Evaluation of serum 1,5 anhydroglucitol levels as a clinical test to differentiate subtypes of diabetes.
OBJECTIVE
Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology.


METHODS
1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology.


RESULTS
Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 microg/ml (5.74-29.74), HNF1A-MODY 4.23 microg/ml (2.12-8.44), type 1 diabetes 3.09 microg/ml (1.45-6.57), LADA 3.46 microg/ml (1.42-8.45), and type 2 diabetes 5.43 (2.12-13.23). Levels in GCK-MODY were higher than in other groups (P < 10(-4) vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes.


CONCLUSIONS
In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.
Pal
Aparna
A
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Farmer
Andrew J
AJ
Dudley
Christina
C
Selwood
Mary P
MP
Barrow
Beryl A
BA
Klyne
Rhiannon
R
Grew
Jilly P
JP
McCarthy
Mark I
MI
Gloyn
Anna L
AL
Owen
Katharine R
KR
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002648:Child; D003404:Creatinine / Q000097:blood; D003847:Deoxyglucose / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000145:classification / Q000209:etiology / Q000235:genetics; D005941:Glucokinase / Q000235:genetics; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D012372:ROC Curve; D055815:Young Adult
D001786:Blood Glucose; D003404:Creatinine; D003847:Deoxyglucose; D005941:Glucokinase; D006442:Glycated Hemoglobin; D051538:Hepatocyte Nuclear Factor 1-alpha; C496487:HNF1A protein, human; C006584:1,5-anhydroglucitol