What is insulin resistance?

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From the Guidelines

Insulin resistance is a condition where cells in the body don't respond properly to insulin, a hormone that regulates blood sugar, and it is a key feature of type 2 diabetes, which can be improved through lifestyle modifications and medications to reduce the risk of cardiovascular disease and other complications 1.

Definition and Description

Insulin resistance is characterized by decreased biological responses to insulin, making it difficult for cells to take up glucose from the bloodstream. This condition often develops gradually and is associated with excess weight, physical inactivity, poor diet, genetics, certain medications, and hormonal disorders.

Causes and Risk Factors

Several factors contribute to insulin resistance, including:

  • Excess weight, especially around the abdomen
  • Physical inactivity
  • Poor diet high in processed carbohydrates
  • Genetics
  • Certain medications
  • Hormonal disorders

Diagnosis and Management

Insulin resistance can be improved through lifestyle modifications such as:

  • Regular exercise
  • Weight loss
  • A balanced diet low in refined carbohydrates
  • Adequate sleep In some cases, medications like metformin may be prescribed to improve insulin sensitivity. Early detection and management of insulin resistance is important because it can help prevent progression to type 2 diabetes and reduce the risk of cardiovascular disease, as stated in the most recent guidelines 1.

Importance of Early Detection and Management

The duration of glycemic burden is a strong predictor of adverse outcomes, and there are effective interventions that prevent progression from prediabetes to diabetes, highlighting the importance of early detection and management of insulin resistance 1.

From the FDA Drug Label

ACTOS decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes. Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant patients. ACTOS enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin, and improves dysfunctional glucose homeostasis

Insulin resistance is a condition where the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. This leads to increased blood sugar levels, as the body is unable to effectively use insulin to absorb glucose from the bloodstream. Insulin resistance is often associated with type 2 diabetes and can be improved with medications such as pioglitazone, which enhances cellular responsiveness to insulin and increases insulin-dependent glucose disposal 2.

From the Research

Definition of Insulin Resistance

  • Insulin resistance, also known as impaired insulin sensitivity, is a condition where the body's cells do not respond effectively to insulin, leading to impaired glucose uptake and utilization 3, 4.
  • It is characterized by a decreased reaction of insulin signaling for glucose levels, resulting in increased plasma insulin levels, also known as hyperinsulinemia 3, 5.

Causes and Consequences of Insulin Resistance

  • Insulin resistance can be caused by various factors, including genetic abnormalities, fetal malnutrition, and increases in visceral adiposity 4.
  • It is often associated with increased triglyceride and decreased HDL-cholesterol concentrations, and increased small LDL particles, which can lead to atherosclerosis and cardiovascular disease 6, 5.
  • Insulin resistance can also lead to the development of type 2 diabetes, polycystic ovarian syndrome, and other metabolic disorders 3, 4.

Molecular Mechanisms of Insulin Resistance

  • Insulin resistance involves impaired insulin-dependent PI3K activation and downstream signaling in skeletal muscle, leading to reduced glucose transport and utilization 7.
  • The molecular basis of insulin resistance is complex and involves multiple signaling cascades, including the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K) pathways 7.

Health Implications of Insulin Resistance

  • Insulin resistance is a major risk factor for developing type 2 diabetes and cardiovascular disease, and is associated with increased morbidity and mortality 3, 5.
  • Hyperinsulinemia, a consequence of insulin resistance, can increase the risk of obesity, type 2 diabetes, and cardiovascular disease, and decrease health span and life expectancy 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Changes in Cells Associated with Insulin Resistance.

International journal of molecular sciences, 2024

Research

Insulin resistance: definition and consequences.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2001

Research

Molecular mechanism of insulin resistance in obesity and type 2 diabetes.

The Korean journal of internal medicine, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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