic studies may help. With respect to the potential value of novel risk factors for diabetes risk prediction, we illustrate why this work is very much in its infancy and currently not guaranteed to reach clinical utility. Indeed, the existence of several more easily measured powerful predictors of diabetes, suggests that the additional value of novel markers may be limited. Nevertheless, several suggestions to improve relevant research are given. Finally, we show that several risk factors for diabetes are only weakly associated with the risk of incident vascular events, an observation that highlights the limitations of attempting to devise unified criteria (e.g. metabolic syndrome) to identify individuals at risk of both CHD and diabetes.
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HOMA-IR reflects insulin resistance and ectopic and total fat.
“insulin resistance and ectopic and total fat (HOMA-IR). 2,29-31”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [31]
The Adipose-derived predictors section calls HOMA-IR an index of insulin resistance. The paper discusses ectopic hepatic fat separately, using fasting glucose, triacylglycerol and ALT as indicators; the passages do not establish that HOMA-IR reflects ectopic or total fat. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredGGT reflects liver adiposity in addition to alcohol intake signals.
“liver adiposity in addi tion to alcohol intake signals (GGT)”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [31]
The review’s biomarker table (PAI-1 section; page unavailable) groups GGT with liver-derived enzymes and lists liver fat among their positive correlates, supporting the liver-adiposity part. It lists alcohol intake as a factor adjusted for in the diabetes analysis, but does not say that GGT signals alcohol intake. (LLM, conf=0.78)
Experimental — accuracy not yet measuredLeptin reflects total obesity or percent fat mass.
“consistent with their roles as biomarkers reflecting total obesity or percent fat mass (leptin)”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [31]
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- Authors
- Sattar, N., Wannamethee, S. G., & Forouhi, N. G.
- Affiliations
- University of Glasgow (GB)
- The Royal Free Hospital (GB)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Sattar, N.
- Venue
- Diabetologia
- Published
- 2008-04-08
- Volume
- 51
- Issue
- 6
- Pages
- 926-940
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2098783546
- Cited by
- 143
- References
- 95
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 11 · 2015: 12 · 2014: 6 · 2013: 16 · 2012: 8
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation
- Diabetes UK
- 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
- type 2 diabetes, novel risk factors, diabetes pathogenesis, residual confounding, causality, genetic research, diabetes risk prediction, metabolic syndrome, cardiovascular risk, coronary artery disease, vascular events
- MeSH terms
- Alanine Transaminase, Diabetes Mellitus, Type 2, Endothelium, Vascular, gamma-Glutamyltransferase, Humans, Inflammation, Predictive Value of Tests, Risk, Risk Factors, Biomarkers, Adiponectin
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