Measuring Insulin Resistance in Humans

Abstract

<b><i>Background:</i></b> Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use. <b><i>Summary:</i></b> In this historical perspective, we explore the evolution of the term “insulin resistance” and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. <b><i>Key Message:</i></b> Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.

Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance

“…HOMA-IR does correlate with these tests, and remains a commonly used, pragmatic surrogate in clinical trials. 22 In the initial investigations of pioglitazone as diabetes medication, the lower doses of 15 and 30 mg were shown to be less efficacious in reducing fasting plasma glucose and HbA1c than the eventually maximum approved dose of 45 mg. 23 This led to the recommendation in the package label to advance the dose to 45 mg in those not responding adequately to lower doses from the standpoint of glycaemia. Weight gain was also dose-related in these studies.…”

“…In a large clinical trial such as IRIS, testing beyond fasting labs would introduce significant cost and complexity. HOMA‐IR does correlate with these tests, and remains a commonly used, pragmatic surrogate in clinical trials 22 …”

MALDI-TOF MS Characterisation of the Serum Proteomic Profile in Insulin-Resistant Normal-Weight Individuals

“…This study aimed to assess the protein-peptide profile among normal-weight patients with IR to understand the mechanisms and define new risk biomarkers. Currently, the diagnostic criteria for IR are based on biochemical parameters such as glucose and insulin level [9]. We suggest that exploring the molecular mechanism of IR development will contribute to its early prevention, while preventing the development of metabolic syndrome, cardiovascular diseases, and the associated complications.…”

“…However, in usual clinical practice involving indirect methods, the basis of fasting glucose and insulinemia are used, for example, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The HOMA-IR values may be influenced by many factors; therefore, it is difficult to determine an appropriate cut-off point [9]. For the Polish population with normal glucose tolerance and a body mass index (BMI) <25 kg/m 2 , the value was determined to be above 2.1 [10].…”

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

“…In the adipose tissue, insulin inhibits lipolytic pathways and induces glucose uptake and lipogenesis ( 84 , 87 , 88 ). Thus, insulin resistance is a pathophysiological condition characterized by a reduced insulin response by peripherical tissues, contributing to hyperglycemia, dyslipidemia, hyperinsulinemia and other alterations ( 2 , 89 ).…”