The predictors of birthweight (scBWT) in normal pregnancy are well established. The objectives of this study were to characterize and determine predictors of scBWT among women diagnosed with scGDM. A cohort of 436 scGDM full-term pregnancies (followed 1978-1989) were examined using data abstracted from the Royal Victoria Hospital Antenatal Diabetic Clinic charts and McGill Obstetric and Neonatal Database. Women were treated with insulin and/or diet. Dietary treatment (mean 2047 kcal/d) significantly decreased the rate of weight gain and mean fasting plasma glucose (scFPG). Regression analysis identified several predictors of scBWT (mean 3520 g): prepregnancy body mass, height, smoking, pre-diagnostic rate of weight gain, scFPG, gestational age, infant gender, and length of treatment. Stratification by body mass indicated that among non-obese women with scGDM, scFPG and length of treatment were not significant predictors of scBWT. In conclusion, since women with normal pregravid mass and prediagnostic weight gain are at lower risk of high scBWT, these require consideration, in addition to plasma glucose criteria, when treating scGDM.

<p>Increasing diabetes prevalence rates, poor involvement of and limited knowledge among health care professionals in disease management, and poor implementation of guidelines are barriers to quality diabetes care. This thesis aimed to develop, implement and evaluate an on-site diabetes pharmacotherapy program for public sector pharmacists. Qualitative and quantitative research methods were used inthe pre- and post-intervention study.</p>

No abstract available. / Thesis (M.D.)-University of Natal, 1982.

Previous research has demonstrated that those who perceive they have high perceptions of control generally have better health outcomes, including diabetes. The purpose of this research was to gain a better understanding of factors associated with perceived control in a Manitoba First Nations community. Data were collected using questionnaires in a community-based participatory research study between June 2011 and February 2012. Logistic regression was utilized to determine factors associated with perceived control over diabetes prevention and the prevention of diabetic complications. Many participants reported they had little or no control over the prevention of diabetes (47.8%) or diabetes complications (42.0%). Factors associated with high perceived control over diabetes prevention included having dyslipidemia, reporting hearing gossip about yourself and experiencing racism. Factors associated with high perceived controllability of preventing complications included having ≥ grade ten education, having dyslipidemia, reporting high chronic stress, and high perceived negative impact from residential school.

SIRT1 has emerged as a critical regulator of glucose homeostasis and metabolism in the past decade. Glucose homeostasis is tightly regulated by insulin however, the factors affecting insulin release are still incompletely understood. Relatively recent evidence has shown SIRT1 to be a positive mediator of insulin secretion although its mechanism is largely unknown. Therefore, the aim of this study was to determine how SIRT1 regulates insulin release. Using a pancreatic beta cell-specific Sirt1 knockout mouse model (Sirt1BKO), oral glucose challenge revealed a glucose intolerant phenotype with reduced insulin secretion. Isolated Sirt1BKO islets also secreted less insulin without changes to insulin content or islet morphology. Intracellular defects were localized to the mitochondria and showed suppressed bioenergetics negatively affecting downstream glucose-induced calcium influx. This is the first study using a Sirt1BKO mouse model to show novel mitochondrial genes under SIRT1 regulation and when impaired, results in reduced insulin secretion.

SIRT1 has emerged as a critical regulator of glucose homeostasis and metabolism in the past decade. Glucose homeostasis is tightly regulated by insulin however, the factors affecting insulin release are still incompletely understood. Relatively recent evidence has shown SIRT1 to be a positive mediator of insulin secretion although its mechanism is largely unknown. Therefore, the aim of this study was to determine how SIRT1 regulates insulin release. Using a pancreatic beta cell-specific Sirt1 knockout mouse model (Sirt1BKO), oral glucose challenge revealed a glucose intolerant phenotype with reduced insulin secretion. Isolated Sirt1BKO islets also secreted less insulin without changes to insulin content or islet morphology. Intracellular defects were localized to the mitochondria and showed suppressed bioenergetics negatively affecting downstream glucose-induced calcium influx. This is the first study using a Sirt1BKO mouse model to show novel mitochondrial genes under SIRT1 regulation and when impaired, results in reduced insulin secretion.

The objectives of this research were to determine the impact of 4 different bedtime snack compositions on prevention of nocturnal hypoglycemia and to determine whether optimized titration and delivery of bedtime insulin using multiple daily injections of insulin (MDI) or continuous subcutaneous insulin infusion (CSII) could prevent nocturnal hypoglycemia in the absence of bedtime snacks. We also sought to determine whether 3 months of CSII therapy would improve catecholamine response and symptom awareness to experimentally-induced hypoglycemia. The need for and the most appropriate composition of bedtime snacks were dependent on the glycemic level at bedtime. No bedtime snacks were necessary at bedtime glycemic levels > 10 mmol/L. At bedtime glycemic levels between 7-10 mmol/L , a standard snack and cornstarch-containing snack worked best and at bedtime glycemic levels < 7mmol/L, a standard and protein-rich snack were most effective. Despite optimized titration and delivery of bedtime insulin, including the use of CSII, "the gold standard" of nocturnal insulin replacement, the incidence of nocturnal hypoglycemia over 181 nights was 54 episodes per 100 patientnights. However, there was a substantial reduction, by 36% (p=0.17), in the incidence of nocturnal hypoglycemia with the use of bedtime snacks. Therefore bedtime snacks, tailored to the bedtime glycemic level, are recommended for ail adults undergoing intensive management with MDI or CSII. Although, 3 months of CSII therapy did not improve catecholamine response and symptom awareness to experimentally-induced hypoglycemia, it did not deteriorate the responses either. Therefore, CSII therapy is a viable option in intensive management of adults with type 1 diabetes.

Rosuvastatin treatment prevented diabetic deficits in endothelium-dependent relaxation to acetylcholine of mouse aorta and cavernosum, and prevented diabetic deficits in NANC-mediated relaxation, in the presence of atropine and guanethidine, of rat and mouse cavernosum precontracted with the adrenergic agonist phenylephrine. Similarly, rosuvastatin partially reversed established diabetic deficits of endothelium-dependent relaxation of mouse aorta and cavernosum, and NANC-relaxation of mouse cavernosum. However, plasma lipids were unaltered by either diabetes or rosuvastatin treatment in mice, indicating that the beneficial actions of the statin were not dependent on lipid-lowering. Co-treatment with mevalonate, the product of HMG-CoA redustase, ameliorated the beneficial actions of rosuvastatin confirming that the effects were dependent on cholesterol biosynthesis pathway inhibition. The endothelium and NANC-dependent responses of the isolated tissues were dependent on the production of nitric oxide (NO), as they were abolished following tissue incubation with the non-specific NO synthase (NOS) inhibitor <i>N</i>^G-nitro-L-arginine. As specific inhibitors for the endothelial, neuronal and inducible NOS isoforms are lacking, the secondary aim of this thesis was to investigate the specific roles of the NOS isoforms on aortic and cavernosal function of mice lacking the respective NOS genes (NOS KO's). The variations in response from NOS KO aorta and cavernosum were multiple, however, taken together suggest that mice lacking specific NOS isoforms develop compensatory mechanisms to retain NO-dependent functions. In summary, this thesis demonstrates that vascular and nervous NO-dependent functions can be improved by rosuvastatin therapy in diabetic rodents and that further investigation of the roles of the specific NOS isoforms may lead to therapeutic approaches for diabetes mellitus.

Single channel recordings from CRI-G1 insulin-secreting cells were used to characterize a novel ion channel. The presence of both Ca²⁺ and β-NAD⁺ at the cytoplasmic aspect of the membrane are required for channel activity. This is the first ion channel described which requires internal β-NAD⁺ for activity (thus termed NS_NAD). The channel was found to be permeable to all monovalent (Na⁺, K⁺and Cs⁺) and divalent cations tested (Ca²⁺, Mg²⁺, Ba²⁺, and Mn²⁺). The slope conductance is relatively large (70 - 90pS) compared to other non-selective cation channels and also has extremely slow kinetics (open and closed times in the range of seconds). Whole-cell voltage clamp experiments illustrate that internal β-NAD⁺ activates a cation current consistent with activation of the NS_NAD channel. Similar to the single NS_NAD channel, the β-NAD⁺-activated current was sensitive to the internal concentrations of both Ca²⁺ and β-NAD⁺. The non-selective nature of this cation current was confirmed by replacement of the internal K⁺ with Cs⁺ which did not diminish the β-NAD⁺-activated current. Additionally, replacement of external cations with the impermeant NMDG abolished the β-NAD⁺-activated current. The diabetogenic agent alloxan was found to irreversibly depolarize CRI-GI cells by opening a non-selective cation channel with characteristics similar to the NS_NAD channel. The channel activated by alloxan is characterized by a slope conductance of approximately 70 pS and very slow (seconds) kinetics. Channel activity is lost upon excision of the patch, but can be re-activated by the application of internal β-NAD⁺. The mechanism of alloxan-induced depolarization and channel activation appears to be through the production of reactive oxygen species (ROS). This data indicates that oxidative stress generated by both alloxan and H₂O₂ causes the activation of the NS_NAD channel which results in irreversible collapse of the membrane potential and massive Ca⁺ influx leading to eventual cell death. This may represent a component of the destruction of pancreatic β-cells during type I diabetes and possibly other pathologies in which oxidative stress is implicated.

The present studies investigated the relationship between altered renal carbohydrate intermediary metabolism and kidney functional and structural changes in the adult Spraque-Dawley rat. Both the acute (upto 28 days) and chronic (60-120 days) diabetic states were invstigated. The single intraperitoneal injection of streptozotocin at a dose of 45mg/kg body weight produced a stable, non-ketotic, non-insulin dependent and reproducible diabetic state. Compared to age matched control animals (AMC), diabetic animals (DA) demonstrated a progressive increase in mean UFR, plasma glucose, creatinine, glycosuria values and urea clearance rate over the experimental course while creatinine clearance (CCR) fell from day 21 onwards reaching 50% of AMC values by day 120. Changes in renal and hepatic metabolite concentrations were apparent after 4 days of diabetes and two patterns emerged. Renal and hepatic glucose, glocuse-1-phosphate and β-hydroxybutyric acid concentrations progressively increased over the 120 days experimental period while reduced concentrations of glycolytic and other metabolic intermediates, namely, glucose-60-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone 3- phosphate and malonyl-CoA concentrations were present. Increased concentrations of BHBA in both the liver and kidney was accompanied by the progressive reduction of malonyl-CoA. Since gluconeognesis is favoured at the expense of glycolysis in these diabetic animals, the absence of phosphofructokinase activity may be explained by a decreased concentration of fructose-6-phosphate. Renal gluconeogenic enzymes such as fructose-1,6-phosphatase were mainly located in the kidney cortex, predominantly located in the proximal tubular epithelium and that glycolytic enzymes such as hexokinase occurred mainly in the kidney medulla, restricted essentially in distal segments. Histological examination demonstrated an increasing degree of renal clear cell changes affecting from 5-20% of cells noted from day 10 to day 120, respectively in the cortical renal tubules. In addition acute pyelonephritis was also observed in all diabetic animals on days 90 and 120.