Familial hypercholesterolaemia patients with obesity face higher diabetes risk

Patients with heterozygous familial hypercholesterolaemia do not appear to be protected against type 2 diabetes (T2D), which markedly increases in the presence of obesity, according to a worldwide cross-sectional study.

Researchers used data from the EAS FHSC registry and identified adults with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Exclusion criteria were suspected homozygous familial hypercholesterolaemia and type 1 diabetes.

Prevalence of T2D, the main study outcome, was evaluated overall and by WHO region, as well as in relation to obesity (BMI ≥30.0 kg/m²) status and lipid-lowering medication use.

The analysis included 46,683 adults from 44 countries, of which 24,784 had heterozygous familial hypercholesterolaemia (genetically diagnosed in 80 percent). T2D prevalence in the total population was 5.7 percent, with 4.1 percent in the genetically diagnosed cohort.

T2D prevalence was higher in the Eastern Mediterranean (29.9 percent), South-East Asia and Western Pacific (12.0 percent), and the Americas (8.5 percent) than in Europe (excluding the Netherlands; 8.0 percent). Risk factors for T2D included advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication.

Looking at the 12 risk categories, the odds of T2D were greater in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; odds ratio [OR], 74.42, 95 percent confidence interval [CI], 47.04–117.73) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Notably, the odds of T2D were relatively lower among patients without obesity, despite being in the upper age tertile and receiving statins (OR, 24.42, 95 percent CI, 15.57–38.31).

In the genetically diagnosed cohort, the ORs for T2D were 65.04 (95 percent CI, 40.67–104.02) among patients with obesity in the highest risk category and 20.07 (95 percent CI, 12.73–31.65) among those without obesity.

The findings underscore the importance of managing obesity in patients with heterozygous familial hypercholesterolaemia to mitigate the risk of T2D.