What are the implications of hyperinsulinemia?

From the Guidelines

Hyperinsulinemia is associated with an increased risk of developing cardiovascular disease, type 2 diabetes, and certain types of cancer. Prolonged exposure to elevated insulin levels can lead to insulin resistance, which may be managed with medications such as metformin, typically initiated at a dose of 500mg orally twice daily, with gradual titration up to 1000mg twice daily as needed 1, 2.

Key Implications of Hyperinsulinemia

• Dyslipidemia: characterized by elevated triglycerides and reduced high-density lipoprotein (HDL) cholesterol, which may require treatment with statins, such as atorvastatin, at a dose of 10-20mg orally once daily 3, 4.
• Increased risk of cancer: hyperinsulinemia has been linked to poor outcomes in patients with early-stage malignancies, and may be associated with an increased risk of certain types of cancer, such as breast cancer and colorectal cancer 4.
• Cardiovascular disease: hyperinsulinemia is associated with an increased risk of cardiovascular disease, including hypertension, atherosclerosis, and cardiac arrhythmias 2, 5.

Management of Hyperinsulinemia

• Lifestyle modifications: weight loss, exercise, and dietary changes may help to improve insulin sensitivity and reduce the risk of developing insulin resistance and related diseases 5, 6.
• Medications: metformin, statins, and other medications may be used to manage insulin resistance, dyslipidemia, and other related conditions 1, 2.

From the Research

Implications of Hyperinsulinemia

The implications of hyperinsulinemia are numerous and can have significant effects on the body. Some of the key implications include:

• Increased risk of obesity, type 2 diabetes, and cardiovascular disease 7, 8, 9, 10
• Decreased health span and life expectancy 7
• Promotion of energy storage and lipid synthesis, hindering lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure 8
• Disturbance of the balance of the insulin-GH-IGF axis, shifting the insulin:GH ratio towards insulin and away from GH 8
• Increased risk of cancer, with hyperinsulinaemia and increased bioavailable insulin-like growth factor I (IGF-I) playing a role in tumor initiation and progression 11
• Association with an atherogenic plasma lipid profile, including elevated plasma triglyceride and low high-density lipoprotein cholesterol concentrations 9, 10
• Increased risk of cardiovascular disease, with insulin resistance and hyperinsulinemia increasing the likelihood of hypertension, dyslipidemia, and atherosclerosis 9, 10

Mechanisms Underlying the Implications of Hyperinsulinemia

The mechanisms underlying the implications of hyperinsulinemia are complex and multifaceted. Some of the key mechanisms include:

• Selective impairment of insulin signaling, causing less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS) 7
• Increased insulin secretion, decreased insulin pulses, and/or reduced hepatic insulin clearance, leading to hyperinsulinemia 8
• Increased production of reactive oxygen species (ROS) that can damage DNA, contributing to mutagenesis and carcinogenesis 11
• Systemic inflammation, resulting in a protumorigenic environment 11
• Sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells, contributing to the association between insulin resistance and essential hypertension 10