'AIDA on-line' Explanations
Explanations provided on this page regarding:
Blood glucose units Display options Insulin types utilized Peripheral glucose utilization (PGU) Net hepatic glucose balance (NHGB) Renal excretion of glucose Glucose absorption rate (GAR) Blood glucose level (BGL) Plasma insulin level Renal Threshold of Glucose Renal Function Insulin sensitivity values HbA1c (glycosylated haemoglobin) values Upper & lower bounds / limits Use your browser's BACK button to return to the previous page
Blood glucose units
This option switches the units for handling blood glucose values from mmol/L (the standard in some countries, e.g. the UK) to mg/dL (the standard in other countries, e.g. the USA).
(1 mmol/L of glucose = 18 mg/dL)
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Display options
This option switches the display of simulated curves from standard to advanced.
'Standard' displays the simulated blood glucose and plasma insulin curves.
'Advanced' displays the simulated blood glucose and plasma insulin curves, together with graphs of the model's glucose fluxes (glucose absorption from the gut, glucose excretion from the kidneys, glucose utilization in the periphery, and the net hepatic glucose balance - the production or utilization of glucose in the liver).
The advanced display option is obviously more complex and only intended for users who wish to look into the simulations in greater detail.
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Insulin types utilized
This option switches the insulin types utilized from standard to pre-mixed.
'Standard' mode provides for two different types of insulin which can be user selected from a variety of different insulins whose action profiles are pre-stored. The first insulin type can be chosen from a range of short-acting (Actrapid-like) insulin preparations, while the second insulin type can be chosen from a range of intermediate-acting (NPH-like), or long-acting (Ultratard-like) insulin preparations.
'Pre-mixed' mode provides a single type of insulin which can be user selected from a range of different insulins whose actions profiles have been pre-stored. All of these 'pre-mixed' insulins are bi-phasic preparations - containing a pre-specified ratio of short- to intermediate-acting insulin. For example, Mixtard 30/70 contains 30% of a short-acting (Actrapid-like) preparation pre-mixed with 70% of an intermediate-acting (NPH-like) preparation.
Please note:
Whichever insulin type is chosen, this may be superseded if a particular case scenario is then selected which uses the other type of insulin preparations.
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Peripheral glucose utilization (PGU)
All tissues in the body make use of glucose (a key nutrient). In the central nervous system (CNS) and red blood cells (RBC) glucose is taken up independent of the plasma insulin level (so called insulin-independent glucose utilization). In the periphery - in muscle and adipose tissue (fat) - the uptake of glucose is dependent on the plasma insulin levels (insulin-dependent glucose utilization).
Peripheral glucose utilization (PGU) represents the grouped uptake of glucose by the CNS, RBC, muscles and adipose tissue.
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Net hepatic glucose balance (NHGB)
The liver can produce or take up glucose depending on the blood glucose and plasma insulin levels. The net hepatic glucose balance (NHGB) represents the production (positive NHGB) or utilization (negative NHGB) of glucose by the liver. The NHGB is calculated as the sum of gluconeogenesis, glycogen breakdown and glycogen synthesis derived from experimental data published in the literature.
Please note:
Because of the discrete 15 minute step size which is used for simulation, and the discrete raw data which is used for simulating the NHGB, minor numerical instability can occur within the model leading to oscillation / 'saw tooth' simulation curves. This can become most apparent when viewing the model functions in advanced (fluxes) mode - and will predominate for the net hepatic glucose balance curve - although a 'knock on' effect might be observed with other model functions.
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Renal excretion of glucose
The kidneys do not excrete glucose into the urine below the renal threshold of glucose (RTG). Above the RTG the amount of glucose excreted into the urine is dependent on the renal function (how well the kidneys are working).
The renal excretion of glucose represents the amount of glucose which is excreted into the urine (glycosuria). Generally in the presence of diabetes glycosuria is a sign of raised blood glucose levels and therefore may indicate relatively poor glycaemic control.
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Glucose absorption rate (GAR)
Glucose is absorbed from the gut following a meal. The rate of glucose absorption is dependent on the size of the meal as well as the length of time which has passed since the meal.
The glucose absorption graph highlights the systemic appearance of glucose following a carbohydrate meal.
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Blood glucose level (BGL)
Depending on the carbohydrate content of the various meals and the amount of insulin injected, together with the insulin sensitivity of the case and the renal function and renal threshold of glucose, the model is able to simulate a blood glucose profile. This profile provides a 'steady state' representation of the blood glucose level - i.e. assuming that the meal plan and insulin regimen were followed for a number of days.
This graph does not permit transient conditions to be simulated. Nor can it be taken to represent any individual patient's blood glucose profile. Rather the simulations should be regarded as what might happen to a typical insulin-dependent diabetic patient following changes in diet or insulin therapy.
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Plasma insulin level
Depending on the amount and type of insulin injected, and the relative timings of the various injections - the AIDA model is able to simulate a plasma insulin profile. It is important to understand that this profile has not been individualised for any particular patient - and therefore this curve simply represents the typical reponse which might be expected following injection of this particular regimen. This is more than adequate for educational use - but cannot be used in any way for individual patient therapy planning.
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Renal Threshold of Glucose
The renal threshold of glucose (RTG) is the blood glucose concentration at which glucose begins to be excreted by the kidneys into the urine. This usually occurs in healthy adults at approximately 9 - 10 mmol/L (162 - 180 mg/dL).
In many adults, particularly those with long-standing diabetes, the RTG may increase substantially. Thus, raised blood glucose levels may exist without glucose being detected in the urine. Conversely, some individuals, particularly children and pregnant women, may have very low or variable renal thresholds for glucose, resulting in glucose being present in the urine, even with normal blood glucose values.
The values used by AIDA on-line for the Renal threshold of glucose (RTG) are:
Low = 7 mmol/L (126 mg/dL)
Normal = 9 mmol/L (162 md/dL)
High = 11 mmol/L (198 mg/dL)
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Renal Function
Renal function is simply a measure of how well the kidneys are working. The higher the renal function value, the better they work. The value used for the simulation is taken from the creatinine clearance rate (CCR), which provides an estimate for the glomerular filtration rate (the rate of filtration from blood in the glomerulus of renal capillaries to the fluid in the Bowman's capsule).
For the simulations used by AIDA on-line, the following values are used:
Normal renal function is a CCR of 100 mL/min
Reduced renal function is a CCR of 40 mL/min
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Insulin sensitivity values
The insulin sensitivities used by AIDA on-line refer to normalised values which represent the liver and periphery's sensitivity to insulin. Different people respond to insulin in different ways. People with insulin resistance (low insulin sensitivity) require much more insulin to change their blood glucose concentration than people with high insulin sensitivities (low insulin resistance).
I.e. with low insulin sensitivity a lot of insulin is required to have a small effect on the blood glucose profile, while with a high insulin sensitivity a small amount of insulin is required to have a large effect on the blood glucose profile.
The liver value represents the insulin sensitivity of the liver while the peripheral value represents the insulin sensitivity of the rest of the body.
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HbA1c (glycosylated haemoglobin) values
In the blood, glucose binds irreversibly to haemoglobin molecules within red blood cells. The amount of glucose that is bound to haemoglobin is directly linked to the concentration of glucose in the blood. Since red blood cells have a lifespan of approximately 90 days, measuring the amount of glucose bound to haemoglobin can provide an assessment of average blood glucose control during the 60 to 90 days prior to the test. This is the purpose of the glycated haemoglobin tests, most commonly the haemoglobin A1c (HbA1c) measurement.
The HbA1c level is provided here in AIDA on-line2 to offer an indication of what the longer term glycaemic control might be, for the simulated case, if this sort of blood glucose profile was maintained for a 2-3 month period. The HbA1c level is offered purely as an indicator - and potentially as a focus for simulation & discussion in an educational setting.
Clearly the estimation of the HbA1c level - which is based on a simulation model - like the rest of the AIDA / 'AIDA on-line' model is subject to certain assumptions and caveats which need to be read and understood. The HbA1c predictions - like the rest of the simulation output from AIDA - are not accurate enough to be used for individual patient prediction or therapy planning.
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The material in this on-line Diabetes / Insulin Tutorial has been drawn from a number of different sources.
However the original Web-based version can be found at the AIDA Website at: http://www.2aida.org/tutorial.
