Islet Autoantibody Testing Averts Ketoacidosis in Children

Daniel M. Keller, PhD

September 16, 2011

September 16, 2011 (Lisbon, Portugal) — Regular screening for islet autoantibodies in children at high risk for type 1 diabetes can prevent diabetic ketoacidosis (DKA) and other morbidities associated with the onset of the disease. However, interruptions in screening and follow-up diminish these benefits, Arleta Rewers, MD, associate professor of pediatrics at the University of Colorado in Denver, reported here at the European Association for the Study of Diabetes 47th Annual Meeting.

DKA, which affects 10% to 70% of children at the time type 1 diabetes is diagnosed, is a life-threatening condition. Dr. Rewers and colleagues therefore set out to determine if a program of diabetes education and regular screening for islet autoantibodies in children at high genetic risk would decrease the incidence of DKA and the level of glycated hemoglobin (HbA1c) at diagnosis.

The investigators enrolled children treated at the Barbara Davis Center for Childhood Diabetes, University of Colorado, in Denver, from 1998 to 2001 and 2006 to 2009, in the Diabetes Autoimmunity Study in the Young (DAISY).

The Barbara Davis Center has followed children at increased risk for type 1 diabetes for up to 17 years. The DAISY participants were 1120 healthy young first-degree relatives of type 1 diabetes patients and 1422 healthy infants in the general population who were screened as newborns and found to have the human leukocyte antigen (HLA)-DR and HLA-DQ genotypes associated with type 1 diabetes risk. In DAISY, 181 children developed persistent islet autoantibodies and 71 progressed to type 1 diabetes.

The rate of DKA at diagnosis among the 71 participants with type 1 diabetes was compared with the rate in the 1101 children diagnosed with type 1 diabetes in the community who were in the Barbara Davis Center database. DKA was defined as a venous pH level below 7.3 or a bicarbonate level below 15 mmol/L and the presence of hyperglycemia (glucose greater than 250 mg/dL) and ketosis.

Participants were 17 years or younger, had physician-diagnosed diabetes, and were receiving insulin treatment. Children were excluded if they had diabetes secondary to other conditions.

The demographics of the DAISY and community cohorts were similar (about half female; 89% and 75% non-Hispanic white, respectively; with an age of onset of about 8.4 years).

Children were screened for antibodies to insulin and for 4 different islet autoantibodies (GADA, IAA, IA-2A, and ZnT8A) at birth, at 9, 15, 24, and 36 months, and annually thereafter. If an individual was positive for 2 or more antibodies, he or she was referred to a pediatric endocrinologist and the family was educated about home blood glucose monitoring and was asked to test whenever there were symptoms of diabetes or any illness.

"DKA was present in 7% of DAISY cases and 37% of the community controls," Dr. Rewers told the delegates (P < .001). The 5 cases of DKA in the DAISY cohort included a 10-month-old infant 2 months after the initial DAISY visit and 3 children who were lost to follow-up for the 5 to 11 years before diagnosis. Four children were lost to follow-up for 2 to 11 years but did not have any episodes of DKA.

The prevalence of DKA when type 1 diabetes was diagnosed was 37% in the community cohort, 3% in the DAISY cohort with continuous follow-up, and 43% in the DAISY cohort eventually lost to follow-up.

"To our knowledge, during the study period, at least 3 children died at diagnosis from complications related to DKA in the community, but none of the DAISY participants [died of DKA]," Dr. Rewers reported.

The median HbA1c values at diagnosis were 11.2% in the community participants, 6.6% in active DAISY participants, and 12.4% in DAISY participants later lost to follow-up.

"Annual screening of high-risk children for the presence of islet autoantibodies and counseling of parents of children with pre–type 1 diabetes can prevent most of the morbidity associated with type 1 diabetes onset," Dr. Rewers concluded; the benefit is lost with longer interruptions of follow-up.

Session moderator Henk-Jan Anstoot, MD, PhD, a pediatrician in Rotterdam, the Netherlands, told Medscape Medical News that the study is interesting because "you could diminish an enormous amount of problems in these patients, but the other side of the coin is the difficulty of doing these tests."

Screening requires drawing blood on a regular basis. The tests are not inexpensive, "so we have to look into easier ways of doing this," he said.

Even identifying families with children at high risk for screening can miss up to 90% of cases, because 90% arise in families without a history of type 1 diabetes. To detect them, one would have to screen an entire population on a regular basis.

The study received no commercial funding. Dr. Rewers and Dr. Anstoot have disclosed no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 47th Annual Meeting: Abstract 79. Presented September 14, 2011.

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