Insulin Sensitivity Markers – Meaning and Values

What Are Insulin Sensitivity Markers?

Insulin sensitivity markers are biological measurements – known as biomarkers – that describe how effectively the cells of the body respond to the hormone insulin. Insulin is produced in the pancreas and plays a central role in enabling glucose (sugar) from the blood to enter the body´s cells for energy use. When insulin sensitivity is reduced, this is referred to as insulin resistance – a key risk factor for type 2 diabetes, cardiovascular disease, and metabolic syndrome.

Why Are Insulin Sensitivity Markers Important?

Declining insulin sensitivity often develops gradually and remains without symptoms for a long time. By regularly measuring appropriate markers, high-risk individuals can be identified early and targeted interventions can be initiated before overt diabetes develops.

• Early detection of insulin resistance and prediabetes
• Risk stratification for type 2 diabetes and cardiovascular disease
• Monitoring of existing insulin resistance or diabetes progression
• Evaluating the response to treatment (e.g., lifestyle changes or medication)

Key Insulin Sensitivity Markers at a Glance

Fasting Plasma Glucose (FPG)

The fasting plasma glucose test is the simplest and most commonly used screening parameter. A value between 100 and 125 mg/dL (5.6–6.9 mmol/L) indicates prediabetes, while values of 126 mg/dL (7.0 mmol/L) or higher are diagnostic for diabetes mellitus.

Fasting Insulin and HOMA-IR

The HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a calculated index derived from fasting blood glucose and fasting insulin levels:
HOMA-IR = (fasting glucose [mmol/L] × fasting insulin [µU/mL]) ÷ 22.5
Values above 2.0–2.5 are generally considered indicative of clinically relevant insulin resistance in most guidelines.

HbA1c (Glycated Haemoglobin)

The HbA1c value reflects the average blood glucose level over the past two to three months. It is a well-established marker of long-term glycaemic control. Values between 5.7% and 6.4% (39–47 mmol/mol) are considered the prediabetes range.

Oral Glucose Tolerance Test (OGTT)

In the oral glucose tolerance test, blood glucose is measured two hours after the patient drinks a defined sugar solution (75 g glucose). This test assesses the body´s ability to process glucose efficiently and is considered the gold standard for diagnosing impaired glucose tolerance.

Fasting Insulin and Insulin Secretion

Elevated fasting insulin levels may indicate compensatory overproduction of insulin that occurs when cells are less responsive to it. This is often an early sign of insulin resistance, appearing even before blood glucose levels begin to rise.

HOMA-Beta (Beta Cell Function)

HOMA-Beta is a complementary index used to assess the function of the insulin-producing beta cells of the pancreas. It provides a more nuanced picture: is insulin resistance present, or is insulin production already declining?

Triglycerides and HDL Cholesterol

Elevated triglyceride levels and low HDL cholesterol (the so-called good cholesterol) are indirect markers of impaired insulin sensitivity and are commonly found in individuals with metabolic syndrome. The triglyceride-to-HDL ratio is a practical surrogate marker for insulin resistance.

Adiponectin

Adiponectin is a hormone secreted by adipose (fat) tissue that promotes insulin sensitivity. Low adiponectin levels are associated with insulin resistance, type 2 diabetes, and cardiovascular disease. Measurement of adiponectin is increasingly being used as a supplementary marker in clinical assessments.

C-Peptide

C-peptide is a by-product of insulin synthesis and allows a reliable evaluation of the body´s own insulin production. It is used to differentiate between type 1 and type 2 diabetes and to assess beta cell function over time.

Factors Influencing Insulin Sensitivity

Insulin sensitivity is influenced by numerous factors:

• Body weight and body fat: Overweight, particularly visceral abdominal fat, is the strongest risk factor for insulin resistance.
• Physical activity: Regular exercise significantly increases insulin sensitivity.
• Diet: A high-fibre, low-sugar diet supports healthy insulin sensitivity.
• Sleep: Sleep deprivation and poor sleep quality reduce insulin sensitivity.
• Stress: Chronic stress elevates cortisol, which inhibits insulin action.
• Genetics: A family history of diabetes increases the risk of insulin resistance.
• Medications: Certain drugs (e.g., corticosteroids) can reduce insulin sensitivity.

Diagnosis and Clinical Assessment

Insulin sensitivity markers are typically measured through a simple blood draw, usually taken in a fasted state. In clinical practice, markers are evaluated in combination to obtain a complete picture of metabolic health. Testing is especially recommended for individuals with:

• Overweight or obesity (BMI above 25 kg/m²)
• Family history of diabetes or cardiovascular disease
• Polycystic ovary syndrome (PCOS)
• History of gestational diabetes
• High blood pressure or elevated blood lipids

Treatment and Improving Insulin Sensitivity

Improved insulin sensitivity is well achievable through lifestyle modifications:

• Weight loss: Even a reduction of 5–10% of body weight can significantly improve insulin sensitivity.
• Exercise: Both aerobic exercise and strength training enhance glucose uptake in muscles and improve insulin action.
• Dietary changes: A Mediterranean or low-carbohydrate diet can improve insulin sensitivity.
• Pharmacological therapy: When needed, medications such as metformin can pharmacologically improve insulin sensitivity.

References

1. World Health Organization (WHO): Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. WHO Press, Geneva, 2006.
2. Matthews DR et al. – Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419.
3. American Diabetes Association – Standards of Medical Care in Diabetes 2024. Diabetes Care. 2024;47(Suppl 1).