glucuronyl-glucosamine-glycan-sulfate and Diabetes-Mellitus--Type-1

Sulodexide is a heterogeneous group of sulfated glycosaminoglycans (GAGs) that is mainly composed of low-molecular-weight heparin. Clinical studies have demonstrated that sulodexide is capable of reducing urinary albumin excretion rates in patients with type 1 and type 2 diabetes, suggesting that sulodexide has renal protection. However, this efficacy remains inconclusive. In this article, we used meta-analysis to summarize the clinical results of all prospective clinical studies in order to determine the clinical efficacy and safety of sulodexide in diabetic patients with nephropathy. Overall, sulodexide therapy was associated with a significant reduction in urinary protein excretion. In the sulodexide group, 220 (17.7%) achieved at least a 50% decrease in albumin excretion rate compared with only 141 (11.5%) in the placebo. The odds ratio comparing proportions of patients with therapeutic success between the sulodexide and placebo groups was 3.28 (95% confidence interval, 1.34-8.06; P=0.01). These data suggest a renoprotective benefit of sulodexide in patients with diabetes and micro- and macroalbuminuria, which will provide important information for clinical use of this drug as a potential modality for diabetic nephropathy, specifically, the prevention of end-stage renal disease that is often caused by diabetes.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glycosaminoglycans; Humans

To evaluate the effectiveness of sulodexide for the treatment of hard exudates (HE) in non-proliferative diabetic retinopathy (NPDR).. This was a randomized, placebo-controlled, multicenter trial involving 130 patients (65 for each group) who had mild-to-moderate NPDR with macular HE. Participants were given a daily dose of either 50 mg sulodexide or a matching dose of placebo orally for 12 months. Main outcome measure was an improvement in HE defined as a decrease in severity by at least two grades on a 10-grade severity scale. This was evaluated by fundus photography over 12-month period.. The sulodexide group showed significantly greater improvement in HE severity than that shown by the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P = 0.023) for the effect of treatment once adjustments were made for demographic, prognostic and disease confounders. Intention to treat and per-protocol analysis yielded similar results. Sulodexide's safety was comparable to that of the placebo.. Oral sulodexide therapy over 12 months improved macular HE in patients with mild-to-moderate NPDR, without leading to detectable adverse events. The study protocol was registered on clinicaltrial.gov under identifier NCT01295775.

Topics: Administration, Oral; Aged; Anticoagulants; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Double-Blind Method; Female; Fluorescein Angiography; Glycosaminoglycans; Humans; Male; Middle Aged; Visual Acuity

Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine < or =150 micromol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d, 100 mg/d, or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 +/- 0.18 at T0 to 3.98 +/- 0.11 at T4 (P < 0.05), which was maintained till T8 (4.11 +/- 0.13; P < 0.05 versus T0). Moreover, the sulodexide-induced percent reductions in AER at T4 were significantly different from the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%], P = 0.03; 49% [30 to 63%], P = 0.0001; and 74% [64 to 81%], P = 0.0001 in the sulodexide 50, 100, and 200 mg/d groups, respectively. At T8, the sulodexide 200 mg/d group maintained a 62% (45 to 73%) AER significant reduction versus placebo (P = 0.0001). Subanalysis by type of diabetes (DM1 versus DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versus not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.

Topics: Administration, Oral; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Double-Blind Method; Glycosaminoglycans; Humans

Investigation of sulodexide effects on renal function, hemostasis and lipid metabolism in patients with diabetes mellitus.. 20 diabetics (diabetes mellitus type I and II) received sulodexide (Vessel due F) for 3 weeks. This mixture of low molecular heparin and dermatan sylphate was injected i.m. once a day for 5 days a week with a 2-day interval. Micro- and macro-albuminuria diminished after treatment but further returned to baseline levels. The rate of glomerular filtration, blood levels of glucose and cholesterol, hemostatic parameters remained unchanged. Blood triglycerides fell.. Sulodexide may be useful in pathogenetic treatment of diabetic nephropathy.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycosaminoglycans; Hemostasis; Heparin, Low-Molecular-Weight; Humans; Kidney; Lipids; Male; Time Factors

Fifteen out-patients with type I diabetes mellitus and microalbuminuria (mean +/- SEM: 95.4 +/- 13.9 micrograms/min), were administered the glycosaminoglycan sulodexide, with the aim of investigating its influence on the rate of albumin excretion. Sulodexide was given intramuscularly in a dose of 600 lipoproteinlipase releasing units/day for three weeks. Albumin excretion was measured before dosing, at weekly intervals during dosing and also during the subsequent follow-up period of six weeks. Sulodexide yielded a clear-cut and statistically significant lowering of albumin excretion after the first week of treatment (from 95.4 +/- 13.9 micrograms/min to 53.6 +/- 11.1 micrograms/min; p = 0.0055); albumin excretion was further decreased after three weeks of treatment (26.5 +/- 6.05 micrograms/min; p = 0.0007) and was maintained during the follow-up period, at the end of which the mean value was still significantly lower than at baseline (39.6 +/- 10.3 micrograms/min; p = 0.01). Sulodexide short-term administration did not influence the routine haematological, haematochemical and coagulative tests performed contemporaneously. Patients' compliance with treatment was very good and no adverse events were reported.

Topics: Adolescent; Adult; Aged; Albuminuria; Diabetes Mellitus, Type 1; Female; Glycosaminoglycans; Humans; Injections, Intramuscular; Male; Middle Aged; Patient Compliance; Pilot Projects

A novel pathogenetic approach to treatment of diabetic nephropathy (DN) as a severe complication of diabetes mellitus is aimed at inhibiting DN progression or its involution by means of reestablishment of heparan sulfate synthesis by glycosaminoglycane drug. In the study of 9 patients with microalbuminuria and 9 with proteinuria this drug was low-molecular heparin-sulodexide (Alfa-Wasserman, Italy). The treatment course of 3 weeks resulted in albuminuria fall in 89% of patients. In patients with microalbuminuria protein excretion returned to normal values in a week of treatment. This effect was persistent after the drug discontinuation. This was not so for protein excretion in proteinuria patients which became low after 3 weeks of treatment, but the effect was not long-lasting. The authors believe that glycosaminoglycanes hold great promise in DN, especially at early stages of renal diabetic affection.

Topics: Adolescent; Adult; Albuminuria; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glycosaminoglycans; Heparin, Low-Molecular-Weight; Humans; Hypoglycemic Agents; Middle Aged; Time Factors

Albuminuria is a dominant biochemical feature of developing diabetic nephropathy. A disturbed metabolism of heparan sulphate characterized by an increased loss of anionic charges in the basement membrane has been considered as one of the main factors causing an increased albumin output into urine. All therapeutic approaches inducing a reduction of the albumin excretion rate (AER) have a protective effect on renal function. The effect of glycosaminoglycan sulodexide on albuminuria was studied in a group of 53 diabetic patients (26 Type 1 and 27 Type 2) with micro and macroalbuminuria. Sulodexide (Vessel Due F) was administered intramuscularly in one daily dose (600 lipasemic units) for 3 weeks followed by a 6 week wash-out period. A significant decrease of AER was found in a total cohort of patients following just 1 week of sulodexide treatment (mean 162 micrograms/min, range 10-2708 micrograms/min vs mean 248 micrograms/min, range 20-3160 micrograms/min, P < 0.001). This effect lasted 3-6 weeks after drug withdrawal. Similar results were obtained if Type 1 and Type 2 diabetic patients were evaluated separately but a delay of the AER reduction was observed in the latter group. In all patients the mean AER was reduced to 60-65% of the initial values. A greater effect of sulodexide on albuminuria was observed in patients with AER above 200 micrograms/min than in those with microalbuminuria (a reduction to 47 vs 65% of the initial output). Sulodexide did not significantly reduce albuminuria in 28% of diabetic patients ('non-responders'). In conclusion, glycosaminoglycan sulodexide may reduce AER in patients with micro or macroalbuminuria and it could slow down development of diabetic nephropathy.

Topics: Adult; Aged; Albuminuria; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Glycosaminoglycans; Humans; Hypolipidemic Agents; Male; Middle Aged; Pilot Projects; Serum Albumin; Time Factors

The aim of this study was to investigate whether sulodexide treatment is capable of influencing urinary albumin excretion rate (UAER) in insulin-dependent diabetes mellitus patients (type I) with micro- or macroalbuminuria. A total of 14-inpatients (seven with micro and seven with macroalbuminuria) were enrolled and were treated first intramuscularly with a 60 mg vial of sulodexide/day for 10 days, and then orally with 25 mg capsules twice a day for 21 days. UAER was estimated before starting treatment (T0), after the i.m. treatment phase (T1) and at the end of the oral treatment (T2). No statistically significant differences in hematochemical and coagulative parameters were registered after treatment, with respect to basal values. On the contrary, a marked decrease in UAER mean values was registered at the end of both the parenteral and the oral treatment periods (T0: 349.9 mg/24 h, range 80-820; T1: 237 mg/24 h, range 7-620; T2: 91.4 mg/24 h, range: 2-306). All the differences were statistically significant (P < 0.001) versus baseline. At T2, a normalisation of UAER was observed in three microalbuminuric and in two macroalbuminuric patients, and a remarkable decrease was found in additional four and five patients, respectively. UAER was found to be still significantly lower than at baseline after 6 weeks of follow-up. This preliminary study suggests that sulodexide is effective in reducing UAER in type I patients with diabetic nephropathy.

Topics: Adolescent; Adult; Albuminuria; Diabetes Mellitus, Type 1; Female; Glycosaminoglycans; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Reference Values; Time Factors; Treatment Outcome

Sulodexide (Vessel 2F, Italy) was given to 20 patients with diabetes mellitus type I with initial nephropathy. Urine excretion of albumin significantly fell in 18 patients and remained so in 15 patients 6 weeks after the drug discontinuation. Plasma total cholesterol tended to lowering. No changes were registered in hemostasis and carbohydrate metabolism. The authors propose combined administration of sulodexide and inhibitors of angiotensin-converting enzyme for treatment and prevention of diabetic nephropathy progression.

Topics: Adult; Analysis of Variance; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Evaluation; Female; Glycosaminoglycans; Humans; Hypoglycemic Agents; Male; Statistics, Nonparametric; Time Factors

The usefulness of sulodexide in the treatment of severe necrosis of right hand in 42 diabetic patient performing by himself CAPD exchanges is described. Very good results of this treatment, induced us to discuss clinical indications for this drug, which--according to our opinion--is particularly recommended for treatment of severe vascular complications in patients with diabetes and irreversible renal failure.

Topics: Adult; Diabetes Mellitus, Type 1; Glycosaminoglycans; Hand; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Necrosis; Peritoneal Dialysis, Continuous Ambulatory