scholarly journals The impact of empagliflozin on kidney injury molecule-1: a subanalysis of the Effects of Empagliflozin on Cardiac Structure, Function, and Circulating Biomarkers in Patients with Type 2 Diabetes CardioLink-6 trial

2020 ◽  
Vol 35 (5) ◽  
pp. 895-897 ◽  
Author(s):  
Erika Opingari ◽  
Subodh Verma ◽  
Kim A Connelly ◽  
Cyril David Mazer ◽  
Hwee Teoh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Structure Function ◽  
Kidney Injury ◽  
Cardiac Structure ◽  
Circulating Biomarkers ◽  
Kidney Injury Molecule 1 ◽  
The Impact

scholarly journals Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

2019 ◽  
Vol 126 (3) ◽  
pp. 626-637 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Matthew T. Lewis ◽  
Jonathan D. Kasper ◽  
Paul D. Chantler ◽  
Robert W. Wiseman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Structure Function ◽  
Vascular Structure ◽  
Gk Rats ◽  
The Impact

Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type 2 diabetes without obesity on skeletal muscle microvascular structure/function and on active hyperemia with elevated metabolic demand, we used 17-wk-old Goto-Kakizaki (GK) rats to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased thromboxane (Tx)A2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK rats were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK rats, primarily because of blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (V̇o2) across the muscle and accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ-29548) or production (dazmegrel) improved muscle perfusion, V̇o2, and muscle performance. These results suggest that type 2 diabetes mellitus in GK rats impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased reactive oxygen species/inflammation-induced TxA2 production/action on network function as a major contributing mechanism. NEW & NOTEWORTHY The impact of type 2 diabetes mellitus on vascular structure/function remains an area lacking clarity. Using diabetic Goto-Kakizaki rats before the development of other risk factors, we determined alterations to vascular structure/function and skeletal muscle active hyperemia. Type 2 diabetes mellitus reduced arteriolar endothelium-dependent dilation associated with increased thromboxane A2 generation. Although modest microvascular rarefaction was evident, there were no other alterations to vascular structure/function. Skeletal muscle active hyperemia was blunted, although it improved after antioxidant or anti-thromboxane A2 treatment.

Cardiovascular risk assessment and association with novel biomarkers in patients with Type 2 diabetes mellitus

2021 ◽  
Author(s):  
Ane KM Néri ◽  
Geraldo B da S Junior ◽  
Gdayllon C Meneses ◽  
Alice MC Martins ◽  
Elizabeth De F Daher ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Kidney Injury ◽  
Cross Sectional Study ◽  
Risk Scores ◽  
Cross Sectional ◽  
Novel Biomarkers ◽  
Independent Association ◽  
Kidney Injury Molecule 1

Aim: To investigate the association between cardiovascular risk and biomarkers in patients with Type 2 diabetes (T2DM). Methods: Cross-sectional study, with evaluation of traditional and new biomarkers (serum FGF-23, Syndecan-1 – Sdc-1 and vascular cell adhesion molecule-1 – VCAM-1 and urinary VEGF and kidney injury molecule-1 – KIM-1) and risk scores (Framingham-FRS and UK Prospective Diabetes Study – UKPDS). Results: 128 diabetics were included, with predominance of high risk by FRS and low risk by UKPDS. There was an independent association of VCAM-1 and VEGF with higher risk by FRS-lipids and UKPDS. Conclusion: There was an independent association of VCAM-1 and VEGF with higher cardiovascular risk, showing a subclinical endothelial dysfunction in T2DM. The inclusion of novel biomarkers to risk scores may increase accuracy when assessing cardiovascular risk of diabetic individuals.

scholarly journals Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial

2021 ◽  
pp. 1-8
Author(s):  
João Pedro Ferreira ◽  
Patrick Rossignol ◽  
George Bakris ◽  
Cyrus Mehta ◽  
William B. White ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Acute Coronary Syndrome ◽  
Kidney Function ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Cox Models ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Kidney Injury Molecule 1

<b><i>Introduction:</i></b> Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. <b><i>Aims:</i></b> Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. <b><i>Methods:</i></b> WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR &#x3c;15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. <b><i>Results:</i></b> 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a <i>p</i> value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06–7.96), <i>p</i> value &#x3c;0.0001. <b><i>Conclusion:</i></b> Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.

scholarly journals The role of metformin in the prevention of diabetic nephropathy in experimental type 2 diabetes

2016 ◽  
Vol 15 (3) ◽  
pp. 70-80
Author(s):  
V. K. Bayrasheva ◽  
A. Yu. Babenko ◽  
Yu. V. Dmitriev ◽  
A. A. Bairamov ◽  
S. G. Chefu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Metformin Treatment ◽  
Protective Effects ◽  
Metformin Therapy ◽  
Kidney Injury Molecule 1

Introduction and purpose. A number of landmark trials have demonstrated clear benefits of metformin therapy in the prevention of macrovascular outcomes. Nevertheless, there is a lack of robust evidence to suggest whether metformin therapy will have similar beneficial outcomes in one of the most serious type 2 diabetes-related renal microvascular complications known as diabetic nephropathy. The study aimed to evaluate the effects of ten-week metformin treatment on renal morphofunctional changes in rats with non-genetic type 2 diabetic nephropathy. Materials and methods. Starting at 3 weeks after unilateral nephrectomy, adult male Wistar rats were fed the high-fat diet for 5 weeks, and then successively received nicotinamide (230 mg/kg) and streptozotocin (65 mg/kg) intraperitoneally in 15-min interval. Results. Starting at 11 weeks after confirmation of diabetes, metformin treatment did not attenuate routine renal dysfunction markers such as creatinine, creatinine clearance and albuminuria compared to placebo-treated diabetic group, and glomerulosclerosis index and glomerular expression of type IV collagen didn't significantly change either. Nevertheless, level of urinary kidney injury molecule-1, considered to be the marker of tubular damage in diabetes, was significantly lower in metformin-treated animals. Moreover, reduction of tubulointerstitial lesion tended to be significant. Conclusions. Under conditions of diabetic nephropathy modeling, metformin has shown direct protective effects against diabetic tubular disturbance. To assess long-term renal outcomes of these findings, more pre-clinical studies and clinical trials are required.

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