Presenting in DKA Predicts Worse Long-term Diabetes Control

Miriam E Tucker

July 10, 2017

Children who present with diabetic ketoacidosis (DKA) at the time of type 1 diabetes diagnosis are at risk for poorer long-term glycemic control independently of demographic and socioeconomic factors, new research indicates.

The findings were published online June 30 in Diabetes Care by Lindsey M Duca, PhD, of the Barbara Davis Center for Diabetes and the University of Colorado, Aurora.

In the study of nearly 4000 Colorado children diagnosed with type 1 diabetes between 1998 and 2012, factors such as ethnic minority status and lack of health insurance were associated with both DKA at diagnosis and higher HbA1c levels over 15 years of follow-up. But even after adjustment for those and other confounders, DKA at diagnosis still predicted worse control and was present in almost 40% of cases.

The authors hypothesize that exacerbation of beta-cell loss by hyperglycemia and inflammation associated with DKA may play a role. Moreover, DKA can impair cognitive function, which could diminish self-care capacity.

"I think people do not realize the long-term implications of DKA.…We've shown it persists for at least 15 years. This is how long we had data, but I'm pretty sure the effect lasts even beyond 15 years," study coauthor Arleta Rewers, MD, an emergency physician in the University of Colorado's department of pediatrics, told Medscape Medical News.

The most important immediate clinical implication is for the need to recognize the signs and symptoms of diabetes on presentation — including polydipsia, polyuria, and weight loss — and to institute insulin treatment to prevent DKA, Dr Arleta Rewers said, noting that even today there are many missed cases.

Moreover, as ketone levels rise, "It's important for physicians to recognize that if a child presents with nausea and vomiting but not diarrhea it could potentially be diabetes and not gastroenteritis," she noted.

Call for Universal Pediatric Screening for Type 1 Diabetes

The new data also lend further fuel to an ongoing push for universal pediatric autoantibody screening for type 1 diabetes, now being spearheaded at the Barbara Davis Center and led by another coauthor and center executive director Marian Rewers, MD, PhD. (The Rewerses are spouses.)

In 2015, a joint statement from JDRF, the Endocrine Society, and the American Diabetes Association proposed a new three-stage classification system for the progression of autoantibody status leading up to clinical type 1 diabetes, with the intermediate stage signifying sufficient autoantibody positivity to virtually guarantee the development of the condition beyond 5 years without intervention.

At the time, the classification was primarily meant for research purposes and the authors explicitly stated, "Risk screening and staging as outlined here are not recommended at this time for clinical practice in the absence of cost-effective screening, staging, and effective interventions that delay progression to symptomatic type 1 diabetes."

But some experts have maintained that the prevention of DKA justifies screening, as people would be made aware of the risk and take quick action at the first symptoms of hyperglycemia.

Since January 2017, a program at the Barbara Davis Center called Autoimmunity Screening for Kids, cosponsored by JDRF and the Helmsley Charitable Trust, has screened for both pancreatic islet and celiac antibodies in 2500 healthy Denver kids aged 2 to 17 years, the majority of whom have no family history of type 1 diabetes.

Thus far, about one in 30 have been identified as at risk for one of the two autoimmune conditions. Full results will be presented at the International Society for Pediatric and Adolescent Diabetes meeting in October.

The aim is to argue the case for establishment of routine screening of young children and for the adoption of that screening as a covered benefit under health plans, Dr Marian Rewers told Medscape Medical News.

 DKA Independently Predicts Worse Control

The newly published study included 3364 Colorado residents aged 0 to 17 years diagnosed with type 1 diabetes between 1998 and 2012 and monitored at the Barbara Davis Center for Diabetes for 1 to 17 years.

Of those, 1297 (38.6%) presented with DKA (blood glucose >250 mg/dL and venous pH <7.3 or bicarbonate <15 mEq/L). And of those with DKA, one-third had severe DKA (pH <7.10 or bicarbonate <5 mEq/L).

Compared with the children without DKA at diagnosis, those who presented with it were younger, more often from ethnic minorities, uninsured or insured by a government plan, and less likely to have first-degree relatives with type 1 diabetes.

Throughout the entire 14-year study period, HbA1c levels in children presenting in DKA remained 0.3 to 1.0 percentage points (3.3–10.9 mmol/mol) higher than those diagnosed with milder symptoms, with an apparent dose-response relationship by DKA severity.

And in multivariate analysis, HbA1c in the children who presented with severe DKA tracked 1.4% (15.3 mmol/mol) higher than in those without DKA, while those with mild/moderate DKA tracked 0.9% (9.8 mmol/mol) higher (both < .0001).

These were independent of ethnic minority status and lack of health insurance at diagnosis, which predicted higher HbA1c by 0.5 (5.5 mmol/mol) and 0.2 (2.2 mmol/mol) percentage points, respectively (both < .0001).

The effect of DKA at diagnosis was also independent of subsequent insulin-pump use or having a first-degree relative with type 1 diabetes. Those predicted lower HbA1c by 0.4 (4.4 mmol/mol; < .0001) and 0.2 (2.2 mmol/mol); = .01) percentage points, respectively.

The authors conclude, "DKA at diagnosis of type 1 diabetes is not just an acute complication but is also a harbinger of increased morbidity and mortality associated with poor glycemic control.

"Consequently, effective prevention of DKA at diagnosis may provide enduring benefits. Future studies are warranted to assess the effectiveness of DKA prevention at type 1 diabetes onset on improving long-term glycemic control."

Support for the study was provided by the Children's Diabetes Foundation and the Richard S Abrams Endowment for Clinical Research. The authors have no relevant financial relationships.  

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Diabetes Care. Published online June 30, 2017.  Abstract



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