MODY syndrome

Obesity blamed for 'emerging epidemic.'

Mitchel L. Zoler, Philadelphia Bureau, contributed to this report.

New guidelines are designed to help physicians manage children who have a condition that until recently has been viewed only as an adult problem: type 2 diabetes.

The guidelines, issued jointly by the American Diabetes Association and the American Academy of Pediatrics, were developed in response to the recent "alarming rise" in type 2 diabetes in children and adolescents and the dearth of information about the disease in young people.

It's a trend that Dr. Dana Hardin has observed firsthand in her work as a pediatric endocrinologist at the University of Texas in Houston.

In a series of 244 Houston-area children with diabetes, nearly 10% (24) had type 2 diabetes, compared with 2%-3% in previous studies, Dr. Hardin reported at the annual meeting of the Southern Society for Pediatric Research in New Orleans.

She expects the prevalence of type 2 diabetes in youth to increase dramatically over the next few years because of the growing prevalence of obesity among children and adolescents.

In light of mounting evidence supporting such a prediction, it's dear that "type 2 diabetes in children is an emerging epidemic," Dr. Arlan Rosenbloom, chair of the eight-member consensus panel that drafted the ADA/AAP guidelines, said in a statement.

"This document is an up-to-date resource for health care professionals to help them diagnose, treat, and ultimately lower the risk of complications of this disease in children and adolescents," said Dr. Rosenbloom, distinguished service professor emeritus of pediatrics at the University of Florida, Gainesville.

The guidelines address six aspects of type 2 diabetes in children and adolescents: classification, epidemiology, pathophysiology, testing, treatment, and prevention (Pediatrics 105[3]:671-80, 2000 and Diabetes Care 23[3]:381-89, 2000).

Testing is recommended only for children at substantial risk for type 2 diabetes. This group consists of overweight children (body mass index [greater than]85th percentile for age and sex, weight for height [greater than]85th percentile, or weight [greater than]120% of ideal for height) who also have two of the following three risk factors:

* Family history of type 2 diabetes in a first- or second-degree relative.

* Race/ethnicity (American Indian, African American, Hispanic, Asian/Pacific Islander).

* Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome).

The panel recommended that glucose testing be done in these high-risk children every 2 years, starting at age 10, or at the onset of puberty if it begins before age 10. The fasting plasma glucose (FPG) and the 2-hour plasma glucose test are both acceptable, but the FPG is preferred because it is less costly and more convenient.

Treatment of type 2 diabetes is aimed at normalizing blood glucose (fasting [less than]126 mg/dL) and hemoglobin [A.sub.1c] ([less than]7%), as well as control of blood pressure and lipids.

Initial treatment depends on clinical presentation. Children who present with diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic coma are likely to need insulin, which might be tapered off or stopped once their blood sugar is brought back to normal. Consultation with a pediatric endocrinologist should be considered for these patients.

Comprehensive self-management education is essential for all children with type 2 diabetes and their families. This should include self-monitoring of blood glucose, referral to a dietician for culturally appropriate nutrition guidance, and a daily exercise program, the guidelines state.

Dietary change and exercise may be sufficient initially for patients who are not ill at diagnosis, but adult studies suggest that fewer than 10% of patients can successfully manage the disease over the long term without drug therapy.

Insulin is the only drug approved for treating diabetes in children, but most pediatric diabetologists are now using oral agents in those with type 2 diabetes, the guidelines note.

Metformin should be the first-line oral therapy for type 2 diabetes in children; it reduces [HbA.sub.1C] to the same degree as sulfonylureas, but without the associated hypoglycemia or weight gain. Metformin also can improve lipid profiles and may normalize ovulation in girls with polycystic ovary syndrome.

At the meeting, Dr. Hardin reported that she has successfully used metformin to treat 10 of her patients, aged 14-17 years. She starts with a 500-mg dose every morning. After 2 weeks, she checks the patient's electrolytes; if these are normal, she increases the dose to 500 mg b.i.d.

Among the 10 children she has treated with metformin, fasting and postprandial insulin levels normalized after 6 months of treatment. Nine of the children lost weight.

Dr. Hardin suggested that once a patient has lost weight, metformin can he stopped to see how well the diabetes is controlled by weight control alone.

The ADA/AAP guidelines recommend that if monotherapy with metformin isn't successful after about 3-6 months, the addition of a sulfonylurea, meglitinide, glucosidase inhibitor, or insulin may be considered. Routine use of thiazolidinediones in children is not recommended because not enough safety data are available.

Dilated-eye examination and microalbuminuria screens should be done yearly. Hypertension and hyperlipidemia also must be carefully controlled.

To prevent the development of type 2 diabetes in high-risk children, physicians also are urged to encourage lifestyle modification.

Development of the guidelines was supported in part by educational grants from Bristol-Myers Squibb Co., Eli Lilly and Co., Parke-Davis, and Pfizer Inc.

Separating Time 1 and Type 2 Diabetes

Mitchel L. Zoler

Besides obesity, the dues that a child may have type 2 diabetes rather than type 1 include later age of disease onset, the presence of acanthosis nigricans, and the absence of severe diabetic ketoacidosis, Dr. Hardin said.

She reported these findings from her study of a series of 244 children:

* Those with type 2 diabetes had an average age of disease onset of 12.5 years, vs. 7.5 years for type 1 disease.

* Acanthosis nigricans occurred in 52% of the children with type 2 diabetes, versus 4% of those with type 1 disease.

* None of the patients with type 2 diabetes had severe diabetic ketoacidosis (serum pH of less than 7.2) at the time of their initial diagnosis, but 31% of the type 1 diabetics were that acidotic. Of the children who had type 2 disease, 38% were mildly acidotic (serum pH of less than 7.4 but more than 7.25), she said.

* Finally, the children with type 2 diabetes were much more obese. In subsets of both groups that were matched for gender and age, 13 children with type 2 diabetes had an average body mass index of about 32 kg/[m.sup.2], compared with 17 kg/[m.sup.2] among 101 children with type 1 diabetes.

Both type 1 and type 2 diabetes must be distinguished from the unique genetic syndromes that are called maturity onset diabetes of youth (MODY), Dr. Hardin noted. MODY is associated with five different genotypes that can be identified through tests that are now available at some medical centers.

Fewer than 1% of the diabetic children in her series were classified as having one of the MODY variants, she said.

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