OBJECTIVE
Proteomic profiling can identify useful biomarkers. Monozygotic (MZ) twins discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well-characterized cohorts.
RESEARCH DESIGN AND METHODS
A broad, multiplex analysis of 4,068 proteins in serum samples from MZ twins concordant (n = 43) and discordant (n = 27) for type 1 diabetes identified major differences that were subsequently validated by a trypsin(ogen) assay in MZ pairs concordant (n = 39) and discordant (n = 42) for type 1 diabetes, individuals at risk for (n = 195) and with (n = 990) type 1 diabetes, as well as individuals with noninsulin-requiring adult-onset diabetes diagnosed as either autoimmune (n = 96) or type 2 (n = 291).
RESULTS
Proteomic analysis identified major differences between exocrine enzyme levels in discordant MZ twin pairs despite a strong correlation between twins, whether concordant or discordant for type 1 diabetes (P < 0.01 for both). In validation experiments, trypsin(ogen) levels were lower in twins with diabetes than in the cotwin without diabetes (P < 0.0001) and healthy control participants (P < 0.0001). In recently diagnosed participants, trypsin(ogen) levels were lower than in control participants across a broad age range. In at-risk relatives, levels <15 ng/mL were associated with an increased risk of progression (uncorrected P = 0.009). Multiple linear regression in recently diagnosed participants showed that trypsin(ogen) levels were associated with insulin dose and diabetic ketoacidosis, while age and BMI were confounders.
CONCLUSIONS
Type 1 diabetes is associated with altered exocrine function, even before onset. Twin data suggest roles for genetic and nongenetically determined factors. Exocrine/endocrine interactions are important underinvestigated factors in type 1 diabetes.
<p> </p>
<p><em>Objective</em></p>
<p>Proteomic profiling can identify useful biomarkers. Monozygotic(MZ) twins, discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well characterised cohorts.</p>
<p><em>Research Design and Methods</em></p>
<p>A broad, multiplex analysis of 4068 proteins in sera from MZ twins concordant (n=43) and discordant for type 1 diabetes (n=27) identified major differences which were subsequently validated by a trypsin(ogen) assay in MZ pairs concordant (n=39) and discordant (n=42) for type 1 diabetes, individuals at-risk (n=195) and with type 1 diabetes (n=990), as well as with non-insulin requiring adult-onset diabetes diagnosed as either autoimmune (n=96) or type 2 (n=291).</p>
<p><em>Results</em></p>
<p>Proteomic analysis identified major differences between exocrine enzyme levels in discordant MZ twin pairs despite strong correlation between twins, whether concordant or discordant for type 1 diabetes (p<0.01 for both). In validation experiments, trypsin(ogen) levels were lower in twins with diabetes compared with non-diabetic co-twins (p<0.0001) and healthy controls (p<0.0001). In recently-diagnosed cases, trypsin(ogen) levels were lower than in controls across a broad age range. In at-risk relatives, levels <15 ng/ml were associated with increased risk of progression (uncorr. p=0.009). Multiple linear regression in recently-diagnosed cases showed that trypsin(ogen) levels were associated with insulin dose and diabetic ketoacidosis while age and BMI were confounders.</p>
<p><em>Conclusions</em></p>
<p>Type 1 diabetes is associated with altered exocrine function, even before onset. Twin data suggest roles for genetic and non-genetically determined factors. Exocrine/endocrine interactions are important under-investigated factors in type 1 diabetes.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.