Artificial Pancreas Artificial pancreas is a device or system of

integrated devices which substitutes for an endocrine pancreas.

It sense the blood glucose level, determining the amount of insulin needed, and then delivering the appropriate amount of insulin.

Components of an artificial pancreas :

- automatic glucose monitor;

- automatic insulin delivery system;

- algorithm to link blood glucose levels with

insulin delivery.

Artificial Pancreas

Artificial PancreasINSULIN PUMP A device to deliver insulin, usually small about a size of a pager. Contains reservoir filled with insulin. A microcomputer will adjust amount of insulin delivered. Insulin is pumped through an infusion line fitted with a tiny plastic

tube (called a cannula) that is inserted just under the skin -usually low on the stomach- and taped in place.

External and portable. Pump design could based on motorized syringe or miniature roller

pump. Advantages : - Flexibility of meal, activity timing. - Freedom from multiple daily injections. - Precise insulin delivery pattern. - Improved glycemic control. Limitation : - Skin infection. - Device must always be weared.

Artificial Pancreas

Insulin Pumps (external

and implantable)

Artificial PancreasIMPLANTABLE INSULIN PUMP There is also implantable type insulin pump. Implantable pump could provide better comfort for patient since it is

unobtrusive and no infection at skin catheter junction. Can be used generally as implantable drugs infusion device.Pumping Mechanism Some product use electrically driven piston pumps (e.g. Minimed

MIP 2001, Siemens Promedos ID 3). Displacement of piston draws insulin from reservoir into piston

chamber. When piston move to original position, insulin forced through a free-

floating catheter. The catheter usually inserted into peritoneal cavity. Electrical energy required to operate piston, piston chamber inlet

and outlet valve and pump electronics. Other type of pump (e.g Infusaid) is gas powered pump. Freon gas is used to produce positive pressure.

Artificial Pancreas The pressure will push insulin from reservoir into valve-

type accumulator and into the catheter. Electrical energy is required to operate the accumulator

inlet and outlet valves and the pump electronics. Insulin Refill Reservoir refilled 1-3 months according to patient’s

requirement, reservoir volume and concentration of insulin preparation.

Hypodermic needle is used for insulin refill. Inserted directly through the patient's skin into the

pump's reservoir. Removes any unused insulin and replaces it with a fresh

supply. *A hypodermic needle is a hollow needle commonly

used with a syringe to inject substances into the body.

Artificial Pancreas

Artificial Pancreas

Insulin Refill

Artificial PancreasAdvantages of Implantable Insulin Pump :

- Safe and effective.

- Refills are practical and safe

- Improved metabolic control.

- Hypoglycemia can be lessened. Limitations :

- Catheters and insulin are vulnerable

point.

- Batteries power limited.

Artificial PancreasVAPOUR PRESSURE PUMP MECHANISM The driving force generated by gas vapour (usually Freon). Consists of two chambers : stored insulin and vapour system. Vapour in a compartment will push against bellow chamber that

contains insulin. Pressure against bellow is constant regardless of amount of insulin. Infusion rate is determined by an outflow restrictor.

Artificial Pancreas Based on diagram in previous slide, there is two outflow restrictor. When valve activated, one of the flow restrictor will be bypassed. If valve not activated, insulin will still flow out but infusion rate is

restricted. Thus, insulin will be continuously delivered. The amount of insulin (i.e infusion rate) depends on outflow

restrictor. No parts giving rise to friction. No need of electrical energy for pumping. But care must be taken in the vapor pressure. Pressure might rise due to ambient pressure and other factors. This might lead to uncontrollable infusion.

Artificial PancreasGLUCOSE SENSOR Glucose monitoring system measure hydrogen peroxide. Hydrogen peroxide produced by the enzymatic reaction

of glucose at the site of the immobilized glucose oxidase membrane.

Glucose + O2 → Gluconiuc acid + H2O2 For needle type glucose sensor, sensor consisting of a

platinum anode and a silver cathode. The electrodes, loaded with 0.6 V polarographic voltage,

measure hydrogen peroxide. Needle-type glucose sensors were inserted into the

subcutaneous tissue of the forearm or the abdomen.

Artificial Pancreas

Artificial Pancreas There is also microdialysis type sensor. A catheter incorporating a thin dialysis fibre is introduced

into the patient’s subcutaneous fatty tissue. The fibre is irrigated with isotonic glucose-free fluid. Via pores in the dialysis fibre and catheter, this irrigating

fluid is in a state of constant interchange with the ISF surrounding the catheter.

As a result of the prevailing concentration gradient, glucose migrates from the ISF into the glucose-free perfusion fluid.

The perfusion solution is pumped to a glucose sensor situated outside the body, where its glucose concentration is measured continuously.

Artificial Pancreas

Waste

GOD solution

Artificial Pancreas Glucose can also be measured non-invasively. Use of electromagnetic radiation, e.g. light, is one possible way of

determining glucose concentration. information about glucose concentration can be obtained by : - measuring direct interactions between glucose molecules and electromagnetic irradiation. - indirect effects of glucose on skin properties. The former use measurement of light absorption by spectroscopic

methods. The latter use measurement of changes in the refractive index of

intracutaneous (within the skin), intravascular (within vessels), interstitial and intracellular fluids.

Increase in glucose concentration in these fluids leads to an increase in the refractive index of the fluids concerned.

Only near-infrared light in the wavelength range of 600–1300 nm is able to penetrate intact skin to layers that are perfused by blood.

Artificial Pancreas

Artificial PancreasOPEN-LOOP SYSTEM Open loop system includes glucose sensor, and doctor/user decides

to the amount and time of insulin that will be given. A manual control is applied. User need to know about insulin dosing; when and how much? Insulin is infused only after acknowledgement or adjustment of the

dose by medical staff or the patient. Open-loop infusion pumps constantly replace basal insulin

according to programmed infusion rates that must be manually altered when necessary.

Infusion of mealtime bolus insulin requires data entry or a series of calculations before delivery of an appropriate dose can occur.

Pump can accurately deliver small increments of insulin compared to an injection.

Electronic controls permit shaping a bolus over time to match the insulin profile required for a given situation.

Pump controlled manually by the pump user to bolus on command based on a snap shot of the recent blood glucose level and an estimate of the grams of carbohydrate consumed.

Artificial Pancreas Once a bolus has been calculated and delivered, the pump

continues to deliver its basal rate insulin in the manner that has been programmed into the pump controls based on the predicted insulin requirements of its user.

*Bolus - administration of a medication, drug or other compound that is given to raise blood concentration to an effective level.

*Basal - minimal level that is necessary for health or life.

Artificial PancreasBolus Calculation Insulin to carbohydrate ratio multiplied by grams of carbohydrate. Number of grams of carbohydrate is estimated by measuring foods. Bolus calculator devices are available to ease bolus calculation. The user enters the grams of carbohydrates to be consumed, and

the device calculates the number of units of insulin needed. It adjusts for the most recent blood glucose level and the insulin on

board, and then suggests the best insulin dose to the user to approve and bolus.

Artificial PancreasCLOSE-LOOP SYSTEM Computer controls the amount of insulin delivered by a

portable insulin infusion pump on the basis of readings obtained by an in-vivo glucose sensor so as to keep the patient’s blood glucose at near normal levels at all times.

The computer calculates the required insulin doses using a feedback algorithm.

The computer system must be able to sample, filter and interpret the glucose sensor data, compare the reading with allowable normals, and accurately order just enough insulin to maintain normoglycemia.

Must operate correctly all of the time, because errors could lead to severe hypo- or hyperglycemia .

Artificial Pancreas

Artificial Pancreas

Artificial PancreasChallenge in developing closed-loop The primary barrier is the development of longer-term

reliable blood glucose sensors. For example, glucose sensor readings will include

random error and will drift over time. The computer must be able to decide whether to accept

or ignore an extreme sensor reading . This is important because the sensor reading is used not

only to determine the amount of insulin infused, but to continuously recalibrate the basic equation establishing how much insulin is required to reduce blood glucose by a given amount.

Insulin dose - response relationship varies by body weight and metabolic function and must be constantly recomputed using the latest sensor data.

Computer must also recognize sensor malfunction.

Artificial Pancreas Difference between pancreatic insulin and insulin replacement by

artificial pancreas: the insulin dose is predicted based on measured food (where

accuracy of measured carbohydrate is difficult) whereas pancreatic insulin is released in proportional response to actual blood glucose levels;

pancreatic insulin is released into to the portal vein, where it flows almost directly to the liver, which is the major organ for storing glycogen (50% of insulin produced is used by the liver);

pancreatic insulin is pulsatile which helps maintain the insulin sensitivity of hepatic tissues;

injected insulin is delivered subcutaneously (under the skin) but not directly to the bloodstream, so there is a delay before injected insulin begins to reduce blood glucose (although this can be compensated by injecting insulin 15 minutes before eating);

replacement insulin therapy does not include amylin (although Symlin is now available for use), which can reduce the insulin need by 50%;