Insulin Resistance Assessment in Metabolic Disorders

Insulin resistance underlies the pathogenesis of metabolic disorders ranging from type 2 diabetes to cardiovascular disease and non-alcoholic fatty liver disease. Precise assessment of insulin sensitivity and β-cell function has traditionally relied on labour-intensive techniques such as the hyperinsulinaemic–euglycaemic clamp, the intravenous glucose tolerance test and the frequently sampled hyperglycaemic clamp. To broaden applicability in large cohorts or routine care, surrogate indices have been developed that exploit fasting or post-load measures of glucose, insulin or C-peptide. These include HOMA-IR, QUICKI, Matsuda and other ratio-based indices. Recent work has sought to refine these assessments by optimising test protocols, integrating high-throughput proteomic data and incorporating anthropometric and lipid variables into sex-specific prediction models. Together, these advances aim to improve risk stratification, enable early detection of insulin resistance and guide targeted interventions in diverse populations.

Research from Nature Portfolio

A recent analysis of the intravenous glucose tolerance test has demonstrated that standard weight-based glucose loads may introduce bias in the immediate glycaemic excursion used to calculate the acute insulin response. By analysing more than 3,800 patient and volunteer profiles and conducting in silico simulations, investigators showed that adjusting the glucose load according to body surface area yields an invariant initial glucose rise (ΔG₀) across subjects. This refinement minimises variation unrelated to β-cell function and restores the reliability of the acute insulin response metric, particularly in obese individuals whose mass-volume relationships differ from lean counterparts. These findings standardise IVGTT protocols and enhance the precision of insulin secretory assessments in research and clinical settings.

Insulin Resistance Assessment in Metabolic Disorders publication trend

The graph below shows the total number of articles in insulin resistance assessment in metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Hyperinsulinaemic–euglycaemic clamp: The gold-standard technique for quantifying whole-body insulin sensitivity by infusing insulin and adjusting glucose to maintain normoglycaemia.

Intravenous glucose tolerance test (IVGTT): A dynamic test in which a bolus of glucose is administered intravenously and serial insulin and glucose measurements assess β-cell responsiveness.

HOMA-IR: Homeostatic Model Assessment of Insulin Resistance; a fasting index calculated from glucose and insulin concentrations to estimate insulin sensitivity.

LASSO regression: A statistical method that applies regularisation to select a sparse set of predictive variables from high-dimensional data, such as proteomic panels.

Visceral adiposity index (VAI): A sex-specific mathematical model integrating waist circumference, BMI, triglycerides and HDL-cholesterol to approximate visceral fat function and cardiometabolic risk.

References

1. The importance of intravenous glucose tolerance test glucose stimulus for the evaluation of insulin secretion. Scientific Reports (2024).
2. Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts. Diabetologia (2023).
3. Sex-Specific Models to Predict Insulin Secretion and Sensitivity in Subjects with Overweight and Obesity. International Journal of Molecular Sciences (2023).
4. Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states. Cardiovascular Diabetology (2024).