scholarly journals Disturbed Homocysteine and Methionine Cycle Intermediates S-Adenosylhomocysteine and S-Adenosylmethionine Are Related to Degree of Renal Insufficiency in Type 2 Diabetes

2005 ◽  
Vol 51 (5) ◽  
pp. 891-897 ◽  
Author(s):  
Wolfgang Herrmann ◽  
Heike Schorr ◽  
Rima Obeid ◽  
Julia Makowski ◽  
Brian Fowler ◽  
...  

Abstract Background: Diabetic nephropathy is a common complication in patients with type 2 diabetes that may increase atherothrombotic risk. Hyperhomocysteinemia (HHcy) further increases the risk in those patients. We studied concentrations of total homocysteine (tHcy) and its related metabolites S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in relation to B-vitamin status and renal function in patients with type 2 diabetes who developed diabetic nephropathy. Methods: The study included 93 patients with renal failure and type 2 diabetes. Chronic kidney disease was classified into four subgroups according to the National Kidney Foundation based on glomerular filtration rate plus pathologic abnormalities or markers of kidney damage. Results: Serum or plasma concentrations of the metabolites increased significantly with worsening of renal function, whereas serum concentrations of the B vitamins (folate, vitamins B12 and B6) did not differ appreciably between the groups. Moreover, plasma concentrations of AdoHcy and AdoMet were markedly increased in patients with kidney failure compared with those in stage 2 (median AdoHcy, 112.7 vs 10.5 nmol/L; median AdoMet, 162.0 vs 80.0 nmol/L). The AdoMet/AdoHcy ratio was more than 80% lower in patients with renal failure compared with stage 2. Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine. Conclusions: Increased plasma concentrations of tHcy and methionine cycle intermediates (AdoMet, AdoHcy) are related to disturbed renal function in patients with type 2 diabetes. Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet. The effect of therapeutic doses of the B vitamins on AdoMet, AdoHcy, and their ratio should be tested in renal patients.

1989 ◽  
Vol 61 (03) ◽  
pp. 522-525 ◽  
Author(s):  
M P Gordge ◽  
R W Faint ◽  
P B Rylance ◽  
H Ireland ◽  
D A Lane ◽  
...  

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.


2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Hidenori Hirukawa ◽  
Shinji Kamei ◽  
Tomohiko Kimura ◽  
Atsushi Obata ◽  
Kenji Kohara ◽  
...  

It is very important to explore how we can reduce urinary albumin excretion which is an independent risk factor for ischemic heart disease. In this study, we retrospectively evaluated the effects of RAS inhibitor therapy on diabetic nephropathy in Japanese subjects whose urinary albumin levels were within normal range. We enrolled 100 subjects with type 2 diabetes who did not take any renin-angiotensin system (RAS) inhibitor. We defined the subjects taking RAS inhibitor for more than 3 years as RAS inhibitor group. RAS inhibitor exerted protective effect on the progression of urinary albumin excretion in subjects with type 2 diabetes without diabetic nephropathy. In addition, RAS inhibitor exerted more protective effects on renal function especially in subjects with poor glycemic control. In conclusion, RAS inhibitor could protect renal function against the deleterious effect of chronic hyperglycemia in Japanese subjects with type 2 diabetes even before the onset of diabetic nephropathy.


Author(s):  
Sebastian Hörber ◽  
Angela Lehn-Stefan ◽  
Anja Hieronimus ◽  
Sarah Hudak ◽  
Louise Fritsche ◽  
...  

Abstract Background Type 2 diabetes mellitus (T2DM) promotes the development of atherosclerosis and is a major risk factor for cardiovascular disease. High-sensitivity cardiac troponin I (hs-cTnI) assays fundamentally improved the diagnosis of myocardial injury and even enable the prediction of future cardiovascular events in the general population. However, data about the association of hs-cTnI with cardiovascular risk factors and carotid intima media thickness (cIMT) as a marker of atherosclerosis are limited, especially in patients with T2DM. Methods In this cross-sectional study we analyzed clinical and laboratory parameters of 234 patients (43% women) with T2DM and a median age of 65 years (interquartile range: 57–71). The median duration of diabetes mellitus was 10 years (6–17). Anthropometric data, blood pressure, glycemic parameters and lipid profiles were determined. Hs-cTnI plasma concentrations were measured on an ADVIA Centaur XPT immunoassay analyzer and cIMT was evaluated by high-resolution ultrasound. Results Hs-cTnI plasma concentrations were below the gender-specific 99th  percentile in 93% of T2DM patients with a median concentration of 4.0 ng/l (interquartile range: 2.0–10.0). Hs-cTnI was significantly associated with gender, renal function and C-reactive protein in the entire study cohort. Gender-specific analyses revealed cIMT and renal function to be significantly associated with hs-cTnI in men. Contrary, only age was significantly associated with hs-cTnI in women. Conclusion In a real-world clinical setting in patients with T2DM, cIMT is a predictor of subclinical myocardial damage in men, but not in women.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kachonsak Yongwatana ◽  
Ouppatham Supasyndh ◽  
Bancha Satirapoj

Background. Glycosaminoglycan plays an important role in the maintenance of glomerular charge selectivity of diabetic nephropathy. Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has shown a nephroprotective effect in an experimental model of diabetic nephropathy. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects in patients with type 2 diabetes with significant proteinuria have not been established. Objectives. The study was aimed at investigating the effects of sulodexide on proteinuria and renal function in patients with type 2 diabetes and nephropathy. Methods. Fifty-two patients with proteinuria between 500 and 3000 mg/day received sulodexide 200 mg/day for 12 months, while 56 matched patients with type 2 diabetes constituted the control group. All patients received standard metabolic and blood pressure controls. Primary outcome was evaluated as percentage of reduced proteinuria compared with the control group. Renal function was assessed using estimated glomerular filtration rate (GFR). Results. Proteinuria significantly increased in the control group [0.9 (IQR 0.3 to 1.78) to 1.16 (IQR 0.44 to 2.23) g/gCr, P=0.001], whereas it remained stable in the sulodexide group [0.66 (IQR 0.23 to 0.67) to 0.67 (IQR 0.17 to 1.51) g/gCr, P=0.108]. At 12 months, proteinuria was higher by 19.4% (IQR 10.3 to 37.6) in the control group while proteinuria was lower by -17.7% (IQR -53.1 to 3.2) in the sulodexide group with a significant difference between groups (P=0.001). Renal function was noted as a change of estimated GFR, and serum creatinine decreased significantly during the study in both groups but did not significantly differ between groups. No significant changes in the blood pressure, fasting plasma glucose, and hemoglobin A1C were reported. Conclusion. In addition to standard treatment, sulodexide is efficient in maintaining proteinuria in patients with type 2 diabetes with nonnephrotic range proteinuria, but it did not provide an additional benefit concerning renal disease progression.


Author(s):  
S.I. Ismailov ◽  
◽  
S.U. Muminova ◽  

Aim of the study: To study the effect of prescribing inhibitors of sodium glucose cotransporter type 2 (iSGLT-2) and inhibitors of dipeptidyl peptidase-4 (iDDP-4) on the parameters of carbohydrate metabolism in patients with type 2 diabetes. Materials and methods: A prospective study included 80 patients with type 2 diabetes. The average age was 52.7 ± 3.78 years; diabetes experience - 8 years; BMI-30 ± 0.17; Hb1C-9.2 ± 0.4%; fasting glycemia –10.2 mmol/; eGFR-78 ml/min; TG-2.7 ± 0.44; total cholesterol-3.4 ± 0.72; MAU 32 ± 0.125. The patients were divided into 2 groups: group 1 - 30 patients with DN with impaired renal function and 30 patients with diabetic nephropathy without renal dysfunction in the presence of metformin + iSGLT- 2; 2 group of 30 patients with impaired renal function and 30 patients with diabetic nephropathy without impaired renal function on the background of metformin + iDPP-4. Results: The study of the effect of the inclusion of drugs iSGLT-2 (group 1) and iDPP-4 (group 2) showed a positive dynamics of carbohydrate metabolism indicators in patients with type 2 diabetes. So if the initial indicators in the groups were comparable in terms of glycemic control indicators, then by the 3rd month of treatment there was a significant decrease in HbA1c in the 1st group of patients in relation to the 2nd group. The result of the correction performed within 3 months was the achievement of the state of compensation in the 1st group in 36.7%, and in the 2nd group in 28.3%, 48.3% of the patients of the 1st group were brought into the state of sub compensation and 31.7 % of patients of the 2nd group. Conclusion: On the combination of metformin and INGLT-2, a larger number of patients managed to achieve the set goals of therapy with a lower risk of overt hypoglycemia, then this combination should be considered not only more effective.


2012 ◽  
Vol 1 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Ram P Narayanan ◽  
Bo Fu ◽  
Adrian H Heald ◽  
Kirk W Siddals ◽  
Robert L Oliver ◽  
...  

ObjectiveInsulin-like growth factors are implicated in the development of diabetic nephropathy. IGF-binding protein 2 (IGFBP2) and IGF2 are expressed in the kidney, but their associations with diabetic nephropathy are unclear. We therefore tested the hypothesis that circulating levels of IGF2 and IGFBP2 predict longitudinal renal function in individuals with type 2 diabetes.Design and methodsIGFBP2 and IGF2 measurements were performed in 436 individuals (263 males) with type 2 diabetes. Linear mixed-effect regression analysis was used to model the relationship between plasma IGFBP2 concentration and longitudinal changes in estimated glomerular filtration rate (eGFR) over an 8-year period. Analyses were also performed for IGF1, IGF2, IGFBP1 and IGFBP3 concentrations as predictors of longitudinal renal outcomes.ResultsHigh IGFBP2 concentration at baseline was associated with a decreased eGFR over an 8-year period (β=−0.02, (95% confidence interval −0.03 to −0.01), P<0.001). High IGFBP1, IGFBP2 and IGFBP3 were also associated with low baseline eGFR concentration.ConclusionThis study demonstrates that IGFBP2 is a predictor of longitudinal deterioration of renal function in type 2 diabetes.


2021 ◽  
Vol 10 (23) ◽  
pp. 1794-1798
Author(s):  
Lata Kanyal Butola ◽  
Roshan Kumar Jha ◽  
Ranjit Ambad ◽  
Deepika Kanyal ◽  
Jayshri Jankar

Several studies have confirmed the increased incidence of vitamin B12 deficiency in patients with type 2 diabetes mellitus. Metformin is currently the most commonly used anti-diabetic drug, metformin being prescribed as first-line therapy for patients with type 2 diabetes mellitus (T2DM) worldwide. Other disorders including insulin resistance, such as polycystic ovary syndrome (PCOS), can also be treated with metformin. Metformin has positive effects on metabolism, weight loss, and vascular defence of carbohydrates, but it also has significant side effects. Patients on long-term treatment with metformin, for example, have been shown to be at risk of anemia. This may be because of a decrease in metformin-related vitamin B12. It is estimated that 30 percent of patients undergoing long-term metformin treatment have experienced vitamin B12 malabsorption, with a 14 percent to 30 percent reduction in serum vitamin B12 concentration. A critical nutrient for wellbeing is vitamin B12. It plays a significant role in the functioning and the production of red blood cells in the brain and nervous system. In addition to anemia, a deficiency of vitamin B12 may increase the severity of peripheral neuropathy in T2DM patients. In addition, since vitamin B12 is involved in the most critical homocysteine (Hcy) metabolism pathway, a decrease in vitamin B12 will increase plasma concentrations of Hcy, which in patients with T2DM and PCOS is closely linked to cardiovascular disease. Evaluating serum vitamin B12 levels will also provide an early diagnosis of the status of the deficiency. This will offer an incentive for harm caused by routine screening and early detection to be reversed. KEY WORDS Vitamin B12, Metformin, Diabetes Mellitus, Glycated Hb


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Yen-Ling Chiu ◽  
Wan-Chuan Tsai ◽  
Ruo-Wei Hung ◽  
I-Yu Chen ◽  
Kai-Hsiang Shu ◽  
...  

Abstract Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.


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