Early predictors of microvascular complications in type 1 diabetic patients.

OBJECTIVES: To investigate the possibility of depending on adiponectin and leptin as early predictors of microvascular complications in type 1 diabetic subjects. DESIGN AND METHODS: We studied 63 type 1 diabetic subjects from the National Institute of Diabetes (30 normoalbuminuric and 33 microalbuminuric). Clinical, demographic characteristics and kidney function tests were monitored. Plasma levels of adiponectin, leptin, interlukein-6 (IL-6), and the high sensitive C-reactive protein (CRP) were measured in these subjects. RESULTS: Microalbuminuric subjects showed a significant elevation in adiponectin levels and a significant decrease in leptin levels as compared to normoalbuminuric subjects. Adiponectin showed a significant positive correlation with microalbuminuria concentrations while leptin showed a significant negative correlation with both fasting blood glucose and glycated hemoglobin A(1c). CONCLUSION: The results of this study introduced the possibility of depending on adiponectin and leptin as early, reliable, and sensitive predictors for the microvascular complications monitored by microalbuminuria concentration and glycemic control indices.

Adiponectin, leptin, and lipid profile in type 1 diabetic children and adolescents.

BACKGROUND: Adipose tissue is known to produce and secrete a variety of bioactive substances known as adipocytokines. Adiponectin and leptin are considered to be among the most important adipocytokines: OBJECTIVES: We sought to explore the relationships between adipocytokines (adiponectin and leptin), plasma lipoprotein lipid, and diabetic control indices in type 1 diabetic subjects. SUBJECTS AND METHODS: In this study 63 clinically diagnosed type 1 diabetic subjects and 30 age- and sex-matched healthy control subjects were analyzed. Age, sex, diabetic duration, family history of diabetes, daily insulin dose, weight, height, body mass index, and systolic and diastolic blood pressure were recorded. Fasting blood glucose, glycated hemoglobin A(1c), total hemoglobin, plasma lipoprotein, lipid and plasma concentrations of adiponectin and leptin were measured in type 1 diabetic subjects and control subjects. RESULTS: In this study a significant increase in triglycerides and high-density lipoprotein cholesterol in plasma of type 1 diabetics was found as compared with normal control subjects. In type 1diabetic subjects, plasma adiponectin was significantly elevated, whereas leptin showed a significant decrease as compared to a normal control group. Leptin concentrations showed a positive correlation with body mass index and systolic blood pressure but a negative correlation with both fasting blood glucose and glycated hemoglobinA(1c). CONCLUSION: The results of this study suggest that blood leptin but not adiponectin concentrations have a significant correlation with indices of glycemic control.

Construction of bacterial artificial chromosome libraries from the parasitic nematode Brugia malayi and physical mapping of the genome of its Wolbachia endosymbiont.

The parasitic nematode, Brugia malayi, causes lymphatic filariasis in humans, which in severe cases leads to the condition known as elephantiasis. The parasite contains an endosymbiotic alpha-proteobacterium of the genus Wolbachia that is required for normal worm development and fecundity and is also implicated in the pathology associated with infections by these filarial nematodes. Bacterial artificial chromosome libraries were constructed from B. malayi DNA and provide over 11-fold coverage of the nematode genome. Wolbachia genomic fragments were simultaneously cloned into the libraries giving over 5-fold coverage of the 1.1 Mb bacterial genome. A physical framework for the Wolbachia genome was developed by construction of a plasmid library enriched for Wolbachia DNA as a source of sequences to hybridise to high-density bacterial artificial chromosome colony filters. Bacterial artificial chromosome end sequencing provided additional Wolbachia probe sequences to facilitate assembly of a contig that spanned the entire genome. The Wolbachia sequences provided a marker approximately every 10 kb. Four rare-cutting restriction endonucleases were used to restriction map the genome to a resolution of approximately 60 kb and demonstrate concordance between the bacterial artificial chromosome clones and native Wolbachia genomic DNA. Comparison of Wolbachia sequences to public databases using BLAST algorithms under stringent conditions allowed confident prediction of 69 Wolbachia peptide functions and two rRNA genes. Comparison to closely related complete genomes revealed that while most sequences had orthologs in the genome of the Wolbachia endosymbiont from Drosophila melanogaster, there was no evidence for long-range synteny. Rather, there were a few cases of short-range conservation of gene order extending over regions of less than 10 kb. The molecular scaffold produced for the genome of the Wolbachia from B. malayi forms the basis of a genomic sequencing effort for this bacterium, circumventing the difficult challenge of purifying sufficient endosymbiont DNA from a tropical parasite for a whole genome shotgun sequencing strategy.

An aspartate aminotransferase of Wolbachia endobacteria from Onchocerca volvulus is recognized by IgG1 antibodies from residents of endemic areas.

Wolbachia are intracellular alpha-proteobacteria, closely related to Rickettsia, that infect various arthropods and filarial parasites. In the present study, the cDNA encoding the aspartate aminotransferase (AspAT) of Wolbachia from the human pathogenic filarial parasite Onchocerca volvulus (Ov-WolAspAT) was identified. At the amino acid level, the identity of the Ov-WolAspAT was 56% to Rickettsia prowazekii AspAT and 54% to the AspAT of the nitrogen-fixing bacterium Sinorhizobium meliloti, but the highest degree of identity was found to the putative AspAT of Wolbachia from Brugia malayi and Drosophila melanogaster (85%). All of these bacterial AspATs are members of the AspAT subclass Ib. A 35 kDa fragment of the Ov-WolAspAT was expressed in Escherichia coli, and immunolocalization using polyclonal antibodies against this antigen revealed that Ov-WolAspAT is present in a considerable proportion of the Wolbachia from O. volvulus, as well as in the endobacteria of several other filarial parasites. Western blot analysis using recombinant Ov-WolAspAT as antigen showed that IgG1 antibodies were present in 70 (51%) individuals living in areas endemic for O. volvulus, B. malayi or Wuchereria bancrofti and no IgG4 or IgE antibodies were found. Among 40 sera of persons from Uganda and Liberia who were putatively not infected with human filarial parasites, 11 (28%) individuals presented IgG1 antibodies, while none of the 33 sera from healthy Europeans and none of the 14 sera from patients with proven Rickettsia or Brucella infections reacted with the antigen. These results also show that an intracellular protein of Wolbachia endobacteria (WolAspAT) acts as antigen in human filariasis.