Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.

Smulders, Yvo M.; Rakic, Melina; Slaats, Ed H.; Treskes, M.; Sijbrands, Eric J.G.; Odekerken, D. A. M.; Stehouwer, Coen D.A.; Silberbusch, J.

doi:10.2337/diacare.22.1.125

Cited by 131 publications

(88 citation statements)

References 15 publications

(17 reference statements)

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“…The association of increased tHcy concentrations with age [15], diabetic retinopathy [35], and nephropathy has been shown to be closely related to declining GFR below a normal value of 80 ml·min·(1.73 m 2 ) -1 [35,36]. After adjustment for GFR, tHcy remained a strong predictor for CHD disease in normotensive Type II diabetic patients, but not for diabetic nephropathy [35,36] or retinopathy [35]. Our data from a larger number of study patients confirms these findings.…”

Section: Discussionsupporting

confidence: 80%

“…Adjustment of the study results for GFR, the more sensitive predictor of renal function, however, has been done by only a few investigators recently. The association of increased tHcy concentrations with age [15], diabetic retinopathy [35], and nephropathy has been shown to be closely related to declining GFR below a normal value of 80 ml·min·(1.73 m 2 ) -1 [35,36]. After adjustment for GFR, tHcy remained a strong predictor for CHD disease in normotensive Type II diabetic patients, but not for diabetic nephropathy [35,36] or retinopathy [35].…”

Section: Discussionmentioning

confidence: 86%

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Total plasma homocysteine is associated with hypertension in Type I diabetic patients

et al. 2002

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Aims/hypothesis. Although hyperhomocysteinaemia and methylenetetrahydrofolate reductase gene polymorphism are accepted risk factors for cardiovascular disease, their association with micro angiopathy or blood pressure in diabetic patients is still being debated. This study explores the relation between plasma homocysteine concentrations, methylenetetrahydrofolate reductase gene polymorphism, hypertension, diabetic microvascular and macrovascular complications associated with kidney function. Methods. Vascular complications, hypertension, methylenetetrahydrofolate reductase genotype (RFLP with Hinf I digestion), and total plasma homocysteine (HPLC) were investigated in 389 well-characterized Type I (insulin-dependent) diabetic patients with normal (GFR≥75 ml·min -1 ·(1.73 m 2 ) -1 ; n=273), or impaired renal function (GFR <75 ml·min -1 ·(1.73 m 2 ) -1 ; n=116). Results. Patients with microvascular and macrovascular complications showed higher total plasma homocysteine concentrations than those without complications. However, after the data for GFR (main determinant for plasma homocysteine) was adjusted we observed that plasma homocysteine concentrations greater than 8.6 µmol/l in patients with normal GFR are not related to vascular complications, but to hypertension (8.6-11.3 µmol/l: OR 1.9; >11.3 µmol/l: OR 3.7). The risk for coronary heart disease (CHD) was also enhanced by a plasma homocysteine concentration greater than 11.3 µmol/l (OR 5.9). Although the T allele was an independent determinant of plasma homocysteine, the methylenetetrahydrofolate reductase gene polymorphism was neither associated with diabetic vascular complications nor with hypertension. The excess mortality in patients with Type I (insulindependent) diabetes mellitus is related to the development of diabetic nephropathy [1], which is associated with an increasing incidence of CHD, retinopathy and rising blood pressure. Epidemiological studies have shown that the risk and severity of those diabetic microvascular and macrovascular complications are strongly related to the duration of diabetes, poor glycaemic control, and hypertension. However, results of interventional trials indicated that intensified insulin treatment and antihypertensive therapy could not en- Conclusion

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 86%

Total plasma homocysteine is associated with hypertension in Type I diabetic patients

et al. 2002

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“…After removal of unbound proteins by washing of the columns with buffer B (20 mmol/l Tris [pH 7.5], 0.5 mmol/l EDTA, 0.5 mmol/l EGTA, and 10 mmol/l ␤-mercaptoethanol), fractions containing PKC were eluted with buffer C (Tris [pH 7.5], 0.5 mmol/l EDTA, 0.5 mmol/l EGTA, 10 mmol/l ␤-mercaptoethanol, and 0.2 mol/l NaCl). Eluates were analyzed for PKC activity, following the optimum conditions of the assay, by measuring the incorporation of 32 P into the synthetic peptide Ac-myelin basic protein (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The specificity of the assay was determined by subtracting the radioactivity obtained in the presence of the pseudosubstrate inhibitor PKC(19-36) from total radioactivity.…”

mentioning

confidence: 99%

Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages

Beauchamp

Renier

2002

Diabetes

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Hyperhomocysteinemia is an independent risk factor for cardiovascular disease in human diabetes. Among the multiple factors that may account for the atherogenicity of homocysteine (Hcys) in patients with diabetes, macrophage (Mo) lipoprotein lipase (LPL) has unique features in that it is increased in human diabetes and acts as a proatherogenic factor in the arterial wall. In the present study, we determined the direct regulatory effect of Hcys on Mo LPL gene expression and secretion.

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“…In recent years HHcy has been recognized as an independent risk factor for early atherosclerotic changes both in the general population (22,23) and in patients with type 2 DM (12,15), in whom HHcy has been associated with renal dysfunction, i.e. development of nephropathy, whereas diabetes mellitus per se most likely is not the cause of increased plasma homocysteine levels (24).…”

Section: Discussionmentioning

confidence: 99%

“…Given that kidney has a leading role in the metabolism of Hcy, plasmatic levels of Hcy largely depend on renal function (10). In type 2 DM Hcy level can be elevated, decreased or unchanged compared to a general population of adequate age (11)(12)(13). This is due to glomerular hyperfiltration or hypofiltration which is characteristic of DM type 2.…”

Section: Introductionmentioning

confidence: 99%

Determining the Relationship Between Homocysteinemia and Biomarkers of Inflammation, Oxidative Stress and Functional Kidney Status in Patients with Diabetic Nephropathy

Čabarkapa¹,

Đerić²,

Stosić³

et al. 2013

Journal of Medical Biochemistry

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Summary Background: One of the leading causes of terminal renal failure is diabetic nephropathy. The aim of this study was to determine the relationship between homocysteine levels and the biomarkers of renal function, inflammation and oxidative stress, as well as the incidence of macrovascular complications in patients with diabetic nephropathy. Methods: Sixty-four patients with diabetic nephropathy were included in this study. They were divided according to their homocysteine levels into two groups: hyperhomocysteinemic (HHcy, n=47) and normohomocysteinemic patients (NHCy, n=17). The re sults were compared to a control group (n=20) with normal renal function and without diabetes. Besides homocysteine, cystatine C, creatinine, urea, albuminuria, creatinine clearance, lipid status parameters, apolipoprotein A-I and B, lipo protein (a), CRP, fibrinogen, oxidative LDL were determined using appropriate methods. The incidence of macro vascular diabetic complications was also determined. Results: The results indicate that the level of renal dysfunction is greater in HHcy than in NHcy patients (p<0.05). In HHcy patients levels of oxLDL were also higher compared to NHcy patients (119.3±140.4 vs. 71.4±50.8 ng/mL, disp< 0.05) as well as fibrinogen levels (4.3±1.3 vs. 3.7±0.8 g/L, p<0.05). The in cidence of macrovascular complications is more frequent in HHcy than in NHcy patients (55.3. vs. 35.3 %, p>0.05), and in patients with macroalbuminuria compared to patients with microalbuminuria (65% vs. 39%, p<0.05). Conclusions: It can be concluded that HHcy is significantly present in patients with diabetic nephropathy, especially if there is greater reduction of renal function. Besides that, significantly higher concentrations of inflammatory (fibrinogen) and oxidative stress (oxLDL) markers were present in HHcy patients with diabetic nephropathy compared to NHcy patients.Therefore in diabetic nephropathy patients it is useful to regularly monitor the levels of homocysteine, as well as inflammatory and markers of oxidative stress.

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Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.

Cited by 131 publications

References 15 publications

Total plasma homocysteine is associated with hypertension in Type I diabetic patients

Total plasma homocysteine is associated with hypertension in Type I diabetic patients

Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages

Determining the Relationship Between Homocysteinemia and Biomarkers of Inflammation, Oxidative Stress and Functional Kidney Status in Patients with Diabetic Nephropathy

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