chondroitin-sulfates and Diabetes-Mellitus--Type-2

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Topics: Adult; Aged; Analysis of Variance; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Exudates and Transudates; Female; Follow-Up Studies; Heparitin Sulfate; Humans; Kidney Function Tests; Male; Middle Aged; Proteinuria; Reference Values; Statistics, Nonparametric; von Willebrand Factor

Topics: Administration, Oral; alpha-Amylases; Animals; Blood Glucose; Cattle; Chondroitin Sulfates; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Inhibitory Concentration 50; Male; Mice; Sharks; Species Specificity; Streptozocin; Swine; Treatment Outcome

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1β, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm

Topics: Aging; Animals; Bone Density; Bone Resorption; Chondroitin Sulfates; Collagen Type II; Diabetes Mellitus, Type 2; Gene Expression Regulation; Glucosamine; Humans; Inflammation; Interleukin-1beta; Mice; Mice, Inbred NOD; Oxidative Stress; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Diabetic foot ulcers may lead to nontraumatic amputations of the foot, leading to a decrease in patient quality of life. Transmetatarsal amputations (TMAs) represent an effective surgical procedure in cases of severe foot infection, but the tissue reconstruction is complicated and additional procedures should be considered. The present case report evaluates the wound closure of an open TMA in a patient with diabetes treated with a new aerogel composed of chitosan (ChS) and chondroitin sulphate (CS), without needing a skin graft.. A 72-year-old man with diabetes and a history of successive amputations was admitted to a hospital in Valdivia, Chile, due to a severe infection of toes 2 and 4 of the right foot. After the diagnosis of gangrene and osteomyelitis, the patient underwent a TMA of his right forefoot. The surgeon proposed the incorporation of ChS and CS aerogels to accelerate wound healing to avoid another surgical procedure. The TMA surgical wound area closed 50% after day 28 from starting treatment with aerogels. Complete closure was achieved at day 94 of treatment with aerogels, with good epithelial tissue and favorable cosmetic results and without residual limb deformities. The patient experienced minimal physical and psychological impairment from the procedure. Other surgical procedures were not necessary.. Due to the results of this patient, use of ChS and CS aerogels could represent an alternative treatment for forefoot TMA wound closure and prevent further surgical procedures, such as skin grafting. Future works should consider a larger number of cases.

Topics: Aged; Amputation, Surgical; Chitosan; Chondroitin Sulfates; Diabetes Mellitus, Type 2; Diabetic Foot; Gangrene; Gels; Humans; Male; Metatarsus; Osteomyelitis; Wound Healing

Diabetes mellitus is a global health problem representing the fifth leading cause of mortality and a major risk factor for cardiovascular diseases. In the last years, we reported an association among urinary trypsin inhibitor (UTI), a small proteoglycan that plays pleiotropic roles in many inflammatory processes, and both type 1 and 2 diabetes and developed a method for its direct quantitation and structural characterization.. Urine from 39 patients affected by type 1 diabetes, 32 patients with type 2 diabetes, and 52 controls were analysed. UTI was separated from the main glycosaminoglycans physiologically present in urine by anion exchange chromatography, treated for chondroitin sulphate (CS) chain complete depolymerisation, and analysed for both UTI content and CS structure. UTI identification was performed by nano-LC-MS/MS analysis.. We evidenced increased UTI levels, as well as reduced sulphation of its CS moiety in association with diabetes, regardless of both age and medium-term glycaemic control. Furthermore, no association between UTI and albumin excretion rate was found.. Evidences suggest that UTI levels are not directly correlated with renal function or, otherwise, that they may increase before the onset of renal impairment in diabetes, representing a potential marker for the underlying inflammatory condition.

Topics: Adolescent; Adult; Aged; Biomarkers; Carbohydrates; Case-Control Studies; Chondroitin Sulfates; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Electrophoresis; Female; Glycoproteins; Humans; Male; Middle Aged; Renal Insufficiency; Urinalysis; Young Adult

Endoplasmic reticulum (ER) stress-associated inflammation positively contributes to insulin resistance. It is also known that fucosylated chondroitin sulphate from Cusumaria frondosa (Cf-CHS) can mitigate insulin resistance; however, its effects on ER stress and inflammation are not well understood. Therefore, we investigated whether Cf-CHS-influenced ER stress, inflammatory response and signaling in insulin-resistant mice. Our results showed that Cf-CHS lowered serum and hepatic ROS, NO, and FFA levels. Furthermore, Cf-CHS decreased serum proinflammatory cytokines TNF-α, CRP, MIP-1, IL-1β and IL-6 concentrations as well as their hepatic mRNA expression, and increased the anti-inflammatory cytokine IL-10 levels. Moreover, Cf-CHS reduced the ER stress markers Bip, ATF6, PERK, and XBP1 mRNA or protein expression, and PERK, eIF2α, and IRE1α phosphorylation. These reductions were accompanied by a reduced activation of JNK1 and IKKβ, NFκB nuclear translocation, and IR/IRS-2 serine phosphorylation in Cf-CHS-treated mice. These findings suggested that the Cf-CHS supplementary-induced alleviation of RE stress-associated inflammation could be the mechanism responsible for its beneficial effects against insulin resistance.

Topics: Animals; Chondroitin Sulfates; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; I-kappa B Kinase; Insulin Resistance; Interleukin-10; Interleukin-1beta; Interleukin-6; Liver; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Sea Cucumbers

The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease.. Healthy control (n=15), type 2 diabetic patients with normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first morning urine was evaluated by 1,9-dimethylmethylene blue method and the composition was determined by agarose gel electrophoresis. Urinary chondroitin sulfate was quantified by a combination of treatment with specific lyase digestions and separation of products by SAX-HPLC.. GAGs concentration significantly increased in diabetic patients with microalbuminuria compared to diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an increase in LSC-PG in the urine of patients with diabetes compared to healthy controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6-sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically significant difference in ratio of 6-sulfated disaccharide to 4-sulfated disaccharide among the three groups.. GAGs were significantly increased in diabetic patients with microalbuminuria. The levels of urinary GAGs, ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides could be useful markers for diagnosis of patients with diabetic nephropathy.

Topics: Chondroitin Sulfates; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Electrophoresis, Agar Gel; Female; Heparitin Sulfate; Humans; Male; Methylene Blue; Middle Aged

A decrease in anionic change and the loss of heparan sulfate proteoglycan have previously been observed in the glomerular basement membrane (GBM) during diabetic glomerulosclerosis. We studied the chronological changes in the anionic character and the glycosaminoglycan content in the GBM of WBN/ Kob rats with spontaneous diabetes. Two types of cationic probes were used: polyethyleneimine (PEI) and cationic colloidal gold (CCG). Immunogold labeling was performed with anti-monoclonal-heparan-sulfate-glycosaminoglycan (HS-GAG) and anti-chondroitin-sulfate-glycosaminoglycan (CS-GAG) antibodies. The GBM width, the anionic sites and the GAG sites were investigated in diabetic WBN/Kob rats at 2, 10 and 19 months, compared with control rats. Diabetes was confirmed in WBN/Kob rats after 8 months in this study. The GBM width gradually thickened with age. The PEI anionic sites significantly decreased in the lamina rara externa (LRE) at 19 months (vs. 2 and 10 months). The HS-GAG sites also significantly decreased in the LRE at 10 and 19 months (vs. 2 months). However, the CCG anionic sites and the CS-GAG sites significantly increased in the LRE and the lamina densa at 10 months (vs. 2 months) and, after 19 months, returned to the level seen at 2 months. Results indicate that there is an early transient increase in CS-GAG in the GBM while HS-GAG decreases. We noticed a transient increase in the CCG anionic sites at this early stage of diabetic glomerulosclerosis as well. The increase in CS-GAG may provide a marker for early diabetic changes in the GBM.

Topics: Animals; Anions; Antibodies, Monoclonal; Basement Membrane; Chondroitin Sulfates; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Heparitin Sulfate; Immunohistochemistry; Kidney Glomerulus; Male; Rats; Rats, Wistar