BOSTON-There’s an epidemic of Type 2 diabetes among some groups of American children that seems linked to a rise in obesity.
Much of the childhood hyperglycemia-newly recognized among minority ethnic adolescents and children as young as 4-resembles adult forms of insulin-resistant disease. But some of it doesn’t fit neatly into Type 1 or 2. Diabetologists are flailing about in search of reliable treatment protocols.
The prevalence of Type 2 diabetes among Eskimos in northern Ontario was found in 1995 to exceed that of Type 1 disease among all Pennsylvania youths, says Dr. Dorlinda House of Orlando, who was part of a University of Florida team that helped document the phenomenon. And the frequency of non-insulin-treated diabetes in Hispanic and African American children is on the rise.
In a study of medical records of 1,027 consecutive patients from birth to age 19 diagnosed with diabetes between 1982 and 1994, Dr. Philip Zeitler’s team at Children’s Hospital in Cincinnati found Type 2 diagnoses had risen from 4% to 16%.
The rise was linked closely to an increase in childhood obesity. Among 10- to 19-year-olds, Type 2 accounted for 33% of new cases of diabetes in 1994, says Dr. Zeitler. Mean age at diagnosis was 13.8 years, and mean body mass index was 37.7. At least 21% had one other condition associated with obesity. The incidence increased tenfold, from 0.7 per 100,000 in 1982 to 7.2 per 100,000 in 1994.
There have been similar increases among 15- to 20-year-old Native Alaskans, Pima Indians, and black and Hispanic youths, says Dr. House. And in the Bogalusa (La.) Heart Study, there’s been a 20-year rise in obesity among youths ages 5 to 14.
Pediatric endocrinologists at the American Diabetes Association meeting here admitted they are ill-prepared to cope with childhood diabetes’ changing epidemiology. Diagnosis and treatment are knotty problems, they said, because Type 2 in children is not homogeneous. Three major variants of non-insulin-requiring diabetes are emerging.
By far the most common, says Dr. House, is the same kind of nonketotic Type 2 disease that’s seen in adults. Onset is insidious, family history variable, and patients generally obese.
But obesity isn’t an absolute hallmark of maturity-onset diabetes of the young, a form that’s also insidious in onset. MODY is autosomally dominant, and Gainesville’s Dr. William Winter cites at least four distinct genetic variants.
Like Type 1 diabetics, patients with atypical diabetes of African Americans (ADM) are ketosis-prone at onset, but their initial insulin dependence gives way months or years later to a more typical Type 2 course. About 40% are moderately obese, and ADM, too, is autosomally dominant.
HLA typing and the appearance of autoantibodies can usually pinpoint Type 1 disease, says pediatrician Allan Drash of the University of Pittsburgh, but 10% to 20% of newly diagnosed Type 1 patients with identical clinical syndromes have no markers of autoimmunity. Between 5% and 15% of adults with Type 2 diabetes also have islet-cell autoantibodies, adds Dr. House, though the frequency in children with non-Type 1 disease is unreported.
Other lab findings may help distinguish one type from another. Dr. House’s own studies of glucose and insulin responses to a standard mixed meal turned up some differences among 49 ADM patients, 23 Type 1 patients, 16 black Type 2 patients, 19 black controls, and 15 nondiabetic relatives of ADM patients.
Both ADM and Type 2 patients were hyperglycemic, but to a lesser degree than Type 1 patients. And the C peptide-to-glucose ratio for ADM was intermediate between that of Type 1s and 2s. The two control groups were normal on both counts.
Persistent insulin secretion in ADM patients, says Dr. House, can help distinguish that disease from Type 1, which has a more abrupt fall.
Treatment of non-Type 1 disease in children is even tougher than diagnosis, says the University of Colorado’s Dr. Georgeanna Klingensmith. No oral hypoglycemic agents have been approved for children, though she thinks pediatricians will use them.
Just a few years ago, she adds, no one would have dreamed of treating any diabetic child with anything but insulin. It was only happenstance that the Florida group learned some kids-those lost to follow-up who later returned off insulin because their diabetic adult relatives didn’t require it-can do without it.
Though 80% of non-Type 1 patients treated by the Colorado team still start on insulin (half for initial metabolic stabilization), Dr. Klingensmith has weaned children from insulin to sulfonylureas. But though both treatments can maintain normal glucose metabolism, neither addresses insulin resistance or weight.
One that seems to do so is metformin (Glucophage, Bristol-Myers Squibb), but she warns that more children than adults are apt to stop treatment because of GI discomfort. She pleads with any diabetologist trying any other drug to publish on it.
British studies suggest that Type 2 disease in childhood has its roots in the womb, says Dr. House. They found lower birthweight linked to a fourfold increase in disease. In a study of boys, lower birthweight has been associated with higher glucose levels at age 7.
Because perinatal nutrition influences numbers of fat cells, Dr. House says, preventing low birthweight could give diabetes prevention a two-for-one punch. -Judy Ismach
BOSTON-There’s an epidemic of Type 2 diabetes among some groups of American children that seems linked to a rise in obesity.
Much of the childhood hyperglycemia-newly recognized among minority ethnic adolescents and children as young as 4-resembles adult forms of insulin-resistant disease. But some of it doesn’t fit neatly into Type 1 or 2. Diabetologists are flailing about in search of reliable treatment protocols.
