A DEATH-DEFYING ROUTINE

RON GASBARRO, R.Ph., M.S.

Though there is nothing comical about it, diabetics know what a circus managing their lifestyle can be.

Diabetics teeter on a thin tightrope as they tailor their diets to keep blood sugar levels steady. They juggle all the "junk" diabetics need to deal with their disease: the glucose monitors and batteries, the test strips and lancets, the alcohol wipes and needles, the hypoglycemic drugs and the insulin.

Appreciate their role, too, as trapeze artists as they swing from specialist to specialist -- from podiatrist to dietitian to ophthalmologist -- to keep their organs functioning. One slip and they plummet into a lion's den of retinopathy, neuropathy and nephropathy. It's the quintessential death-defying act.

"If it wasn't happening to me, if it wasn't so tragic, it would be like watching a circus sideshow," agrees Jim, a 40-year-old insulin-dependent diabetic.

"Diabetes has become my life and for what? Because of my diabetes, I'm impotent," says Jim. "My wife says she doesn't care, but I care. I've recently had laser surgery on my eyes and I am just beginning to develop tics in my neck and face. "I have always maintained my blood sugar religiously. But after a while, the disease catches up with you. It's like falling and there's no net to catch you."

As this example shows, despite the diligence of patients, diabetics will experience damage to every major organ system as a result of their disease.

However, there is some good news for diabetics willing to follow an intensive regimen of blood glucose monitoring and insulin administration.

A new study has confirmed what many researchers in the field had long suspected: By following a strict medical regimen, diabetics can measurably slow or even prevent nerve and vascular damage that can lead to blindness, kidney failure or amputation.

The Stockholm Diabetes Study, which began in 1982, with results published in 1993, showed that intensive treatment of patients with insulin-dependent diabetes mellitus, or IDDM, reduced the development or progression of microvascular complications. In study participants, nephropathy was reduced as much as 80%; the development of clinical neuropathy was reduced by up to 60%, and the development of retinopathy was reduced by 75%.

On the heels of such news, pharmacies stocked up and hunkered down to wait for the onslaught of wannabe normoglycemics that never came.

The problem is that to be truly at the intensive level of management means not just pricking your finger twice a day to get a blood glucose reading -- but four to 10 times a day or more -- for life. And you don't inject your insulin twice a day -- you do it four times a day or more -- for life.

The pharmacist can play a lead role under the diabetic's big top to help diabetics minimize the complications of their disease. First, they should identify populations known to be at risk for developing noninsulin-dependent diabetes mellitus, or NIDDM, and encourage early detection and prevention. Second, they should keep the diagnosed diabetic on track with education and by linking up with medical specialists who focus on this disease. Third, pharmacists should help keep diabetics motivated to closely monitor their condition. And finally, they can act as a resource, including informing diabetics about studies of new treatments that they might want to participate in.

Pharmacists say interest in the intensive regimen and sales have been disappointing compared with the expectations fueled by the study because many diabetics are just not willing or able to be that disciplined.

"A good number of diabetics cannot keep up this new regimen for long," says O.N. Odom, pharmacist at Alford's Supermarket, Port Arthur, Texas. "They don't want to stick themselves that many times a day."

"Many diabetics realize they should test themselves more often and use more insulin, but many cannot afford it," adds Stephen Young, a pharmacist at a Pay-Less Drug store in Salt Lake City. "Some have insulin pumps, but those people are very few because of the cost."

Dr. Alan M. Jacobson of the Joslin Diabetes Center at Harvard Medical School said of those diabetics asked to become total slaves to their disease by going on the strict regimen, "their response is they feel pretty good,

so why bother? Why change?"

On top of that, Medicare reimbursements for blood glucose monitors and the test strips they use are being slashed, partly in response to manufacturer rebate promotions of the meters.

The government's action, say pharmacists, will reduce their ability to provide the kind of training and support necessary to ensure proper patient use of the equipment.

In general, pharmacists find most diabetics to be well in-formed and eager to learn more about their disease.

"Most of the diabetics I see are well educated and will ask me questions about their disease," says Young of Pay-Less. "We do the best we can here, although we don't have an organized diabetes counseling program as such. We sell strips and insulin at cost and encourage diabetics to call us if they have problems -- not to wait until they get into trouble before they seek help."

"Diabetics today are an informed lot and seem to know what they need to buy and how to use it," adds Alford's Odom.

The number of diabetics is increasing and not just because they are living longer, thanks to the availability of oral hypoglycemics and insulin. The rates of adult-onset diabetes are soaring.

The Framingham Heart Study that began in 1949 and followed 5,200 patients for 40 years with no prevalence of diabetes in that patient population had risen 300% in the last 30 years, with no plateau in sight.

Another, more exotic study, published in Annales Nestle in Switzerland, looked at previously remote areas of the world and plotted the increase of NIDDM. Between 8% and 19% of Australian Aborigines, for example, develop NIDDM, depending on their dependence on outside food supplies. The more their diet consisted of lizards, wallabies, nuts, bush berries and seeds, the lower the chances of becoming glucose-intolerant. But in towns where urbanization has brought a westernization of diet, along with a decrease in exercise, even the extreme leanness of the Aborigines did not preclude them from having fasting glucose levels that were high and lethal.

This pattern continues to be seen throughout the world including among certain Native American groups. North American Indian populations, specifically Pima-Papago tribes, have the highest rates of NIDDM in adulthood -- 35%. Yet 80 years ago, the Pimas rarely had diabetes. Between the years 1967 and 1977, prevalence in this one tribe quadrupled.

Although NIDDM is often associated with aging and obesity, the disease also is found in young people. NIDDM responds to diet and exercise without the need for administration of insulin.

Because adult-onset diabetes mellitus can be an insidious disease, often not manifesting symptoms until the fifth decade of life, it is very likely that the disorder develops in childhood or adolescence in populations at risk.

For the pharmacist, a careful, complete patient history can be invaluable in helping improve the diabetic's prognosis or even delaying the onset of the disease. For example, knowing that having a family history of diabetes increases the risk of both types, NIDDM and IDDM, indicating a possible genetic disposition, pharmacists can counsel the patient to always be aware of possible signs and symptoms of the disease.

Diabetics who are likely to develop nephropathy can be identified by the detection of small amounts of urinary albumin -- this is something about which pharmacists can tell their patients so they can ask their doctors. Measures to slow or prevent nephropathy include optimizing glycemic control, restricting dietary protein and aggressively treating hypertension.

Angiotensin-converting enzyme, or ACE, inhibitors appear to have some renal-protective effects and have been shown to slow the progression of existing kidney disease. The pharmacist can intervene by encouraging proper diet and by making sure antihypertensive prescriptions are refilled regularly.

Pregnancy is another fairly common precipitating factor, particularly among over- weight women over the age of 30 who have a family history of diabetes. For these wom-en, careful consulting about signs and symptoms to look for can stabilize their health and the health of their baby.

Pharmacists can triage their diabetic patients with insight. If a known diabetic comes into a store and asks a pharmacist to recommend something for his athlete's foot, the pharmacist should stop and consider whether it is really a fungal infection or a secondary staph infection. Because it could be the latter, the patient should be referred to his doctor.

A patient might tell the pharmacist that her glucose meter said her blood sugar level was 268 last night and 305 this morning and her insulin dose has not changed. Is something wrong with her glucose monitor or does she have an underlying infection such as a urinary tract infection that is causing her blood sugar to rise? A pharmacist will know what advice to give.

There are reasons to be hopeful. The Food and Drug Administration has authorized a protocol for a new oral hypoglycemic to treat certain patients with NIDDM. Metformin hydrochloride appears to act by increasing the metabolic response to endogenous insulin, rather than by stimulating insulin secretion, the mode of action of the sulfonylurea hypoglycemic agents -- like glyburide and glipizide.

Metformin HCl is a biguanide. This class of hypoglycemics is only active in patients with some endogenous insulin secretion and appears to work at three levels: by suppressing gluconeogenesis in the liver, stimulating glycolysis and inhibiting glucose absorption in the intestine. The drug may even lower total cholesterol and triglyceride levels to boot.

Sounds ideal. But the biguanide family of oral hypoglycemics is not new. A congener of metformin, phenformin, was used in the United States until 1977, when it was withdrawn from the market because of an increased incidence of lactic acidosis. According to FDA, metformin has been used in other countries for many years and lactic acidosis has been reported. But some epidemiological data suggest that the risk of lactic acidosis is significantly smaller than with phenformin. Studies continue, but for now this investigational drug is available for use by qualified physicians through its sponsor, Lipha Pharmaceuticals, New York, (212) 223-1280.

Finally, the National Institutes of Health has begun the first large-scale trial to see if IDDM can be prevented and are looking to recruit more than 800 volunteers, ages 3 to 45, for the study. Eli Lilly is providing $1 million worth of Humulin for the trial and some volunteers will be testing an oral form of insulin. For more information, call (800) 425-8361.