Levels of three proteins in the blood can help detect undiagnosed prediabetes

Scientists have used proteomics methods to identify signatures of three proteins in the blood, which could improve detection of isolated impaired glucose tolerance, a form of prediabetes
.
The study, led by scientists from the Department of Epidemiology at the Medical Research Council (MRC) at the University of Cambridge in the UK and the Berlin Institute for Health Research (Charité) in Germany, was published today in
the journal Nature Medicine.

Medical and behavioral interventions for people with prediabetes are effective in delaying or preventing the onset of type 2 diabetes, but current clinical screening and diagnostic techniques ignore a significant proportion of people with
prediabetes.
Isolated impaired glucose tolerance (isolated IGT) is a common subtype of diabetes prodromal and can only be determined by oral glucose tolerance tests, as they have normal
results in more common trials.
The oral glucose tolerance test is a time-consuming process that requires repeated blood draws and is not part of
a routine clinical screening strategy for type 2 diabetes.

Using proteomic methods, the authors measured levels of nearly 5,000 proteins in plasma samples from more than 11,000 participants in the Finnish study, all of whom underwent oral glucose tolerance tests
.
The authors created a machine learning algorithm capable of extracting a core set of proteins from thousands of measured proteins that were most informative
for identifying people most likely to isolate IGT before taking an oral glucose tolerance test.

The authors found signatures of only three proteins that, when combined with standard screening techniques for impaired glucose tolerance, improved recognition of IGT individuals isolated in the Finnish study cohort, a finding
that was subsequently confirmed in the independent Whitehall II study.
Their results also show that fasting before blood samples are collected does not significantly alter the reliability of identifying the three protein signatures in people with impaired glucose tolerance, which will greatly increase the use of
the test in clinical practice.

Julia Carrasco Zanini, a PhD student with lead author of the paper, said: "The Finnish study is unique in that it combines genetic data and blood sampling with objective measures of a range of clinical features, including oral glucose tolerance tests
.
By combining this resource with extensive capture proteomics techniques, we are able to identify protein signatures that greatly improve the detection
of impaired glucose tolerance.
”

The authors suggest that by replacing the two-step screening strategy recommended in the current guidelines with a three-step screening strategy that includes three protein signature tests, the number of individuals requiring oral glucose tolerance testing to identify isolated cases of IGT can be substantially reduced
.
However, they note that some isolated individuals with IGT will still be missed, which is an important consideration for
clinical implementation.

Senior author Professor Claudia Langenberg said: "Our strategy has the potential to address an important unmet clinical need: identifying a significant proportion of people with prediabetes, which remains undetected
at the moment.
Early diagnosis will facilitate preventive lifestyle and behavioural interventions to improve the health of affected individuals and reduce the burden
on health care systems due to delayed diagnosis.
We now want to evaluate the characteristics of these three proteins in other populations and ethnic groups, and eventually test a three-step strategy
for identifying prediabetes in randomized screening trials.
" ”