Serum Fibroblast Growth Factor 19 (FGF19) Levels Are Associated with Atherogenic Dyslipidemia in Patients with Type 2 Diabetes
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by chronic hyperglycemia resulting from multiple etiological factors. This condition is associated with significant microvascular and macrovascular complications, including lipid metabolism disorders that can lead to atherosclerosis. Cardiovascular complications, particularly atherosclerotic cardiovascular disease, are the leading cause of mortality in T2D patients, accounting for approximately two-thirds of deaths. The prevalence of macrovascular complications in T2D is around 32%, highlighting the critical need for early detection and intervention strategies.
Currently, there are no clinical indicators that can accurately predict the cardiovascular complications of T2D. Identifying biomarkers for atherogenic dyslipidemia in T2D patients could facilitate early diagnosis of diabetic macrovascular disease, enabling timely interventions to improve clinical outcomes, reduce mortality, and alleviate the economic burden associated with these complications.
Fibroblast growth factor 19 (FGF19) is a hormone secreted by the distal small intestine that plays a crucial role in regulating lipid and glucose metabolism. While some studies have explored the relationship between circulating FGF19 levels and coronary artery disease (CAD), as well as major cardiovascular adverse events in stable CAD, the specific role of FGF19 in the progression of T2D to atherogenic dyslipidemia remains unclear. Previous research has demonstrated that FGF19 can predict the progression of subclinical atherosclerosis in men with T2D, suggesting its potential as a biomarker for cardiovascular complications.
This study aimed to investigate the relationship between serum FGF19 levels and the risk of atherogenic dyslipidemia in patients with T2D, and to explore whether FGF19 could serve as a biomarker for the early diagnosis of atherogenic dyslipidemia in this population. The study was conducted in accordance with the Helsinki Declaration of the World Medical Association and was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University. Informed consent was obtained from all participants.
A total of 81 patients with T2D and 45 age- and sex-matched healthy controls were enrolled at the Second Xiangya Hospital of Central South University between March 2007 and June 2008. T2D was diagnosed based on the 1999 World Health Organization criteria. Atherogenic dyslipidemia was defined as having one or more of the following criteria: triglycerides (TG) ≥1.70 mmol/L, high-density lipoprotein cholesterol (HDL-C) <1.03 mmol/L (men) or <1.29 mmol/L (women), low-density lipoprotein cholesterol (LDL-C) ≥3.36 mmol/L, or being on lipid-lowering drugs according to the National Cholesterol Education Program Adult Treatment Panel III.
Participants underwent a complete physical examination, including measurements of height, weight, waist circumference, and hip circumference. Body mass index (BMI) was calculated as weight divided by height squared (kg/m²). Fasting blood samples were collected to measure fasting blood glucose (FBG), postprandial blood glucose (PBG), cholesterol, and TG levels using the hexokinase method. Fasting insulin (FINS) concentration was determined by a chemiluminescent immunometric assay, and insulin resistance was estimated using the homeostasis model assessment index of insulin resistance (HOMA-IR). Serum FGF19 levels were measured using enzyme-linked immunosorbent assay kits, with a detection range of 31.2 to 2000 pg/mL.
The study found that patients with T2D had higher BMI, waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), FBG, PBG, hemoglobin A1c (HbA1c), FINS, HOMA-IR, total cholesterol (TC), TG, HDL-C, and LDL-C compared to healthy controls. However, there were no significant differences in serum FGF19 levels between T2D patients and healthy controls. Notably, serum FGF19 levels were significantly higher in T2D patients with atherogenic dyslipidemia compared to those without atherogenic dyslipidemia and healthy controls.
In all subjects, serum FGF19 levels were positively correlated with FBG, LDL-C, TG, FINS, and HOMA-IR. Significant correlations were also found between serum FGF19 levels and FINS, as well as HOMA-IR, in healthy controls. In T2D patients, serum FGF19 levels were positively correlated with TG and LDL-C, even after adjusting for age, sex, and BMI. Multiple linear regression analysis identified TG and LDL-C as independent predictors of serum FGF19 levels in T2D patients.
A multiple logistic regression model revealed that FGF19 was significantly associated with the development of atherogenic dyslipidemia in T2D patients, independent of other factors such as DBP. This suggests that elevated FGF19 levels may represent a compensatory response to atherogenic dyslipidemia in T2D patients.
The findings of this study indicate that serum FGF19 levels are elevated in newly diagnosed T2D patients with atherogenic dyslipidemia compared to those without atherogenic dyslipidemia and healthy controls. This suggests that FGF19 may serve as a potential biomarker for the early diagnosis of atherogenic dyslipidemia in T2D patients, providing a basis for the early identification of diabetic macrovascular complications. Furthermore, FGF19 could represent a novel therapeutic target for the early prevention and treatment of these complications.
However, the conclusions of this study need to be confirmed in larger prospective studies. Further research is also required to elucidate the mechanisms by which FGF19 contributes to cardiovascular complications in diabetes, which could guide early diagnosis and treatment strategies. The identification of FGF19 as a biomarker for atherogenic dyslipidemia in T2D patients represents a significant step forward in the management of this complex and multifactorial disease.
doi.org/10.1097/CM9.0000000000001574
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