M.Sc. (Med.), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand, 2011

Hemoglobin A1c (HbA1c) levels are indicators for managing Diabetes Mellitus. This study investigated the effectiveness of Diabetes Mellitus education classes based on participants’ HbA1c levels. The HbA1c and body mass index (BMI) values were analyzed using t-tests to determine significant (P ≤ 0.05) differences between baseline (N = 46) levels compared to three months, six months, and 12 months after class participation and reported as means ± standard deviations. The study was not able to track all participants as some did not attend all follow-up sessions. Mean HbA1c levels were lower at three months (8.1% ± 2.1, P = 0.002, n = 31), six months (8.11% ± 2.6, P = 0.001, n = 39), and 12 months (8.7% ±± 2.3, P = 0.050, n = 29) compared to baseline (9.5% ± 2.4). The baseline BMI was 36.7kg/m2 ± 9.7 with similar (P > 0.05) values after class attendance.

1.5 million Ontarians, representing 10.2% the population, lived with diabetes in 2015. Treating this number of people with diabetes cost the public healthcare system approximately $6 billion. A staggering 2.3 million Ontarians, representing 13.5% of the population, are projected to have diabetes in the year 2025. This will raise public spending on diabetes to approximately $7.7 billion. Current therapies for Type 2 diabetes only focus on controlling glucose levels and do not target or reverse disease progression and complications, which allows the prevalence of diabetes to continue to rise unchecked. Targeting the source of insulin resistance, as opposed to attempting to control the symptoms of insulin resistance, represents a better strategy for the discovery of novel therapies. We have recently reported that loss of T-Cell Death-Associated Gene 51 (TDAG51) is associated with mature-onset obesity, Type 2 diabetes, and fatty liver. TDAG51 expression is significantly diminished in mice fed a high fat diet, which leads to insulin resistance and obesity, as well as in the leptin-deficient mouse model, a well-established genetic model of Type 2 diabetes and obesity. We have now discovered that restoring TDAG51 protein expression in the livers of TDAG51-null and leptin-deficient mouse models improves response to insulin and reduces total weight gain. We have shown that exogenous TDAG51 protein expression is significantly reduced in two mouse models of insulin resistance compared to healthy controls. The potential for post-translational degradation of TDAG51 protein in insulin-resistant livers is supported by five independent models of fatty liver in which TDAG51 protein expression is diminished while TDAG51 mRNA expression remained unchanged. We have also explored a number of mechanisms by which TDAG51 protein may be regulated post-translationally, and have provided suggestions of how TDAG51 protein may be modified in a fatty liver that would impact its stability. Collectively, we have highlighted the therapeutic potential of increasing liver TDAG51 expression in Type 2 diabetic conditions, and have laid a strong foundation for discovering how TDAG51 expression is regulated. / Thesis / Master of Science (MSc) / 1.5 million Ontarians, representing 10.2% the population, lived with diabetes in 2015. Treating this number of people with diabetes cost the public healthcare system a staggering $6 billion. Current therapies for Type 2 diabetes do not target or reverse disease progression and its complications, which allows the prevalence of diabetes to continue to rise unchecked. We have recently reported that loss of the protein T-Cell Death-Associated Gene 51 (TDAG51) is associated with mature-onset obesity, Type 2 diabetes, and fatty liver. Additionally, TDAG51 protein expression is nearly diminished in three different mouse models of insulin resistance and hepatic steatosis, though the mechanism by which the protein is reduced is unknown. We have now discovered that restoring TDAG51 expression in two mouse models of Type 2 diabetes can reduce weight gain and improve insulin signalling. We have also explored a number of mechanisms by which TDAG51 protein is regulated, and have devised a method for determining how TDAG51 protein might be regulated in normal versus fatty liver. Collectively, we have highlighted the therapeutic potential of increasing liver TDAG51 expression in Type 2 diabetic conditions, and have laid a strong foundation for discovering how TDAG51 expression is regulated.

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n/a / Thesis / Master of Science (MSc)

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Yes

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The principal objective of this study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60g) were randomly divided into six groups namely: Normal Control (NC), Diabetic/Streptozotocin Control (STZ), Fructose-10 (FR10+STZ), Fructose-20 (FR20+STZ), Fructose-30 (FR30+STZ) and Fructose-40 (FR40+STZ) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40mg/kg BW) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose >300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20+STZ, FR30+STZ and FR40+STZ were eliminated from the study due to the severity of diabetes and the FR10+STZ group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-beta) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BW STZ injected rat can be an excellent alternative model for T2D. To validate this newly-developed model, an acute intervention trial study was conducted to investigate the anti-diabetic effects of L-Carnitine and white mulberry leaf tea extracts in the newly developed animal model of type 2 diabetes (T2D). Male Sprague-Dawley rats (mean BW 191.88g±16.40g) were randomly divided into 5 groups namely: Normal Control (NC), Diabetic/Streptozotocin control (FR10+STZ), Mulberry Tea Low (FR10+STZ+MTL, 0.25%), Mulberry Tea High (FR10+STZ+MTH, 0.5%), and L-Carnitine (FR10+STZ+CARN). In first three weeks, T2D was induced in all other groups except NC group by using above-mentioned procedure. Mulberry tea was supplied ad libitum and L-carnitine was administered to the FR10+STZ+CARN group at a concentration of 500mg/kg BW once daily during week 4-8 of the intervention trial. The FR10+STZ+CARN group had significantly (p < 0.05) lower total cholesterol, triglycerides, total proteins and fluid intake compared to the diabetic control (FR10+STZ). The NFBG non-significantly reduced in FR10+STZ+CARN group compared to the FR10+STZ group, whereas MT did not. FR10+STZ+MTL had significantly higher serum triglycerides level compared to the NC group, and significantly higher HDL-cholesterol and fluid intake compared to the FR10+STZ group. FR10+STZ+CARN and FR10+STZ+MT groups had significantly lower total proteins compared to NC and FR10+STZ groups, but significantly lower albumin compared to NC group only. The data of the this section of the study suggest that CARN may be effective in normalizing lipid profiles rather than blood glucose in diabetic rats which may aid in the reversal of insulin resistance. On the other hand, MT used in this study did not display any significantly beneficial anti-diabetic effects at least in this experimental condition. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2011.

Objetivo: El propósito del estudio fue determinar la relación entre el test de Tolerancia oral a la glucosa( TTOG) en las puérperas con macrosomia fetal y plantearlo como un método de diagnostico retrospectivo de diabetes gestacional. Diseño de estudio: Estudio Clínico, Observacional, Prospectivo, Analítico, Comparativo (de casos y controles pareados), con 142 puérperas pareadas por edad, paridad y tipo de parto, 71 con recién nacidos macrosómicos y 71 con recién nacidos con pesos en percentiles de la normalidad. Previo consentimiento informado, se realizó un TTOG modificado de dos horas (basal, 1h y 2 h) con 100 gr de glucosa (positivo si [Glicemia 2h – Basal] + [Glicemia 1h – Basal] > 110 mg/dl) a todas las participantes entre las primeras 8 y 48 horas posparto en el IEMP, entre Abril a Junio del 2003. Se utilizó el paquete SPSS v.10.0 para crear la base de datos y realizar el análisis estadístico que consistió en un análisis univariado, bivariado para evaluar la hipótesis, y finalmente un análisis multivariado. Resultados: El test de tolerancia oral a la glucosa anormal resultó un factor de riesgo para macrosomia fetal, con un odds rate ajustado de 5.93; 95% IC, 2.626-13.393. Se encontró una asociación significativa el antecedente de macrosomia fetal odds rate 15.690; 95% IC, 1.993-123.553 y el control prenatal odds rate 5.696, 95% IC, 1.192-26.828. Conclusión: Existe una relación entre el TTOG en puérperas y macrosomia fetal que puede ser usada como un test de Diagnóstico retrospectivo de Diabetes Gestacional. PALABRAS CLAVES: Test de Tolerancia Oral a la Glucosa, Macrosomia fetal, Diabetes Gestacional.