Hormonal
Genetic variants in PCSK9 that lower LDL cholesterol are associated with an increased risk of type 2 diabetes, higher fasting glucose, increased bodyweight, and higher waist-to-hip ratio.
If you are considering PCSK9 inhibitor therapy (like evolocumab or alirocumab) to lower cholesterol, be aware that genetic studies suggest it may slightly increase your risk of developing type 2 diabetes and increase body weight. However, this risk is generally considered acceptable compared to the significant protection against heart attacks and strokes these drugs provide. Regular monitoring of blood sugar is recommended.
Combined analyses of four independent PCSK9 variants... showed associations with increased fasting glucose (0·09 mmol/L...), bodyweight (1·03 kg...), waist-to-hip ratio (0·006...), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50).
Why this rating
Mendelian randomization using large-scale genetic data (n>550,000) provides robust causal inference for on-target effects.
Source
PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study
Amand F. Schmidt et al. · The Lancet Diabetes & Endocrinology · 2016
DOI 10.1016/s2213-8587(16)30396-5
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