Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia

Abstract

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486–0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

Risk of cardiovascular disease outcomes in primary care subjects with familial hypercholesterolaemia: A cohort study

“…This may indicate that subjects with co-existing type 2 diabetes and CVD have been excluded, or may indicate potential misclassification of hypercholesterolaemia as FH rather than due to secondary causes such as diabetes. However, the prevalence is actually lower than prevalence of type 2 diabetes in genetically-confirmed FH subjects (5.9%) in a recent EU registry study [33]. The selection criteria for non-FH subjects included cholesterol testing within six months of their matched FH cases, so these individuals represent a cohort of high-risk subjects who are being monitored with regular cholesterol testing.…”

Familial Hypercholesterolaemia in a Bulgarian Population of Patients with Dyslipidaemia and Diabetes: An Observational Study

“…As noted previously, patients with heterozygous FH are reported to be at much lower risk of developing T2DM (approximately 50% lower) than are individuals without FH [21,22], although the risk may depend on the specific type of FH-associated gene mutation involved [21,24,25]. This apparent protective effect of FH might reflect impaired intracellular cholesterol uptake [16,21].…”

“…Patients with heterozygous FH are reported to be at much lower risk of T2DM (approx. 50% lower) than are individuals without FH [21,22], as well as being at lower risk of statin-associated incident T2DM [23]. There are an estimated 95,000 patients with T1DM or T2DM in Bulgaria being treated with insulin/insulin analogues, DPP-4 inhibitors, GLP-1 RA and/or SGLT2 inhibitors, Thus, we planned to initially include 15 large diabetes centres across the country, with the option to increase this number to a maximum of 20 centres if required to meet our target of 453 FH patients.…”

How do we know that statins are diabetogenic, and why? Is it an important issue in the clinical practice?

“…A recent study by Spanish authors [24] is discordant with the above results by Besseling et al [23]. The aim of the Spanish study was to evaluate the incidence of type 2 diabetes in patients with heterozygous FH (based on the National Dyslipidaemia Registry of the Spanish Atherosclerosis Society) and the effect of LDL-C level and the presence of FH-causative mutations on the risk of type 2 diabetes in these patients.…”