Estudo da associação dos genes RANk, RANKL e OPG com a osteopatia diabética

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

Alterações hepáticas na expressão gênica e atividade da catalase e superóxido dimutase em ratos diabéticos induzidos por estreptozootocina

The correlation between the type 1 diabetes mellitus and oxidative stress have been described in several studies, however its underlying mechanisms are not fully elucidated. The present work aimed to evaluate the effects of four weeks of streptozootocin-induced (STZ) diabetes in the redox homeostasis of rat hepatocytes. Thus, the liver of male Wistar rats from control and diabetic groups were collected and the activity and expression of antioxidant enzymes, as well the main markers of oxidative stress and content of H2O2 in these tissues were measured. The diabetes induced the activity of superoxide dismutase (SOD) and the gene expression of its mitochondrial isoform, SOD2. However, the expression of SOD1, the cytoplasmic isoform, was reduced by this disease. The activity and expression of catalase (CAT), as well the expression of glutathione peroxidase 1 (GPX1) and peroxiredoxin 4 (PRX4) were drastically reduced in the hepatocytes of diabetics rats. Even with this debility in the peroxidases mRNA expression, the content of H2O2 was reduced in the liver of diabetics rats when compared to the control group. The diabetes caused an increase of lipid peroxidation and a decrease of protein thiol content, showing that this disease causes distinct oxidative effects in different cell biomolecules. Our results indicate that four week of diabetes induced by STZ is already enough to compromise the enzymatic antioxidant systems of the hepatocytes.

Use of BARD scoring system in non-alcoholic fatty liver disease patients and its correlation with ultrasonographic grading in Gizan, Saudi Arabia

Purpose: To assess the efficacy of the BARD scoring system in Saudi non‐alcoholic fatty liver disease (NAFLD) patients attending Gizan General Hospital and to identify the clinical variables associated with advanced fibrosis. . Methods: The cross-sectional study involved 120 patients aged ≥ 18 years who attended the Ultrasound Department of Gizan General Hospital, Gizan, Saudi Arabia, during January – June 2013. BARD scoring system comprised the following variables: body mass index (BMI) ≥ 28 = 1 point, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio ≥ 0.8 = 2 points, and type 2 diabetes mellitus = 1 point. Results: Patients with advanced fibrosis were older (55.0 years) than patients with no/mild fibrosis (48.6 years), albeit not significantly so. A higher BMI was associated with advanced fibrosis in males, females and all study participants (p = 0.013, 0.016 and 0.001, respectively). Advanced fibrosis was more common in older patients with a higher weight to height ratio. Logistic regression suggested that age ≥ 50 years was associated with a 2.52-fold increase in the risk of advanced fibrosis, but this did not have a significant clinical impact (p = 0.087). BMI > 28 was associated with a 26.73-fold increased risk of advanced fibrosis, while AST/ALT ≥ 0.8 was associated with an 18.46-fold increased risk of advanced liver fibrosis (p = 0.002 and 0.006, respectively). Conclusion: The major risk factors for advanced fibrosis using BARD scoring system in patients with NAFLD were old age, BMI > 28, and AST/ALT ≥ 0.8. In addition, grade 3 ultrasonographic fatty liver significantly correlated with advanced fibrosis.

Chronic condition management and self-management in Aboriginal communities in South Australia : outcomes of a longitudinal study

OBJECTIVES: This paper describes the longitudinal component of a larger mixed methods study into the processes and outcomes of chronic condition management and self-management strategies implemented in three Aboriginal communities in South Australia. The study was designed to document the connection between the application of structured systems of care for Aboriginal people and their longer-term health status. METHODS: The study concentrated on three diverse Aboriginal communities in South Australia; the Port Lincoln Aboriginal Health Service, the Riverland community, and Nunkuwarrin Yunti Aboriginal Health Service in the Adelaide metropolitan area. Repeated-measure clinical data were collected for individual participants using a range of clinical indicators for diabetes (type 1 and 2) and related chronic conditions. Clinical data were analysed using random effects modelling techniques with changes in key clinical indicators being modelled at both the individual and group levels. RESULTS: Where care planning has been in place longer than in other sites overall improvements were noted in BMI, cholesterol (high density and low density lipids) and HbA1c. These results indicate that for Aboriginal patients with complex chronic conditions, participation in and adherence to structured care planning and self-management strategies can contribute to improved overall health status and health outcomes. CONCLUSIONS: The outcomes reported here represent an initial and important step in quantifying the health benefits that can accrue for Aboriginal people living with complex chronic conditions such as diabetes, heart disease and respiratory disease. The study highlights the benefits of developing long-term working relationships with Aboriginal communities as a basis for conducting effective collaborative health research programs.

Gruppbaserad patientutbildning - en del av en förändringsprocess : En kvalitativ intervjustudie bland patienter med nydebuterad typ 2-diabetes

Syfte: Syftet var att beskriva upplevelser av gruppbaserad patientutbildning bland patienter med nydebuterad typ 2-diabetes.Metod: Studien genomfördes med hjälp av semistrukturerade intervjuer. Data bearbetades med hjälp av kvalitativ innehållsanalys.Resultat: Tre huvudteman kunde urskiljas; (1) ett sammanhang med andra skapar möjlighet till utveckling av egenvård, (2) hinder som komplicerar framsteg i egenvård och (3) svårigheter med gruppbaserad patientutbildning. Många vittnade om att förändringsprocessen startade redan vid diagnostillfället, men att den gruppbaserade patientutbildningen gav ytterligare möjlighet till kunskapsinhämtning och tillämpning av kunskap. Gruppdeltagarna delgav varandra värdefull kunskap och stärkte och gav stöd åt varandra, vilket ledde till personliga vinster. Det fanns hinder som försvårade framsteg i egenvård exempelvis bristande insikt och personliga egenskaper. Deltagarna uttryckte negativa synpunkter såsom att inte uppskatta deltagande i grupp och om svårigheter i delar av undervisningen. Slutsats: Deltagarna upplevde den gruppbaserade patientutbildningen positiv och berikande och som en betydelsefull del av förändringsprocessen. Kunskapsutbytet och gemenskapen i gruppen ansågs vara de viktigaste beståndsdelarna. Samtliga deltagare hade gjort positiva förändringar i levnadsvanor och framsteg i egenvård tack vare den gruppbaserade patientutbildningen. Det fanns dock hinder som försvårade förändringsprocessen.

Insulintherapie bei Typ-2-Diabetes: ein Review vom «Wann» übers «Wie» bis zum «Warum»

Der progressive Charakter des Typ- 2-Diabetes mellitus führt in vielen Fällen nach Ausschöpfen der oralen antidiabetischen Therapie zum Einsatz von Insulin. Insulin kann aber durch- aus auch in der Frühphase direkt nach Diabetesdiagnose oder intermittierend bei Verschlechterung der glykämischen Kontrolle im Rahmen von Infekten oder Medikamenteneinnahmen (wie z.B. Kortison) hilfreich und indiziert sein. Auf jeden Fall stellt die Insulintherapie keine Einbahnstrasse dar und kann gerade in diesen Fällen durchaus auch wieder sistiert werden. Der Beginn einer Insulintherapie soll eher vorsichtig mit einer bedarfsmässigen Anpassung im Verlauf erfolgen. Diese Anpassung kann nach entsprechender Schulung durchaus auch durch den Patienten selbst erfolgen.

Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes

OBJECTIVE: Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS: Type 1 diabetes, N = 79 (mean age 20.32 ± 4.24 years), and healthy control participants, N = 50 (mean age 20.53 ± 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient. RESULTS: Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age-related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time. CONCLUSIONS: We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified.

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes

Background Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. Objective We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. Methods Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. Results Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). Conclusions Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae.

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children

OBJECTIVE To investigate the impact of new-onset diabetic ketoacidosis (DKA) during child- hood on brain morphology and function. RESEARCH DESIGN AND METHODS Patients aged 6–18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients under- went magnetic resonance imaging (MRI) and spectroscopy with cognitive assess- ment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at base- line in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well.

Amplitude of accommodation in type 1 diabetes

Purpose People with diabetes have accelerated age-related biometric ocular changes compared with people without diabetes. We determined the effect of Type 1 diabetes on amplitude of accommodation. Method There were 43 participants (33 ± 8 years) with type 1 diabetes and 32 (34 ± 8 years) age-balanced participants without diabetes. There was no significant difference in the mean equivalent refractive error and visual acuity between the two groups. Amplitude of accommodation was measured using two techniques: objective — by determining the accommodative response to a stimulus in a COAS-HD wavefront aberrometer (Wavefront Sciences), and subjective — with a Badal hand optometer (Rodenstock). The influences of age and diabetes duration (in years) on amplitude of accommodation were analyzed using multiple regression analysis. Results Across both groups, objective amplitude was less than subjective amplitude by 1.4 ± 1.2 D. People with diabetes had lower objective (2.7 ± 1.6 D) and subjective (4.0 ± 1.7 D) amplitudes than people without diabetes (objective 4.1 ± 2.1 D, subjective 5.6 ± 2.1 D). For objective amplitude and the whole group, the duration of diabetes contributed 57% of the variation as did age. For the objective amplitude and only the diabetes group this was 78%. For subjective amplitude, the corresponding proportions were 68% and 103%. Conclusions Both objective and subjective techniques showed lowered amplitude of accommodation in participants with type 1 diabetes when compared with age-matched controls. The loss correlated strongly with duration of diabetes. The results suggest that individuals with diabetes will experience presbyopia earlier in life than people without diabetes, possibly due to metabolic changes in the lens.

Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy

Purpose To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. Methods A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) and were quantified using a fully-automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. Results At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared to controls (P<0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm2, P=0.01) in the neuropathy group compared to controls, which was associated with age (β=-0.06, P=0.04) and duration of diabetes (β=-0.08, P=0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (rs, 0.38 and 0.40, P<0.05). Conclusion This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of DPN.

Corneal confocal microscopy shown an improvement in small-fibre neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared to multiple daily injection

Improved glycemic control is the only treatment that has been shown to be effective for diabetic peripheral neuropathy in patients with type 1 diabetes (1). Continuous subcutaneous insulin infusion (CSII) is superior to multiple daily insulin injection (MDI) for reducing HbA1c and hypoglycemic events (2). Here, we have compared the benefits of CSII compared withMDI for neuropathy over 24months....