Estimating the effect of lipid-lowering agents on novel subtypes of adult-onset diabetes.
Diabetes Metab Res Rev
; 40(4): e3793, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38661109
ABSTRACT
AIMS:
The aims of the present study were to assess the effects of lipid-lowering drugs [HMG-CoA reductase inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors] on novel subtypes of adult-onset diabetes through a Mendelian randomisation study. MATERIALS ANDMETHODS:
We first inferred causal associations between lipid-related traits [including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoproteins A-I, and apolipoproteins B] and novel subtypes of adult-onset diabetes. The expression quantitative trait loci of drug target genes for three classes of lipid-lowering drugs, as well as genetic variants within or nearby drug target genes associated with LDL-C, were then utilised as proxies for the exposure of lipid-lowering drugs. Mendelian randomisation analysis was performed using summary data from genome-wide association studies of LDL-C, severe autoimmune diabetes, severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes.RESULTS:
There was an association between HMGCR-mediated LDL-C and the risk of SIRD [odds ratio (OR) = 0.305, 95% confidence interval (CI) = 0.129-0.723; p = 0.007], and there was an association of PCSK9-mediated LDL-C with the risk of SIDD (OR = 0.253, 95% CI = 0.120-0.532; p < 0.001) and MOD (OR = 0.345, 95% CI = 0.171-0.696; p = 0.003). Moreover, NPC1L1-mediated LDL-C (OR = 0.109, 95% CI = 0.019-0.613; p = 0.012) and the increased expression of NPC1L1 gene in blood (OR = 0.727, 95% CI = 0.541-0.977; p = 0.034) both showed a significant association with SIRD. These results were further confirmed by sensitivity analyses.CONCLUSIONS:
In summary, the different lipid-lowering medications have a specific effect on the increased risk of different novel subtypes of adult-onset diabetes.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Diabetes Mellitus Tipo 2
/
Dislipidemias
/
Inhibidores de PCSK9
/
Hipolipemiantes
Límite:
Humans
Idioma:
En
Revista:
Diabetes Metab Res Rev
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
China