What are the implications of hyperinsulinemia in females?

From the Guidelines

Elevated insulin levels in women can be effectively managed through lifestyle modifications and medical interventions, with a primary focus on improving insulin sensitivity and reducing the risk of associated conditions such as polycystic ovary syndrome (PCOS), type 2 diabetes, and cardiovascular disease. The most recent and highest quality study, published in 2024 1, emphasizes the importance of weight loss and lifestyle changes in managing PCOS and insulin resistance.

Key Recommendations:

• Adopt a low-glycemic diet rich in vegetables, lean proteins, and healthy fats while limiting refined carbohydrates and sugars.
• Engage in regular exercise, including a combination of aerobic activity (30 minutes, 5 days weekly) and strength training (2-3 sessions weekly), to improve insulin sensitivity.
• Achieve a weight loss of 5-10% of body weight to significantly reduce insulin levels in overweight women.
• Consider metformin (starting at 500mg daily, potentially increasing to 1000-2000mg daily in divided doses) to improve insulin sensitivity, particularly for women with PCOS.
• Inositol supplements (2000-4000mg daily) may also be beneficial, especially for women with PCOS.
• Prioritize adequate sleep (7-9 hours nightly) and stress management techniques like meditation to further regulate insulin levels.

Importance of Monitoring:

Regular monitoring of blood glucose levels and periodic insulin testing are crucial for tracking improvement and adjusting treatment plans as necessary. Elevated insulin (hyperinsulinemia) often indicates insulin resistance, increasing the risk of type 2 diabetes, cardiovascular disease, and specific issues in women such as PCOS, irregular menstrual cycles, and fertility problems.

Considerations:

The interaction between insulin resistance, obesity, and PCOS is complex, with obesity exacerbating PCOS symptoms and insulin resistance contributing to hyperandrogenism 1. Therefore, managing weight and improving insulin sensitivity are critical components of treating PCOS and related metabolic issues.

Recent Findings:

Recent studies highlight the importance of sex-specific considerations in the management of diabetes and cardiovascular disease, with women potentially having different risk profiles and responses to treatment compared to men 1. However, the primary approach to managing elevated insulin levels remains focused on lifestyle modifications and improving insulin sensitivity, with medical interventions tailored to the individual's specific needs and conditions.

From the Research

Elevated Insulin in Women

• Elevated insulin levels are often associated with polycystic ovary syndrome (PCOS), a common endocrine-metabolic disorder in women 2.
• Studies have shown that insulin-sensitizing agents, such as metformin and pioglitazone, can improve insulin resistance and reduce androgen levels in women with PCOS 3, 4.
• Combination therapy with metformin and pioglitazone has been shown to be more effective in reducing insulin resistance and inflammatory biomarkers than metformin alone 4.
• Low-dose spironolactone combined with metformin has also been shown to decrease insulin resistance and improve clinical features in patients with PCOS 3.
• Glucagon-like peptide-1 receptor agonists have been found to be more beneficial for weight loss and insulin resistance improvement compared to metformin in overweight/obese women with PCOS 5.

Treatment Options

• Metformin is a commonly used insulin-sensitizing agent for the treatment of PCOS, but it may not be effective in all patients 2, 3.
• Pioglitazone, a thiazolidinedione, has been shown to improve insulin sensitivity and reduce androgen levels in women with PCOS 4.
• Spironolactone, an anti-androgen, has been used in combination with metformin and pioglitazone to improve clinical features and reduce insulin resistance in patients with PCOS 3, 6.
• Glucagon-like peptide-1 receptor agonists may be a promising treatment option for overweight/obese women with PCOS, but further studies are needed to confirm their efficacy and safety 5.

Biomarkers

• Fetuin-A, a glycoprotein produced in the liver, has been found to be lower in girls with PCOS and can be normalized with treatment using a low-dose combination of spironolactone, pioglitazone, and metformin 6.
• Inflammatory biomarkers, such as IL-6 and IL-8, have been found to be elevated in women with PCOS and can be reduced with treatment using metformin and pioglitazone 4.