3. Electronic Theses and Dissertations (ETDs) - All submissions
Permanent URI for this communityhttps://wiredspace.wits.ac.za/handle/10539/45
Browse
2 results
Search Results
Item Insulin to carbohydrate ratios with increasing carbohydrate loads(2011-01-28) Marran, Kerry JoanBackground: 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.Item Cytokines associated with insulin resistance in critically ill patients.(2009-02-13T07:38:59Z) Wilgen, UrsAbstract Mortality of patients requiring intensive care treatment for greater than 5 days has been shown to be about 20% worldwide. Hyperglycaemia is common in critically ill patients. Strict glucose control with insulin in critically ill patients was shown to reduce mortality and morbidity significantly. Several interrelated mechanisms are involved in the development of “stress hyperglycaemia” in critically ill patients. These include dextrose containing intravenous infusions and total parenteral nutrition; the counter regulatory hormones (catecholamines, cortisol, glucagon and growth hormone) which oppose the effects of insulin; nervous system signaling; increased insulin clearance; and excess production of cytokines that interfere with intracellular insulin signaling pathways. Aim of study: To determine if the cytokines TNFα, IL-6 and adiponectin are significant determinants of insulin resistance in critically ill patients. Methods: The study was a prospective observational study conducted in the intensive care unit (ICU) at the Chris Hani Baragwanath hospital. Forty sequential adult ICU admissions that met with the inclusion criteria were enrolled. Blood specimens were drawn for adiponectin, TNF, and IL-6 at the time of ICU admission, on day 3, day 7 and on discharge from the ICU. Demographic data and clinical data were recorded, and body mass index (BMI) and APACHE II scores were calculated on admission. Blood glucose was measured every 2 to 4 hours, recorded and a mean value was calculated over the 24 hour period. Insulin infusions were started when the blood glucose values exceeded 6.0mmol/l. Administration of insulin was according to a fixed sliding scale. The total amount of insulin administered intravenously over that 24 hour period was recorded. Other factors known to be related to insulin sensitivity, such as inflammation (as indicated by C-reactive protein), vii triglycerides, insulin, C-peptide and cortisol levels were also drawn in addition to the blood drawn for routine investigations. Results: Duration of stay in ICU correlated with severity of illness as assessed by the APACHE II score (r = 0.44, p = 0.004). There was no significant difference in the mean 24 hour plasma glucose concentration throughout the duration of stay in ICU, there were however significant differences in the amount of insulin administered to maintain normoglycaemia. The amount of administered insulin required was found to peak on day 3 and decline thereafter. The main determinant of insulin administered was mean glucose (r = 0.79, p < 0.00001). The measured insulin concentrations on admission correlated with mean plasma glucose (r = 0.41, p = 0.009) and C-peptide (r = 0.45, p = 0.004) levels. The main determinants of mean plasma glucose levels on admission were BMI (r = 0.38, p = 0.013) and serum cortisol (r = 0.41, p = 0.008) levels. Serum triglycerides levels showed a significant difference from admission to discharge, with values increasing from admission levels. Adiponectin levels showed a significant increase from admission to discharge. IL-6 levels showed a significant decrease. TNFα levels did not show statistically significant changes. No statistically significant correlations were found between the levels of TNFα or IL-6 and administered insulin. Adiponectin concentrations showed a negative correlation with amount of administered insulin on discharge (r = -0.457, p = 0.0049). There were significant gender differences in BMI, administered insulin on admission, serum cortisol and C-peptide concentrations, with females having higher values than males. BMI was shown to account for the gender differences in administered insulin and C-peptide levels. viii There were significant differences in IL-6 and TNFα concentrations between the survivors and nonsurvivors, with higher levels being seen in non-survivors. Adiponectin levels were lower in nonsurvivors, but this did not reach statistical significance. Conclusion: Although there was a demonstrable change in insulin sensitivity during the stay in ICU, there was no statistically significant association between the cytokines TNFα or IL-6 and insulin administration. There was a negative correlation between adiponectin concentrations and administered insulin on discharge. This data also demonstrates that mortality is associated with increased levels of proinflammatory cytokines.