scholarly journals Endothelin-1 predicts incident diabetic peripheral neuropathy in Type 2 Diabetes: a cohort study

2020 ◽  
Vol 182 (4) ◽  
pp. 429-438
Author(s):  
Sharon Li Ting Pek ◽  
Su Chi Lim ◽  
Keven Ang ◽  
Pek Yee Kwan ◽  
Wern Ee Tang ◽  
...  

Introduction Diabetic peripheral neuropathy (DPN) is a common microvascular complication in patients with type 2 diabetes (T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, implicated in the causal pathway of microangiopathy. We investigated whether baseline plasma endothelin-1 and other metabolic and vascular risk factors predicted the incidence of DPN. Design This is a 3-year observational, cohort study. Methods In patients with T2D (n = 2057), anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements. Forearm cutaneous endothelial reactivity was assessed by iontophoresis and laser Doppler flowmetry/imaging. Measurements were repeated on follow-up. Incident DPN was considered present if an abnormal finding in monofilament (<8 of 10 points) or neurothesiometer testing was ≥25 volts on either foot at 3-year follow-up, but normal at baseline. Plasma endothelin-1 was assessed by ELISA. Results At baseline, mean age of patients was 57.4 ± 10.8 years old and prevalence of DPN was 10.8%. Of the 1767 patients without DPN, 1250 patients returned for follow-up assessment ((2.9 ± 0.7) years), with a 10.7% incidence of DPN. Patients with incident DPN had significantly higher baseline endothelin-1 (1.43 (1.19–1.73) vs 1.30 (1.06–1.63)) pg/mL, P < 0.0001. Multivariable Cox proportional hazards ratio showed a 1-s.d. increase in log endothelin-1 (adjusted HR: 4.345 (1.451–13.009), P = 0.009), systolic blood pressure (per 10-unit) (adjusted HR: 1.107 (1.001–1.223), P = 0.047) and diabetes duration (adjusted HR: 1.025 (1.004–1.047), P = 0.017) predicted incident DPN, after adjustment for glycemic control, eGFR, albuminuria, peripheral arterial disease and retinopathy status. Conclusion Higher baseline endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of endothelin-1 in DPN.

2020 ◽  
Author(s):  
Kai-Cheng Chang ◽  
Shih-Chieh Shao ◽  
Shihchen Kuo ◽  
Chen-Yi Yang ◽  
Hui-Yu Chen ◽  
...  

Abstract Background Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. Methods We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016-2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every three months in the one-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. Results A total of 1,512 subjects receiving dulaglutide and 1,513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: -1.06%, p<0.001; liraglutide: -0.83%, p<0.001), with a significant between-group difference (-0.23%, 95% confidence interval: -0.38 to -0.08%, p<0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: -1.14 kg, -3.08 U/L and -2.08 ml/min/1.73 m2, p<0.01; liraglutide: -1.64 kg, -3.65 U/L and -2.33 ml/min/1.73 m2, p<0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (-2.47 mmHg, p<0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. Conclusions In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Liu ◽  
Xiaoling Guan ◽  
Zhongshang Yuan ◽  
Meng Zhao ◽  
Qiu Li ◽  
...  

Aim. It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes. Methods. A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis. Results. The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10–1.52; P=0.002) or 1.12- (95% CI 1.01–1.27; P=0.039) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively. Conclusion. Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.


2019 ◽  
Vol 3 (2) ◽  
pp. 17-25
Author(s):  
Rima Novia Putri ◽  
Agung Waluyo

Type 2 diabetes mellitus is one of the chronic diseases that has increased globally and is a cause of various organ dysfunction such as diabetic peripheral neuropathy. Early detection of diabetic peripheral neuropathy and identification of risk factors can reduce the morbidity of diabetic peripheral neuropathy. This literature review was written to present the risk factors of diabetic peripheral neuropathy in type 2 diabetes mellitus patients. Literature search was conducted to obtain appropriate articles through the electronic database Medline, Cinahl, Proquest, and Clinical Key with  keywords:  prevalence of diabetic peripheral neuropathy, risk factors and type 2 diabetes mellitus. The results obtained 16 articles according to the topic and through a review, it is known that risk factors of  diabetic peripheral neuropathy in type 2 diabetes mellitus patients are old age, male sex, duration of diabetes mellitus, poor glycemic control, retinopathy, nephropathy, and risk factors of cardiovascular diseases such as: obesity, overweight, hypertension,and  dyslipidemia.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Cheng Chang ◽  
Shih-Chieh Shao ◽  
Shihchen Kuo ◽  
Chen-Yi Yang ◽  
Hui-Yu Chen ◽  
...  

Abstract Background Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. Methods We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016–2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every 3 months in the 1-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. Results A total of 1512 subjects receiving dulaglutide and 1513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: − 1.06%, p < 0.001; liraglutide: − 0.83%, p < 0.001), with a significant between-group difference (− 0.23%, 95% confidence interval − 0.38 to − 0.08%, p < 0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: − 1.14 kg, − 3.08 U/L and − 2.08 mL/min/1.73 m2, p < 0.01; liraglutide: − 1.64 kg, − 3.65 U/L and − 2.33 mL/min/1.73 m2, p < 0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (− 2.47 mmHg, p < 0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. Conclusions In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.


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