Class of 2014 Abstract / Specific Aims: To assess the effect of aerobic exercise dose has on diabetes control monitoring parameter of HbA1c and BMI. Methods: Studies were found from previous studies and through a search of PubMed. These studies were screened for eligibility and data was extracted using a data extraction tool. The outcomes of HbA1c and BMI were analyzed using Comprehensive Meta-Analysis software and standardized mean difference (SMD) was used to assess the impact of different doses of exercise on the outcome measures. Variability was measured using the I2 statistic and publication bias was assessed. Main Results: Nineteen studies met inclusion criteria and were analyzed. Moderate dose aerobic exercise was found to have moderate effect in reducing HbA1c and BMI (p = 0.00 & 0.03 respectively). Low dose and high dose aerobic exercise were not to reduce HbA1c (p = 0.07 & 0.13) or BMI (p = 0.61 & 0.25). There was excess variation found in both the HbA1c analysis and the BMI analysis (I2 = 72.28 & 84.04 respectively). There was no publication bias found (Kendall’s tau = 0.809). Conclusion: Moderate dose aerobic exercise was effective in reducing HbA1c and BMI, while low dose and high dose aerobic exercise were not found to have a statistically significant effect on either HbA1c or BMI.

Heart failure (HF) is one of the commonest complications of Diabetes Mellitus (DM) with the prevalence of DM reported at around 30% in many pivotal heart failure studies. However the pathophysiological mechanisms that contribute to HF development in diabetes are poorly understood. To investigate this we used a novel human relevant mouse model of DM (GENA348) in which there is a point mutation in the glucokinase (Gck) gene, the glucose sensor which regulates insulin secretion. A mutation in the same gene is known to underlie Maturity Onset Diabetes of the Young Type 2 (MODY 2) in humans. The mutant mice developed significant hyperglycaemia with normal insulin levels due to the altered glucose sensing. We examined the molecular mechanisms that contribute to the HF phenotype in DM. Mean random blood glucose was found to be increased in the GENA348 mutant(HO) mice compared to wild type (WT) litter mates (WT 6.9±0.3mmol/L vs HO20.6±0.8mmol/L, P<0.001). Serial echocardiography was performed, at 3, 6 and 12 months. No significant changes in echocardiographic parameters were observed at 3 months, although by 6 months development of significant cardiachypertrophy in HO mice was observed characterised by a 20% increase in the diastolic posterior wall thickness (dPW). At 12 months of age left ventricular dilatation was also evident. Systolic function was preserved although significant diastolic dysfunction was evident at 6 and 12 months. Histological staining illustrated significant cellular hypertrophy with real time PCR data demonstrating a relative 150% increase in the hypertrophic marker BNP. Hypertrophic pathways were examined through western blot analysis revealing an age dependent increase in Akt phosphorylation (6 months-140%, 12 months-460%). Serum levels of advanced glycation end products (AGEs) and expression of their receptors RAGE were also elevated. In vitro cellular experiments also revealed AGEs directly activate Akt through phosphorylation and increase levels of the receptor RAGE. AGE induced phosphorylation of Akt is inhibited in the presence of wortmannin, suggesting a PI3K dependent signalling mechanism. Wortmannin blocked the development of cardiac hypertrophy in the diabetic mice. In conclusion we demonstrate that the human relevant GENA348 mouse model of diabetes develops a progressive cardiac phenotype including cardiachypertrophy, LV dilatation and diastolic dysfunction similar to the clinical manifestations of diabetic cardiomyopathy. We propose a novel RAGE/PI3K/Akt pathway that for the first time provides insight into the molecular mechanisms that underlie the development of HF. Moreover, we show raised glucose alone is able to cause cardiotoxicity independently of insulin.

Chronic diabetic patients have a higher incidence of and mortality from cardiac disease. A wide spectrum of cardiac problems plague the chronic diabetic including coronary artery disease, congestive heart failure and diabetic cardiomyopathy. Cardiac disease in the diabetic is not simply due to accelerated atherosclerosis alone, but is also due to a combination of microangiopathy, autonomic neuropathy, and various other factors which produce biochemical, functional and structural alterations in the heart. Recently, cardiac function was studied in animals with experimentally-induced diabetes and cardiac-dysfunction was reported in acute as well as chronic phases of experimental diabetes. Since cardiac disease is a consequence of long-standing diabetes in diabetic patients, investigation of myocardial function at various time points after induction of experimental diabetes would yield information regarding the development and progression of cardiac dysfunction in diabetes. We. therefore investigated cardiac function and pharmacology in isolated perfused working hearts obtained from 7, 30, 100, 180, 240 and 360-day alloxan and streptozotocin (STZ) diabetic and age-matched control hearts. Diabetes was induced in the rat by injecting either alloxan (65 or 40 mg/kg) or STZ (50 or 60 mg/kg) into the tail vein. Diabetic and age-matched control rats were sacrificed at various time points after the induction of diabetes and hearts were isolated and perfused on a working heart apparatus. Cardiac function was studied at various left atrial filling pressures and was expressed in terms of left ventricular developed pressure (LVDP), rate of rise of left ventricular pressure (positive dP/dt) and rate of decline of left ventricular pressure (negative dP/dt). Dose-response curves to carbachol and isoproterenol were also performed. Blood samples were collected at the time of sacrifice, serum was separated and analyzed for insulin and glucose content. Both alloxan and STZ produced diabetes in the rat as shown by fasting hypoinsulinemia and hyperglycemia. Cardiac function was not altered in 7-day alloxan and STZ diabetic rats. Depressed function at various left atrial filling pressures was seen in hearts isolated from 30-day alloxan diabetic rats but not in 30-day STZ diabetic rats. Hearts isolated from 100-day alloxan and STZ diabetic rats, 180- and 360-day STZ diabetic rats and 240-day alloxan diabetic rats, all exhibited cardiac functional abnormalities. Cardiac functional abnormalities observed in d.iabetic rats were, depressed >LVOP and -positive«.and negative dP/dt at high left atrial filling pressures. Diabetic rat hearts exhibited no change in either sensitivity or responsiveness to the negative inotropic effect of carbachol at 7 and 30 days after induction of the disease. A sub-sensitivity to carbachol was observed in diabetic rat hearts at 100 days after induction of diabetes as compared to age-matched control rat hearts. However, 180- and 240-day diabetic rat hearts exhibited supersensitivity to the negative inotropic effect of carbachol. Isoproterenol produced an identical positive inotropic effect in control as well as diabetic rat hearts at all of the time points studied. However, the maximum changes produced by isoproterenol in negative dP/dt of diabetic rat hearts were depressed at various time points as compared to those in age-matched control rat hearts. We also studied the effect of isoproterenol on the cyclic AMP content and phosphorylase a activity in hearts obtained from 3 and 100 to 120 day control and diabetic rats. Basal cyclic AMP content and phosphorylase a activity were not altered in acute and chronic diabetic and age-matched control rat hearts. Isoproterenol produced similar time- and dose-dependent changes in cyclic AMP content and positive and negative dP/dt in isolated perfused working hearts obtained from 3 and 100 to 120 day control and diabetic rats. However, isoproterenol caused a significantly greater activation of phosphorylase enzyme in hearts isolated from 3 and 100 to 120 day diabetic rats as compared to age-matched controls. Diabetic rat hearts had a significantly higher total phosphorylase activity at 100 to 120 days as compared to age-matched controls. Prostaglandin E₁, a drug which increases cyclic AMP content without altering phosphorylase a activity in perfused rat hearts, increased phosphorylase a activity in acute as well as chronic diabetic rat hearts but not in control rat hearts. Cholinergic muscarinic receptors in the ventricles obtained from 180-day control and STZ diabetic rats were studied by performing radioligand binding studies. [³H]NMS was used as a radioligand to stereospecifically label all of the muscarinic receptor binding sites present in the ventricular membrane preparation. There was no change in either the receptor density or in the binding constants for antagonists and agonists at the muscarinic receptor site in 180-day diabetic rat hearts as compared to control. Ventricular noradrenaline content was estimated using an HPLC method, in 180-day alloxan and STZ diabetic and age-matched control rat hearts. There was no significant change in the noradrenaline content of diabetic rat hearts. Results obtained in the above studies demonstrate that various functional, pharmacological and biochemical alterations occur in the heart in experimental diabetes. Depressed cardiac performance was observed in isolated perfused diabetic rat hearts at various time points after the induction of diabetes and may represent the preclinical ventricular dysfunction phase of a developing diabetic cardiomyopathy. Changes noticed in the sensitivity of the.diabetic myocardium towards the negative inotropic effect of carbachol may represent various stages of a parasympathetic autonomic neuropathy of the heart in diabetes. The unaltered positive inotropic effect of Hsoproterenol and unchanged noradrenaline content in diabetic rat hearts indicate the absence of a sympathetic autonomic neuropathy. The depressed cardiac relaxant effect (maximum changes produced in negative dP/dt) of isoproterenol in diabetic rat hearts suggest defects in cardiac muscle relaxation, Ca²⁺ handling by the sarcoplasmic reticulum and perhaps ATP production and utilization. The enhanced sensitivity of the phosphorylase enzyme to agonists in diabetic rat hearts may be an outcome of alterations in Ca²⁺ homeostasis and other acute metabolic derangements in the heart caused by diabetes. All these changes could contribute to the pathogenesis of a diabetic cardiomyopathy. / Pharmaceutical Sciences, Faculty of / Graduate

Diabetic individuals have been found to have consistently higher levels of a minor hemoglobin component, HbAIc, than non-diabetic individuals. Previous investigators have suggested that variation in these high levels of HbAIc may be a reflection of the degree of diabetic hyperglycemia, of hypertriglyceridemia in diabetes, and of diabetic control. To date, evaluation of HbAIc as a clinically useful parameter has been hampered by the complexity of the method of measurement, the inconsistency in ranges of normal values reported, and the lack of a broad data base for comparison with new results. This investigation began with a critical appraisal of the methods currently in use for measurement of HbAIc, followed by a simplification and standardization of theJ assay. Then the levels of HbAIc in 16 non-diabetics and 47 diabetics were determined and the mean values for these 2 groups compared. The relationships between HbAIc levels in the diabetics and selected clinical data |fasting blood sugar, 24-hour urinary sugar, age,duration of illness, dietary record, insulin dosage, and family history of diabetes) were examined. Finally, the degree of diabetic control in each of the diabetic patients was estimated by the attending physician on a scale of 1 to 5 (1=very good, 2=good, 3=fair, 4=poor, 5=very poor) and was compared with the HbAIc measurement. Results of the investigation have shown that the chromatographic measurement of HbAIc is unusually sensitive to the pH of developers used and also somewhat variable with respect to the length of storage time and the optical density at which samples are read. The comparison of mean values of HbAIc for diabetics and non-diabetics has confirmed the approximately twofold higher concentration of HbAIc in diabetics. Significant correlations were found between HbAIc and fasting blood sugar (r = .442), fat content of diet (r=-. 300) , family history of diabetes (r=-.312) and degree of diabetic control (r=.529). Thus, HbAIc values tend to be higher in patients whose fasting blood sugar is high, whose diet contains relatively little fat, whose relatives are diabetic and /or whose diabetic control is poor. Correlations between HbAIc and duration of diabetes, HbAIc and insulin dosage or HbAIc and 24-hour urinary sugar were not statistically significant (r=-.131, r=-.264, r=„067, respectively). The HbAIc level appears to be an accurate reflection of fasting blood sugar levels averaged over a prolonged period of time (r=.587). In conclusion, HbAIc levels were found to provide an objective measure of diabetic control. The improved assay method makes it a practical and valuable tool for the clinician as well as the investigator. Measurement of HbAIc levels in diabetics presents a considerable advantage over currently available measures of diabetic control in assessing the long-term effectiveness of diabetic management. / Land and Food Systems, Faculty of / Graduate

Orientador: Luiz Gonzaga Gandini Junior / Banca: Adriano Marotta Araujo / Banca: Luiz Cavalcante de Albuquerque Junior / Banca: Lídia Parsekian Martins / Banca: Ary dos Santos Pinto / Resumo: O objetivo deste estudo foi avaliar o efeito da terapia com laser de baixa intensidade (LBI) sobre as alterações histológicas do ligamento periodontal, osso alveolar e complexo dentinapolpa de dentes submetidos à movimentação ortodôntica em ratos diabéticos e osteopênicos. Para tanto, induzimos o diabetes e osteopenia em ratos Wistar, por meio da administração de aloxana e por ovariectomia, respectivamente. Animais normoglicêmicos e ratas não ovariectomizadas funcionaram como controles. Posteriormente, o primeiro molar superior direito foi submetido à tracionamento mesial. A LBI foi realizada a 780 nm. Após o sacrifício em 7, 13 e 19 dias, os tecidos foram removidos, processados e analisados histologicamente. Em animais osteopênicos e diabéticos, a LBI reduziu significativamente a intensidade da resposta inflamatória, modulou a diferenciação osteoclástica/osteoblástica e aumentou a vascularização do ligamento periodontal, além de aumentar a organização arquitetural das fibras periodontais. Adicionalmente, a LBI também atenuou a inflamação e incrementou a vascularização em polpas dentais de dentes tracionados em ratos diabéticos, embora tenhamos observado um aumento importante na colagenização pulpar. Concluímos que ambos os distúrbios metabólicos promoveram alterações morfológicas importantes nos tecidos pulpar e periodontais durante a movimentação ortodôntica e que o laser de baixa intensidade é capaz de reverter parcial, mas não totalmente, as modificações histológicas periodontais e do complexo dentina-polpa. / Abstract: The purpose of the current study was to assess the effect of the low level laser therapy (LLLT) on the histological changes of the periodontal ligament, alveolar bone, and dentinpulp complex of teeth subjected to orthodontic movement in diabetic and osteopenic rats. Therefore, we induced diabetes and osteopenia in Wistar rats, by the administration of aloxan and by ovariectomy, respectively. Normoglycemic and non-ovariectomized animals were regarded as controls. Subsequently, the upper right first molar was submitted to mesial traction. The LLLT was carried out at 780 nm. After the sacrifice of the rats in 7, 13 and 19 days, the tissues were removed, processed and analyzed in light microscope. In both osteopenic and diabetic animals, the LLLT significantly reduced the intensity of the inflammatory response, modulated the osteoblastic/osteoclastic differentiation, and increased the blood vessels content of the periodontal ligament, as well as provided better architectural arrangement of the periodontal collagen fibers. In addition, the LLLT also attenuated the inflammation and improved vascularization in dental pulps of pulled teeth of diabetic rats, although we also observed a significant increment in the pulp collagenization. We concluded that both metabolic disturbances promoted morphological changes in the pulp and periodontal tissues during dental movement, as well as that LLLT is able to partially, but not completely, reverse the histopathological findings seen in the periodontal tissues and pulp-dentin complex. / Doutor

Orientador : Antonio Carlos Boschero / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-16T21:56:08Z (GMT). No. of bitstreams: 1 Pinheiro_ElianadeCassia_M.pdf: 3617602 bytes, checksum: 71e9afaaf788da08e091cb55bd3e0231 (MD5) Previous issue date: 1988 / Resumo: Ratos com grau moderado de diabetes não apresentaram alterações significativas na severidade do mesmo, avaliada por glicemia, evolução ponderal, ingestão de água, diurese de 24 horas, consumo de reação, pesos do rim direito da gordura epididimal e da gordura perirrenal, pelo tratamento diário com 10 mg de gentamicina/kg peso corporal/dia. Ratos com diabetes moderado tratados com 50 mg de gentamicina/kg peso corporal/dia não apresentaram alterações na glicemia, na evolução ponderal, na ingestão de água, no consumo de ração, nos pesos do rim direito, da gordura epididimal e da gordura perirrenal. Por outro lado, apresentaram aumento da diurese de 24 horas, da uréia sérica e tendência deu aumento da diurese de 24 horas, da uréia sérica e tendência e aumento da creatinina sérica. Esses dados avaliados em conjunto sugerem o desenvolvimento de alterações renais provocadas pela alta dose do antibiótico do que para o aumento da severidade do diabetes. Ratos com diabetes moderado tratados diariamente com 2 x 25 mg de gentamicina/Kg peso corporal apresenta diminuição da glicemia no período de tratamento, a qual se manteve no período de recuperação. Tal alteração poderia significar a ação hepática do antibiótico aumentando a captação de glicose e/ou diminuindo a ação do glucagom, também á nível hepático: aumento da sensibilidade periférica da insulina e/ou diminuindo a secreção de outros hormônios hiperglicemiantes / Mestrado / Fisiologia / Mestre em Ciências Biológicas

Objetivo: Evaluar si existe asociación entre Obesidad Abdominal e Hiperuricemia en pacientes diagnosticados con DM tipo 2 que fueron atendidos en el programa “Cuídate” en la Clínica Internacional en la ciudad de Lima - Perú en el año 2018. Materiales y Métodos: Estudio observacional analítico de tipo transversal, de una base secundaria, en una muestra de 815 historias clínicas de pacientes diagnosticados con DM tipo 2, que fueron atendidos en el programa “Cuídate” en la Clínica Internacional en la ciudad de Lima - Perú en el año 2018. Variables principales: Obesidad Abdominal, Hiperuricemia.

Selenium, the essential trace element, is well known as its antioxidant function, antiviral properties, and its anti-inflammatory function to human health. The relationships between selenium status and diabetes mellitus have been widely studied, but the consistency of results is lacking. This study used diagnosed diabetes incidence from year 2004 to 2012 and soil selenium content by counties within 48 contiguous states in the U.S. with Generalized Linear Mixed Model- R-Side as the major statistical method to determine whether there is a significant correlation or not. Results showed that the diagnosed diabetes population had been increased from 2004 to 2012 for all 48 states. The South region showed the highest increased rate whereas the Northeast region showed the least. Also, Kentucky, Louisiana, Maryland, and Massachusetts are the four states showed the significant correlation between soil selenium content and diabetes incidence. However, improved analytical methods and data are needed for further research.

No description available.

Yes / Medical Research Council, Innovate UK and Epistem Ltd.