The action of aminoguanidine on the liver of trained diabetic rats

Background: This study evaluated the effect of aminoguanidine on liver of diabetic rats subject to physical exercises using histological and histochemical techniques.Methods: The rats used in this study were divided into five groups: sedentary control, sedentary diabetic, trained diabetic, sedentary diabetic and treated with aminoguanidine, trained diabetic and treated with aminoguanidine.Results: The results showed no effect of aminoguanidine on the liver tissue, although there was improvement with exercise training showing cytological, morpho-histological and histochemical alterations in liver cells of animals from groups trained diabetic and/or treated diabetic compared to those individuals in the sedentary control and sedentary diabetic. These changes included: hepatocytes hypertrophy, presence and distribution of polysaccharides in the hepatocytes cytoplasm and, especially, congestion of the liver blood vessels.Conclusion: Our results suggest that aminoguanidine is not hepatotoxic, when used at dosage of 1 g/L for the treatment of diabetes complications, and confirmed that the practice of moderate physical exercise assuaged the damage caused by diabetes without the use of insulin. © 2013 e Nico et al.; licensee BioMed Central Ltd.

Histoquímica e ultra-estrutura da musculatura ventricular esquerda de ratos diabéticos: efeitos do exercício físico

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Polyneuropathies--short and sweet

Complaints of sensory loss and (painful) tingling in a stocking distribution are not uncommon in primary care. These symptoms are especially troublesome while getting asleep. Characteristically, ankle tendon reflexes and vibration perception are diminished. These are the hallmarks of distal-symmetric sensory polyneuropathy (PNP), with diabetes mellitus being the most common cause in our patient population. PNP presents itself only after years of suboptimal glycemic control in diabetes type 1. In patients with type 2, symptoms of PNP can precede formal diagnosis of diabetes! In this mini-review we present an algorithm for diagnosis and management of PNP's in general practice.

Nephrin and the Pathogenesis of Nephropathy - Emphasis on Type I Diabetes

End-stage renal disease is an increasingly common pathologic condition, with a current incidence of 87 per million inhabitants in Finland. It is the end point of various nephropathies, most common of which is the diabetic nephropathy. This thesis focuses on exploring the role of nephrin in the pathogenesis of diabetic nephropathy. Nephrin is a protein of the glomerular epithelial cell, or podocyte, and it appears to have a crucial function as a component of the filtration slit diaphragm in the kidney glomeruli. Mutations in the nephrin gene NPHS1 lead to massive proteinuria. Along with the originally described location in the podocyte, nephrin has now been found to be expressed in the brain, testis, placenta and pancreatic beta cells. In type 1 diabetes, the fundamental pathologic event is the autoimmune destruction of the beta cells. Autoantibodies against various beta cell antigens are generated during this process. Due to the location of nephrin in the beta cell, we hypothesized that patients with type 1 diabetes may present with nephrin autoantibodies. We also wanted to test whether such autoantibodies could be involved in the pathogenesis of diabetic nephropathy. The puromycin aminonucleoside nephrosis model in the rat, the streptozotocin model in the rat, and the non-obese diabetic mice were studied by immunochemical techniques, in situ -hybridization and the polymerase chain reaction -based methods to resolve the expression of nephrin mRNA and protein in experimental nephropathies. To test the effect of antiproteinuric therapies, streptozotocin-treated rats were also treated with aminoguanidine or perindopril. To detect nephrin antibodies we developed a radioimmunoprecipitation assay and analyzed follow-up material of 66 patients with type 1 diabetes. In the puromycin aminonucleoside nephrosis model, the nephrin expression level was uniformly decreased together with the appearance of proteinuria. In the streptozotocin-treated rats and in non-obese diabetic mice, the nephrin mRNA and protein expression levels were seen to increase in the early stages of nephropathy. However, as observed in the streptozotocin rats, in prolonged diabetic nephropathy the expression level decreased. We also found out that treatment with perindopril could not only prevent proteinuria but also a decrease in nephrin expression in streptozotocin-treated rats. Aminoguanidine did not have an effect on nephrin expression, although it could attenuate the proteinuria. Circulating antibodies to nephrin in patients with type 1 diabetes were found, although there was no correlation with the development of diabetic nephropathy. At diagnosis, 24% of the patients had these antibodies, while at 2, 5 and 10 years of disease duration the respective proportions were 23%, 14% and 18%. During the total follow-up of 16 to 19 years after diagnosis of diabetes, 14 patients had signs of nephropathy and 29% of them tested positive for nephrin autoantibodies in at least one sample. In conclusion, this thesis work could show changes of nephrin expression along with the development of proteinuria. The autoantibodies against nephrin are likely generated in the autoimmune process leading to type 1 diabetes. However, according to the present work it is unlikely that these autoantibodies are contributing significantly to the development of diabetic nephropathy.

Factors influencing hospital readmission and length of stay of Vietnamese patients with type 2 diabetes and cardiac disease

Background: Increased hospital readmission and longer stays in the hospital for patients with type 2 diabetes and cardiac disease can result in higher healthcare costs and heavier individual burden. Thus, knowledge of the characteristics and predictive factors for Vietnamese patients with type 2 diabetes and cardiac disease, at high risk of hospital readmission and longer stays in the hospital, could provide a better understanding on how to develop an effective care plan aimed at improving patient outcomes. However, information about factors influencing hospital readmission and length of stay of patients with type 2 diabetes and cardiac disease in Vietnam is limited. Aim: This study examined factors influencing hospital readmission and length of stay of Vietnamese patients with both type 2 diabetes and cardiac disease. Methods: An exploratory prospective study design was conducted on 209 patients with type 2 diabetes and cardiac disease in Vietnam. Data were collected from patient charts and patients' responses to self-administered questionnaires. Descriptive statistics, bivariate correlation, logistic and multiple regression were used to analyse the data. Results: The hospital readmission rate was 12.0% among patients with both type 2 diabetes and cardiac disease. The average length of stay in the hospital was 9.37 days. Older age (OR= 1.11, p< .05), increased duration of type 2 diabetes (OR= 1.22, p< .05), less engagement in stretching/strengthening exercise behaviours (OR= .93, p< .001) and in communication with physician (OR= .21, p< .001) were significant predictors of 30-dayhospital readmission. Increased number of additional co-morbidities (β= .33, p< .001) was a significant predictor of longer stays in the hospital. High levels of cognitive symptom management (β= .40, p< .001) significantly predicted longer stays in the hospital, indicating that the more patients practiced cognitive symptom management, the longer the stay in hospital. Conclusions: This study provides some evidence of factors influencing hospital readmission and length of stay and argues that this information may have significant implications for clinical practice in order to improve patients' health outcomes. However, the findings of this study related to the targeted hospital only. Additionally, the investigation of environmental factors is recommended for future research as these factors are important components contributing to the research model.

Diabetesassocierade autoantikroppar hos barn med nydiagnostiserad typ 1 diabetes i relation till demografiska och kliniska faktorer

Syftet med studien var att undersöka sambanden mellan de diabetesassocierade autoantikropparna ICA, IAA, GADA, IA-2A och klinisk manifestation, HLA-genotyp, släktanamnes samt demografiska faktorer såsom ålder och kön hos finländska barn under 15 år med nydiagnostiserad typ 1 diabetes. Analyserna baserades på ett utdrag ur det finländska pediatriska diabetesregistret (2257 barn). Antikroppsfrekvenserna fastställdes utgående från halterna i serum. Alla barn HLA-genotypades och indelades i DR3- och DR4-positiva. Småbarnen (?5 år) hade ofta 3-4 positiva antikroppar. Äldre barn hade färre autoantikroppar men en allvarligare metabolisk dekompensering vid diagnostillfället. Diabetisk ketoacidos var vanligare hos flickor. I gruppen med endast en positiv autoantikropp var IA-2A-barnen oftare acidotiska, i övrigt påverkade inte antikroppsprofilen den kliniska bilden. Högriskgenotypen DR4/non-DR3 var associerad med IA-2A, som verkar fungera som en markör för betacelldestruktion. Det omfattande patientmaterialet gav stöd åt tidigare rapporter om samband mellan autoantikroppar och ålder, kön samt genotyp. Den allvarligare metaboliska dekompenseringen hos äldre barn tyder på att de inte diagnostiseras lika snabbt som småbarn.

Depression and Cognition in Type 2 Diabetes from a Life Course Perspective

Background: Type 2 diabetes is linked to several complications which add to both physical and mental distress. Depression is a common co-morbidity of diabetes which can occur both as a cause and a consequence of type 2 diabetes. Depression has been shown to correlate with glucose regulation and treating depression might prove beneficial for glucose regulation as well as for mental well being. Another complication which might affect diabetes management is cognitive decline. Several risk factors and complications of diabetes might modify the risk for developing cognitive impairment, which is increased 1.5 times among subjects with type 2 diabetes. Type 2 diabetes, depression and impaired cognitive performance have all been linked to low birth weight. This thesis aimed to explore the effects and interactions of birth weight, depression and cognitive ability in relation to type 2 diabetes from a life course perspective. Subjects and methods: Studies I, II and V were part of the Helsinki Birth Cohort Study. 2003 subjects participated in an extensive clinical examination at an average age of 61 years. A standard glucose tolerance test (OGTT) was performed and depressive symptoms were assessed using the Beck Depression Inventory (BDI). In addition data was obtained from child welfare clinics and national registers. A subset of the cohort (n=1247) also performed a test on cognitive performance (CogState ®) at the average age of 64. Studies III and IV were randomised clinical trials where mildly depressed diabetic subjects were treated with paroxetine or placebo and the effect on metabolic parameters and quality of life was assessed. The first trial included 14 women and lasted 10 weeks, while the second trial included 43 subjects, both men and women, and lasted 6 months. Results: Type 2 diabetes was positively associated with the occurrence of depressive symptoms. Among diabetic subjects 23.6% had depressive symptoms, compared to 16.7% of subjects with normal glucose tolerance (OR = 1.77, p<0.001). Formal mediation analysis revealed that cardiovascular disease (CVD) is likely to act as a mediator in the association. Furthermore, low birth weight was found to modify the association between type 2 diabetes, CVD and depression. The association between BDI score and having type 2 diabetes or CVD was twice as strong in the subgroup with low birth weight (≤ 2500g) compared with the group with birth weight > 2500g (p for interaction 0.058). In the six months long randomised clinical trial (study IV) paroxetine had a transient beneficial effect on glycosylated haemoglobin A1c (GHbA1c) and quality of life when compared to placebo after three months of treatment. In study V we found that subjects with known diabetes had a consistently poorer level of cognitive performance than subjects with normal glucose tolerance in most of the tested cognitive domains. This effect was further amplified among those born with a small birth weight (p for interaction 0.002). Conclusions: Type 2 diabetes is associated with a higher occurrence of depressive symptoms compared to subjects with normal glucose tolerance. This association is especially strong among subjects with CVD and those born with a low birth weight. Treating depressed diabetic subjects with paroxetine has no long term effect on glucose regulation. Physicians should be aware of depression as an important co-morbidity of type 2 diabetes. Both depression and the cognitive decline often seen among diabetic subjects are increased if the subject is born with a low birth weight. Physicians should recognise low birth weight as an additional risk factor and modifier of diabetic complications.

Multiple superoxide dismutase 1/splicing factor serine alanine 15 variants are associated with the development and progression of diabetic nephropathy:the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics study

Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes.

Lipoprotein composition in HNF1A-MODY: Differentiating between HNF1A-MODY and Type 2 diabetes.

INTRODUCTION:

The young-onset diabetes seen in HNF1A-MODY is often misdiagnosed as Type 2 diabetes. Type 2 diabetes, unlike HNF1A-MODY, is associated with insulin resistance and a characteristic dyslipidaemia. We aimed to compare the lipid profiles in HNF1A-MODY, Type 2 diabetes and control subjects and to determine if lipids can be used to aid the differential diagnosis of diabetes sub-type.
METHODS:

1) 14 subjects in each group (HNF1A-MODY, Type 2 diabetes and controls) were matched for gender and BMI. Fasting lipid profiles and HDL lipid constituents were compared in the 3 groups. 2) HDL-cholesterol was assessed in a further 267 patients with HNF1A-MODY and 297 patients with a diagnosis of Type 2 diabetes to determine its discriminative value.

RESULTS:

1) In HNF1A-MODY subjects, plasma-triglycerides were lower (1.36 vs. 1.93 mmol/l, p = 0.07) and plasma-HDL-cholesterol was higher than in subjects with Type 2 diabetes (1.47 vs. 1.15 mmol/l, p = 0.0008), but was similar to controls. Furthermore, in the isolated HDL; HDL-phospholipid and HDL-cholesterol ester content were higher in HNF1A-MODY, than in Type 2 diabetes (1.59 vs. 1.33 mmol/L, p = 0.04 and 1.10 vs. 0.83 mmol/L, p = 0.019, respectively), but were similar to controls (1.59 vs. 1.45 mmol/L, p = 0.35 and 1.10 vs. 1.21 mmol/L, p = 0.19, respectively). 2) A plasma-HDL-cholesterol > 1.12 mmol/L was 75% sensitive and 64% specific (ROC AUC = 0.76) at discriminating HNF1A-MODY from Type 2 diabetes.

CONCLUSION:

The plasma-lipid profiles of HNF1A-MODY and the lipid constituents of HDL are similar to non-diabetic controls. However, HDL-cholesterol was higher in HNF1A-MODY than in Type 2 diabetes and could be used as a biomarker to aid in the identification of patients with HNF1A-MODY.

Barns upplevelser av att leva med diabetes mellitus typ 1 : samt sjuksköterskans betydelse i deras omvårdnad

Syftet med denna studie har varit att beskriva hur barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom samt vilken betydelse sjuksköterskan kunde ha i omvårdnaden av dessa barn. Studien har utförts som en systematisk litteraturstudie och tillvägagångssättet har varit att systematiskt söka, kritiskt granska och sammanställa resultat inom det valda ämnesområdet från olika studier. Sökningen har skett i databaserna Elin@Dalarna, Cinahl och Blackwell Synergy. Sökorden som har använts var: diabetes mellitus type 1, diabetes mellitus, children, adolescents, experiences, perspective, nurs* och care i olika kombinationer. Sammanställningen från resultatet visade att barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom olika utifrån sina egna förutsättningar, kön eller ålder. Det framkom även att sjuksköterskan hade en viktig roll när det gällde att fånga upp barnens upplevelser kring den förändrade livssituationen som uppstått och utifrån detta kartlägga barnens resurser att hantera denna situation. Att då kunna bemöta barnen och deras familjer utifrån egna förutsättningar och att motivera dessa till att sköta den livslånga behandlingen, kan vara avgörande för att få en bra kontroll över diabetes och på så sätt en ökad livskvalité och ett gott välbefinnande.

Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1

Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1D

Avaliação da qualidade de vida de pacientes com Diabetes Mellitus tipo 1: dados do primeiro estudo multicêntrico no Brasil

O Diabetes Mellitus tipo 1 (DM1) é a endocrinopatia mais comum da infância e adolescência e impacta negativamente na qualidade de vida (QV). O EuroQol é um instrumento que afere o estado de saúde e vem sendo utilizado na grande maioria dos estudos multicêntricos mundiais em diabetes e tem se mostrado uma ferramenta extremamente útil e confiável. O objetivo desse estudo é avaliar a QV de pacientes com DM1 do Brasil, país de proporções continentais, por meio da análise do EuroQol. Para isso, realizou-se estudo retrospectivo e transversal, no qual foram analisados questionários de pacientes com DM1, respondidos no período de dezembro de 2008 a dezembro de 2010, em 28 centros de pesquisa de 20 cidades das quatro regiões do país (sudeste, norte/nordeste, sul e centro-oeste). Foram também coletados dados sobre complicações crônicas micro e macrovasculares e perfil lipídico. A avaliação da qualidade de vida pelo EuroQol mostra que a nota média atribuída ao estado geral de saúde é nitidamente menor que a encontrada em dois outros estudos populacionais com DM1 realizados na Europa (EQ-VAS da Alemanha, Holanda e Brasil foram de 82,1 ± 14; 81 ± 15 e 72 ± 22, respectivamente). O EuroQol demonstra que a região Norte-Nordeste apresenta melhor índice na avaliação do estado geral de saúde quando comparada a região Sudeste e menor frequência de ansiedade-depressão autorreferidas, quando comparada às demais regiões do país (Norte-Nordeste = 1,53 ± 0,6, Sudeste = 1,65 ± 0,7, Sul = 1,72 ± 0,7 e Centro-Oeste = 1,67 ± 0,7; p <0,05). Adicionalmente, diversas variáveis conhecidas (idade, duração do DM, prática de atividade física, HbA1c, glicemia de jejum e presença de complicações crônicas se correlacionaram com a QV (r = -0,1, p <0,05; r = -0,1, p <0,05; r = -0,1, p <0,05; r = -0,2, p <0,05; r = -0,1, p <0,05 e r= -0,1, p <0,05, respectivamente). Esse é o primeiro estudo a avaliar a qualidade de vida de pacientes com DM1 a nível populacional no hemisfério sul. Nossos dados indicam uma pior qualidade de vida dos pacientes com DM 1 no Brasil quando comparado a dados de países europeus. Apesar de ter sido encontrado uma inferior duração do DM e menor presença de complicações microvasculares na região Norte/ Nordeste, quando comparada à outras regiões, nossos dados sugerem a existência de elementos adicionais responsáveis pela melhor QV e menor presença de ansiedade/depressão encontradas nesta região. Novos estudos são necessários para identificar esses possíveis fatores.

Dinâmica não linear da frequência cardíaca em jovens com diabetes mellitus tipo 1

Pós-graduação em Fisioterapia - FCT

Necessidades especiais de escolares com diabetes mellitus tipo 1 identificadas por familiares

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dinâmica linear e não linear da variabilidade da frequência cardíaca: sensibilidade, especificidade, valor preditivo e correlação de características físicas e clínicas no Diabetes Mellitus tipo 1

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)