STEAMBOAT SPRINGS, COLO. – New-onset type 1 diabetes in an obese youth cannot reliably be distinguished from pediatric type 2 diabetes on clinical grounds in this era of epidemic obesity.
“The only way to distinguish obese type 1 diabetes from type 2 diabetes is to measure diabetes autoantibodies. And those autoantibody panels are commercially available now. Signs and symptoms, diabetic ketoacidosis, family history – they don't really help you. We get an autoantibody panel routinely in obese kids above age 10 presenting with new-onset diabetes,” said Dr. Charlotte M. Boney, chief of the division of pediatric endocrinology and metabolism at Hasbro Children's Hospital in Providence, R.I.
Diabetic ketoacidosis is widely thought of as incompatible with type 2 diabetes. Not true. Close to 20% of youth with type 2 diabetes present with DKA. Similarly, while a history of recent weight loss is considered a classic presenting symptom of type 1 diabetes, it's also present in about one-quarter of young people presenting with type 2 diabetes, Dr. Boney noted.
The presence of pancreatic autoantibodies spells type 1 diabetes metabolically, even if the patient appears phenotypically to have type 2 disease.
“Some pediatric endocrinologists call this 'type one-and-a-half' diabetes. No, no, no. Let's not make things any weirder than they already are. They have autoimmune diabetes, which is clearly type 1 diabetes. It just happens to be a little more complicated in them because they also have the morbidity of obesity,” she explained at the meeting.
The obesity epidemic has muddied the diagnostic waters, because now 20%–30% of patients with new-onset type 1 diabetes are obese, as is a similar proportion of the general pediatric population. At the same time, the obesity epidemic has led to an increase in type 2 diabetes.
But it's important to bear in mind that most youths with new-onset diabetes still have type 1 disease, she said.
In the landmark, prospective The SEARCH for Diabetes in Youth study, nearly all children who presented under age 10 years had type 1 diabetes. Among 10- to 19-year-olds, the proportion with type 2 disease was 15% among whites, but considerably greater among racial minorities: 58% among African Americans, 46% in Hispanics, 70% in Asian/Pacific Islanders, and 86% among Native Americans (JAMA 2007;297:2716–24).
In the ongoing, multicenter, National Institutes of Health–sponsored Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which enrolled 1,206 subjects with a presumptive diagnosis of type 2 diabetes, 9.8% proved to be positive for GAD-65 and/or insulinoma-associated protein 2 autoantibodies. They had to be excluded from participation in the treatment phase (Diabetes Care 2010;33:1970–5).
As a practical approach to the initial therapy of young patients with new-onset diabetes, Dr. Boney urged that those with DKA and ketosis should be started on intravenous fluids and insulin, regardless of their age and body habitus. If they are over age 10 and obese, however, pancreatic autoimmunity should be ruled out before transitioning to long-term therapy. For autoantibody-negative patients whose clinical picture is consistent with type 2 diabetes, the treatment is metformin, the only Food and Drug Administration–approved therapy for children. Extensive experience shows that it's a very safe drug, she said.
The TODAY trial is designed to determine whether the best treatment for type 2 diabetes in youth is metformin alone, metformin plus rosiglitazone, or metformin and an intensive lifestyle intervention aimed at achieving a 7%–10% weight loss.
The use of metformin to try to prevent diabetes in obese children with insulin resistance and the metabolic syndrome is the subject of large ongoing clinical trials. Until the results come in, Dr. Boney said she sees no role for off-label prescribing of metformin, given that weight loss and exercise are quite effective in improving insulin sensitivity.
Maturity Onset Diabetes of the Young, or MODY, is worth considering in white youth who are pancreatic autoantibody–negative and have a strong history of parental non–type 1 diabetes. MODY is a single-gene disorder that causes diabetes and is inherited from a parent.
“There are a lot of experts in the MODY field that think we're grossly underdiagnosing monogenic diabetes,” said Dr. Boney.
The treatment for MODY is not insulin or metformin, but rather oral sulfonylureas, although those agents are not FDA-approved for use in children, she observed.
Dr. Boney reported having no financial conflicts.