Progression Of Nephropathy In Type Research Articles

Association of glycosylated hemoglobin with urinary albuminuria for early detection and progression of renal damage in patients with type 2 diabetes mellitus

Background: Regular screening of levels of glycosylated hemoglobin and microalbuminuria (MA), diabetic nephropathy can be prevented.Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus (T2DM) patients. Aim and Objectives: This study was carried out to correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with T2DM. Materials and Methods: This was a case–control study was conducted at tertiary care institute of India. A total 300 subjects included in the present study diagnosed with T2DM according to American diabetes association criteria and the cases are sub grouped based on albumin creatinine ration, the 100 patients T2DM with normoalbuminuria (NA) (ACR Ratio: <30 mg/dL) and 100 patients T2DM with MA (ACR Ratio: 30–299 mg/dL) along with that 100 healthy subjects were included in the study.FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C, and Urinary Albumin was analyzed using laboratory standard methods. Results: The plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin levels were increased in two groups of T2DM Patients when compared to healthy controls. Significantly elevated levels of plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin are observed in all the parameters elevated in between patients T2DM with MA when compared to patients T2DM NA. Conclusion: Elevated levels of Glycated hemoglobin as well as urinary albumin were useful for detection and progression of different stages of nephropathy in patients with T2DM and also this study suggest that continuous monitoring of these investigations were useful for treatment of different stages of T2DM.

IDF21-0124 Relationship between Serum Zinc Status and Diabetic Nephropathy in Algerian Patients with Type 2 Diabetes

Background: Diabetic nephropathy is a microvascular complication associated with diabetes that causes the kidneys to slowly deteriorate, leading to end-stage renal disease. Nephropathy associated with diabetes has been attributed to oxidative stress. Chronic zinc deficiency generally results in an increased sensitivity to the effects of oxidative stress. Zinc deficiency is often seen in diabetic patients. This alteration in zinc status appears to be involved in the development of microvascular complications of diabetes. Aim: The objective of this study will be to explore the relationship between zinc status and the progression of nephropathy in type 2 diabetes. Method: The study involved 80 normotensive diabetic patients with positive microalbuminuria and 60 healthy non-diabetic subjects of corresponding age. For all subjects, a serum zinc assay was performed on the ICE 3300 atomic absorption spectrometer from Thermo Fisher, a serum creatinine assay on Cobas 501 from Roche Diagnostic with evaluation of GFR, as well as a microalbuminuria assay. on the DCA Vantage from Siemens. Results: Serum zinc levels were low (p <0.001) in diabetic patients compared to non-diabetic control subjects. Elevated levels of microalbuminuria (p <0.001) were observed in diabetic patients with low serum zinc levels compared to those with normal serum zinc levels. Serum zinc level in diabetic patients was inversely correlated with serum creatinine (r = −0.51, p <0.001), microalbuminuria (r = −0.587, p <0.001) and positively with GFR (r = 0.24, p <0.01). Discussion: The results of our study support the observation that diabetes affects zinc status with a significant decrease in serum zinc levels at the onset of diabetic complications. During progression to the stages of diabetic nephropathy, morphological and structural changes occur in the glomerular and basal membrane of the kidneys, hyperfiltration, thickening of the glomerular basement membrane. All of these changes will cause albumin with trace metals to leak into the urine. Therefore, the hypozincemia seen in diabetics can be attributed to hyperzincuria. The results of this study are consistent with results reported by others.

Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients.

Vitamin D is a locally acting hormone, which plays a major role in skeletal health. Previous studies reported an important role of vitamin D in modulation of inflammatory response. We aimed to investigate the role of vitamin D deficiency and hypoxia-inducible factor (HIF-1α) as markers for the progression of diabetic nephropathy in Saudi patients with type 2 diabetes mellitus (T2DM). We included 174 Saudi patients with T2DM in addition to 60 healthy control subjects. Patients were classified according to urinary Albumin to Creatinine Ratio (ACR) into three groups: Group AI: ACR < 30 µg/mg, Group AII: ACR levels of 30 - 300 µg/mg and Group AIII: ACR > 300 µg/mg. We estimated fasting blood glucose, HbA1c, lipid profile, serum creatinine, hemoglobin concentration (Hb), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, serum 25 hydroxyvitamin D, calcium, parathyroid hormone (PTH), tumor necrosis factor (TNF-α), C- reactive protein (CRP), and hypoxia-inducible factor (HIF-1α). There was a significant difference among studied groups regarding serum levels of vitamin D, calcium, PTH, TNF-α, CRP, and HIF-1α levels. The level of vitamin D was lower in diabetic patients in comparison to the controls and was significantly related to the severity of renal nephropathy as indicated by the level of albumin in urine. Moreover, vitamin D levels showed significant negative correlation with the inflammatory markers: TNF-α, CRP, and HIF-1α levels. Vitamin D deficiency and elevated HIF-1α serum levels showed a significant correlation to progression of nephropathy in Saudi patients with T2DM.

Correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with type 2 diabetes millitus

diabetic nephropathy is a one of the most leading disorder in patients with type 2 diabetes mellitus. Urinary albuminuria used for detection of nephropathy in type 2 diabetes mellitus but its not an a sensitive and specific biomarker for DN. Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus patients.A total 150 subjects included in the present study in that 100 patients diagnosed with type 2 diabetes mellitus and 50 healthy controls. All the subjects included after informed consent and blood, urine samples were collected from the all the subjects. FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C and Urinary Albumin was analysed by using laboratory standard methods.statistically elevated levels of plasma FBS, PPBS, HbA1C in both the groups of type 2 diabetes mellitus when compared to healthy controls. Serum Urea, Creatinine and Uric Acid levels elevated in type 2 diabetes mellitus with microalbuminuria when compared to other two groups of study subjects. The Glycosylated hemoglobin positively correlated with urinary microalbuminuria in patients with two groups of type 2 diabetes mellitus.This study suggest that the poor glycemic control leads to increased further complications in patients with type 2 diabetes mellitus. Continuous monitoring of HbA1C and Urinary Albumin Levels were useful for progression and treatment of patients with type 2 diabetes mellitus.

Depression Is Associated With Progression of Diabetic Nephropathy in Type 1 Diabetes

To investigate the relationship between depression and diabetic nephropathy progression in type 1 diabetes. Data from 3,730 participants without end-stage renal disease (ESRD) at baseline, participating in the Finnish Diabetic Nephropathy Study, were included. Depression was assessed in three ways. Depression diagnoses were obtained from the Finnish Care Register for Health Care. Antidepressant agent purchase data were obtained from the Drug Prescription Register. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Based on their urinary albumin excretion rate (AER), participants were classified as those with normal AER, microalbuminuria, and macroalbuminuria. Progression from normal AER to microalbuminuria, macroalbuminuria, or ESRD; from microalbuminuria to macroalbuminuria or ESRD; or from macroalbuminuria to ESRD, during the follow-up period, was investigated. Over a mean follow-up period of 9.6 years, renal status deteriorated in 18.4% of the participants. Diagnosed depression and antidepressant purchases before baseline were associated with 53% and 32% increased risk of diabetic nephropathy progression, respectively. Diagnosed depression assessed during follow-up remained associated with increased risk of disease progression (32%). BDI-derived symptoms of depression showed no association with the progression, but the total number of antidepressant purchases modestly reduced the risk (hazard ratio 0.989 [95% CI 0.982-0.997]), P = 0.008). With the sample divided based on median age, the observations followed those seen in the whole group. However, symptoms of depression additionally predicted progression in those age ≤36.5 years. Diagnosed depression and antidepressant purchases are associated with the progression of diabetic nephropathy in type 1 diabetes. Whether successful treatment of depression reduces the risk needs to be determined.

1139-P: Remogliflozin (SGLT2 Inhibitor) Significantly Reduces Albuminuria and Delays the Progression of Nephropathy in Type 2 Diabetes Mellitus Patients

Remogliflozin is a novel SGLT2 inhibitor approved and available in India for the treatment of type 2 diabetes mellitus patients. This study was designed to determine the effect of Remogliflozin on diabetic nephropathy patients compared with placebo on the reduction of the albuminuria. We conducted a 24 week, double-blind, randomized, parallel-group study with 94 type 2 diabetics subjects with diabetic nephropathy (micro albuminuria range from 30 to 300) and HbA1c of 7.5 - 9.3%. Subjects were randomized to Remogliflozin (100 mg bid) and placebo with 1000 mg metformin OD. The primary end point was change in HbA1C from baseline, with secondary end points including change in fasting plasma glucose (FPG), body weight, and change in albuminuria. Safety and tolerability were also characterized. Result: As shown in Table in image. Conclusion: Result of our study revealed that Remogliflozin significantly reduced albuminuria (p value &amp;lt;0.001) in type 2 diabetes mellitus patients with delay in progression of diabetic nephropathy as compared to placebo. Disclosure V.K. Gupta: None.

Potential application of nanoemulsified garlic oil blend in mitigating the progression of type 2 diabetes-mediated nephropathy in Wistar rats.

The renoprotective potential of nanoemulsified garlic oil blend (GNE) in alleviating the progressive stages of hyperlipidemia-mediated diabetic nephropathy was examined. The study was carried out in high fat-fed, streptozotocin-induced type 2 diabetic Wistar rats for five months. The diabetic rats showed a significant increase of area under the curve in OGTT (p < 0.01) and IPITT (p < 0.01), increased urinary albumin (p < 0.01), urinary microprotein (p < 0.001), total cholesterol (p < 0.01), triglycerides (p < 0.001) and LDL cholesterol (p < 0.001), with decreased serum albumin (p < 0.01), serum protein (p < 0.001) and HDL-cholesterol levels (p < 0.05) than the control rats. The histopathological analysis evidenced mesangial expansion and hypercellularity at the end of the first and third month, and glomerulosclerosis and tubular atrophy at the end of the fifth month in diabetic rats. Moreover, on disease progression, increase in urinary podocalyxin, NGAL and CD36 was observed, and the renal mRNA and protein expression of podocalyxin decreased significantly with a concomitant increase in NGAL and CD36 expression from first till fifth month end. The treatment with GNE (20mg/kg) significantly ameliorated the serum albumin (p < 0.001) and urine albumin (p < 0.01) from the end of the third month with significant attenuation in the lipid profile than GO (20mg/kg) or Ator (8mg/kg). Moreover, GNE reverted the histopathological alterations and attenuated the aberrant mRNA, protein expression and urinary excretion level of renal CD36, podocalyxin and NGAL in diabetic rats from an early stage of disease till the end of the study period. This study demonstrated the enhanced efficacy of GO in nanoemulsified form in mitigating the progression of nephropathy in type 2 diabetic rats.

The Evaluation of SCUBE-1 and sCD40L Levels in Diabetic Nephropathy

Aim: There is a close link between diabetic nephropathy and atherosclerotic heart disease. We aimed to evaluate the changes of SCUBE-1 and sCD40L, which play role in the course of atherosclerosis, with the progression of nephropathy in patients with type 2 diabetes.Material and Methods: Thirty healthy subjects (group 1) and 74 patients with type 2 diabetes (divided into 3 groups as normal albuminuria group (group 2, n=33), moderately increased albuminuria group (group 3, n=22) and severely increased albuminuria group (group 4, n=19)) were enrolled in the study. Plasma SCUBE-1 and sCD40L levels were measured using the enzyme-linked immunosorbent assay technique.Results: Mean SCUBE-1 levels were significantly higher in group 4 compared to group 1 and group 2 (p=0.005 and p=0.014, respectively) and in group 3 compared to group 1 and group 2 (p=0.011 and p=0.028, respectively). Mean sCD40L levels were significantly higher in group 4 than in other three groups (all p&amp;lt;0.001), and in group 3 than in group 1 and group 2 (p=0.001 and p=0.016, respectively). Furthermore, SCUBE-1 level was positively correlated with total cholesterol level (r=0.212, p=0.031) and triglyceride (r=0.194, p=0.049). Likewise, sCD40L level was positively correlated with only creatinine level (r=0.297, p=0.002).Conclusion: SCUBE-1 and sCD40L levels increased with the progression of nephropathy in type 2 diabetes. This increment suggested that SCUBE-1 and sCD40L may play key role in the course of atherosclerosis due to diabetic nephropathy and, diabetic nephropathy may affect the levels of these parameters.

Anti- Asprosin: A Potential Protective Role Against the Progression of Diabetic Nephropathy in Type 2 Diabetic Rats

Anti- Asprosin: A Potential Protective Role Against the Progression of Diabetic Nephropathy in Type 2 Diabetic Rats

Reno-protective effect of angiotensin converting enzyme inhibitor and angiotensin II receptor blockers in type 2 diabetic nephropathy with elevated urine albumin to creatinine ratio

Background: Nephropathy is responsible for an End Stage Renal Disease (ESRD) in type 2 diabetics if uncontrolled. The monotherapy/combination of Angiotensin Converting Enzyme inhibitor (ACEi) and Angiotensin II Receptor Blockers (ARBs) can retard the progression of urine albumin to creatinine ratio in diabetic nephropathy but, the data shows an inconsistency in the efficacy of these drugs. So, the present study was aimed at comparing the reno-protective effect of ACEi/ARBs in type 2 diabetics.Methods: A prospective, randomized study is conducted at Maharaja’s Institute of Medical Sciences, Nellimarla, Vizianagaram, Andhra Pradesh, India with 100 patients, who are randomly categorised and equally distributed among the two groups and treated with Enalapril (ACEi) and Losartan (ARBs) for 6 months. 24-hour urine albumin to creatinine ratio and HbA1c are recorded before and after the treatment.Results: Enalapril and losartan showed a non-significant reduction in urine albumin to creatinine ratio from 196.2±17.5 to 185.9±15.2 (p=0.66) and 236.8±16.3 to 193.7±20.6 (p=0.11) respectively. A strict glycemic control has shown a reduction in HbA1c in both the groups.Conclusions: Present findings suggested that losartan is relatively more effective than enalapril in reducing the 24-hour urine albumin to creatinine ratio of diabetic nephropathy patients. Along with these drugs, regulation of blood glucose will assist in retarding the progression of nephropathy in type 2 diabetics.

Effects of sarpogrelate on microvascular complications with type 2 diabetes.

Background Diabetes is a major cause of microvascular complications. Renin-angiotensin-aldosterone blockers have been known to have the benefits of delaying onset and progression of diabetic complications including nephropathy. Objective To evaluate the effect of sarpogrelate, an antiplatelet agent, on the new onset diabetic complications in patients with type 2 diabetes mellitus. Setting A 1108-bed tertiary university hospitalin Korea. Methods A retrospective cohort study was conducted using electronic medical records between 2010 and 2015 in Korea. The study cohort of the propensity score matched patients with or without sarpogrelate was evaluated for the diabetic complications identified with the diagnosis codes in T2DM patients on the metformin based antidiabetic therapy. Nephropathy was further evaluated for progression of kidney function. Main outcome measure The incidence of composite microvascular complications included nephropathy, neuropathy, and retinopathy. Results The 1:2 propensity score matched 478 out of 14,440 patients were included in the final analysis with or without sarpogrelate (162 vs. 316 patients). The incidence of nephropathy, neuropathy, and retinopathy was 1.23% versus 5.38% (HR 0.21, 95% CI 0.05-0.92), 1.23% versus 4.43% (HR 0.26, 95% CI 0.06-1.14), and 6.17% versus 6.33% (HR 0.93, 95% CI 0.43-1.97) with sarpogrelate and without sarpogrelate, respectively. Changes in the estimated glomerular filtration rate and urine albumin creatinine ratio were not significantly different between the groups. Conclusion In Korean patients, sarpogrelate, an antiplatelet agent, was associated with reducing the incidence and progression of nephropathyin type 2 diabetes, but not associated with the composite endpoints including neuropathy and retinopathy.

Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1

AimsDiabetic nephropathy (DN) that progress to end stage renal failure is a serious health problem. Autophagy is involved in DN pathogenesis. Finding renal prognostic biomarkers can help in the future renal status prevision. Therefore, the aim of current study was to evaluate and correlate circulating levels of autophagy regulator protein Unc-51-like kinase 1 (ULK-1) with the widely expressed receptor in mammalian kidney; epidermal growth factor receptor (EGFR); and the key functional podocyte protein podocin (PDCN). MethodsSerum levels were assessed by ELISA in 72 type 2 diabetic patients classified according to their urinary albumin/creatinine ratio; 19 normoalbuminuric, 37 microalbuminuric and 16 macroalbuminuric patients; age and sex matched with 18 healthy controls. ResultsMicroalbuminuria and macroalbuminuria patients exhibited decreased ULK-1, EGFR and PDCN levels. Only EGFR showed lower levels in normoalbuminuria compared with controls. ULK-1 and EGFR were significantly higher in normoalbuminuria compared with microalbuminuria and macroalbuminuria patients. ULK-1, EGFR and PDCN were correlated with each other and with some metabolic parameters. ConclusionsULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive DN risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.

Serum Galectin-3 and All-Cause Mortality in Type 2 Diabetes

Background and Aims: Galectin-3, a member of the multifunctional galectin family, is ubiquitously expressed and acts a broad-spectrum biological response modifier. It is involved in tissue fibrosis, tumorigenesis, immunity and inflammatory response. It can also act as a receptor for advanced glycation end products. Recent evidence suggests that galectin-3 is associated with heart failure and with progression of nephropathy in type 2 diabetes. We have therefore evaluated whether serum galectin-3 level is associated with all-cause mortality in patients with type 2 diabetes. Materials and Methods: Galectin-3 was measured in the baseline serum samples by ELISA in 1495 type 2 diabetic patients followed up in a teaching hospital specialist diabetes clinic. All-cause mortality was ascertained from hospital electronic medical records. Results: The mean age of the subjects was 55.3 ± 9.9 years and 54% were male. During a median follow-up of 11 years, 169 subjects died from all causes, and baseline serum galectin-3 levels were significantly higher in subjects with a fatal outcome (9.86 ± 3.11 ng/ml vs. 8.15 ± 2.73, p&amp;lt;0.01). When galectin-3 was analyzed as quartiles, individuals in the third quartile [hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.2-3.2, p&amp;lt;0.01] and the highest quartile (HR 3.9, 95% CI 2.6-6.0, p&amp;lt;0.01) had significantly elevated risk of a fatal outcome compared to those in the lowest quartile. Multivariable Cox regression analysis showed a significant association between serum galectin-3 level and all-cause mortality and the association remained significant even after adjustment for potential confounders including age, sex, body mass index, duration of diabetes, smoking, baseline HbA1c, systolic blood pressure, LDL and albuminuria status. Conclusion: Elevated serum galectin-3 level was independently associated with all-cause mortality in patients with type 2 diabetes. Galectin-3 may potentially be useful as a predictor of adverse outcome. Disclosure K.C.B. Tan: None. S. Shiu: None. J.K.Y. Lam: None. A.C. Lee: None. Y. Wong: None.

Klotho Prevented Epithelial-to-Mesenchymal Transition in High-Fat Diet/Streptozotocin-Induced Mice by Targeting NFkB/Microrna-21/Smad7 Signaling Pathway

Klotho is an antiaging hormone present in the kidney that protect renal via attenuating the nuclear factor-kB (NFkB) p65 activity. And in kidney epithelium miRNAs become active in response to injury. But little is known regarding to the role of Klotho on miRNAs in the pathogenesis of diabetic nephropathy(DN). In this study, we found that the expression of Klotho was reduced with upregulation of miR-21 and key parameters of DN in HFD/STZ-induced diabetic mice. Klotho-treatment reduced p65 nucleus expression in association with modulation of miR-21/Smad7 and amelioration of fibrosis. Furthermore, we found that Klotho expression was decreased in high glucose induced HK2 at both mRNA and protein, accompanied by the significantly increased miR-21 expression. NF-κB was demonstrated to regulate miR-21 expression by directly binding to its promotor. Additionally, exogenous addition of Klotho or inhibition of NF-kB restrained the activity of miR-21/Smad7 signaling pathways, which suppressed fibrosis in high glucose cultured HK2. This study provides a new basis to elucidate the protection mechanism of anti-aging protein Klotho in diabetic kidney. We firstly found that Klotho treatment could delay the fobrosis progression of diabetic nephropathy in type 2 diabetic mice via inhibition of NF-kB/miR-21/Smad7 signaling cascade pathways. Disclosure M. Xue: None. F. Hu: None. Y. Li: None. Y. Jia: None. Y. Xue: None.

Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus.

Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum galectin-3 level is associated with progressive kidney disease in type 2 diabetes. Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30mlmin-1 1.73m-2. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline. Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60mlmin-1 1.73m-2 compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29ng/ml vs 6.10 ± 1.91ng/ml, respectively, p < 0.01). In the whole diabetic cohort, after a mean follow-up of 9years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24, p < 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30, p < 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria. Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.

Urate-Lowering Therapy Ameliorates Kidney Function in Type 2 Diabetes Patients With Hyperuricemia.

BackgroundHyperuricemia often causes kidney dysfunction which increases serum urate, forming a vicious cycle in the kidney. In this study, urate-lowering therapy was demonstrated in type 2 diabetic patients with hyperuricemia to evaluate the effect on diabetic nephropathy.MethodsType 2 diabetic patients with hyperuricemia (n = 34) were treated by urate-lowering drugs. Serum urate levels, estimated glomerular filtration rate (eGFR), blood pressure, HbA1c, and urinary albumin-to-creatinine ratio (UACR) were measured for 52 weeks. The parameters at the endpoint when serum urate decreased to below 6.0 mg/dL and at 52 weeks were compared to the initial levels at week 0.ResultsSerum urate level decreased to the endpoint in all patients and was maintained at under 6.0 mg/dL throughout the observation period. eGFR significantly increased at the endpoint and also at 52 weeks. Overall UACR did not change after 52 weeks; however, the treatment decreased UACR significantly in patients with no microalbuminuria. There was a negative relationship between the change of serum urate levels and the change of eGFR, and a negative relationship between the baseline UACR and the change of UACR when patients with macroalbuminuria were excluded. There were no changes in HbA1c levels and blood pressure before and after the treatment.ConclusionsThere were significant improvements in kidney function by lowering serum urate levels to under 6.0 mg/dL and the effect was maintained for at least 52 weeks. This treatment may be one strategy to slow the progression of nephropathy in type 2 diabetic patients with hyperuricemia.

The Efficacy of Niacin-Bound Chromium to Slow the Progression of Diabetic Nephropathy in Type II Diabetic Rats

Animal and clinical studies suggest niacin-bound chromium (NBC) added to the diet improves glucose-insulin sensitivity, the ability to ameliorate inflammation, hypertension, and proteinuria. In addition to its lipid-lowering actions, NBC possesses potent antioxidant and anti-inflammatory properties. Rat studies demonstrated that T2DM decreases both the production and bioavailability of nitric oxide (NO), and we hypothesized that NBC supplementation will preserve NO production via increased endothelial nitric oxide synthase (eNOS) and decreased neuronal nitric oxide synthase (nNOS). NBC supplementation decreased levels of plasma creatinine in the treated diabetic rats compared to the untreated diabetic rats, and therefore preserved glomerular filtration rate (GFR). We provide evidence that this effect may also be due to increased levels of eNOS, which leads to renal microvascular vasodilation. Supplementation of NBC also lowered nNOS levels, which is a significant finding when considering the role of nNOS in T2DM. Marked improvements in fasting glucose and lower body weights were observed in the treated diabetic rats compared to the untreated diabetic rats. Therefore, these results demonstrate that NBC supplementation slows the progression of diabetic nephropathy (DN) in type 2 diabetic rats.

Association of Postbreakfast Triglyceride and Visit-to-Visit Annual Variation of Fasting Plasma Glucose with Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes.

Urinary albumin/creatinine ratio (ACR) was measured at baseline and after a median follow-up of 6.0 years in 161 patients with type 2 diabetes. Intrapersonal means and SD of HbA1c, systolic BP, fasting, and postmeal plasma glucose (FPG and PMPG, resp.) and serum triglycerides (FTG and PMTG, resp.) were calculated in each patient during the first 12 months after enrollment. Associations of these variables with nephropathy progression (15 patients with progression of albuminuric stages and 5 with ACR doubling within the microalbuminuric range) were determined by multivariate logistic regression analysis providing odds ratio with 95% confidential interval. Patients with nephropathy progression, compared with those without nephropathy progression, had higher HbA1c (p < 0.01). They also had higher means and SD of FPG (both p < 0.05), FTG (both p < 0.05), and PMTG (p = 0.001). Multivariate logistic regression analysis demonstrated that SD-FPG (1.036, 1.001–1.073, p = 0.04) and PMTG (1.013, 1.008–1.040, p = 0.001) were significant predictors of progression of nephropathy even after adjustment for mean FPG and SD-FTG, age, sex, BMI, waist circumference, diabetes duration and therapy, means and SDs of HbA1c, PPG, FTG and systolic BP, baseline ACR, smoking status, and uses of antihypertensive and lipid-lowering medications. Consistency of glycemic control and management of postmeal TG may be important to prevent nephropathy progression in type 2 diabetic patients.

Myrciaria cauliflora extracts attenuate diabetic nephropathy involving the Ras signaling pathway in streptozotocin/nicotinamide mice on a high fat diet

Diabetic nephropathy (DN) is a major cause of end-stage renal disease and its mortality is continuously increasing worldwide. Previous studies indicate that reactive oxygen species play an important role in high glucose-induced renal injury. Myrciaria cauliflora has been reported as a functional food rich in anthocyanins possessing anti-oxidative and anti-inflammatory properties. This study examined whether M. cauliflora extracts (MCE) can attenuate diabetic nephropathy progression in type 2 diabetes mellitus mice. First, the composition of the anthocyanins and polyphenols of MCE were determined by high-performance liquid chromatography and spectrophotometry. One hundred mg/kg of streptozotocin and 240 mg/kg nicotinamide were administered to C57BL/6J mice fed a high fat diet and varied concentrations of MCE. The plasma glucose concentration, body weight, oral glucose tolerance, blood pressure, renal ultrasound ultrasonic wave were monitored every 2 weeks. Following euthanasia, the kidneys of the mice were analyzed using hematoxylin–eosin, periodic acid Schiff, Masson's trichrome, and immunohistochemistry staining. The results showed that MCE stabilized the plasma glucose and indirectly improved insulin sensitivity in diabetic mice. In addition, diabetes-caused glomerular atrophy, accumulation of saccharide, and formation of collagen IV were recovered or reduced under treatment with MCE in diabetic mice. Our results indicate that MCE has beneficial effects in DN and the mechanism has been confirmed to inhibit Ras/PI3K/Akt and kidney fibrosis related proteins. This work illustrates the potential of MCE rich in anthocyanins and polyphenols as a natural food to inhibit DN.

The Value of Serum Prolidase Activity in Progression of Microalbuminuria in Patients With Type 2 Diabetes Mellitus.

Prolidase is a cytosolic exopeptidase that plays a pivotal role in collagen turnover. Diabetic nephropathy (DN) is associated with structural changes in glomerular basement membrane accompanied with increased amounts of collagen. Prolidase is known to be abundant in kidney and collagen accumulation is increased in DN, so we aimed to determine the value of serum prolidase activity (SPA) in predicting the progression of nephropathy in type 2 diabetes mellitus (DM). Thirty type 2 DM patients having microalbuminuria (microalbuminuric group), 30 type 2 DM patients without albuminuria (normoalbuminuric group), and 28 healthy controls (control group) were enrolled. Study groups had similar age, sex distribution, and body mass index (BMI). Metabolic parameters, SPA and urinary microalbumin were determined. SPA was significantly higher in microalbuminuric group when compared with normoalbuminuric and control groups (P = 0.05 and P < 0.001, respectively). Triglyceride levels were significantly higher and high density lipoprotein cholesterol (HDL-C) levels were significantly lower in microalbuminuric group compared to control group (Both P < 0.05). SPA showed a negative correlation with HDL-C level and a positive correlation with urinary albumin excretion (r = -0.219, P < 0.05 and r = 0.39, P < 0.001 respectively). In regression analysis, albumin excretion was the sole parameter influencing SPA. SPA appears to be higher in type 2 DM patients having microalbuminuria compared to patients without microalbuminuria and healthy controls. The pathophysiological role and the significance of SPA in predicting DN need to be further evaluated.