Pediatric Annals

EDITORIAL 

A Pediatrician's View

Robert A Hoekelman, MD

Abstract

Juvenile Diabetes: Prevention, Control, and Cure

Abstract

Juvenile Diabetes: Prevention, Control, and Cure

This month's issue of Pediatrie Annals on Diabetes has as its Guest Editor Arlan L. Rosenbloom, MD, Professor of Pediatrics at the University of Florida College of Medicine Health Science Center. He and his contributing authors bring us up to date on diabetes in children and adolescents, how best to manage them, and what we can expect in the future in terms of prevention, improved control, and cure of the disease.

In the United States, there are 11 to 12 million persons who have diabetes, 10% of whom have type 1 insulin-dependent diabetes mellitus (IDDM). Among persons younger than 20 years of age, the prevalence of IDDM is approximately 1 in 300 and the incidence of newly diagnosed cases is 12 to 15 per 100 000 - more than 10 000 each year.1 Among the chronic diseases that affect this population throughout their lives, asthma and cancer are the only ones that carry a greater risk of occurrence.2 Furthermore, although morbidity and mortality among juvenile diabetics is uncommon, their quality of life is affected adversely by their disease throughout their lives and their life expectancy is reduced considerably. Vascular complications of diabetes, which may begin to occur during the third decade of life, lead to retinopathy (the most frequent cause of blindness among 20- to 74-year-olds in the United States), nephropathy (the most frequent cause of end-stage renal disease in the United States), and premature death caused by coronary artery disease.3

Thus, it behooves primary care pediatricians, who may have several IDDM patients in their practice at any given time, to maintain familiarity with all aspects of the disease, not only how to diagnose it, which is relatively easy, and how to manage it in collaboration with pediatrie diabetologists, but also how to advise their patients and parents to deal with the disease on a daily basis so that they can live their lives as normally as possible.

Part of this latter task depends on pediatricians being well aware of all the aspects of IDDM prevention among family members of patients who have the disease, including the following.

Risk. Risk of IDDM is 30% to 40% for a monozygotic twin, 5% to 10% for a dizygotic twin, 6% for other siblings, 2% to 3% for those whose mothers have diabetes, and 5% to 6% for those whose fathers have it. Overall, only 3% to 5% of first-degree relatives of diabetics are at risk, compared with 0.3% to 0.5% of the general population.4

Screening. First-degree family members must be screened for their potential for developing IDDM by testing them for the presence of islet cell antibodies, insulin autoantibodies, and a variety of others, the most sensitive of which at present is antiglutamic acid decarboxylase, and by determining if their insulin response is normal by using oral and intravenous glucose tolerance tests. These screening methods, if accepted by the family of a given child, would need to be repeated annually for 4 to 5 years, beginning at age 3 to 4 years. One must remember that 95% to 97% of first-degree IDDM family members will not develop IDDM, even when some of them have positive screening tests, albeit investigators in this field are reasonably confident that they can identify those who carry a 70% risk for developing IDDM by using these markers.5

Delaying the onset of IDDM. Instituting measures to delay the onset of IDDM in those who have positive screening tests (primary prevention) or to retard the progression of the disease, once it has become overt clinically (secondary prevention). This is done by using:

* medications to alter the patient's immune system, which is attacking and destroying insulin-producing islet cells - medications such as glucocorticoids, azathioprine, and cyclosporin that have significant side effects,

* medications to counter islet cell inflammation, and

* a variety of nonspecific immunomodulators and semispecific immunotherapeutic agents, most of which are invasive, expensive, and not without risks.

The most attention and experience in delaying the onset of IDDM in persons shown to be at risk or retarding its progress, once diagnosed, has been via insulin given orally, subcutaneously, or intravenously by using various regimens, some more vigorous than others. These methods have had some success (believed to be due to either resting the islet cells or immunizing the body against insulin) in animal models and in limited human trials.6 A large-scale, nationwide, multicenter diabetes prevention trial supported by the National Institutes of Health, involving 3 lfz- to 45-yearold first- and second-degree relatives of persons who have IDDM is underway. First, it determines who is at risk and then randomizes those who are into two groups, treating one group with insulin and not treating the other.

Primary care pediatricians also need to know that genetic factors, as important as they are for families who have experienced diabetes, play less of a role in the etiology of diabetes than do environmental factors, given that 90% of new IDDM patients have no family history of the disease. Environmental etiologic factors are, no doubt, multitudinous, but none yet has been proven to cause diabetes in either genetically susceptible or nongenetically susceptible individuals. Viruses such as mumps, coxsackie B, and rubella, chemical toxin exposure early during gestation and after birth, and early ingestion of cow milk during infancy, for example, have been suspected of playing a role in the pathogenesis of IDDM (either as a primary cause or as a trigger mechanism in genetically predisposed individuals) but not proven so.

The most convincing arguments in favor of an environmental etiology for IDDM are:

* the tremendous variation in the incidence among countries throughout the world in which there is no significant difference in the genetic predisposition of their population (approximately 28/100 000 in Finland versus 1/100 000 in Mexico for persons younger than 15 years of age),

* the seasonal variation in onset of new cases (greater during the winter months),

* the highest incidence in countries that have the coolest median yearly temperature, and

* the year-to-year fluctuations in incidence within countries or geographic regions.

In terms of primary prevention of IDDM, the most promising approach is to identify those environmental factors and to determine how they interact with susceptible hosts (and nonsusceptible hosts) to produce disease. Primary care pediatricians can help to identify environmental factors, perhaps better than others, by determining the circumstances that precede the onset of IDDM in their patients.7

Beyond being aware of what is happening in the realm of preventing IDDM, pediatricians must be familiar with all of the methods currently available to control the disease and prevent its complications. These include the usual dietary, exercise, and stress modifications in daily living and the use of exogenous insulin and blood glucose monitoring to avert hyperglycemia and hypoglycemia. New methods for continuous glucose monitoring, coupled with an automatic feedback system to adjust, appropriately, the rate of insulin delivered via a pump implanted under the skin, probably will be available within the next decade to enable stricter glycemic control and thereby reduce the risk of vascular complications, as well as episodes of severe hypoglycemia.3

Because a specific gene responsible for IDDM has not been and most likely will not be isolated, enabling a gene-substitution cure, the best bet for a cure at present seems to be the development of a biohybrid pancreatic device implanted within the body. Such a device would use animal islet cells (human islet cells are too scarce to meet the needs of all patients with IDDM) contained in a synthetic, selectively permeable membrane that isolates them from destructive components of the patients immune system (thereby preventing rejection of the transplant and the need for immunosuppressive therapy, with its severe side effects), but allows permeation of nutrients, electrolytes, and oxygen into the implant and permeation of insulin out of it.3 Let's hope it works, because if it does, IDDM patients will be cured, in the sense that they no longer will have to rely on glucose monitoring and the use of exogenous insulin, to adhere to dietary or exercise restrictions, or to worry about the long-range complications of diabetes.

REFERENCES

1. LaPorte RE, Cnikishanks KJ Incidence and rid: fclots fat insulin-dependent diabetes. In; Diabaes in America. Washington, DG National Diabetes Data Group; 1985. National Institute of Health publication 85-1488.

2. Sultz HA, Schlesinger ER. Mechen WE, Feldman JG. Long-Term Childhood Illnesses. Pittsburgh, PA: University of Pittsburgh Press; 1972.

3. Wolfsdorf Jl, Laffee LMB. Diabetes in childhood: predicting the future. Pediatr Am. 1994:23:306-312.

4. Styler JS. Marks JB. Immune intervention in type I diabetes mellitus. Diabetes Review. 1993;1:15-42.

5. Clark WL. Preventing diabetes. Juvenile Diabetes Foundation International Countdown. 1994:11:28-35.

6. Keller RJ, Eisenbarth GS, Jackson RA. Insulin prophylaxis in individuals at high risk for type 1 diabetes. Lancet. 1993;341:927-928.

7. Moy CS. LaPorte RE. Why do so many children in the United States develop diabetes? Practcal Diabetology. 1989;8:1-6.

10.3928/0090-4481-19940601-04

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