Nonlinear methods of heart rate variability analysis in diabetes

Background: The autonomic dysfunction stands out among the complications associated to diabetes mellitus (DM) and may be evaluated through the heart rate variability (HRV), a noninvasive tool to investigate the autonomic nervous system that provides information of health impairments and may be analyzed by using linear and nonlinear methods. Several studies have shown that HRV measured in a linear form is altered in DM. Nevertheless, a few studies investigate the nonlinear behavior of HRV. Therefore, this study aims at gathering information regarding the autonomic changes in subjects with DM identified by nonlinear analysis of HRV.Methods: For that, searches were performed on Medline, SciELO, Lilacs and Cochrane databases using the crossing between the key-words: diabetic autonomic neuropathy, autonomic nervous system, diabetes mellitus and heart rate variability. As inclusion criteria, articles published on a period from 2000 to 2010 with DM type land type II population which assessed the autonomic nervous system by nonlinear indices HRV were considered.Results: The electronic search resulted in a total of 1873 references with the exclusion of 1623 titles and abstracts and from the 250 abstracts remaining, 8 studies were selected to the final analysis that completed the inclusion criteria.Conclusions: In general, the analysis showed that the nonlinear techniques of HRV allowed detecting autonomic changes in DM. The methods of nonlinear analysis are indicated as a possible tool to be used for early diagnosis and prognosis of autonomic dysfunction in DM.

A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: Evidence for phenotypic variability in mother and child

Congenital hypothyroidism associated with thyroid hypoplasia can be caused by several genetic defects, including mutations in the TSH beta -subunit, the TSH receptor, the G(A)alpha -subunit, and the transcription factor PAX8. Four girls with sporadic congenital hypothyroidism and hypoplastic thyroid glands were analyzed for mutations in PAX8 and TTF2 (FKHL15). Mutations in the coding region of the TSH beta -subunit gene, the TSH receptor gene, and exons 8 and 9 of G(mu)alpha had been excluded previously. Serum TSH concentrations were 150 mU/liter or more, TG levels were within normal limits, and thyroid autoantibodies were absent. Technetium scintigraphies did not reveal the presence of thyroid tissue, but ultrasonography documented hypoplastic, normally located glands.One patient was found to harbor a heterozygous transversion 119A -->C in exon 3 of PAX8 replacing a conserved glutamine by proline in the paired box domain (Q40P). Analysis of her family members revealed that her mother, who has a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, is also heterozygous for this mutation. Functional analyses of the PAX8 Q40P mutation showed impaired binding to a PAX8 response element and absent transactivation of a thyroid peroxidase promoter luciferase reporter gene.These findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. The absence of mutations in the coding sequences of the analyzed genes in the three other patients supports the concept that the pathogenesis of congenital hypothyroidism associated with thyroid hypoplasia is diverse.