Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study

Shi, Jie; Zhang, Weiwei; Niu, Yixin; Lin, Ning; Li, Xiaoyong; Zhang, Hongmei; Hu, Renming; Ning, Guang; Fan, Jian‐Gao; Qin, Li; Su, Qing; Yang, Zhen

doi:10.1186/s12933-020-01185-3

Cited by 15 publications

(17 citation statements)

References 39 publications

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“…age, prediabetes, metabolic syndrome) were at an even increased risk [ 19 ]. A Chinese study reported on the association between elevated circulating PCSK9 levels and an increased risk for T2D in women with prediabetes [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Fischer

Hochfellner

Knoll

et al. 2021

Cardiovasc Diabetol

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Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

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Section: Discussionmentioning

confidence: 99%

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Fischer

Hochfellner

Knoll

et al. 2021

Cardiovasc Diabetol

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“…Sample size of 300 was evaluated according to a GDM prevalence of 11.91% in China ( 6 ). Referring to a recent study, the mean (SD) of PCSK9 in healthy populations was 283.68 (97.09) ng/ml ( 12 ). In our study, to detect a 50-ng/ml difference in PCSK9 values with a significance level of 0.05 between two groups, the power was 83.6% (α = 0.05).…”

Section: Methodsmentioning

confidence: 93%

“…Previous data observed that PCSK9 levels were increased in type 2 diabetes mellitus/metabolic syndrome patients and positive correlations of PCSK9 levels with LDL, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin, and insulin resistance ( 10 , 11 ). Moreover, a recent population-based longitudinal study observed a positive association between serum PCSK9 levels and the incidence of T2DM in the prediabetic populations ( 12 ). In contrast, evidence from an animal study indicated that PCSK9 deficiency reduced insulin secretion and promoted glucose intolerance ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Correlation Between Circulating PCSK9 Levels and Gestational Diabetes Mellitus in a Chinese Population

Shi

et al. 2022

Front. Endocrinol.

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BackgroundPrevious studies reported that proprotein convertase subtilisin/kexin type 9 (PCSK9) was a key player in the regulations of lipid metabolism and glucose homeostasis. The current study aimed to detect the expression of PCSK9 in pregnant women with gestational diabetes mellitus (GDM) and investigate the possible relationships between PCSK9 and related metabolic phenotypes in GDM.MethodsCirculating PCSK9 levels were determined by ELISA kit in a cohort of subjects with GDM (n = 170) and normal glucose tolerance (NGT; n = 130). We collected blood samples from all participants for the biochemical index determinations. Diagnosis of GDM was made according to the International Association of the Diabetes and Pregnancy Study Groups Consensus Panel. Correlation analysis and logistic regression analysis were used to study the potential associations between PCSK9 and GDM.ResultsGDM women presented significantly higher circulating PCSK9 levels than those in NGT pregnant subjects (268.07 ± 77.17 vs. 254.24 ± 74.22 ng/ml, P < 0.05). In the GDM group, serum PCSK9 levels were positively correlated with fasting plasma glucose (FPG) (R = 0.251, P = 0.015), glycated hemoglobin (HbA1c) (R = 0.275, P = 0.009), total cholesterol (TC) (R = 0.273, P = 0.010), and low-density lipoprotein cholesterol (LDL-C) (R = 0.326, P = 0.002) after adjustment of age and gestational age. Logistic regression found that age [odds ratio (OR) = 5.412, P = 0.02] and serum PCSK9 levels (OR = 4.696, P = 0.03) were independently associated with GDM. Compared with the lowest serum PCSK9 level quartile group, the prevalence of GDM was significantly higher in the highest quartile group, the ORs of GDM were 3.485 (95% CI 1.408–8.627, P < 0.05 for the trend), after adjusting for potential confounders.ConclusionsCirculating PCSK9 levels were associated with dyslipidemia, pathoglycemia, and the risk of incident GDM, indicating a potential link between PCSK9 and GDM.

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“…We have read the article with great interest by Shi et al on the relationship of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration with the risk of incident type 2 diabetes mellitus (T2DM) in prediabetic Chinese population [ 1 ]. They concluded that elevated PCSK9 levels were associated with an increased incidence of T2DM in female individuals with prediabetes (pre-DM).…”

mentioning

confidence: 99%

“…Interestingly, Shi et al found a positive relationship with elevated baseline circulating PCSK9 levels and incidence of T2DM in female population with pre-DM during 3.1 years follow-up, which was the first study to undertake a longitudinal analysis of circulating PCSK9 concentration and the development of T2DM in prediabetic individuals [ 1 ]. Although their finding provided an additional information on the association with circulating PCSK9 concentration and the incident risk of new-onset T2DM, there were several issues might be worth deliberating before making a conclusion.…”

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confidence: 99%

The predictive utility of circulating PCSK9 levels on diabetes mellitus

Jia

Zhu

2021

Cardiovasc Diabetol

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Increasing data including ours have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9), a novel regulator of cholesterol metabolism, may also play an important role in the development of type 2 diabetes mellitus (T2DM) and is associated with clinical outcomes in diabetic patients. Previous studies revealed that elevated plasma PCSK9 levels had a higher incidence of new-onset T2DM. Moreover, the results of available epidemiological, preclinical, and clinical studies have indicated that plasma PCSK9 concentration is correlated with glycemic parameters and can predict the adverse cardiovascular events in diabetic patients with coronary artery disease. However, there is currently no general agreement about the association of PCSK9 with T2DM. The usefulness of the circulating PCSK9 concentration as a predictor for the risk of new-onset T2DM should be clinically prudential.

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Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study

Cited by 15 publications

References 39 publications

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Correlation Between Circulating PCSK9 Levels and Gestational Diabetes Mellitus in a Chinese Population

The predictive utility of circulating PCSK9 levels on diabetes mellitus

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