The genetic abnormality in the beta cell determines the response to an oral glucose load.
OBJECTIVE
We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT).


METHODS
We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor -1 alpha ( HNF-1alpha) gene mutations.


RESULTS
BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2 % glucokinase subjects and 46 % HNF-1 alpha subjects ( p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1 alpha subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38 % vs 22 %, glucokinase vs HNF-1 alpha) or 2-h values (19 % vs 44 %) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects ( r = -0.047, p = 0.65) but were strongly correlated in HNF-1 alpha subjects ( r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT.


CONCLUSIONS
The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.
Stride
A
A
Department of Diabetes and Vascular Medicine, Postgraduate School of Medicine and Health Science, University of Exeter, Exeter, UK.
Vaxillaire
M
M
Tuomi
T
T
Barbetti
F
F
Njølstad
P R
PR
Hansen
T
T
Costa
A
A
Conget
I
I
Pedersen
O
O
Søvik
O
O
Lorini
R
R
Groop
L
L
Froguel
P
P
Hattersley
A T
AT
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D005951:Glucose Tolerance Test; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
D001786:Blood Glucose; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase