What Is Insulin?  

Insulin is a hormone produced by pancreatic b-cells and is responsible for regulating glucose homeostasis.¹ Under normal conditions, pancreatic b-cells secrete insulin in response to increasing blood glucose levels. By predominantly acting on muscle, liver, and adipose tissues, insulin allows the glucose molecules to be taken up, stored, and utilized as energy sources.

What Is Hyperinsulinemia?

Excessive secretion of insulin under normal physiological states will lead to hypoglycemia, or low blood glucose levels.² Hyperinsulinemia, however, describes a condition of elevated insulin levels in the blood without associated hypoglycemia. Hyperinsulinemia is commonly observed in obesity and metabolic disorders such as type 2 diabetes mellitus (T2DM).  

What Is the Relationship Between Hyperinsulinemia and Insulin Resistance?

Insulin resistance describes impaired physiological response to insulin on target tissues and is frequently found in conjunction with hyperinsulinemia in various metabolic disorders.^1,3–6 Their coexistence in disorders has called for questions on whether one causes the other.⁷ It is conventionally thought that insulin resistance leads to increased insulin to achieve glucose homeostasis, ultimately resulting in hyperinsulinemia. However, recent clinical observations are beginning to suggest otherwise.^3,6,7 Although the mechanisms are still being studied, hyperinsulinemia has been observed prior to the development of obesity, impaired glucose tolerance, hyperglycemia, and T2DM, leading some experts to suggest that hyperinsulinemia may precede insulin resistance.^3,7 Some genomic studies point to defects in pancreatic b-cells as the primary cause of T2DM, not insulin resistance, leading to the hypothesis that inappropriate hypersecretion of insulin by defected pancreatic b-cells leads to insulin resistance.³ Insulin resistance, in this view, is thought to develop as insulin receptors are downregulated due to high insulin levels; a protective mechanism against hypoglycemia and metabolic stress from increased insulin levels. In mouse models, decreased insulin levels were associated with improved insulin sensitivity, lower fasting glucose levels, and significant extension of lifespan, suggesting that elevated insulin levels may contribute to age-related insulin resistance.⁸

How Is Hyperinsulinemia Related to Metabolic Disorders? 

Hyperinsulinemia is associated with obesity, T2DM, and cardiovascular diseases (ie, diseases of the heart and blood vessels), among other conditions.^2,3 Studies have found that hyperinsulinemia is observed prior to obesity and that individuals with genetic predispositions to greater glucose-induced insulin response are associated with higher body mass index.³ Children with hyperinsulinemia were also found to have a greater risk of developing obesity as adults.⁷ Similarly, hyperinsulinemia is hypothesized to contribute to T2DM development by affecting fat storage, insulin resistance, and pancreatic b-cells.^2,6 Various longitudinal studies have shown that individuals with greater glucose-stimulated insulin response were associated with having a higher risk of developing T2DM in the future.³ Additionally, hyperinsulinemia is associated with disruption of lipid profiles and vascular abnormalities such as atherosclerosis that are linked to cardiovascular diseases and metabolic syndrome.^2,3,6