Understanding Diabetes Mellitus and Home Management Techniques Insulin, which is produced by the pancreas, allows entry of glucose into the cells to be used as energy. When glucose levels are high, such as after a meal, insulin is secreted and binds to insulin receptors on the surface of the cell. This binding activates the receptor which in turn signals glucose transport mechanisms to move glucose into the cell. The amount of glucose in the bloodstream dictates how much insulin is produced, so when the level drops, insulin production also drops. Diabetes mellitus (DM) occurs when the pancreas does not produce enough insulin, or the cells do not bind it properly. So although the pet has plenty of glucose available, it cannot use it, therefore their body feels that it is starving. The result is that the pet has an increased appetite yet still loses weight. When blood glucose levels are in excess of about 200mg/dl, the kidneys are unable to retrieve the spilled glucose, so it is lost into the urine. Glucose is a big molecule, and it draws water along with it, which creates excess fluid loss, and subsequently increased thirst and increased water intake. Therefore, diabetic animals drink excessively because they are keeping up with their losses, and it is important to never restrict their water intake. Increased glucose in the urine predisposes them to urinary tract infections. Infections, as well as obesity can in turn make the patient more difficult to control because they create insulin resistance, as do some hormonal diseases like Cushing’s or hypothyroidism or other increases in endogenous or exogenous hormones such as a dog in estrus (heat) or a cat receiving Ovaban for inappropriate urination. Dog and cats differ in the type of diabetes that they tend to have. Dogs are more like people with juvenile onset diabetes – they have inadequate or no insulin production and they absolutely require insulin for control for the rest of their lives. This can occur spontaneously, or is sometimes the result of a bout of severe pancreatitis. Cats are more like people with adult onset Type II diabetes They start as being insulin resistant, which can sometimes be controlled with diet or oral medication, but eventually their insulin production decreases and they require insulin. However, in cats, the pancreas has the ability to recover if their blood glucose is controlled quickly and insulin production will resume, negating their need for exogenous insulin, and often causing an overdose and hypoglycemia (low blood sugar) if the owner is not aware of the change in their needs. High glucose levels have a toxic effect on the cells of the pancreas. By controlling the glucose, the pancreas can heal and begin to make insulin again. This is one excellent reason to learn to monitor the pet at home, because many animals can have their hypoglycemia caught and appropriate measures can be taken before they end up in the hospital. When insulin is given, it enters the bloodstream and causes a drop in the blood glucose (BG) because the glucose is able to be utilized by the cells. The type of blood glucose curve we prefer is one where the BG is in the normal range (80150) for as much time as possible. If the glucose can be kept below 250mg/dl for most of the day, there will be very few clinical signs and the control would be considered good. If below 200mg/dl for most of the day – this would be excellent control, and may even result in some cats going into remission (no longer needing insulin). If the insulin dose is too low, the animal will remain hyperglycemic (high blood sugar) and continue to have clinical signs. If the dose is too high, they will become hypoglycemic and potentially have a seizure. Occasionally, if the glucose drops to very low levels, or if the drop occurs very quickly, (but not necessarily below normal), the body produces a variety of hormones to try and raise the glucose back to a safe level. Epinephrine, cortisol and glucagon are all released and all contribute to increasing the BG level. These hormones do not dissipate as soon as the glucose reaches normal levels, so glucose continues to rise, often above pre-insulin levels. These effects can last for 1-3 days, so a single excess dose of insulin could actually result in days of high glucose despite continuing to administer insulin. This is called a Somogyi overswing. Misinterpreted, the insulin dose may be raised, creating a vicious cycle that can result in very poor control, or worse, severe complications from the hypoglycemia. It should be suspected if there are increased sleep patterns 2-6 hours after injection, or any dog or cat that has a BG>500mg/dl that is on an adequate dose of insulin (>1u/kg). Insulins There is no PERFECT insulin for all dogs and cats. Each of the insulins have different onsets and durations of action, but different animals may have variable responses to the same dose and type of insulin. So the correct type and dose has to be tailored to each individual animal. Short Acting Insulins Humulin R or Novolin R (regular crystalline insulin) is the most commonly used short acting insulin used in dogs and cats. It’s duration of activity depends on the route of administration. If given SQ (well hydrated animal) is will usually last from 3-6 hours. If given IM, the absorption is faster and it lasts 1-2 hours. It can also be given intravenously, usually in a constant rate infusion, in which case the duration is only minutes. Regular insulin is predominantly used in the hospital in sick diabetic patients that are dehydrated, vomiting or not eating. Because of it’s sort duration of action, small adjustments can be made quickly, especially if given by a constant infusion (CRI). It should never be given SQ in a dehydrated animal because the absorption will be erratic and unpredictable. It is supplied as U-100. Intermediate Acting Insulins This has been the most commonly used category of insulins in the past, but many of the products we used previously were removed from the market in 2005 (Iletin NPH, Humulin L – lente, and Humulin U ultralente). There are only two remaining intermediate duration insulins. Humulin N or Novolin N (NPH) is recombinant human insulin as opposed to the discontinued Iletin NPH with was porcine based insulin. (dog insulin is closest in structure to pigs, and cat insulin is closest to cows). The duration of action is approximately 12 hours and it is supplied as U-100 (100 units per ml). It can be prescribed from any pharmacy. Vetsulin (porcine lente) – duration of action approximately 10-11 hours and it comes as U-40. Although the manufacturer states that many dogs can be controlled with once daily dosing, most people find that the more routine 0.25-0.5mg/kg SQ BID is preferential. It is important to remember that Vetsulin requires a different syringe and is a veterinary only product. Long Acting Insulins PZI is an intermediate to long acting insulin and contains 90% beef and 10% pork insulin. It is supplied in U-40 strength, and the duration of action 12-24 hours. It also requires U-40 syringes. PZI is made by some other compounding pharmacies, and can be found in U-40, U-50 and U-100 – however, significant variability in activity has been shown between different pharmacies and from batch to batch. PZI would be used primarily in cats since it is mostly of beef origin. Lantus (Glargine) is human recombinant insulin that is marketed for humans as a “peakless” insulin. It has been modified in such a way that it forms crystals under the skin after administration which slowly dissolve – resulting in a sustained release of insulin over a 24 hour time period. Although it has a long duration of action, in cats it has been shown to be more effective when administered BID than just once daily. It is supplied as U-100. Glargine has gained wide acceptance for use in cats over the last few years with excellent results. Levemir (detemir) is similar in action to Lantus. Some people believe there is less day to day variability with Levemir, but it has not been as extensively studied as Lantus. The designation of U-100 or U-40 refers to the concentration of the insulin – either 100 units per ml or 40 units per ml. It is important to have the appropriate size syringe for the type of insulin you are using or large dose mistakes can be made. Most insulins are good for approximately 2 months if kept in the refrigerator after being opened. Glargine has been shown to be stable for up to six months although it is only labeled for 28 days. Most insulins need to be mixed prior to use. Never shake a bottle of insulin, the molecules are fragile, and vigorous mixing can cause the insulin to lose potency. Mixing is best done by gently rocking the bottle. For those with vision or dexterity problems, there are products that help to guide the syringe into the bottle or to magnify the numbers on the syringe such as the BD MagniGuide or TruHand. These can be found online or in pharmacies. Home Blood Glucose Monitoring Human glucometers are devices used to test the amount of glucose in the blood by analyzing a drop of blood. These kits usually come with a case, a lancet, a few lancet needles, a few test strips, a control solution and the glucometer. There is also a veterinary glucometer available called Alpha Trak which is calibrated specifically for dogs and cats. Today, most of the test strips work by capillary action so you can hold the glucometer in any position you need to- just touch the appropriate end of the test strip to the drop of blood and it pulls it into the machine. You do need to make sure it goes to the fill line or you will get an error code. If purchasing a human glucometer, make sure to check the box to see how much blood is needed for sampling. One microliter or less is ideal, especially when using an ear vein. The glucometers and test strips can vary greatly in price. It is a good idea when purchasing a glucometer to have your veterinarian compare the glucometer reading to one done on a chemistry analyzer from the same sample to get an idea of how accurate the meter is. Human meters tend to provide numbers that are about 20 mg/dl lower than the actual reading. Regardless of the site used, preparation is important. I recommend shaving a small spot to maximize visualization and minimize hair, but this may not be necessary in cats or dogs with thin coats. When using the ear, testing should be done from the outside, haired side of the ear where the vein is closer to the surface. Place a cotton ball or a rolled up piece of gauze under the area to be tested to give you a firm surface to press against and to protect your finger. In large dogs, a callus on the elbow works very well because it is hairless and has very little sensation. A sparsely haired area on the rump above the tail also works well depending on the type of coat. A very important tip is to put a little petroleum jelly or triple antibiotic ointment on the site. This prevents the blood from wicking through the hair and makes a nice clean drop. Most lancets come with variable depth settings. Cats and dogs with thin ears (Yorkies, Maltese) usually need one of the middle settings. Most dogs will need one of the deepest settings on the ear, callus or rump. ost animals tolerate testing extremely well and this allows the pet owner to become more involved and knowledgeable about what affects their pet’s glucose levels. They are also better able to detect problems much earlier than they would have before which can help prevent expensive hospital stays or severe complications. When to test varies based on what type of insulin you are using. Your veterinarian can make the best recommendation on when to test based on your individual needs. When well controlled, a diabetic pet can go on to lead a normal, happy life.