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MMed, Paediatrics, University of the Witwatersrand, Faculty of Health Sciences / Background: To reduce the risks and prevent progression of diabetic complications average blood glucose and glucose variability need to be kept as close to the non diabetic range as possible. Post prandial glucose excursions contribute significantly to average blood glucose and to glycemic variability. Dietary carbohydrate is the primary determinant of meal related blood glucose excursions. Carbohydrate counting is a method of insulin dosing that matches carbohydrate load to insulin dose using a fixed ratio. Many patients and current insulin pumps, calculate insulin delivery for meals based upon a linear carbohydrate to insulin relationship. Hypothesis: A non-linear relationship exists between the amount of carbohydrate consumed and the insulin required to cover it. Rather, an exponential increase in insulin is needed to cover an increasing load of carbohydrate. Aim: To document blood glucose exposure, as measured by AUC, in response to increasing carbohydrate loads on fixed carbohydrate to insulin ratios. Sample and Methods: 5 Type-1 diabetic adolescents and young adults on insulin pump therapy with good control were recruited. Morning basal rates and carbohydrate to insulin ratios were optimized prior to the study start. A Medtronic glucose sensor was worn by each participant for 5 days on which standardized meals of increasing carbohydrate content were consumed. After the 5 days the glucose sensors were downloaded and the glucose area under the curve was analyzed for each carbohydrate load for each participant. Results: Only subjects with 5 days of complete recordings covering the test meals were included for analysis, resulting in 5 complete analyses. Sensor failure and hypoglycaemic v episodes prior to test meals accounted for failures. Increasing carbohydrate loads on a fixed carbohydrate to insulin ratio resulted in increasing glucose area under the curve (AUC).The log (Average AUC) was linear confirming that this relationship is exponential. An Analysis of Covariance performed on the log (AUC) data confirmed a highly significant exponential relationship (p<0.0001) although no significant differences were found between the profiles of the 5 individuals. Late post prandial hypoglycaemia followed carbohydrate loads greater than 60 grams and this was often followed by rebound hyperglycaemia that lasted more than 6 hours. Conclusion: A non linear relationship exists between carbohydrates consumed and the insulin required to cover them when using premeal bolus insulin. This has implications for control of postprandial blood sugars, especially when consuming large carbohydrate loads. Because of the late post prandial hypoglycaemia that follows the larger doses of insulin used with larger amounts of carbohydrate it is not possible to simply increase the amount of the insulin bolus using an exponential formula. Further studies need to be done looking at the optimal ratios of insulin needed for increasing carbohydrate loads, the duration and type of boluses needed to cover these high carbohydrate loads and the possibility of changing the linear equation used in current insulin pumps to one that would better cover the increase in post prandial glucose load with large carbohydrate meals.

Leishmaniasis is the second largest parasitic killer in the world (after malaria) responsible for an estimated 500,000 cases each year worldwide. Visceral leishmaniasis infections (i.e. internal organs) are more complicated to diagnose due to the lack of visible symptoms. Current tests of the disease look for antibodies against the parasite, but these antibodies are expressed long after the infection. It has been found the Leishmania parasite excretes a unique phosphoglycan repeat unit: By testing for this repeat unit, the diagnostic test will be looking for an active infection in the patient. It has been found that there are 4 monoclonal antibodies to detect this uniquely excreted phosphoglycan. This provides a basis for a test kit, the biomarker (i.e. the phosphoglycan repeats), and the way to detect the biomarker. For the construction of a dipstick style test or an ELISA format assay, a synthetic repeat unit phosphoglycan is needed to act as a positive control in a dipstick test or as a known comparison in a ELISA. The synthetic structure must also be anchored to a solid surface for testing. Biotin will be used as the anchor, it has shown many different uses in biotechnology and its very high affinity to the avidin proteins make it very useful. A 6-aminohexanol spacer arm will also be included. After many attempts to introduce the biotin spacer moiety to the repeat unit at the D-mannose 1-phosphate, it was decided to change the strategy and integrate the biotin-spacer moiety as a phosphate at the D-galactose unit. This meant performing chain elongation from the reducing end, with the first disaccharide unit being capped at the D-mannose anomeric position with a methyl group. Below are examples of the targeted biotinylated phosphoglycan structures to be prepared in this project.

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Thesis (Ph.D.)--Boston University / It is now generally recognized that insulin facilitates the transfer of certain sugars through cytostructural barriers. If the transfer of a utilizable sugar into the cell is affected by a rate-limiting reaction, then all subsequent enzymatic reactions of this sugar in the cell would be dependent upon this reaction. This study has involved an investigation of factors which regulate the transfer of sugar into muscle cells. [TRUNCATED]