- Title
- Optimising insulin dosing for dietary fat and protein in people with type 1 diabetes using intensive insulin therapy
- Creator
- Smith, Tenele Alyce
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- BACKGROUND: Postprandial glycaemia is a key determinant of glycated haemoglobin A1c (HbA1c) and represents an important therapeutic target for the prevention of diabetes related complications in people with type 1 diabetes (T1D). To maintain postprandial glycaemic control, clinical practice guidelines recommend that insulin be matched to the carbohydrate content of the meal. Despite accurate carbohydrate quantification and insulin dose calculation, people using this method often experience postprandial hyperglycaemia. There is now a substantial body of evidence that recognises the significant contribution of other dietary macronutrients, fat and protein to postprandial glucose excursions. These findings have led to revised guidelines from both the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes who now recommend adjusting the insulin dose and delivery for higher fat and protein meals to compensate for delayed postprandial hyperglycaemia. However, there is limited evidence regarding the optimal insulin dose and delivery pattern for these types of meals that is preventing the development of a simple, effective and safe algorithm to guide insulin dosing and delivery for fat and protein in practice; and the implementation of these best-practice guidelines into routine clinical care. AIMS AND METHODS: To address this evidence gap, this thesis sought to identify and evaluate the effectiveness of insulin dosing and delivery strategies in managing the glycaemic impact of dietary fat and protein in people with T1D using intensive insulin therapy. This aim was addressed through the conduct of four distinct, but complementary studies. Study 1: A systematic literature review was conducted to identify and evaluate the efficacy of existing insulin strategies for fat and fat and protein meals in preventing postprandial hyperglycaemia (and hypoglycaemia) in T1D. Four medical databases were searched from 1995-2021. Inclusion criteria were randomised controlled trials that measured the effect of an insulin strategy for fat and/or fat and protein meals on postprandial glycaemia and reported ≥1 of the following: mean glucose, area under the curve, time in range or hypoglycaemia. Study 2: A scoping, cross-sectional survey of 100 families of children and young people (2-18.9 years) living with T1D attending a primary tertiary referral centre in Australia was undertaken to examine foods that are problematic for managing postprandial glucose, the strategies, if any employed to manage these foods and if continuous glucose monitoring had impacted nutritional management. Eligible families were approached at routine clinic appointments and invited to complete a questionnaire. Questionnaires were administered by the same two investigators in a face-to-face structured interview (10-15 min). Study 3: A randomised controlled trial was undertaken to determine the amount of additional insulin required to optimise glycaemia following a high fat, high protein meal in children and young people (8-25 years) with T1D using pump therapy. On four days, participants ate the same high fat, high protein meal, 100% (control), 120%, 140% or 160% of the insulin to carbohydrate ratio (ICR) derived dose was given in random order. Insulin was delivered in a combination bolus (60:40, 3 hr). Postprandial sensor glucose was measured for 6 hr. Study 4: A randomised controlled trial was conducted to evaluate the effectiveness of increasing the meal insulin dose, alone and in combination with strategies to prolong insulin action in managing glycaemia following a high fat, high protein meal in children and adults with T1D (8-40 years) using multiple daily injections. On four days, participants ate the same high fat, high protein meal. Four insulin strategies were tested in random order; 100% ICR given in a single dose using aspart insulin (control), 125% ICR given in a single dose using aspart or regular insulin and 125% ICR given in a split dose (100:25, 1 hr) using aspart insulin. Postprandial sensor glucose was measured for 5 hr. RESULTS: Study 1: Eighteen papers were included and four insulin strategies to manage postprandial glycaemia following fat and fat and protein meals were identified, including increasing the insulin dose, altering the pattern of insulin delivery, adjusting the insulin dose split and varying the timing of insulin delivery. There was supportive evidence for administration of additional meal insulin equivalent to 24-75% ICR, however, no appropriate method for supplementary insulin dose calculation was identified. In pump therapy, insulin delivery in a combination bolus was identified as superior to a standard and extended bolus with at least 60% ICR. In multiple daily injections the research was equivocal regarding the optimal pattern of insulin delivery. Study 2: The cross-sectional survey found that families living with T1D experience difficulty with managing glycaemia following high fat, high protein, as well as high glycaemic index carbohydrate foods. This study defined a role for continuous glucose monitoring in increasing awareness of problematic foods and illustrated a willingness of families to adopt insulin strategies beyond carbohydrate counting to manage their glycaemic impact, such as increasing the insulin dose and use of a combination bolus. Study 3: The randomised controlled trial in children and young people using pump therapy, demonstrated that a mean insulin dose increase equivalent to 40% of the ICR delivered in a combination bolus, split 60:40 over 3 hr was required to manage hyperglycaemia following a high, fat high protein meal without a significant increase in hypoglycaemia. Study 4: The randomised controlled trial in children and adults using multiple daily injections, found that preprandial administration of an additional 25% of the ICR, using aspart insulin significantly improved glycaemia following a high fat, high protein meal without hypoglycaemia. There was no additional glycaemic benefit from giving insulin in a split dose (100:25%, 1 hr) or replacing aspart with regular insulin. CONCLUSION: The findings of this body of work serve as an important evidence base for clinical decision making around insulin dosing for dietary fat and protein, as well as for the development of a much-needed algorithm to guide the calculation and adjustment of the insulin dose and delivery for meals of varying fat and protein in people with T1D using intensive insulin therapy that is both effective and safe.
- Subject
- type 1 diabetes; paediatric; nutrition; insulin; fat; protein; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1514070
- Identifier
- uon:56807
- Rights
- Copyright 2021 Tenele Alyce Smith
- Language
- eng
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