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Diabetes prevalence lower in patients with familial hypercholesterolemia than unaffected relatives
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Patients with familial hypercholesterolemia had a lower prevalence of type 2 diabetes compared with relatives without familial hypercholesterolemia, according to a cross-sectional analysis.
“If this finding is confirmed in longitudinal analysis, it would raise the possibility of a causal relationship between LDL receptor-mediated transmembrane cholesterol transport and type 2 diabetes,” Joost Besseling, MD, from the department of vascular medicine at Academic Medical Centre, Amsterdam, Netherlands, and colleagues wrote.
The researchers hypothesized that, based on the mechanisms of familial hypercholesterolemia (FH) and statin therapy, transmembrane cholesterol transport would be linked to development of type 2 diabetes.
The cross-sectional study included 25,137 patients with FH and 38,183 unaffected relatives who had DNA testing for FH in a national Dutch screening program from 1994 to 2014.
Diabetes risk lower
The prevalence of type 2 diabetes was 1.75% in patients with FH compared with 2.93% in unaffected relatives (OR = 0.62; 95% CI, 0.55-0.69). After adjustment for age, BMI, HDL, triglycerides, statin use, smoking status and history of CVD, the prevalence of type 2 diabetes in those with FH was even lower at 1.44% (difference, 1.49%; 95% CI, 1.24-1.71; OR = 0.49; 95% CI, 0.41-0.58), according to the researchers.
Prevalence of type 2 diabetes in those with FH varied by mutation type. The adjusted prevalence in patients with mutations in the APOB gene was 1.91% (OR = 0.65; 95% CI, 0.48-0.87) compared with 1.33% (OR = 0.45; 95% CI, 0.38-0.54) for those with mutations in the LDL receptor gene (P for trend < .001). The adjusted prevalence of patients with receptor-deficient mutations in the LDL receptor gene was 1.44% (OR = 0.49; 95% CI, 0.4-0.6) compared with 1.12% (OR = 0.38; 95% CI, 0.29-0.49) for those with receptor-negative mutations in the LDL receptor gene (P for trend < .001).
A possible explanation is that “increased intracellular cholesterol levels are detrimental for pancreatic beta cell function,” Besseling and colleagues wrote.
Implications for statin therapy
“From a clinical perspective, the findings should allay any concerns about the potential diabetogenic effect of statins when treating patients with [FH] from childhood or young adulthood given that these patients appear to be at a low risk for diabetes,” David Preiss, MD, PhD, and Naveed Sattar, MD, PhD, both from BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom, wrote in a related editorial. “Most intriguingly, the results suggest that the expression and function of LDL receptors may be important for glucose homeostasis.”
According to Preiss and Sattar, the study “contributes important evidence to strengthen the previously observed relationship between statin therapy and diabetes risk. However, this does not, and should not, alter guidance regarding the use of these important medications in patients at elevated [CV] risk given the clear overall benefit of statin therapy.” – by Erik Swain
Disclosure: Some researchers report financial ties with Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly, Genzyme, JSiS, Merck, Novartis, Pfizer, Regeneron, Roche and Sanofi. Preiss reports consulting for Sanofi-Aventis and being involved in ongoing PCSK9 inhibitor trials. Sattar reports consulting for Amgen, Kowa Pharmaceuticals and Sanofi-Aventis and being involved in ongoing PCSK9 inhibitor trials.
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