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Insulin resistance serves as a sentinel biomarker for progression toward multiple cardiometabolic diseasesInsulin Resistance May Signal Early Risk for Chronic Diseases

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Key Takeaway
Note that insulin resistance serves as a sentinel biomarker for early progression toward several cardiometabolic diseases.

This guideline provides a narrative review of insulin resistance (IR) as a sentinel biomarker for identifying early progression toward type 2 diabetes, cardiovascular disease, heart failure, chronic kidney disease, and liver disease. The authors synthesize the utility of various diagnostic tools, including the hyperinsulinemic-euglycemic clamp, HOMA-IR, and the triglyceride-glucose (TyG) index.

A primary finding is that IR serves as a significant early indicator of disease progression. However, the authors note that no universally validated IR index currently exists for population-wide screening. Consequently, they recommend targeted assessment for individuals with specific risk factors, such as excess adiposity, family history of type 2 diabetes, or early metabolic risk markers.

Limitations noted include the lack of outcome-driven trials to determine if IR-guided interventions improve the cardiometabolic continuum compared with standard glycemic thresholds. The clinical relevance lies in using targeted IR assessment to identify patients who may benefit from earlier monitoring and lifestyle interventions at the CKM stage 0-1. The evidence for IR as a sentinel biomarker is presented as an association rather than a proven causal link.

How this fits prior evidence

This guideline addresses a gap in the management of metabolic risk. While previous coverage noted that gut-derived metabolites and microbiota may influence ocular-surface health in Type 2 Diabetes, this guideline focuses on the early identification of the cardiometabolic continuum. It specifically addresses the role of insulin resistance as a sentinel biomarker for progression toward conditions like heart failure and chronic kidney disease, which are often associated with metabolic dysfunction.

Insulin resistance is a condition where the body does not use insulin effectively. This review suggests that insulin resistance can serve as a sentinel biomarker. This means it may be an early indicator of progression toward several conditions, including type 2 diabetes, heart failure, and chronic kidney disease.

Doctors can use different tools to measure insulin resistance, such as the HOMA-IR or the triglyceride-glucose index. However, there is currently no single, universally validated test for screening the general public. Instead, experts recommend targeted testing for specific groups, such as people with a family history of diabetes or other early metabolic risk factors.

Because there is no universal test, it is important to note that these findings are based on a narrative review. More research is needed to see if using insulin resistance markers specifically improves health outcomes compared to standard blood sugar checks. Talk to your doctor about your specific risk factors and how these markers might apply to your health.

What this means for you:
Insulin resistance may be an early indicator of several chronic diseases, but it is not yet a standard screening tool.

Common questions

What diseases is insulin resistance linked to?

Insulin resistance is linked to the progression of several conditions. These include type 2 diabetes, cardiovascular disease, heart failure, chronic kidney disease, and liver disease. It can act as an early indicator for these conditions before they become more advanced.

Is there a standard test to check for insulin resistance?

There is no single, universally validated index for screening the general population. However, specific tools like the HOMA-IR and the triglyceride-glucose (TyG) index are used to measure insulin resistance in targeted assessments for people at risk.

Who should get tested for insulin resistance?

Because there is no universal screening tool, testing is currently recommended for specific groups. This includes individuals with excess adiposity, a family history of type 2 diabetes, or other early metabolic risk markers.

Study Details

Study typeGuideline
EvidenceLevel 5
PublishedNov 2026
View Original Abstract ↓
Insulin resistance (IR) is often seen as a curiosity associated with prediabetes and polyendocrine metabolic ovarian syndrome (PMOS, formerly PCOS). However, it is a significant early indicator of progression towards type 2 diabetes, cardiovascular disease, heart failure, chronic kidney disease, and liver disease. This review covers the pathophysiology of IR in the vascular, hepatic, renal, and cardiac systems, its epidemiological impact, and diagnostic tools, including the hyperinsulinemic-euglycemic clamp and accessible indices like HOMA-IR and the triglyceride-glucose (TyG) index. We reviewed the 2023 and 2026 American Heart Association clinical guideline framework for cardiovascular-kidney-metabolic (CKM) syndrome, which highlights insulin resistance and dysfunctional adiposity as early factors in a multi-organ continuum that precedes abnormal conventional risk factors. When assessing routine IR testing in preventive practice, it is crucial to consider diagnostic accuracy, costs, implementation feasibility, and outcomes from prevention trials. These components are essential for evaluating the effectiveness and value of testing in healthcare. While no universally validated IR index exists for population-wide screening, targeted assessment is recommended for individuals with excess adiposity, a family history of type 2 diabetes, or early metabolic risk markers. This research-oriented, risk-stratified approach is preferable to a general recommendation. It may help identify individuals who would benefit from closer monitoring and lifestyle interventions at CKM stage 0-1, pending data from outcome-driven trials. In conclusion, key research priorities include standardizing cutoffs across populations and designing outcome trials to determine whether IR-guided interventions improve the cardiometabolic continuum compared with those based solely on glycemic thresholds.
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