1,5 Anhydroglucitol in gestational diabetes mellitus

Objective

1,5 Anhydroglucitol (1,5 AG) is reported to be a more sensitive marker of glucose variability and short-term glycemic control (1–2?weeks) in patients with type1 and type 2 diabetes. However, the role of 1,5 AG in gestational diabetes mellitus (GDM) is not clear. We estimated the serum levels of 1,5 AG in pregnant women with and without GDM.

Structure and Inhibitor Specificity of L,D-Transpeptidase (LdtMt2) from <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> and Antibiotic Resistance: Calcium Binding Promotes Dimer Formation

The final step of peptidoglycan (PG) synthesis in all bacteria is the formation of cross-linkage between PG-stems. The cross-linking between amino acids in different PG chains gives the peptidoglycan cell wall a 3-dimensional structure and adds strength and rigidity to it. There are two distinct types of cross-linkages in bacterial cell walls. D,D-transpeptidase (D,D-TPs) generate the classical 4?3 cross-linkages and the L,D-transpeptidase (L,D-TPs) generate the 3?3 non-classical peptide cross-linkages. The present study is aimed at understanding the nature of drug resistance associated with L,D-TP and gaining insights for designing novel antibiotics against multi-drug resistant bacteria. Penicillin and cephalosporin classes of β-lactams cannot inhibit L,D-TP function; however, carbapenems inactivate its function. We analyzed the structure of L,D-TP of Mycobacterium tuberculosis in the apo form and in complex with meropenem and imipenem. The periplasmic region of L,D-TP folds into three domains. The catalytic residues are situated in the C-terminal domain. The acylation reaction occurs between carbapenem antibiotics and the catalytic Cys-354 forming a covalent complex. This adduct formation mimics the acylation of L,D-TP with the donor PG-stem. A novel aspect of this study is that in the crystal structures of the apo and the carbapenem complexes, the N-terminal domain has a muropeptide unit non-covalently bound to it. Another interesting observation is that the calcium complex crystallized as a dimer through head and tail interactions between the monomers.     

Circulating levels of insulin-like growth factor binding protein-1 in relation to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai Urban Rural Epidemiology Study 118)

The objective was to assess the association of insulin-like growth factor binding protein-1 (IGFBP-1) with insulin resistance (IR), type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) in Asian Indians. Fifty subjects with normal glucose tolerance (NGT) and 50 with T2DM were randomly selected from the Chennai Urban Rural Epidemiology Study. Insulin-like growth factor binding protein-1 was measured by sandwich enzyme-linked immunosorbent assay. Serum insulin was estimated using Dako (Glostrup, Denmark) kits. Insulin resistance was calculated using the homeostasis model assessment. Subjects with T2DM had significantly decreased levels of IGFBP-1 (21.7 ± 3.5 ng/mL) compared with NGT subjects (34.4 ± 7.6 ng/mL, P < .001). The IGFBP-1 was significantly lower in NGT subjects with IR as measured by the homeostasis model assessment (25.5 ± 6.5 ng/mL) compared with NGT subjects without IR (40.7 ± 9.5 ng/mL, P < .001). On regression analysis, IR showed a significant association with IGFBP-1 even after adjusting for age, sex, body mass index, and glycated hemoglobin (β = -3.714, P < .001). Type 2 diabetes mellitus was significantly associated with IGFBP-1 even after adjusting for age, sex, and body mass index (β = -12.798, P < .001). The IGFBP-1 levels decreased with increasing number of metabolic abnormalities (P for trend < .001). Logistic regression analysis showed that IGFBP-1 had a strong negative association with MS even after adjusting for age and sex (odds ratio, 0.942; 95% confidence interval, 0.914-0.971; P < .001). Among Asian Indians, lower levels of circulating IGFBP-1 are seen in subjects with IR, T2DM, and MS.     

Effects of Methanol Extract of Wedelia chinensis Osbeck (Asteraceae) Leaves against Pathogenic Bacteria with Emphasise on Bacillus cereus

The antibacterial activity of the methanol extract of Wedelia chinensis leave was studied and tested against three pathogenic Gram positive bacteria (Bacillus cereus, B. subtilis and Stapylococcus aureus) and three pathogenic Gram negative bacteria (Escherichia coli, Proteus rettgeri and Pseudomonas aeruginosa) by the disk diffusion assay and broth dilution methods. The extract exhibited favourable antibacterial activity against the bacterial cells but was more potent against Gram positive bacteria with the minimum inhibition concentration of 3.12 to 6.25 mg/ml compared to the Gram negative bacteria which had minimum inhibition concentration values of 25 mg/ml. The time-kill study suggested that the extract possessed bactericidal properties at higher concentrations and eradicated the growth of bacterial cells. The major abnormalities occurred to the bacterial cells after exposed to the extract were complete alterations in their morphology and collapsed of the cells beyond repair. The methanol extract of W. chinensis may be an effective antibacterial agent to treat bacterial infections.     

Association of hypoadiponectinemia with hypoglutathionemia in NAFLD subjects with and without type 2 diabetes

Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes. Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD. Results: T2DM subjects with NAFLD had significantly (p < 0.001) higher levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCO) but lower (p < 0.001) GSH/GSSG ratio and adiponectin levels compared to other three groups. The association of hypoadiponectinemia withNAFLD/Type 2 diabetes was significant even after adjusting for age, gender and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated cells. Conclusion: There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM. In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin.     

Convergence of adipocyte hypertrophy,telomere shortening and hypoadiponectinemia in obese subjects and in patients with type 2 diabetes

ObjectiveAlthough telomere shortening has been linked with type 2 diabetes and most variables of adiposity, a shortcoming of such studies is the measurement of telomere length in leukocytes. Therefore, we tested the association among adipocyte cell size, telomere length (both subcutaneous and visceral adipose tissue) and systemic levels of adiponectin in obese subjects and patients with type 2 diabetes compared to control subjects.MethodsHuman subcutaneous and visceral adipose tissues were obtained from the subjects who have undergone bariatric surgery or other abdominal surgeries. The study groups comprised: i) control subjects, ii) type 2 diabetes patients, iii) obese subjects without diabetes and iv) obese subjects with diabetes. Adipocyte cell size was measured by histological staining. Adiponectin levels were measured by ELISA. Telomere length was determined by Real-time PCR and lipid peroxidation was assessed by fluorimetry.ResultsCompared to control subjects, adipocyte size (both subcutaneous and visceral) from obese, diabetic and obese–diabetic subjects was significantly larger [p < 0.001]. Individuals with adipose hypertrophy also exhibited shortened telomeres and hypoadiponectinemia. Pearson correlation analysis revealed that both visceral and subcutaneous fat cell size showed a positive correlation with FBS, HbA1c, HOMA-IR, LDL, total cholesterol, triglycerides and negatively correlated with HDL and adiponectin. Regression analysis revealed that the association between shortened telomeres and hypoadiponectinemia was lost when adjusted for adipocyte cell size.ConclusionAdipocyte hypertrophy appears to be strongly associated with shortened telomeres, hypoadiponectinemia and poor glycemic and lipid control. Interestingly, these molecular alterations seen in lean diabetics reflect a state of ‘metabolic obesity’.     

Quantitative analysis of retinal microvascular changes in prediabetic and diabetic patients

Purpose:To evaluate and correlate retinal microvascular changes in prediabetic and diabetic patients with functional and systemic parameters.Methods:Optical coherence tomography angiography (OCTA) was performed on all subjects after medical evaluation and laboratory investigations for blood sugar, glycosylated hemoglobin, and others. Automated quantification of vascular indices of the superficial plexus were analyzed.Results:Hundred and eleven persons (222 eyes) were grouped into prediabetic (PDM) (60 eyes), diabetic without retinopathy (NDR) (56 eyes), diabetic with retinopathy (DR) (66 eyes), and healthy controls (CTR) (40 eyes). The superficial retinal capillary plexus showed no significant changes in the prediabetic and NDR groups; however, central foveal thickness (CFT) was significantly reduced in PDM (P = 0.04). The circularity of the foveal avascular zone (FAZ) (P = 0.03) and the vessel density (VD) (P = 0.01) showed significant reduction from PDM to NDR. All vascular parameters were significantly reduced in DR and correlated with disease severity. The CFT correlated significantly with FAZ area. The VD and perfusion density were seen to correlate significantly with HbA1c and contrast sensitivity. The visual acuity was significantly correlated with the FAZ. Logistic regression revealed VD [OR 20.42 (7.9–53)] and FAZ perimeter [OR 9.8 (4.2–23.2)] as the strongest predictors of DR.Conclusion:The changes in OCTA can help predict onset of DR. FAZ changes are seen in early stages and are correlated well with systemic parameters, making it an easy target to monitor and screen for severity of DR. Significant reduction in the CFT in PDM suggests that neuronal damage precedes vascular changes.