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Abstract Background The pathogenesis of type 2 diabetes mellitus is somewhat associated with lipid metabolism. We aim to assess the impact of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) on type 2 diabetes mellitus and its complications through a two-sample Mendelian randomization (MR) study. Method We identified suitable genetic instruments from the GWAS database that represent the expression levels of three genes, interpreting reduced genetically proxied gene expression as indicative of lipid-lowering drug use. We evaluated the causal relationships among these variables employing a two-sample Mendelian randomization approach, with the Inverse Variance Weighted (IVW) analysis serving as the primary method. Coronary artery disease was utilized as a positive control to validate the reliability of the selected genetic instruments. Result Increased genetically proxied HMGCR expression is significantly associated with a reduced risk of type 2 diabetes mellitus (OR = 0.64, 95%CI = 0.55–0.74), which was replicated in the FinnGen study with consistent results (OR = 0.65, 95%CI = 0.53–0.80). Increased genetically proxied HMGCR expression is associated with a reduced risk of diabetic retinopathy (OR = 0.23, 95%CI = 0.12–0.44) and diabetic nephropathy (OR = 0.35, 95%CI = 0.17–0.71). In contrast, increased genetically proxied PCSK9 expression is associated with a decreased risk of diabetic coma (OR = 0.70, 95%CI = 0.50–0.98), diabetic neuropathy (OR = 0.24, 95%CI = 0.14–0.42), diabetic retinopathy (OR = 0.67, 95%CI = 0.48–0.96), diabetic cardiovascular diseases (OR = 0.62, 95%CI = 0.38–0.99), and diabetic nephropathy (OR = 0.62, 95%CI = 0.41–0.95). Conclusions This Mendelian randomization study suggests an association between HMGCR and the pathogenesis of type 2 diabetes mellitus, with increased genetically proxied HMGCR expression reducing the risk of type 2 diabetes mellitus, while PCSK9 and NPC1L1 show no significant association with type 2 diabetes mellitus. These findings may offer more reasonable lipid-lowering drug options for patients with dyslipidemia.

BackgroundSome observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear.MethodsThis study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran’s Q statistic was used to test for heterogeneity of instrumental variables.ResultsThe IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism.ConclusionsThis two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota.

BackgroundThis study aimed to assess the correlation between renal function-related indices and vascular damages among patients with type 2 diabetes mellitus (T2DM) and normal renal function.MethodsWe screened a cohort of eligible patients with T2DM, ultimately including 826 individuals. Utilizing multifactorial logistic regression, we conducted an in-depth analysis to explore the potential associations between renal function-related indices—specifically BUN, Cr, ALB, ACR, and eGFR—and the incidence of diabetic vascular damage. Additionally, to comprehensively understand the relationships, we employed Spearman correlation analysis to assess the connections between these indicators and the occurrence of vascular damage.ResultsIn this cross-sectional study of 532 patients with carotid atherosclerosis (CA), the prevalence of CA was positively correlated with Cr (53.1%, 72.3%, 68.0%, P

BackgroundThe anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of these complications. This study aims to investigate the association between renal function-related indicators and the occurrence of peripheral neuropathy and retinopathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) who currently have normal renal function.MethodsPatients with T2DM who met the criteria were selected from the MMC database and divided into diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR) groups, with a total of 859 and 487 patients included, respectively. Multivariate logistic regression was used to analyze the relationship between blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), urine albumin(ALB), albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and diabetic peripheral neuropathy and retinopathy. Spearman correlation analysis was used to determine the correlation between these indicators and peripheral neuropathy and retinopathy in diabetes.ResultsIn a total of 221 patients diagnosed with DPN, we found positive correlation between the prevalence of DPN and eGFR (18.2, 23.3, 35.7%, p

Background: This study aimed to assess the correlation between renal functionrelated indices and vascular damages among patients with type 2 diabetes mellitus (T2DM) and normal renal function. Methods: We screened a cohort of eligible patients with T2DM, ultimately including 826 individuals. Utilizing multifactorial logistic regression, we conducted an in-depth analysis to explore the potential associations between renal function-related indices--specifically BUN, Cr, ALB, ACR, and eGFR--and the incidence of diabetic vascular damage. Additionally, to comprehensively understand the relationships, we employed Spearman correlation analysis to assess the connections between these indicators and the occurrence of vascular damage. Results: In this cross-sectional study of 532 patients with carotid atherosclerosis (CA), the prevalence of CA was positively correlated with Cr (53.1%, 72.3%, 68.0%, P<0.05) and negatively correlated with eGFR (71.6%, 68.5%, 53.1%, P<0.05). the higher the Cr, the higher the predominance ratio of CA (T1: reference; T2:OR. 2.166,95%CI:1.454,3.225; T3:OR:1.677, 95%CI:1.075, 2.616; P<0.05), along with an eGFR of 66.9% and 52.0% in terms of sensitivity and specificity, with a 95% CI of 0.562-0.644. Conclusion: Within our experimental sample, a noteworthy observation emerged: Creatinine (Cr) exhibited a positive correlation with the prevalence of individuals affected by carotid atherosclerosis (CA), underscoring a potential connection between Cr levels and CA incidence. Conversely, the estimated Glomerular Filtration Rate (eGFR) demonstrated a negative correlation with the occurrence of CA, implying that lower eGFR values might be associated with an increased likelihood of CA development. [ABSTRACT FROM AUTHOR]