Abstract | IMPORTANCE: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in all individuals (n = 63,320) who underwent DNA testing for familial hypercholesterolemia in the national Dutch screening program between 1994 and 2014. EXPOSURES: MAIN OUTCOMES AND MEASURES: RESULTS: The prevalence of type 2 diabetes was 1.75% in familial hypercholesterolemia patients (n = 440/25,137) vs 2.93% in unaffected relatives (n = 1119/38,183) (P < .001; odds ratio [OR], 0.62 [95% CI, 0.55-0.69]). The adjusted prevalence of type 2 diabetes in familial hypercholesterolemia, determined using multivariable regression models, was 1.44% (difference, 1.49% [95% CI, 1.24%-1.71%]) (OR, 0.49 [95% CI, 0.41-0.58]; P < .001). The adjusted prevalence of type 2 diabetes by APOB vs LDL receptor gene was 1.91% vs 1.33% (OR, 0.65 [95% CI, 0.48-0.87] vs OR, 0.45 [95% CI, 0.38-0.54]), and the prevalence for receptor-deficient vs receptor-negative mutation carriers was 1.44% vs 1.12% (OR, 0.49 [95% CI, 0.40-0.60] vs OR, 0.38 [95% CI, 0.29-0.49]), respectively (P for trend <.001 in both comparisons). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis in the Netherlands, the prevalence of type 2 diabetes among patients with familial hypercholesterolemia was significantly lower than among unaffected relatives, with variability by mutation type. 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.
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Authors | Joost Besseling, John J P Kastelein, Joep C Defesche, Barbara A Hutten, G Kees Hovingh |
Journal | JAMA
(JAMA)
Vol. 313
Issue 10
Pg. 1029-36
(Mar 10 2015)
ISSN: 1538-3598 [Electronic] United States |
PMID | 25756439
(Publication Type: Journal Article)
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Chemical References |
- Cholesterol, LDL
- Receptors, LDL
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Topics |
- Adult
- Cholesterol, LDL
(metabolism)
- Confounding Factors, Epidemiologic
- Cross-Sectional Studies
- Diabetes Mellitus, Type 2
(complications, epidemiology)
- Female
- Humans
- Hyperlipoproteinemia Type II
(complications, genetics, metabolism)
- Insulin-Secreting Cells
(metabolism)
- Logistic Models
- Male
- Middle Aged
- Mutation
- Netherlands
(epidemiology)
- Prevalence
- Receptors, LDL
(genetics)
- Registries
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