Kirsty MacDonald

Thesis submitted to fulfil partial requirements for the

Degree of Bachelor of Medical Science

The post prandialpost-prandial glycaemic response of popular takeaway foods in Type 1 Diabetes Mellitus patients on intensive insulin therapy

Supervisor:

Dr Julia Lowe

Research kindly sponsored by Sydney University Glycaemic Index Research Service (SUGiRS)

“I hereby certify that the work embodied in this literature review is the result of original research and has not been submitted for a degree to any other university or institution”


Acknowledgements

This was one of the hardest years of my life, but I had a wonderful time undertaking this project and I am greatly indebted to those people who have helped me.

To my supervisor, Dr Julia Lowe. You were a great inspiration and I would have been lost without your wisdom and encouragement this year. I am sure I asked things that were obvious, but you had the patience of a saint and things would not have run as smoothly without your recommendations and knowledge.

To Melba, you were there to lend a hand with everything- the study, nutrition advice, long days reading over my thesis and lovely dinners whenever I needed a feed! You changed my life for the better 3 years ago, and I wouldn’t be where I am today without you. Thankyou so much.

To my parents. You have always supported me in every aspect of my life. I admire and love you both so much. You have always been there on the other end of the phone giving me good advice and sharing funny moments with me. I wouldn’t be where I am today without your help. Thanks for helping me see that life is fun!

To Drs Fowler and Linjawi- you will both never know how much you turned my life around. Although you both have very different styles, I am so thankful that I met you and was treated by you both. You made me see that endocrinology isn’t my enemy and that is the most important thing I have learned in my whole medical degree so far.

To Mandu- my study partner. Thanks for making my days so fun! You gave me welcome relief when I needed it!

To all my family and friends- thanks for all the laughs, soothing words and “chill-out” days when things were getting tough. You guys were such welcome relief and I love you all.
To David.

You have been by my side for the past 6 years and I hope there are many more years to come. You have been the one person that has always believed in me, given me the confidence to do whatever I wanted and has given me unwavering support. I would not be where I am in my life without you.

You calmed me down when I was stressed about everything. You gave me welcome entertainment when things were getting me down and somehow convinced me to convert to cats! But I love it all and I wouldn’t change a thing.

For being my major proof-reader, constantly annoying you about grammatical questions help with statistics programs and excel, and for never getting annoyed at me in my panic-stricken states, thankyou. You will never know how much just being around you makes me feel better.

I love you.


TABLE OF CONTENTS

Statement of Originality………………………………………………………………. ..2

Acknowledgements……………………………………………………………………..3

Abbreviations…………………………………………………………………………….7

Abstract…………………………………………………………………………………..8

List of Figures……………………………………………………………………………9

List of Tables……………………………………………………………………………10

1 Literature Review

1.1 Background……………………………………………………………….11

1.2 Aims………………………………………………………………………..11

1.3 Procedures………………………………………………………………..12

1.4 Quality of data…………………………………………………………….13

1.5 Definitions………………………………………………………………....14

1.6 Dietary management of diabetes……………………………………….18

1.7 Glycaemic index and glycaemic load in diabetes……………………..20

1.8 Issues with current research…………………………………………….33

1.9 Conclusion and progress of research……………………………….....35

2 Aims and, hypothesis and metho

2.1 dology

2.1 Aims………………………………………………………………………..36

2.2 Hypothesis………………………………………………………………...36

3 Study design and methods

3.1 Study design……………………………………………………………….37

3.2 Study participants…………………………………………………………44

3.3 Participant recruitment……………………………………………………44

3.4 Data collection……………………………………………………………..45

3.5 Ethics approval…………………………………………………………….45

4 Results

4.1 Statistical Analysis………………………………………………………....46

4.2 Descriptive Data………………………………………………………...... 46

4.3 Glycaemic Responses to Meals………………………………………….46

4.4 Incremental Rise in BGLs………………………………………………...54

5 Discussion

5.1 Methods Critique…………………………………………………………..56

5.2 Glycaemic Responses to Meals Tested………………………………...57

5.3 Incremental Rise in BGLs…………………………………………………59

5.4 Nutritional Analysis………………………………………………………...60

5.5 Insulin Action and Food Absorption………………………………………61

5.6 Conclusion and Recommendations………………………………………62

Glossary…………………………………………………………………………………….64

References………………………………………………………………………………….65

Appendices……………………………………………………………………………..….72
ABBREVIATIONS

BGL Blood glucose level

BSL Blood sugar level

CHO Carbohydrate

CSII Continuous subcutaneous insulin infusion

CV Coefficient of variation

FPG Fasting plasma glucose

GI Glycaemic index

GL Glycaemic load

IDDMTYPE 1 DIABETES Insulin dependent diabetes mellitus

IFG Impaired fasting glucose

IGT Impaired glucose tolerance

IIT Intensive insulin therapy

MDIs Multiple daily injections

OGTT Oral glucose tolerance test

PG Post glucose

SD Standard deviation

T1DM Type 1 diabetes mellitus

T2DM Type 2 diabetes mellitus
Abstract

Objective

To examine the effects of popular takeaway foods on individuals with T1DM (type 1 diabetes mellitus) patients and see if they each had the same glycaemic response when they contained consumed meals with the same amount of carbohydrate.

Research Design and Methods

Nine9 participants each consumed a pasta, Thai, McDonald’s and standard meal on four4 different occasions, at least three3 days apart. The meals had different macronutrient quantities but the same amount of carbohydrate. They also had different GIs. The basal insulin the participants’ normally received was maintained however the bolus insulin they would normally give at mealtimes was withheld.

Results

The glycaemic response was significantly lower after ingesting pasta compared to the Thai (p<0.006), McDonald’s (p<0.04) and standard (p<0.008) meals at three3 hours. There was no significant difference between the standard, Thai and McDoanld’s meals. BGLs rose between 3.91-8.44mmol/L at the conclusion of three3 hours, which shows a single CHOcarbohydrate portion (15g) can rise BGLs by 0.98-2.11mmol/L, depending on the GI of the food.

Conclusion

People with tType 1 diabeticspeople with diabetes on IIT (intensive insulin therapy) should not only look at overall carbohydrate content when considering insulin dosages. The overall GIglycaemic index of the food should also be taken into consideration to avoid post prandialpost-prandial hypo- and hyperglycaemia. Current teaching guidelines aboutinto how much a single CHO portion makes BGLs (blood glucose levels) rise also needs revision.
List of Figures

Figure 1. Glycaemic Response to Standard Meal……………………………………..47

Figure 2. Glycaemic Response to Thai Meal…………………………………………..48

Figure 3. Glycaemic Response to Pasta Meal…………………………………………49

Figure 4. Glycaemic Response to McDonald’s Meal………………………………….50

Figure 5. Mean Incremental Values of Meals…………………………………………..53
List of Tables

Table 1. Diagnostic Thresholds for Diabetes and Impaired Glucose Tolerance……….15

Table 21. Pharmacokinetics of Most Commonly used Insulin Preparations……………..16

Table 32. International table of glycemic index (GI) and glycemic load (GL) values: 2002

…………………………………………………………………………………………………...23

Table 43. Nutritional Information of Meals……………………………………………………42

Table 54. Mean Glucose AUC of Meals………………………………………………………51

Table 65. Blood Glucose Responses to Meals………………………………………………52


CHAPTER 1. Literature Review

1.1 Background

Insulin dependent diabeticspeople with diabetes People with insulin- dependent diabetesPeople with type 1 diabetes mellitus are increasingly being placed on intensive insulin regimes, which allows for greater flexibility in meal times, amount of food eaten and frequency of meals. This has been well established in the Hunter region, with the empowerment course and throughout Australia with the results of the DAFNE study [1]. However, there is still great confusion about the complexity of carbohydrate counting and the perceived inconsistency of postprandial blood glucose levels after eating different foods with the same carbohydrate load. Despite accurate counting, there are still variations in blood glucose after eating different meals with the same carbohydrate content [2]. This research aims to highlight the general trends that fast foods have on glycaemic control and is geared towards young people and the choices they make in takeaway foods they make.

1.2 Aims

This literature review aims to present a:

i.  Brief overview of published literature about the dietary treatment of type 1 diabetes mellitus, the relationship between dietary management and insulin therapy and the differences in carbohydrates available.

ii.  Brief overview of the current effects of glycaemic index, glycaemic load and carbohydrate counting on type 1 diabeticspeople with diabetespeople with type 1 diabetes.

iii.  Brief overview of the different effects that foods have on blood glucose levels and how this can be managed by changes in insulin therapy.


1.3 Procedure

A computerised search of MEDLINE and PUBMED for articles published between 1980-2006 was conducted by the author. This time period was allocated due to the advancements in diabetes treatments and the new therapies available. There have also been significant advances in glycaemic index and other dietary information now used to advise diabeticspeople with diabetes about their condition.

The key words used included: diabetes, type 1 diabetes, carbohydrate, carbohydrate therapy, intensive insulin therapy, continuous subcutaneous insulin therapy, diabetes diet, conventional therapy, glyc(a)emic index, glyc(a)emic load, insulin-carbohydrate ratio, blood glucose, insulin, insulin regimes, insulin pump, post prandialpost-prandial response, hyperglycaemia, bolus, dose adjusted eating, nutrition, increase of blood glucose, accuracy, treatment, outcome, improvement, clinical significance.

Reference lists of all relevant articles were checked for further studies.

Eligibility for inclusion in this literature review included:

1. Article printed in English

2. The article was relevant to T1DM patients and their treatment

Exclusion criteria included:

1. Articles comprisingin which the the majority of research was conducted in non-diabetic subjects, patients with Type 2 Diabetes Mellitus or Gestational Diabetes Mellitus.

2. Articles researching the prevention of diabetes rather than the treatment aspects.


1.4 Quality of the Data

The quality of articles varied greatly. When reviewing research methods, the patient selection, the sample size, the design of the study and the validity and reliability were closely examined. The author placed emphasis on using a randomised-control or cross-over design, rather than studies which only observed patients. However, the availability of those studyrandomised-control and cross-over studiesdesigns in this field is rare, and observational studies, meta-analyses and reviews were used to confirm and classify data. The advantages of a randomised control trials isare that it allows for a single variable in a defined group, it has a prospective design and potentially eradicates bias and other variables which might cancel each other out given the 2 groups should be identical. The advantages of meta-analytic studies are that they combine the results of more than one randomised control trial and can provide general trends in the defined population group studied. This increases the precision of results.


1.5 Definitions

Diabetes

The term diabetes mellitus describes several diseases of abnormal carbohydrate metabolism that are characterized by hyperglycaemia. It is associated with a relative or absolute impairment in insulin secretion, along with varying degrees of peripheral resistance to the action of insulin. There are various terms used to describe diabetes and impaired glucose tolerance. Normal levels of fasting plasma glucose (FPG) is <5.6 mmol/L and <7.8mmol/L after a 2-hour oral glucose tolerance test (OGTT) [3]. Impaired fasting glucose is diagnosed when the FPG is 5.7-6.9 mmol/L. Impaired glucose tolerance is diagnosed when the 2-hour OGTT is 7.8-11.0mmol/L. Diabetes is diagnosed when FPG >7mmol/L and OGTT >11mmol/L [3][3]. These diagnostic figures can be found in table 1. The terms type 1 diabetes and type 2 diabetes are widely used now, instead of insulin-dependent (IDDMTYPE 1 DIABETES) or non-insulin dependent diabetes mellitus (NIDDMTYPE 1 DIABETESTYPE 1 DIABETES), , juvenile onset and maturity onset diabetes [4][4].

The FPG and 2-h post-glucose (PPG) are used to diagnose impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), respectively. There is currently no consensus on using one over the other, as both are good indicators of pre-diabetes. However the FPG is used more widely in disadvantaged/ underprivileged populations because of the cheaper cost. These tests are usually performed on patients suspected of suffering from type 2 DM almost exclusively, as patients with T1DM usually present with ketoacidosis or a very high FPG. Although the 2-h post-glucose (PG) is a more sensitive test in most populations [5][5], the FPG is more convenient, more reproducible, and less expensive.


Table 1. Diagnostic Thresholds for Diabetes and Impaired Glucose Tolerance [3]

Test

Category / FPG / 2-hr PG
Normal / <5.6mmol/L / 7.8mmol/L
IFG / 5.6-6.9mmol/L / ---
IGT / --- / 7.8-11.0mmol/L
Diabetes / >7.0mmol/L / >11.1mmol/L

Type 1 Diabetes

Type 1 diabetes is characterized by destruction of the pancreatic beta cells, leading to absolute insulin deficiency. This is usually due to autoimmune destruction of the pancreatic beta cells (type 1A). The American Diabetes Association (ADA) and World Health Organisation (WHO) have developed guidelines for diagnosing diabetes mellitus, including fasting plasma glucose >7mmol/L or a random plasma glucose2-hour post meal BGL >11.1mmol/L [3][3]. Patients with type 1 diabetes must have insulin therapy or they will develop ketoacidosis, a potentially life-threatening condition. The term juvenile-onset and IDDMTYPE 1 DIABETESinsulin dependent diabetes mellitus was often used to describe type 1 diabetes, however due to the overlap of insulin therapy in type 1 and 2 diabetes, these terms are no longer used to describe the type of diabetes the patient has [3][3]. These recommendations were endorsed by the WHO in 1998 [6][6].

Insulin

Insulin is a hormone produced in the beta cells of the pancreas and distributed in the blood stream throughout the body. The action of insulin is to transport glucose carried in the blood stream into the cells of the body. It acts by binding to membrane bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Insulin facilitates entry of glucose into muscle, adipose and other tissues via hexose transporters, including GLUT-4. Insulin also promoted the movement of potassium into cells, by activating the sodium-potassium ATPase system [7]. In diabetes, the beta cells of the pancreas are destroyed due to an autoimmune attack. The body therefore has no insulin to transfer the plasma blood glucose into cells.

There are different types of synthetic insulin produced. There is a medium to long-acting insulin (NPH, glargine, protaphane) which suppresses hepatic production of insulin and maintains normoglycaemia in the fasting state. There is also a regular, and very fasting acting insulin that are given in pre-meal boluses. They are lispro or aspart. These insulins have been chemically modified from the slower-acting insulins, to avoid any metabolic effects[8]. These rapidly absorbed insulins have an onset of action within 5 to 15 minutes, peak action at 30 to 90 minutes, and a duration of action of two to four hours [9-11]. The actions of these insulins is shown in Table 21 [12, 13].