WO2006079124A2 - Apparatus and method for predicting the effect of ingested foodstuff or exercise on blood sugar level of patient and suggesting a corrective action - Google Patents

Abstract

A handheld device is provided for calculating insulin boluses for Type 1 diabetics to improve their blood glucose control. The device takes food intake, exercises, preprandial blood glucose levels and user parameters such as insulin sensitivity and sensitivity to carbohydrates expressed in terms of equivalent teaspoons sugar (ets). All energy values are expressed in terms of newly defined linear energy unit namely equivalent teaspoons sugar (ets). Sugar energy in food available through digestion, energy being expended during exercise and glucose energy in blood are qauntified in terms of ets. The algorithm can be implemented as either a portable electronic device (PED) or a slide rule device. The invention extends further to a method of controlling operation of the insulin dosage calculation device.

Description

APPARATUS AND METHOD FOR PREDICTING THE EFFECT OF

INGESTED FOODSTUFF OR EXERCISE ON THE BLOOD SUGAR LEVEL

OF A PATIENT AND SUGGESTING A CORRECTIVE ACTION

This invention relates to an apparatus and method for calculating corrective action required by a patient to normalise blood sugar level in response to changes effected by ingesting foodstuff or exercising. More particularly, but not exclusively, to an apparatus and method for calculating the required insulin bolus or quantity of carbohydrates required by a diabetic patient to normalise blood sugar level in response to ingestion of foodstuff or exercise, the foodstuff and exercise being characterised in linear units such that blood sugar response is linearly proportional to the amount of linear units gained or lost, through ingestion or exercise, respectively. It will be appreciated that blood sugar levels may be too high or too low for reasons other than exercise or food.

In the treatment of diabetes, characterising blood glucose or blood sugar ("glucose" and "sugar" are used interchangeably throughout this specification) response in an individual in order to estimate the amount of insulin required to normalise the blood sugar level, is critical to maintaining health.

Presently foodstuffs are characterised, inter alia, in terms of the CHO content or the

Glycaemic Index (GI) thereof. An estimate of the bolus of insulin required, which is based on the carbohydrate content or GI of the food ingested, is often inaccurate because there is a poor linear relationship between grams of carbohydrates ingested and/or the GI of the foodstuff and the consequential elevation in blood sugar. The effect of this is that suggested insulin boluses calculated from the anticipated effect on blood sugar level will often be incorrect leading to hypoglycemia or hyperglycemia in a diabetic patient.

Further, there are a number of other physiological factors which differ from patient to patient, that influence the resultant change in blood sugar after eating or injecting insulin. For example, some patients are more sensitive to insulin while others are insulin resistant. Many prior art techniques for estimating the insulin bolus required to neutralise the effect of ingested food on blood sugar do not take these physiological factors into account.

Object of the Invention

It is an object of the present invention to provide an apparatus and method for calculating corrective action required by a patient to normalise blood sugar level in response to changes effected by ingesting foodstuff or exercising, which, at least partially, alleviate some of the abovementioned difficulties.

Summary of the Invention

A first aspect of the invention comprises characterising foodstuffs and/or exercise in terms of a unit of energy (hereinafter referred to as a "linear unit"), in which the quantity of energy in linear units that is associated with an ingested foodstuff is directly proportional to the resultant blood sugar absorbed into the blood of a Type 1 diabetic. The invention also extends to characterising exercise in terms of linear units, such that the quantity of energy in linear units that is expended by a person during exercise, is directly proportional to the resultant decrease in their blood sugar level.

For the purposes of exemplification, Equivalent Teaspoons of Sugar (ETS) are used as the linear unit throughout the specification and the reasons for using this particular linear unit are set out more fully below. Any linear unit which characterises foodstuff or exercise such that the number of linear units gained by eating or lost though exercise, correspond proportionally and linearly to the resultant effect on blood sugar level, could be used.

According to a second aspect of the invention an apparatus is provided for predicting the effect of ingested foodstuff or exercise on blood sugar level and suggesting a corrective action, comprising receiving means for receiving original blood sugar information relating to the original blood sugar level of a patient and energy information relating to the linear units of energy gained by ingesting foodstuff or lost through exercise; and outputting means for outputting the suggested corrective action required to normalise the effect of the gain or loss of energy on the blood sugar level of the patient.

The outputting means may output a suggested insulin bolus required to normalise the effect of the ingested foodstuff on the patient's blood sugar level. Alternatively, the outputting means may output a suggested quantity of linear units of energy to ingest to raise the patient's blood sugar to an accepted normal level. Further alternatively, the outputting means may output a suggestion to take no action.

The suggested corrective action may automatically be implemented, such as when the apparatus is used in conjunction with an automatic blood sugar regulating device.

The system may include a processor for calculating the corrective action required to normalise the effect of the gain/loss of energy on the patient's blood sugar level, given the patient's original blood sugar level and the linear units gained by ingesting the foodstuff or lost through exercise, as inputs.

Further, the receiving means may receive patient specific information, such as any one or more of the patient's : ETS sensitivity (f_ets ); insulin sensitivity

(f _insulin );exercise sensitivity (f_exercise); age; gender; height; normal activity level (E.g. low, medium, high); typical daily routine (E.g. office, house etc.); total daily dose of short- and long-acting insulin; and target blood glucose level and acceptable blood glucose range;

The receiving means may be in the form of a body member displaying a series of original blood sugar levels thereon and a first marker, movable relative to the body member. It is envisaged that a user would align the first marker with the original blood sugar level of a patient displayed on the body member.

The body member may also include a graduated scale of linear units, the scale of linear units being fixed relative to the first marker; and a second marker which is movable relative both to the series of original blood sugar levels and the scale of linear units. It is envisaged that a user will move the second marker to correspond with the number of linear units to be gained when ingesting a particular foodstuff or the number of linear units lost when exercising.

The output means may include a first bolus indicator in the form of a graduated scale provided on the body member and a third marker fixed relative to the second marker, the scale being disposed such that when the second marker is moved to indicate the energy in linear units associated with the ingested foodstuff or exercise, the third marker indicates the suggested insulin bolus required to normalise the effect of ingested foodstuff on blood sugar level.

The output means may include a second bolus indicator in the form of a further graduated scale on the body member, the scale being disposed such that when the second marker is moved to indicate the quantity of energy in linear units associated with the foodstuff the third marker indicates the suggested insulin bolus required to normalise the effect of the energy gain/loss, when physiological characteristics of the patient, such as insulin resistance or sensitivity, are taken into account.

The output means may include a carbohydrate indicator in the form of a graduated scale on the body member and a fourth marker fixed relative to the first marker, the scale being disposed such that when the first marker is located to indicate the original blood sugar level and the second marker is located to indicate the quantity of linear units lost by exercising, the fourth marker indicates the suggested carbohydrates (quantified in ETS) required to be ingested to normalise the blood sugar level of the patient, should this action be required.

The apparatus may be provided in the form of a software application used in conjunction with a Portable Electronic Device (PED). The software application includes receiving means for receiving the original blood sugar level of a patient and foodstuff/exercise information relating to the linear units gained by ingesting a foodstuff or lost through exercise, input by a user; and outputting means for outputting the suggested corrective action to normalise the effect of the ingested foodstuff or exercise on the blood sugar level of the patient.

The receiving means may co-operate with input means provided on the PED. The input means may be provided in the form of a keypad, keyboard, sensor, touch screen, communication port or the like.

The outputting means may co-operate with an electronic display for displaying the corrective action. The corrective action may be provided in the form of a suggested quantity of linear units to ingest, suggested mass of a particular foodstuff to ingest or suggested insulin bolus to receive, for example.

The software application may include accessing means for accessing an electronic storage medium. The electronic storage medium may store a library of foodstuffs and the corresponding linear units associated with a particular mass of that foodstuff. The receiving means may receive information relating to the mass of a particular foodstuff from a user, the accessing means may access the library stored on the electronic storage medium to lookup the energy in linear units associated with that foodstuff and the processor may calculate the quantity of linear units associated with that quantity of foodstuff, by referencing the foodstuff library.

The PED may be provided in the form of a cellular telephone, laptop computer, palm pilot, hand-held electronic diary or the like.

The software application may be provided for use as part of an integrated insulin pump and glucose administration device.

According to a third aspect of the invention, there is provided a method for predicting the effect of ingested foodstuff or exercise on blood sugar level and suggesting corrective action, the method comprising the steps of: - receiving original blood sugar information relating to the original blood sugar of a patient;

- receiving energy information relating to the quantity of linear units gained by ingesting foodstuff or lost through exercise; and outputting the corrective action to normalise the effect of the ingested foodstuff or exercise on the blood sugar level of the patient.

These and other features of the invention are described in more detail below. Brief Description of the Drawings

Numerous embodiments of the invention are described below, by way of example only, and with reference to the accompanying drawings in which:

Figure 1a shows measured insulin response as a function of mass of carbohydrates (CHO) consumed.

Figure 1b shows measured insulin response as a function of the glycaemic index (GI) of consumed food.

Figure 2 shows the measured insulin response as a function of equivalent teaspoons sugar (ETS) consumed.

Figure 3 a shows the distribution of short-acting insulin dose required by

Type 1 diabetic vs. ETS ingested.

Figure 3b shows the distribution of the normalized time integral insulin response for healthy patients vs. ETS ingested.

Figure 4 shows blood glucose response of typical Type 1 diabetic during the ETS and insulin sensitivity test procedure.

Figure 5 shows Illustrative blood glucose and insulin concentration curves of a non-diabetic person after ingesting a meal containing carbohydrates.

Figure 6 shows the Illustrative blood glucose and insulin concentration curves of a Type 1 diabetic after ingesting a meal containing carbohydrates (not using short-acting insulin). Figure 7 shows the linear relationship between ETS ingested and increase in blood glucose level.

Figure 8 shows the information block diagram for a typical bolus calculation device.

Figure 9 shows the bolus calculation scales and use thereof of the bolus calculation slide rule.

Figure 10a shows the front view of the bolus calculation slide rule.

Figure 10 b shows the rear view of the bolus calculation slide rule.

Figure 11 shows the front view of the centre sleeve of the bolus calculation slide rule.

Figure 12a shows the rear view of the main ruler of the bolus calculation slide rule.

Figure 12b shows the front view of the main ruler of the bolus calculation slide rule.

Figure 13 shows the front and rear view small outer sleeve of the bolus calculation slide rule.

Figure 14a-n shows possible interfaces for the bolus calculation software application.

Figure 15a-u shows possible interfaces for the bolus calculation software application implemented on a mobile communication device

(E.g. cellular phone). Figure 16a shows the front view of the characterization slide rule for ETS sensitivity.

Figure 16b shows the top wheel of the characterization slide rule for ETS sensitivity.

Figure 16c shows the centre wheel of the characterization slide rule for ETS sensitivity.

Figure 16d shows the bottom wheel of the characterization slide rule for

ETS sensitivity.

Figure 17a shows the front view of the characterization slide rule for insulin sensitivity.

Figure 17b shows the top wheel of the characterization slide rule for insulin sensitivity.

Figure 17c shows the centre wheel of the characterization slide rule for insulin sensitivity.

Figure 17d shows the bottom wheel of the characterization slide rule for insulin sensitivity.

Figure 18 shows the software flow diagram for patient characterization device determining insulin and ETS sensitivity.

Figure 19a-1 shows the different interfaces for the blood glucose simulation software application.

Figure 20 shows the block diagram for the blood glucose-regulating device using the ETS concept. Detailed Description of the Drawings

A first aspect of the invention comprises characterising the energy gained by ingesting foodstuffs or lost by exercise in terms of linear units of energy, in which the quantity of linear units associated with an ingested foodstuff or duration of a particular exercise is directly proportional to the resultant increase/decrease in blood sugar.

In the present embodiment, foodstuffs and exercise are characterised in terms of Equivalent Teaspoons Sugar (ETS). In this example, ETS are the linear unit used to quantify energy. It is used to quantify the glucose or glucose energy in foodstuff, the sugar energy that is expended during exercising or any other energy quantity relating to energy from glucose or carbohydrates.

Examples of energies that can be quantified in ETS include: glucose energy in the blood, glycogen stored in the liver and energy expended during exercise.

The quality of insulin predictions is examined in more detail for the CHO and the GI methods using measurements by Lee and Wolever-. These measurements give insulin response curves for different healthy test subjects ingesting different amounts of CHO (0 to 100 grams) with varying GI values (23 to 100). The time integrals ( \BI(t)dt) of the Lee and Wolever blood insulin (BI ) response

curves for one subject are normalised and plotted against the amount of CHO consumed (Figure Ia) and against the GI (Figure Ib) of the ingested foods. Pearson's R²-values- were calculated for linearised trend fits through the plotted data. The R²- values for the CHO and the GI methods were 0.603 and 0.558 respectively. For the CHO method the worst spread is at 5Og CHO, namely a factor 12, while for GI at 65 the factor is close to three.

The characterisation of foodstuff and exercise according to the invention is theoretically derived using energy balance techniques-, namely the ingested CHO / blood glucose energy balance.

The quality of insulin predictions by the ETS method are substantially better than the predictions using the prior art methods. The Lee and Wolever- measurements for the same test subject as in Figures Ia and Ib are used again. The results are given in Figure 2. The linear trend line for the ETS method yields an R²- value of 0.929, which is significantly better than those of the other methods.

The same procedure as for the single subject can now be used to investigate more test subjects. The full dataset of Lee and Wolever- as well as another dataset from Wolever and Bolognesi- are used. Correlation coefficients for data of the 15 test subjects are presented in Table 1. The average R²- values for the different methods show the inventive method to be the preferred insulin predictor.

Table 1 Pearson's Revalues for correlations between normalised insulin response integrals ( \BI(i)dt) and CHO, GI and ETS values. The integrals were calculated from insulin response measurements by Wolever & Bolognesi- and Lee & Wolever-.

ETS is used a linear unit because it is an easy concept to comprehend and to use. Firstly, it is evident that less ETS in a meal always leads to less insulin, making food and meal choices very easy. Secondly, ETS values for typical foods and serving sizes are usually less than 10 e.g. tomato = 0.5 ETS, can of soda = 7 ETS, apple = 2.5 ETS. Numbers less than 10 are easy to grasp. Thirdly, in a mixed meal of high CHO content the ETS values of the individual constituents can simply be added to arrive at the total ETS value for the full meal. Fourthly, it is easy to visualise a teaspoon full of sugar, which makes it a practical reference. Fifthly, for Type 1 diabetics the numerical ETS value of an ingested meal corresponds remarkable well with the numerical amount of insulin dosage required.

Figure 3b depicts the spread in f_AUCI between the healthy individuals measured in the Wolever, Lee and Bolognesi^-,- trials. The f_AUCI sensitivity is also important for weight watchers, those having CVD and certain cancers as high insulin concentrations and insulin resistance are prevalent in them-'-'-. By accounting for f_Aυa (and similar factors for the protein and fat cycles) more correct diets could be designed for a specific patient. It is hypothesised that through "self preservation" f_AUCI will increase when a person is on a "fasting" diet to ensure maximum storage. This can make weight loss a little more difficult than expected.

f_AUCI could help explain why people from poor developing nations are prone to

Type 2 diabetes when they change over to high caloric western diets with high ETS (high CHO and high GI). With an evolutionary high f_AUCI to ensure maximum storing efficiency they "over react" to the high ETS, resulting in hyperinsulinemia, weight gain, insulin resistance and eventually Type II diabetes.

The impact of such a predictor on diabetics, endurance sportspeople, weight watchers and those with CVD and certain cancers or those who want to live a healthy life is obvious, hi general all these interest groups strive to minimise insulin response. It is evident that the CHO containing food with the smallest ETS will always lead to the smallest insulin response making food choices easy from now on.

Ongoing clinical trials show that the linearity of increase in blood glucose levels vs ets ingestion holds true for typical portion sizes of well-balanced meals. The food with the lowest ETS will always lead to the smallest insulin response. As shown in Figure 1, such a simple and practical conclusioncould not be drawn from either the CHO or the GI methods.

Insulin Units can be calculated by using a proportionality constant, f_{aucI U} .

f_AUCI is the person specific factor for relating insulin response to ETS ingestion for a specific healthy person. f_{aucI υ} is also a person specific factor to relate the insulin response to the equivalent insulin units I_bolus (U). The two proportionality constants, f_AUCI and f_{aucI U} can be combined into a single constant, f_{BS_I} .

Equation (2) can be used to calculate the number of Insulin Units being secreted by the pancreas of a healthy person, with f_{BS_I} being the person specific proportionality constant. The pancreas of a Type 1 diabetic does not secrete insulin.

This means that after ingesting a meal, the carbohydrates being absorbed into the blood is not stored. The diabetic then has to administer some short acting insulin (bolus) to store the glucose in the blood and thereby lowering the blood glucose level. The ideal would be to mimic the insulin response of the pancreas of a healthy person. f_{BS_I} is a person specific factor and if it can be measured for a specific diabetic, the bolus for a specific meal can also be calculated. It is also known that there is a direct relationship between insulin response (in the case of the Type 1 diabetic - bolus insulin to be administered) and number of ETS ingested. f_{BS_I} is the insulin units per ETS being ingested factor for a specific person. The following method is therefore proposed to determine f_{BS_I} for a Type 1 diabetic. f_{BS_I} can be written as two relational factors, namely f_BS/I and f_BSIets .

f_BS/I is the decrease in blood glucose level after administering bolus insulin. It can be measured by performing a simple procedure. Blood glucose levels are monitored after a meal until it has become stable, BS_{prlor insulin} . An appropriate bolus I_{mits test} is then administered. The blood glucose level is then monitored for a minimum period equalling the total of the onset and duration time of the specific bolus insulin being used. The final stabilized blood glucose level, BS_{post insulin} , is then measured. f_BS/I for the Type 1 diabetic can now be calculated as follows:

With: f_BS/I =Insulin sensitivity of the individual; (mmol / 1.U) or (mg / dl.U)

ΔBS_test = Difference (decrease) in blood glucose levels before and after insulin

I _{units test} ⁼ Units of bolus insulin injected during test procedure (U)

BS _{prior insulin} ⁼ Stabilized blood glucose level before insulin administration

BS_{post insulin} ⁼ Stabilized blood glucose level a while after the insulin injection

See Figure 4. f_BS/I is also called the insulin sensitivity and can be used to calculate the bolus (number of short acting insulin units, I_mjts ) needed to lower the blood glucose level. For convenience, the insulin sensitivity f_BS/I will be denoted by the symbol f_insulin .

f_BS/ets is the increase in blood glucose level after ingesting a meal containing a certain amount of ETS. It can be measured by performing a simple procedure. Blood glucose levels are monitored before a meal until it has become stable, BS_{pHor mea[} . A meal with a known ETS quantity is then ingested. The blood glucose level is then monitored for a minimum period of about one hour. The final stabilized blood glucose level, BS_{post meal} , is then measured. f_BS/ets for the Type 1 diabetic can now be calculated as follows:

With: f _{BS /ets} = ETS sensitivity of the individual; (mmol / Lets) or (mg / dl.ets)

ABS_test= Difference (increase) in blood glucose levels before and after meal

ets_meal = Quantity of ETS being ingested

BS_{prior meal} = Stabilized blood glucose level before test meal

BS_postmeal = Stabilized blood glucose level after the test meal

f_{BS /ets} is called the ETS sensitivity and can be used to calculate the rise in blood glucose level after ingesting a certain quantity of ETS. For convenience the insulin sensitivity will be denoted by the following symbol: f_ets .

Equation (4) can now be used to calculate f_{BS_I} for the specific diabetic. Now a practical blood glucose prediction model for a Type 1 diabetic can be developed.

The blood glucose level of a person is influenced by several factors. These factors include but are not limited to the following: □ Diabetic status: Does the person have diabetes? If so, does the person have Type 1 or Type 2 diabetes? The duration of the illness is also important here.

□ Food intake: Ingested carbohydrates (CHO) are absorbed into the blood and cause the blood glucose level to rise. Certain beverages (e.g. alcoholic beverages can cause blood glucose levels to fall under certain conditions)

□ Long acting insulin (basal): Basal insulin is used for energy utilization. Without this insulin cells cannot use glucose for their metabolism energy.

□ Short acting insulin (bolus): Ingested carbohydrates from food are converted to glucose and absorbed into the blood. Bolus insulin is used to store glucose in the liver and other storage cells.

□ Stress: Stress tends to cause elevated blood glucose levels. The magnitude of the elevation in blood glucose levels is proportional to the intensity of the stress.

□ Illness: Various illnesses (e.g. bacterial infections) cause elevated blood glucose levels.

□ Activity level and exercise: The energy used during a day depends on the activity level of a specific person. The utilization of glucose from the blood for energy plays an important role on blood glucose regulation.

□ Blood glucose counter regulation hormones: When the blood glucose level is too low, various counter regulation hormones will act to restore the blood glucose concentration.

Blood glucose and food ingestion Blood glucose level or blood glucose level refers to the blood glucose concentration of a person at a given time and is expressed in either mmol/1 or mg/dl.

Type 1 diabetics have to control their blood glucose level and therefore measure their blood glucose levels frequently. A variable can be defined to represent the blood glucose level namely, BS. There will be distinguished between the following three blood glucose variables.

□ BS_current : The current blood glucose level measured with a blood glucose monitor.

□ BS_predicted : The predicted blood glucose level calculated from food intake, exercise and other related information.

□ BS_control : The desired blood glucose level (control set point). This value should also include a safety margin to reduce the risk of hypoglycemia. BS_control will therefore be a bit higher than the normal blood glucose level of non-diabetics.

When food is ingested it is decomposed into its three main components (macronutrients) namely carbohydrates, fats and proteins. Carbohydrates are broken down in the digestive track into basic sugars called glucose. Glucose is absorbed into the blood from the digestive track. This absorption of glucose causes the blood glucose level to rise.

In a non-diabetic person the pancreas of the person will sense the increase in blood glucose concentration and start to secrete insulin. The secreted insulin is used to store the excess glucose present in the blood thereby causing a decrease in blood glucose concentration.

The pancreas of Type 1 diabetics cannot secrete insulin and therefore the excess glucose cannot be stored efficiently. When diabetics consume meals it cause their blood glucose levels to stay elevated. This condition is called hyperglycemia and can cause severe long-term effects -. Energy in the form of glucose will be present in the blood of the diabetic.

Without insulin the glucose can neither be stored nor utilized for energy in the cells. The energy needed by the body can therefore not be supplied to cells. The change in blood glucose levels can be measured after ingesting a certain meal. The Equivalent Teaspoons Sugar (ETS) quantification unit will be used.

It was shown that a near linear relationship exists between ETS intake and the increase in blood glucose level after ingesting a meal. This is because ETS is directly linked to the glucose content that can be absorbed from the food'

The rate of the increase in blood glucose level in a meal is dependant upon the composition of the meal (GI, fibers and macronutrient composition) but also on the individual person's digestive characteristics. The peak blood glucose level is usually reached within an hour of consuming a meal. Meals with high fat percentages for example take longer to digest.

Blood glucose and exercise

When a person starts to exercise the muscles initially use the glycogen in the muscle cells. After a while the liver will transform glycogen into glucose, which is released into the blood. This glucose in the blood can then be utilized by the muscle cells for energy. Insulin enables the muscle cells to accept the glucose into the cells-. Prolonged exercise will cause fat to be utilized for energy in the form of fatty acids. These processes are automatically regulated in a non-diabetic with the release of insulin and several other hormones.

During exercise two conditions might result. When there is not enough insulin in the blood during exercise, the cells cannot utilize the glucose for energy. The liver will start to release more glucose in the blood to supply the starving muscle cells with energy. This causes the blood glucose level to continue rising during exercise. Although the blood glucose level rises, there is still not enough insulin to utilize it. Fortunately insulin sensitivity increases during exercise but in some cases it may not be enough to account for the shortage in insulin. If there is too much insulin in the blood during exercise the muscle cells will increase their glucose utilization for energy causing the blood glucose level to fall too low. It is therefore important that the long-acting insulin dosage takes the activity level of a person into account. If the long-acting insulin dosage of a person caters for the energy requirements of the person, exercising will not cause uncontrollable blood glucose disturbances during exercise.

To quantify the effect that exercise has on blood glucose level the exercise energy should be linked to the energy source (fuel) namely glucose. Botha- showed that a linear relationship exists between the area under the insulin concentration curve ( A UC₁ ) of a non-diabetic after consuming a meal containing a certain ETS quantity.

f_AUCI is a proportionality constant relating to the area under the insulin concentration curve over time with the ETS that caused the blood glucose response.

The insulin is secreted to store glucose and thereby removing it from the blood. The area under the insulin concentration curve can be assumed to be nearly proportional to the amount of insulin secreted by the pancreas of a non-diabetic. This can be verified from the fact that when a Type 1 diabetic injects insulin the AUC_I is proportional to the insulin dosage (I) injected.

Equation (5) showed the linear relationship between blood glucose decrease and the insulin injected for a Type 1 diabetic with insulin sensitivity f_insulin .

Therefore the blood glucose decrease is proportional to the area under the insulin concentration integral causing the blood glucose decrease for a Type 1 diabetic person. This is not the case with non-diabetics. Their pancreas help to control the blood glucose level continually.

A proportionality constant f_m can be defined and used to formulate Equation (13).

Equation (13) can be substituted into Equation (9) to give the relationship between blood glucose response and ETS energy. This blood glucose response of a non- diabetic should be mimicked by the Type 1 diabetic. In Equation (14) the blood glucose will decrease by ΔBS _predicted when ets_removed is stored or utilized in the cells by the action of insulin in a Type 1 diabetic.

Equation (14) can be simplified by combining the two proportionality constants f_IBS and f_AUCI into a newly defined proportionality constant f_exercise .

Botha further showed the relationship between ETS blood glucose energy and the exercise activity responsible for expending the energy.

f_expended is a person specific factor for relating the energy expended during an exercise to the amount of ETS used by the body to perform the exercise. The ETS here only accounts for the percentage of energy expended during exercise that is taken from the blood glucose. The amount of ETS expended is dependant on the intensity and duration of the exercise but also on how efficiently energy from glucose is utilized by the human body during exercise.

By substituting Equation (18) into (16) the reduction in blood glucose level for a Type 1 diabetic when expending energy ( E_expended ) during exercise can be written in terms of energy expended.

Equation (19) can further be simplified by defining a single proportionality constant f _exbs .

Using the newly defined f_exbs Equation (19) is reduced to (21)

For Equation (16) or (21) to be used there are a few criteria that have to be met. These equations are only valid for Type 1 diabetics. While exercising glucose in the blood can only be utilized by cells when there is enough insulin in the blood to allow the glucose to enter muscle cells. The long-acting insulin dosage should cater for the daily activity level of the diabetic. Exercise routines should also be taken into account when this dosage is determined.

The calculations can only be used when the counter regulation of the body does not increase the blood glucose level. When blood glucose levels fall below approximately 3.8 mmol/1 the pancreas starts secreting glucagon -. Glucagon promotes the conversion of glycogen stored in the liver to glucose. This glucose is then released in the blood causing the blood glucose level to rise. This effect will therefore influence the accuracy of Equation (16) and (21) because they do not take the counter regulation of the body into account.

Counter regulation is used by the body to prevent hypoglycemia. The blood glucose prediction model can only be used when exercises are performed while blood glucose levels stays higher than this value. It is risky for diabetics to start exercising with a low blood glucose level. When blood glucose levels reaches 3.8 mmol and lower epinephrine, growth hormone, Cortisol and other hormones will also start to counter act the low blood glucose level.

For practical reasons the blood glucose prediction model will use Equation (16). Botha- proposed a method for calculating f_expended, A good approximation of 55 kCal/mmol was used for the average person. f_exercise was measured on a few test subjects and an average value of 0.6 mmol/ETS was found. Due to study constraints only a few test subjects could be used. More measurements are needed to get a better approximation of this value for the average Type 1 diabetic person.

By using the average value of 55 kCal/mmol we can rewrite Equation (18) as follows.

Equation (22) can be used to calculate the exercise energy expended quantified in ETS from existing publicized energy tables. These values are calculated for the average person.

Equation (16) can then be used to calculate the reduction in blood glucose level. If the expended energy quantity is known (ETS), Equation (23) can be used.

An effective ETS quantity called ets_exercise can be defined to the extent that for an average Type 1 diabetic, exercising 1 ETS will cause a reduction of 1 mmol/1.

Exercise tables can be created for the average Type 1 diabetic where exercising one ETS of energy will lead to a reduction of 1 mmol/l in blood glucose level when the criteria mentioned is met. Blood glucose prediction model

The factors can now be combined to give a prediction model with which to calculate the blood glucose level. The different factors are shortly reviewed below. They are then used to formulate the blood glucose prediction model to be used.

The increase in blood glucose level as a result of food or beverage intake:

with f_ets : ETS sensitivity of the diabetic [mmol / (1.ETS)] ets_meal : total amount of ETS in meal [ETS]

The decrease in blood glucose level as a result of exercise (using the correct long-acting dosage):

with f_exercise : exercise sensitivity of the diabetic [mmol / (1.ETS)] ets_exercise : total amount of energy expended during exercise quantified in ETS [ETS]

The decrease in blood glucose level due to insulin:

with f _insulin : insulin sensitivity of the diabetic [mmol / (1.U)] l_{units left} : short-acting insulin left in blood [U]

The difference between the predicted and current blood glucose level can be calculated as the result of the effects that food, exercise and insulin have on the blood glucose level of the diabetic.

The predicted blood glucose level can then be written as follows

and by substituting Equation (28) into (29) the predicted blood glucose level is:

The desired blood glucose level is denoted as BS_control . This level is the control set point. We can now calculate the excess blood glucose level (BS_excess). This value indicates the difference between the predicted blood glucose level and the desired blood glucose level.

If the excess blood glucose value is positive, insulin is needed to lower the blood glucose level to the control (desired) blood glucose level. Insulin sensitivity ( f_hmιHn ) determines the blood glucose level decrease per unit short-acting insulin. The short- acting insulin units needed to lower the blood glucose level can be calculated by dividing the excess blood glucose level by the insulin sensitivity of the diabetic.

If the excess blood glucose level is negative it means that the predicted blood glucose level is below the control (desired) blood glucose level. This indicates a risk of hypoglycemia. The additional ETS to be ingested can be calculated. This ETS should be eaten additionally to the ETS already used for the blood glucose calculation. ETS sensitivity (f_ets ) indicates the blood glucose level increase per unit ETS ingested. The additional ETS to be ingested can therefore be calculated by dividing the excess blood glucose level value with the ETS sensitivity.

It should be noted that diabetics should not exercise while their current blood glucose levels are already low.

These empirical equations derived in this section form the basis of several products aimed at improving the blood glucose control of Type 1 diabetics. The equations are complex and not that easy to use without the help of a computing device. Although the equations are already simplified it gives a good idea of the complex problems the diabetics face everyday trying to control their blood glucose level.

Bolus calculation device

In one embodiment of the invention, the apparatus is provided in the form of a software application for use in conjunction with on a Portable Electronic Device (PED).

The apparatus is first customized for the specific user by characterizing the user 1. This is done by measuring and entering said user's: o ETS sensitivity (f_ets ); o Insulin sensitivity ( f _insulin ); and o Exercise sensitivity ( f_exercise ) . The following less important parameters are then also considered namely: o age; o gender; o height; o normal activity level (E.g. low, medium, high); o typical daily routine (E.g. office, house etc.); o total daily dose of short- and long-acting insulin; o target blood glucose level and acceptable blood glucose range; and o any other relevant information of the user.

The following dynamic variables (daily activities) can also be entered via the input means of the PED and are taken into account when suggesting corrective action: o blood glucose measurements 2 and time thereof; o food and beverage intake 3 including the type, portion size, number of portions, ETS value, other nutritional information (e.g. carbohydrates, proteins, calories etc.) and the time being ingested; o exercise and activities 4 being performed including the time, intensity and duration of the exercise; o insulin administration log 5 - previous insulin administrations have to be accounted for when the injected insulin is still active; and o stress 6 including the duration and intensity.

The customization values and daily activities mentioned above are then used to calculate 7 the corrective measure 8 to be taken using Equations (31) and (32) or (33) as functions of time. The counter regulation ability of the liver need not be accounted for because the target blood glucose level used in these calculations is higher than the hypoglycemic threshold where the counter regulation hormones will start to act.

The calculation will result in one of three types of suggestions 8: o a suggestion to take no action; or o a suggestion for a certain dosage of insulin; or o a suggestion to eat an additional amount of ETS.

General information 9 regarding the analysis of daily food consumed etc. can be displayed to said user. Said invention can also be used to detect potential problems and give the user feedback 10 thereof E.g. if the device detects those, the user's sensitivities for insulin has changed.

In one embodiment of the invention the apparatus is provided in the form of a manual slide rule device. The front and rear view of said slide rule are shown in Figure 10a and 10b respectively. The slide rule device consists of three parts: a main centre ruler 11, a large sleeve 12 and a small sleeve 13. The main ruler 11 is received in the large sleeve 12 and is movable relative to each other, while the large sleeve 12 is received in the small sleeve 13, which is also movable relative to the large sleeve.

The main sleeve 11 has printed on one side a blood glucose scale 19 and on the rear side an insulin dosage scale 18 and a scale for suggesting additional ETS to be consumed 22. The large sleeve has printed on one side an exercise and food ETS energy scale and a first marker 14 to point to a blood glucose value on the blood glucose scale 19 on the centre ruler 11. The remaining surface of the large sleeve is transparent 17. The small sleeve has instructions printed on one side with a second marker 23 to point to exercise or food ETS energy scale 15 and on the rear side a third marker that is set to point to the correct insulin scale 18 according to the measured insulin sensitivity of said user.

The device must first be customized for the patient. This is done by first determine the ETS sensitivity of said user. The resolution of scale 26 for ETS food is then selected so that the distance between two resolution points on the blood glucose scale 19, divided by the distance between two resolution points on the ETS food scale 26 equals the measured ETS sensitivity of said user. The same is done for exercise sensitivity namely the distance between two resolution marks on the blood glucose 19 scale divided by the distance between two resolution marks on the ETS exercise scale 15 should equal the measure exercise sensitivity of the patient. Similarly the insulin sensitivity can be accounted for by selecting the distance between two insulin scale 18 resolution points so that the distance between two successive blood glucose scale 19 resolution points divided by the distance between two successive insulin scale 18 resolution points equals the measured insulin sensitivity of said user. The slide rule device can pre-printed with each of these scales 19, 26, 15 and 18 according to the corresponding sensitivity values. Several scales can also be printed on the device with selection pointers 24 and 23 indicating which scales to use.

The operation of the device can be explained with reference to Figure 9. The slide rule is a simplified implementation of the bolus calculation Equations (31), (32) and (33). It therefore does not have inherent intelligence to compensate for previous insulin injections etc. It does however provide a useful tool with which to calculate bolus insulin required. Figure 9A shows the blood glucose scale 19, ETS food scale 26, ETS exercise scale 15 and insulin scale 18 which can be seen in Figure 9D. The large sleeve is moved relative to the centre ruler so that the first marker 14 points to the measure current blood glucose level on scale 19. The small sleeve is then moved from the first marker 14 upwards and relative to the large sleeve so that the second marker 23 indicates the amount of ETS being ingested. The amount of ETS being ingested can be determined by adding up the ETS value of the corresponding food and beverage items making up the meal being ingested obtained from an ETS value booklet (not shown). The small sleeve is then moved downward by the amount of ETS energy being expended during exercise (if any) according to the exercise scale 15. This resulting blood glucose level can be seen in Figure 9B. By turning over the slide rule device a third marker 24 (printed to indicate the correct insulin sensitivity scale to be used) indicates the corrective measure to be taken which can be either a insulin dosage to be injected, a suggestion to take no action or a suggestion to eat additional ETS (block 22 - in this case a fourth marker 21 will point to the amount of additional ETS to be ingested). Figure 9D shows how this calculation is done on a linear scale. A reference booklet having ETS values for food, beverages and exercise, could accompany the slide rule device.

In a second embodiment of the invention, the corrective action calculation device is provided in the form of a software application for use in conjunction with a portable electronic device, such as a handheld computer, proprietary device, personal computer or other electronic or mechanical device.

The inventive method can be implemented on any of these devices including, but not limited to: a handheld computer, PDA, personal computer, notebook, laptop, desktop computer, micro computer, mobile phone, tabloid computer or any other electronic or mechanical device capable of performing the necessary calculations.

A typical system of this type will consist of the following components: o input means for receiving data and parameters (E.g. keyboard, keypad, voice command system, stylus etc.); o a processor calculating said bolus suggestions; and o output means for outputting said calculated suggestions and other information (E.g. display, voice output, dials etc.)

The software application may include accessing means for accessing an electronic storage medium that contains lookup table. The software application may include the electronic storage medium, such as a database that stores algorithms, data and parameters.

Two possible variations for the software application are shown in Figure 14 and 15. Figure 14 shows the bolus calculator implemented on a handheld computer (PDA) while Figure 15 shows the application implemented on a mobile communication device. The software application includes accessing means for accessing a logbook 14a, 15a to list relevant such as foot intake, exercise, insulin administration, blood glucose measurements etc. which are input by a user via the device's input means. Food or beverages can be added to the logbook by selecting Food, selecting a type of food 14b, 15d and the sub category 14c, 15e of the food and the specific food item 15f. The number or fractions of portions 14d, 15g can then be set and added to the meal.

To add exercise to the logbook, exercise is selected, a type of exercise 14e, 15h is chosen and the time and duration of the exercise is set 14f, 15i. A blood glucose value 15j, 15k can also be logged by selecting blood glucose measurement and entering the time and value of the measurement.

To calculate the bolus, insulin is selected. The user needs to complete four steps, namely measuring the current blood glucose level 14h and entering the time of the measurement, confirming or entering the last short acting insulin administration and time thereof, confirming or entering the amount of ETS being ingested 14j (obtained from the logbook) and the amount of ETS exercise energy to be expended during exercise in the next few hours 14k. A bolus suggestion will then be calculated and can be either a suggestion for a certain amount of short acting insulin, a suggestion to take no action or a suggestion to eat a certain amount of food ETS. For this calculation, Equations (31),(32) and (33) will be used. Certain other effects namely the mixed meal and second meal effects will also be accounted for in the calculations.

The device should first be customized for the specific patient, after the patient has been characterized. After characterization the sensitivities for ETS, insulin and exercise can be entered into the device 14l, 14n, 15t, and 15u.

Similar devices exist at present but these do not use a linear unit such as ETS, as an energy quantification system that is used in Equation (31), (32) an (33).

Another embodiment of the invention is shown in Figures 16 and 17. In this embodiment, a device similar to the slide rule device described earlier is disclosed. The test procedure as previously described can be followed. ETS sensitivity f _{Bs/ ets} value can be calculated using Equation (6).

Referring to Figure 16 A, the device according to this embodiment comprises three concentric cardboard wheels, each printed on one side. All three wheels can be rotated relative to each other around the middle point of the concentric wheels. A back wheel 30 is larger than an upper wheel 28 and centre wheel 29, which are the same size. The back wheel 30 has a blood glucose scale printed on it. The centre wheel (shown in Figure 16C) has several ETS sensitivity values printed on it, and it has a first pointer 29 on the edge of the wheel, which is used to point to a blood glucose value.

The upper wheel has a rectangular transparent or see through window 27, showing the relevant sensitivity values on the centre wheel. The upper wheel also has a second pointer 28 to point to a blood glucose level. Characterization with this device is done by simply pointing with the second pointer 28 on the upper wheel to the blood glucose level prior to the meal BS_{prior meal} and the first pointer on the centre wheel 29 to point to the blood glucose level after the test meal BS _postmeal . The sensitivity value in the rectangular window 27 next to the corresponding number of ETS in the meal ets_meal is the patient's ETS sensitivity, f_BS/ets .

The Insulin sensitivity f_BS/I value can be calculated using Equation (4).

Again a slide rule device is proposed to do the calculation. The test procedure as previously described should be followed. The characterization device shown in Figure 17a comprises three concentric cardboard wheels, each printed on one side. All three wheels can be rotated relative to each other around the middle point of the concentric wheels. The back wheel 33 (Figure 17D) is larger than the upper wheel and center wheel. The back wheel has a blood glucose 33 scale printed on it. The centre wheel (Figure 17C) has several insulin sensitivity values printed on it, and it has a first pointer 32 on the edge of the wheel, which is used to point to a blood glucose value. The upper wheel (shown in Figure 17B) has two rectangular transparent windows 34 and 35, showing the relevant sensitivity values on the centre wheel. The upper wheel has a second pointer 31 to point to a blood glucose level. Characterization with this device is done by simply pointing with the second pointer on the top wheel 31 to the blood glucose level prior to the insulin administration BS _{prior insulin} and the first pointer on the centre wheel 32 to point to the blood glucose level after the insulin administration BS_{post insulin} . The sensitivity value in one of the rectangular windows 34 or 35 next to the corresponding number of insulin units administered in the test procedure I _{units test} is the patient's insulin sensitivity, f_BS/I .

The insulin and ETS sensitivity slide rule wheels can be fixed together back to back on each other to create one device, which can be used to determine both insulin and ETS sensitivity.

A apparatus according to the invention could be incorporated into existing equipment to regulate blood sugar. The apparatus may be provided in the form of a software application. Figure 18 shows a condensed flow diagram for a software application to calculate ETS sensitivity and insulin sensitivity of a patient. The software application makes use of the characterization test procedure as described earlier. The user (E.g. medical doctor) of the software application is given instructions, step-by-step, and is prompted to enter measured blood glucose values of patient (E.g. diabetic being characterized) at certain times.

Said software application can be implemented on any device including, but not limited to the following: handheld computer, PDA, proprietary device, personal computer, notebook, laptop, desktop computer, micro computer, mobile phone, tabloid computer or any other electronic or mechanical device able of performing the necessary calculations. To characterize a patient, the patient has to fast for at least two hours and must have a relatively stable blood glucose level before starting with the procedure. The user is prompted to measure the blood glucose level of the patient. The user then enters the blood glucose level. If the blood glucose level is higher than a predetermined safety threshold BG_high the software application will prompt the user to start with the insulin sensitivity test first (which will cause the blood glucose level to drop). If the blood glucose level is lower than the safety threshold BG_high the patient is given a carbohydrate rich meal containing a known amount of ETS. The software application prompts the user to enter the ETS value of the meal. The user is then prompted to measure and enter the blood glucose values of said patient after 30minutes and then 60 minutes after the meal. The ETS sensitivity is then calculated by taking difference between, the maximum of the two measured values at 30 and 60 minutes, and the initial blood glucose value, and dividing the result by the amount of ETS in the test meal. If the calculated ETS sensitivity value falls within a predetermined range, the value is displayed. If it is not within said range, the software application will prompt the user to repeat test at a later time.

The user is then prompted to measure and enter the blood glucose value of the patient. If it is higher than a predetermined safety threshold, the test can be continued. In this case an appropriate number of short acting insulin units is administered. The software application will prompt the user for this insulin administration and to enter the insulin dosage. The user will then be prompted to measure and enter blood glucose values after 45 and 105 minutes. The insulin sensitivity can then be calculated by, taking the difference between the blood glucose value prior to the insulin administration and the minimum value of the blood glucose values taken at 45 and 105 minutes, and dividing it by the amount of insulin units administered. If this calculated sensitivity value is within a predetermined range of sensitivities, the sensitivity value will be displayed. If it is not within this range the user will be prompted to repeat the test at a later stage. This test procedure is described in more detail above. In a still further embodiment of the invention, the apparatus is provided in the form of a blood glucose simulation application. It uses the energy values quantified in ETS to represent food being ingested, energy being stored in the liver, exercise energy being expended, exercise attempted and the energy made available by the counter regulation system. The interaction between these different energies can easily be demonstrated on the simulation application. It can be used to educate both diabetics and non-diabetics on the topic of blood glucose control, diabetes, stress and the prevention of illnesses etc.

The blood glucose prediction Equation (30) can be expanded to a more accurate one if the counter regulation ability (release of glycogen as glucose on response of glucagon or other hormones) of the liver is included.

ΔBS _counter can be calculated by the following set of rules or conditions: o The maximum value that ΔBS_counter can be is the maximum increase of blood glucose level caused by the glucose being released by the counter regulation system (liver). This is a value that can be estimated and it is known that it decreases with the time after being diagnosed as a Type 1 diabetic. It is also temporarily influenced by alcohol intake, Type 2 diabetic medications etc. o The counter regulation system will try to keep blood glucose levels close to normal if it drops below a certain threshold value. This means that blood glucose levels will stay relatively constant until the glycogen stores in the liver are depleted. o The counter regulation system will elevate blood glucose levels, even when they are already high, when there is not enough insulin to utilise energy. This happens both with daily activities and exercise. This means that the counter regulation system will elevate the blood glucose level when a person exercises and does not have enough readily available insulin in his/her blood, even if the blood glucose level is already high. Although the blood glucose level is already high, the cells cannot utilize the energy efficiently without insulin. This means that the person will have some difficulty in exercising.

One advantage though is that when a person starts exercising the insulin resistance starts decreasing, meaning that less insulin is necessary for the exercise.

The layout of the diabetic simulator application is shown in Figure 19. There are four choices for the simulation characterization namely a quick estimation, accurate characterization and two demonstration characterizations for two different persons with Type 1 diabetes. The Quick estimation is shown in Figure 19b. Here all the body characteristics necessary including, but not limited to, height, weight, activity level, years diagnosed, control blood glucose range, total daily dose long acting insulin, total daily dose short acting insulin, and blood glucose response for different foods and insulin. Estimated characterization values can be calculated by using the information entered but it should be noted that it is not an accurate method of characterization because it relies on the memory of the person being charcaterized. The accurate characterization shown in Figure 19b makes use of the characterization procedure as described earlier. The body characteristics and insulin regime is again necessary but also the sensitivity values for food, insulin and exercise. The two demonstration characterizations have two sets of preprogrammed parameters for all the body characteristics and sensitivity values of two different persons.

The simulation model can be customized further as shown in Figure 19d where sensitivity values, counter regulation ability etc. can be altered.

Figure 19e shows the main interface of the blood glucose simulation application. The location and function of each component can be described as follows:

Blood glucose oval 36: This oval gradually changes colour as the blood glucose value changes. If the blood glucose value is outside the control range, it turns red; if it is close to the target value it turns green; blood glucose values between these two values will cause oval to gradually change colour from green to red. Blood glucose value 47: The blood glucose value can be displayed in either mmol/1 or mg/dl or any other concentration unit.

Manual blood glucose adjustment 46, 45: The blood glucose values can be adjusted manually by clicking on buttons 46 and 45. This can be used to simulate the scenario where the user starts of with a high or low blood glucose value.

Arrows 38, 39, 40, 41, 42, and 43: These arrows are used to represent the quantities of energy they represent in ETS except for the insulin arrow 39, which is measured in U. By dragging these arrows up and down with said input means of device, the values can be altered. Some of these arrows are dependant upon each other and therefore a change in one of these magnitudes might trigger a change in one or more of the other magnitudes.

Arrow 38 - Energy eaten: This arrow represents the food being ingested. The magnitude of this arrow can be changed by either dragging the value, or selecting food button 48 and selecting food or beverage from the database. Figure 19f shows the main food categories; Figure 19g shows an example of the subcategories and food items while Figure 19h shows how the portion size and number of portions are selected. The blood glucose value will generally increase for an increase in energy being eaten, Equation (7).

Arrow 39 - Insulin: The short acting insulin can be changed by dragging the arrow to the left or right. This insulin will generally cause the blood glucose level to fall, Equation (5), except where the counter regulation system is active or where insulin is rather being used for exercise meaning that the body is in utilisation mode rather than storage mode.

Arrow 40 - Energy being stored: When the body is in storage mode, insulin is being used to store glucose (from CHO in meal) in the liver and other cells of the body. Equation (5) can be used to calculate the amount of glucose that is being stored. When energy is needed for exercise, the body will rather go into utilization mode, meaning that less glucose is being stored and more utilized. This means that available insulin is being used for utilization. If there is however too much insulin, utilization and storage will take place at the same time and may lead to hypoglycemia if the counter regulation system cannot successfully counteract.

Arrow 42, 41 - Exercise being attempted and exercise energy being expended: When a person exercises, glucose is utilized by the cells for energy. This utilization of energy can only take place if there is enough insulin in the blood. Fortunately a person's insulin sensitivity temporarily increases up to a factor four during exercise. This means that less insulin is needed for utilizing energy during exercise than for energy used for normal metabolism etc. Arrow 42 represents the exercise being attempted. If there is not enough insulin in the blood, the actual exercise energy being expended, Arrow 21 will be less than the attempted exercise energy. The counter regulation system will react as if there is not enough glucose in the blood and more glucose will be release by the liver, causing the blood glucose level to rise.

Arrow 43 - Energy being released from liver (Counter regulation system): The conditions for the energy being released from the liver namely, ΔBS_comter were discussed earlier in this section.

Maximum counter regulation mark 44: The liver can produce a maximum amount of glucose by converting glycogen in response to the hormone glucagon being secreted. Type 1 diabetics often inject too much insulin resulting in hypoglycemia and thereby putting stress on their livers for glucose production. This ability gradually decreases with time and after about four years; the maximum counter regulation ability may have decreased by up to 80%. This value can also decrease temporarily after consuming alcohol. Insulin regime button 51 / Stress & Illness: This allows the user to graphically demonstrate (Figure 19k and 191) how to calculate an appropriate insulin regime and bring it into balance with daily energy requirements, food intake, stress levels and exercise.

In a further embodiment of the invention, the apparatus is incorporated into a blood glucose-regulating device. This device, similar to an insulin pump, also allows the administration of glucose for low blood glucose levels. Said device is therefore capable of controlling both low and high blood glucose levels. Figure 20 shows the block diagram for the system. The device consists of the following components: o Input means 60 for entering blood glucose control range, target blood glucose value, sensitivity values and other information or commands required. o Output means 53 for communicating the status of device; o Blood glucose sensor 61 for monitoring blood glucose levels. This can be either an integrated system or an external unit capable of communicating with the device. The frequency of blood glucose measurements is dependent upon the type of blood glucose monitor being used. Higher sampling rates will result in better control. o Dispensing units for insulin 54 and glucose 55. These separate units are responsible for the administration of glucose and insulin and the control algorithm of said device determines the rate of administration. o Processing unit 58: This is the core processor responsible for analyzing input data with stored parameters and using them in the control algorithm. This processor communicates with the other internal and/or external components of the system. The processor includes the inventive software application or bolus calculator which uses equation (31), (32) and (33) to determine after food intake the required corrective action. This can be either a suggestion to take no action, a suggestion to inject a certain dosage of insulin, or a suggestion for additional ETS to be ingested. The device can automatically administer the insulin or ETS or the user can be prompted with the suggestion and be instructed to proceed. Equation (45) can also be used to calculate the amount of ETS to be administered in the event of hypoglycemia.

It should be noted that this device would make use of a continuous control algorithm rather than a discrete control algorithm.

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Claims

1. An insulin bolus dosage calculating device is claimed of which the dosage calculation equations rely on the energy quantities being expressed in terms of the newly defined linear energy unit called equivalent teaspoons sugar

(ets).

2. An insulin bolus dosage-calculating device is claimed in which the dosage calculation equations uses the equivalent teaspoons sugar (ets) content value of food and beverage items to calculate the potential blood glucose energy available through digestion.

3. An insulin bolus dosage calculating device is claimed in which the dosage calculation equations uses the equivalent teaspoons sugar (ets) energy values of the exercise or other physical activities items to calculate the energy being expended during the activity.

4. An insulin bolus dosage calculating device is claimed which includes a database, either electronic data or printed, comprising of several food and beverage item entries, with each entry comprising of descriptions of the food or beverage item, a main category, a sub-category, a typical portion size, a volume or weight quantity for the typical portion size mentioned, an energy value expressed in equivalent teaspoons of sugar (ets) as well as other nutritional information including macro and micronutrient contents, water content and fibre content of food or beverage item.

5. An insulin bolus dosage calculating device is claimed which may include a database comprising of descriptions of numerous exercise or physical activities of which each entry contains at least: a description of the exercise and an energy value expressed in terms of equivalent teaspoons sugar (ets) which is normalized to a predefined fixed duration of exercise, an average intensity for said exercise and also for a specific body weight.

6. An insulin bolus dosage-calculating device is claimed comprising of an input means, storage means, processing means as well as an output means.

7. An insulin bolus dosage calculating device is claimed comprising an input means, either electronic key type or manual means, that allows user to select food, beverage or exercise items from said food and beverage database, to enter values such as times and user parameters, numbers of portions to be ingested and/or period of time to exercise.

8. An insulin bolus dosage calculating device is claimed including an output means which can be an electronic or chemical display or an indication to a printed medium; said output means displays database items to user, provides user with visual information on which choices can be made regarding selections from databases and also to display suggestions regarding blood glucose control to said user.

9. An insulin bolus dosage calculation device which is operated by first receiving input information namely food and beverage intake, exercises to be performed within the next few hours, preprandial blood glucose level; input information is then converted to equivalent teaspoons sugar (ets) energy units; information is then processed by the device and a blood glucose level will be predicted which allows device to calculate an appropriate insulin bolus dosage which is displayed to said diabetic used.

10. An insulin bolus dosage calculation device which utilises a user parameter namely equivalent teaspoons sugar (ets) sensitivity value which is defined as the increase in blood glucose level per unit ets ingested for the specific diabetic person.

11. An insulin bolus dosage calculation device, which utilises a user parameter, namely insulin sensitivity value which is defined as the decrease in blood glucose level per unit short acting insulin ingested for the specific diabetic person.

12. An insulin bolus dosage-calculating device is claimed as mentioned in preceding claims that is implemented as a custom built portable electronic device (PED) or integrated into an existing PED.

13. An insulin bolus dosage calculating device is claimed as mentioned in the preceding claims that is implemented as a custom build slide rule device which includes a database booklet with equivalent teaspoons sugar (ets) values for energy contained in food or beverages as well as energy values being expended during exercise; a blood glucose scale on which a pointer can be moved to indicate a change in blood glucose level; an energy scale calibrated in terms of equivalent teaspoons sugar (ets) units that can be shifted parallel to the blood glucose scale and also a pointer which can be shifted parallel to the energy scale and also an insulin dosage scale printed on the reverse side of the slide rule device.

14. A slide rule insulin bolus calculation device wherein operation is defined by first selecting a preprandial blood glucose level by shifting a pointer to the corresponding blood glucose level on the blood glucose scale, secondly by incrementing the pointer from said blood glucose level relative to the amount of equivalent teaspoons sugar (ets) units being ingested; thirdly by decrementing pointer by number of units equivalent teaspoons sugar (ets) energy to be expended during exercise; fourthly by turning device over to see insulin bolus suggestion indicated by pointer on reverse side pointing to an appropriate insulin bolus suggestion or a suggestion to take no action or a suggestion to ingest additional carbohydrates to prevent hypoglycaemia.

15. A slide rule insulin bolus calculation device of which different scales are calibrated relative to the blood glucose scale firstly with the distance between two consecutive blood glucose unit markings divided by the distance between two consecutive food equivalent teaspoons sugar (ets) scale markings equalling the food sensitivity value of the specific diabetic user and similarly the calibration distance of the exercise ets scale indicating the exercise sensitivity of the user and thirdly also similarly the calibration distance of the insulin unit scale on the reverse side indicating the insulin sensitivity of the specific diabetic user.