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A recent study published in Diabetologia from the TrialNet group has found that the shape of the glucose curve during a glucose tolerance test predicted risk of type 1 diabetes (T1D) development. TrialNet is an international network of leading academic institutions, clinicians, scientists and healthcare teams dedicated to the prevention of T1D.

The two hour Oral Glucose Tolerance Test (OGTT) is one method used for the diagnosis of diabetes, as well as for classifying glucose tolerance status as either normal or impaired. Most individuals without diabetes demonstrate a 2 h OGTT pattern that is single phase (“monophasic”), in which there is an initial increase in glucose that peaks at either 30 or 60 min, followed by a steady decline without a secondary increase. Although a secondary increase (“biphasic” pattern) occurring in a minority of people has been observed, its implications are not fully understood. The relevance of the shape of the glucose-response curve during a 2 h OGTT to the development of type 1 diabetes has not yet been studied.

The TrialNet researchers investigated whether the OGTT predicted the development of type 1 diabetes in relatives of people living with T1D. This study followed 2627 autoantibody positive relatives of people with T1D participating in the Pathway to Prevention study, whose baseline OGTT met either a monophasic or biphasic curve, for the development of T1D. 66% of participants had a monophasic curve at baseline while the remainder had biphasic curves.

The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). 9% of people went on to develop T1D in this group. Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). 21% of people within this group went on to develop T1D.

C-peptide, a marker of endogenous insulin production, was also measured throughout the OGTT. The early C-peptide response, C-peptide index and AUC C-peptide were all higher in the biphasic group (p<0.001 for all). The differences in the shapes of the glucose curves appear related to C-peptide responses.

These results indicate that OGGT curve shapes and C-peptide measurements together could be used to aid in prediction of progression of autoantibody positive people to diagnosis of type 1 diabetes.There is an urgent need for more methods to predict who will develop T1D, and research has shown that diagnosing T1D early results in less insulin requirements within the first year after diagnosis, indicating longer preservation of beta cell function, and prevents development of diabetic ketoacidosis if people are regularly monitored. Next, the researchers will investigate whether the shape of the curve changes as the condition progresses. This information will help refine these markers to more accurately predict T1D.

A limitation of the study is that 26% of people did not qualify as either monophasic or biphasic, which could limit the generalisability of the study results to all people with T1D.

See the TrialNet website for information of screening and prevention studies and how to get involved in Australia. If you’d like to hear more about clinical research and currently recruiting clinical trials, you can sign up to be a T1D Game Changer.

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