scholarly journals Lower Plasma Creatinine and Urine Albumin in Individuals at Increased Risk of Type 2 Diabetes with Factor V Leiden Mutation

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Andreas Peter ◽  
Andreas Fritsche ◽  
Fausto Machicao ◽  
Peter P. Nawroth ◽  
Hans-Ulrich Häring ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Factor V Leiden ◽  
Plasma Creatinine ◽  
Factor V ◽  
Protective Effects ◽  
Lower Plasma ◽  
Urine Albumin ◽  
Fvl Mutation

The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P=0.03) and tended to have lower plasma creatinine concentrations (P=0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P=0.048). These observations at a very early “disease” stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies.

Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes

2018 ◽  
Vol 6 (01) ◽  
pp. 50-55 ◽  
Author(s):  
Xin Zhao ◽  
Xiao-Mei Zhang ◽  
Ning Yuan ◽  
Xiao-Feng Yu ◽  
Li-Nong Ji
Keyword(s):  
Bone Mineral Density ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Bone Metabolism ◽  
Early Stage ◽  
Chinese Patients ◽  
Creatinine Ratio ◽  
Mineral Density ◽  
Urine Albumin

Abstract Objective To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). Methods In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients’ data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. Results BMD at every location tested (femoral neck, trochanter, inside hip, Ward’s triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (β-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or β-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and β-CTX (p<0.05). Conclusion In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

scholarly journals Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

2020 ◽  
Vol 20 (2) ◽  
pp. 833-840
Author(s):  
Erhan Onalan ◽  
Yusuf Doğan ◽  
Ebru Onalan ◽  
Nevzat Gozel ◽  
Ilay Buran ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
High Serum ◽  
Control Group ◽  
Diabetic Patients ◽  
Healthy Individuals ◽  
Urine Albumin ◽  
Healthy Control ◽  
Group 2

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

scholarly journals Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Podocyte Loss ◽  
Renal Changes ◽  
Hypoglycemic Drug ◽  
Antioxidant Effects

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

scholarly journals Is there a relationship between factor V Leiden and type 2 diabetes?

2009 ◽  
Vol 7 (1) ◽  
Author(s):  
Corrado Lodigiani ◽  
Paola Ferrazzi ◽  
Pierpaolo Di Micco ◽  
Luca Librè ◽  
Stefano Genovese ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Factor V Leiden ◽  
Factor V

scholarly journals SGLT2 Inhibitors for Treatment of Diabetic Nephropathy

2019 ◽  
Vol 12 (3) ◽  
Author(s):  
Nasser Mikhail
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Sglt2 Inhibitors ◽  
Drug Discontinuation ◽  
Protective Effects ◽  
Renal Protection ◽  
Ras Blockers

Background: Sodium-glucose co-transporter 2 (SGLT2) are medications approved for treatment of type 2 diabetes. Recent evidence suggests that these agents exert Reno protective effects. Methods: Review of literature (English, French, Spanish) from January 1990 to November 10, 2019. Searching terms include sodium-glucose co-transporters 2 inhibitors (SGLT2) inhibitors, chronic kidney disease (CKD), end-stage kidney disease (ESKD). Randomized trials, meta-analysis, expert opinions and guidelines are also reviewed. Results: The effects of canagliflozin on renal events were evaluated in patients with type 2 diabetes and albuminuric diabetic nephropathy already on renin-angiotensin (RAS) blockade. The primary outcome was a composite of the incidence of ESKD, doubling of serum creatinine, renal or cardiovascular (CV) death. Canagliflozin was associated with 30% reduction in the incidence of this primary outcome [hazard ratio (HR) 0.70, 95% CI 0.59-0.82, P=0.00001)]. Similar results were generally reported in large CV trials of canagliflozin, empagliflozin and dapagliflozin although renal events were secondary or post-hoc outcomes. Renoprotection by SGLT2 inhibitors was observed in patients with different degrees of renal function at baseline, with or without albuminuria, and taking or not RAS blockers. SGLT2 inhibitors were generally safe with drug discontinuation rates similar to placebo. Canagliflozin was tolerated in patients with eGFR <60 ml/min/1.73 m2. The incidence of acute renal injury was numerically less frequent with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors slow progression of diabetic nephropathy and should be standard of care on top of RAS blockers for renal protection in patients with type 2 diabetes. Regulatory authorities should consider allowing using canagliflozin 100 mg/d in patients with estimated glomerular filtration rate (eGFR) between 30-45 ml/min/1.73 m2./p>

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.

MO645BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH TYPE 2 DIABETES MELLITUS WITH AND WITHOUT DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Daniela Valentinova Monova ◽  
Russka Shumnalieva ◽  
Simeon Monov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Lumbar Spine ◽  
Postmenopausal Women ◽  
Mineral Density ◽  
Urine Albumin Excretion ◽  
Urine Albumin

Abstract Background and Aims Diabetes mellitus and osteoporosis are both common human diseases. Diabetic nephropathy is characterized by the presence of pathological quantities of urine albumin excretion, diabetic glomerular lesions, and loss of glomerular filtration rate in diabetics. Little evidence has been reported on relationships between BMD and albuminuria. The aim of this study is to compare the bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy. Method We retrospectively analyze the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry in 84 postmenopausal women with T2DM with (39) and without (45) diabetic nephropathy. The serum levels of calcium, phosphorus, total alkaline phosphatase, and urine albumin excretion were measured in all participants. Diagnosis of albuminuria was based on albumin-creatinine ratio (ACR). Results Age, body mass index (BMI) and time since menopause were not significantly different between the two groups. The T-scores of basal BMD at L4 were significantly lower in patients with diabetic nephropathy (-0,94 ± 0,40) compared to patients without nephropathy. No significant differences in serum creatinine were detected between two groups of patients. Our data suggest that ACR was negatively associated with lumbar spine and femoral neck BMD. Conclusion Our results suggest that postmenopausal women with diabetic nephropathy have a lower BMD and are at increased risk of osteoporosis in the lumbar spine compared with postmenopausal women without diabetic nephropathy. ACR was negatively associated with lumbar spine and femur neck BMD. One of the explanations that has been proposed for the association between albuminuria and osteoporosis is that albuminuria is associated with reduced bone blood flow, resulting in a decreased rate of bone remodeling and the development of osteoporosis.

Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5231-5242 ◽  
Author(s):  
Hongjie Wang ◽  
Thati Madhusudhan ◽  
Tao He ◽  
Björn Hummel ◽  
Simone Schmidt ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Factor V Leiden ◽  
Diabetic Patients ◽  
High Dose ◽  
Factor V ◽  
Plasminogen Activator Inhibitor 1 ◽  
Coagulation Activation ◽  
Enhanced Coagulation ◽  
Fvl Mutation

Abstract Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.

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