Efficacy and Safety of Topical Solution of Diperoxochloric Acid for Neuropathic Diabetic Foot Ulcer: Results from a Phase 3, Multicentre, Randomized, Active-controlled, Parallel-group Study.

Diabetic foot ulcer (DFU), if untreated, accounts for lower-limb amputations affecting patients' quality-of-life. Diperoxochloric acid (DPOCL) is known to heal DFU by its antibacterial and fibroblast stimulating activity. This was a phase 3, multicentre, randomized, double-blind, active-controlled, parallel-group study conducted to evaluate the efficacy and safety of topic solution of DPOCL compared with isotonic sodium chloride solution (ISCL). Adult patients with type 1 or 2 diabetes with random blood glucose levels of <250 mg/dL, with ≤ than three full-thickness foot ulcers were enrolled. Primary efficacy endpoint was complete wound closure and secondary was wound surface area. Adverse events were analyzed as safety endpoint. Of 311 enrolled patients, 289 were randomized 1:1 to DPOCL (139) and ISCL (150) treatment (10-weeks [8-Visits]). Percentage of patients with complete wound closure at visit-8, were significantly higher (P = .0156) in DPOCL arm (76% [105/139]) compared to ISCL (62% [93/150]) arm. At end-of-study, mean wound surface area in DPOCL arm (0.639 cm2) was significantly lower (P = .0209) compared to ISCL (0.818 cm2) arm. One death was reported in control arm which was not considered as treatment-related. No important safety finding were observed. Results indicate that, DPOCL can be considered as effective and safe treatment option for DFU compared to ISCL, although future confirmatory studies are warranted.

Serum 25(OH)D Concentration and Cardiovascular Disease Risk Markers Among Middle-Aged Healthy and Type 2 Diabetic Subjects.

Vitamin D deficiency is a major widespread health concern and is linked to a high risk of cardiovascular disease (CVD). Thus, we have investigated the association of vitamin D with various CVD risk markers. The present study comprises 90 control and 90 type 2 diabetes mellitus (T2DM) subjects of both sexes (age range, 30-50 years). The 25 hydroxyvitamin D [25(OH)D] and CVD risk markers including high sensitive C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), intact parathyroid hormone (I-PTH), fibroblast growth factor (FGF)-23, erythrocyte sedimentation rate (ESR), and fibrinogen were measured by using standard assays. Blood viscosity and atherogenic index of plasma calculated using standard formulae. The ten-year cardiovascular risk was assessed using the Framingham risk score (FRS). 25(OH)D, hs-CRP, MCP-1, FGF-23, ESR, fibrinogen, atherogenic index of plasma and FRS were significantly different between control and T2DM groups (p<0.05). 25(OH)D showed a significant negative correlation with MCP-1, ESR, blood viscosity, atherogenic index of plasma and FRS among total study subjects. Further, logistics regression analysis showed an association of 25(OH)D with MCP-1, hematocrit, fibrinogen, and blood viscosity. The association between 25(OH)D and various CVD risk markers suggests that 25(OH)D might help in the prediction of CVD risk.

Serum 25(OH)D concentration and its association with inflammation and oxidative stress in the middle-aged Indian healthy and diabetic subjects.

BACKGROUND: Vitamin D deficiency is associated with inflammation and oxidative stress. We have studied the association of 25-hydroxyvitamin D [25(OH)D] with markers of inflammation and oxidative stress. METHODS: We have recruited total 180 male and female subjects aged between 30 and 50 years and divided them into two groups as control (n = 90) and T2DM (n = 90). We have measured 25(OH)D concentration, markers of inflammation including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) and markers of oxidative stress including malondialdehyde (MDA) and oxidized low-density lipoprotein (Ox-LDL) by using standard methods. RESULTS: We stratified control and T2DM groups by 25(OH)D concentration and it indicates that in severe deficiency and sufficiency category IL-6, IL-1ß, TNF-α, and Ox-LDL were significantly different while in moderate deficiency category only MDA was significantly different, among control and T2DM groups. In an insufficiency category, IL-6, IL-1ß, TNF-α, MDA, and Ox-LDL were significantly different among control and T2DM groups. Correlation analysis indicates a negative correlation of 25(OH)D with IL-6, IL-1ß, TNF-α, and Ox-LDL among total subjects. Further, logistic regression analysis demonstrated a significant association of different categories of 25(OH)D with IL-6, IL-1ß, TNF-α, and Ox-LDL before and after adjustment to body mass index and waist to hip ratio. CONCLUSION: This study suggest that vitamin D may have significant implications in the prevention of inflammation and oxidative stress.

Association of vitamin D deficiency with insulin resistance in middle-aged type 2 diabetics.

BACKGROUND: Vitamin D deficiency contributes to the pathophysiology of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). We investigated the association of 25-hydroxyvitamin D [25(OH)D] with IR and ß-cell function in middle-aged participants. METHODS: We enrolled 90 controls and 90 T2DM patients of both genders aged 30-50 years. Serum 25(OH)D, fasting plasma insulin (FPI), fasting plasma glucose (FPG), HbA1c, and lipid profile were measured by standard methods. Insulin resistance and sensitivity were assessed by triglyceride glucose (TyG) index, homeostatic model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and ß-cell function by HOMA-B. RESULTS: 25(OH)D deficiency was reported as 40% in control and 70% in T2DM patients. 25(OH)D concentration was positively associated with age, blood pressure, T2DM duration, FPG, HbA1c, TyG index, and HOMA-IR and negatively associated with HOMA-B and QUICKI among all the participants (p ≤.001). Participants with severe 25(OH)D deficiency (<10 ng/ml) were 39 times higher odds of being T2DM, while, those with moderate deficiency (10-19ng/ml) and insufficiency (20-29 ng/ml) were 16 times and 13 times higher odds of being T2DM, respectively. CONCLUSION: Sufficient 25(OH)D concentration may lower the risk of development of IR and T2DM in middle-aged control and diabetic participants.

Beyond LDL-c: The importance of serum oxidized LDL in predicting risk for type 2 diabetes in the middle-aged Asian Indians.

AIMS: Oxidized low-density lipoprotein (OxLDL) as the residual lipid plays a crucial role in cardiovascular complications and type 2 diabetes. This study aimed to evaluate the relationship of OxLDL with the conventional risk markers and to find the association of OxLDL with the risk of development of type 2 diabetes in middle-aged (30-50 years) Asian Indians. MATERIALS AND METHODS: A total of 78 type 2 diabetes patients and 78 age-matched controls were recruited. The serum OxLDL concentration was assessed by enzyme-linked immunosorbent assay (ELISA). Other anthropometric and biochemical measures were also carried out. Multiple logistic regression was used to determine the association of OxLDL and OxLDL to non-oxidized lipoproteins with the occurrence of type 2 diabetes. RESULTS: OxLDL was significantly higher in type 2 diabetes cases than controls (p < 0.001) even though there was no significant difference in LDL cholesterol (LDL-c) between type 2 diabetes patients and controls. OxLDL correlated significantly with fasting plasma glucose (FPG) and insulin resistance (HOMA-IR). OxLDL did not show any significant correlation with LDL-c. Multiple logistic regression showed a significant association of OxLDL, OxLDL/LDL-c and OxLDL/HDL-c with type 2 diabetes (p < 0.001). LDL-c showed no association with type 2 diabetes. ROC-AUC curve analyses showed OxLDL/HDL-c to have highest discriminatory power for type 2 diabetes (AUC: 0.710 with 95% CI: 0.629-0.791, p < 0.001). CONCLUSION: Our findings highlight the possibly more attention has to be given to OxLDL for managing lipids and diabetes progression as well as reducing cardiac risk in middle-aged type 2 diabetes patients.