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Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA. 
Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).
The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).
These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.
Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA.
Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).
The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).
These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.
Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA.
Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).
The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).
These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.
Key clinical point:
Major finding: The estimated difference in absolute risk was 5.3 incident cases of diabetes per 1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C.
Data source: A meta-analysis of gene-association analyses in several studies and databases covering 50,775 adults with diabetes and 270,269 control subjects.
Disclosures: This study was supported by the U.K. Medical Research Council, the National Institute of Health Research Biomedical Research Centre, and Wellcome Trust. Dr. Lotta reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.