Study: Autoantibodies could help predict children’s type 1 diabetes risk

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Measuring levels of autoantibodies in the blood can predict the development of type 1 diabetes in young children, according to new research.

The study, known as “The Environmental Determinants of Diabetes in the Young” (or TEDDY) and published in Diabetologia, indicates that autoantibodies reveal whether or not the immune system is attacking insulin-producing beta cells in the pancreas, thereby causing type 1 diabetes in children.

Antibodies are proteins found in the blood. Their presence indicates that the immune system has attacked a foreign body. Autoantibodies indicateautoimmune disease. That is, they suggest that the immune system is attacking healthy, beneficial cells, such as insulin-producing beta cells. This kind of abnormal immune system behaviour is the cause of type 1 diabetes.

If the first autoantibody found in young children attacks insulin, this could indicate the presence of type 1 diabetes. Similarly, if the autoantibody targets GAD65 (a protein found inside insulin-producing beta cells), the child may be likely to develop type 1 diabetes. In some cases, autoantibodies targeting both insulin and GAD65 will be found simultaneously.

The research followed 8,600 children from Sweden, the United States, Germany, and Finland, all of whom were highly likely to develop hereditary type 1 diabetes. 6.5 per cent of them had their first autoantibody before the age of six.

Of these children, 44 per cent had an autoantibody targeting insulin, 38 per cent had GAD65 autoantibodies before two, and 14 per cent had both autoantibodies by the age of three.

The study suggests that autoantibodies can appear earlier than previously thought.

Although the kind of autoantibody was determined by the child’s genetic risk factors, researchers still do not know why the immune attacks insulin-producing beta cells in the pancreas.

Ake Lernmark, lead researcher of the study, suggested that a virus may be responsible: “It is possible that there are two different diseases involved. Perhaps one virus triggers the autoantibodies against insulin and another one the autoantibodies against GAD65.”

Urinary adiponectin predicts diabetic nephropathy progression in type 1 diabetes

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Panduru NM, et al. Diabetes Care. 2015;doi:10.2337/dc14-2276.

Urinary adiponectin strongly and independently predicted the progression of diabetic nephropathy frommacroalbuminuria to end-stage renal disease in patients with type 1 diabetes, according to research published inDiabetes Care.

The findings on urinary adiponectin (uADP) provide added predictive benefit to current biomarkers including albumin excretion rates (AER) and estimated glomerular filtration rates, according to researchers.

“From a clinical point of view, these results are important because the risk of progression to end-stage renal disease in patients with type 1 diabetes is not easy to assess based on either AER or eGFR given each measure’s limitations,” the researchers wrote.

Nicolae M. Panduru, MD, MSc, PhD, of the Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, and colleagues measured uADP in 2,090 patients with type 1 diabetes followed for an average of 5.8 years and in 111 individuals without diabetes.

The researchers defined progression as a change in albuminuria, based on AER, to a higher stage or development of ESRD. Various Cox regression and competing risk models were utilized to assess the predictive value of uADP fordiabetic nephropathy progression.

The investigators estimated the predictive benefit added to AER or eGFR based on area under the receiver operating characteristic curve, integrated discrimination improvement, ongoing net reclassification improvement and other statistical indexes. Multiple regression analyses were used to investigate uADP determinants.

Progression to ESRD was independently predicted by uADP (HR = 1.6; P < .001) with capability greater than AER (P = .04) and as good as eGFR (P = .79).

Further, uADP added significant predictive value when used with AER based on integrated discrimination improvement (0.115; P < .0001) and net reclassification improvement (0.794; P = .03). The same was seen when used with eGFR based on integrated discrimination improvement (0.087; P < .0001) and net reclassification improvement (0.637; P < .001).

Glycemic control, tubular injury and AER were common determinants of uADP.

“In patients with type 1 diabetes and macroalbuminuria, uADP not only is a strong independent predictor for diabetic nephropathy progression to ESRD, but also adds significant predictive benefit when used together with either AER or eGFR,” the researchers wrote. “This may be due to uADP capturing recognized risk factors for diabetic nephropathy progression such as glomerular damage, tubular dysfunction, and glycemic control as well as other factors important for diabetic nephropathy progression like cachexia.” – by Allegra Tiver

Disclosure: Analyses and assays were partly sponsored by Roche Diagnostics. Please see study for full list of researchers’ relevant financial disclosures.