Impaired maximum microvascular hyperaemia in patients with MODY 3 (hepatocyte nuclear factor-1alpha gene mutations).
OBJECTIVE
Functional abnormalities of blood flow and capillary pressure may be involved in the pathogenesis of diabetic microangiopathy. Important differences in microvascular behaviour are observed between Type 1 and Type 2 diabetes mellitus, raising the possibility that the pathogenesis of microangiopathy may differ between these. MODY3 patients have hyperglycaemia as a result of genetic defect of beta-cell function rather than increased insulin resistance and are susceptible to microvascular complications and offer an opportunity to examine microvascular behaviour in this setting.


METHODS
The maximum microvascular hyperaemic response to local heating of the skin was studied in 12 MODY3 patients and age and sex-matched control subjects using laser Doppler fluximetry.


RESULTS
Maximum hyperaemia was reduced in MODY3 patients (median 1.17 (range 0.88-1.92)V vs. 1.70 (1.07-2.19)V normal control subjects; P=0.03) and thus was negatively associated with duration of diabetes (r(s)=-0.79; P = 0.002).


CONCLUSIONS
The results suggest that the duration of diabetes is a determinant of impaired microvascular hyperaemia in MODY3 patients. The pattern of vasodilatory impairment is similar to that observed in Type 1 diabetes mellitus and differs from that seen in Type 2 diabetes. This provides support for the concept that beta cell dysfunction and insulin resistance may have differing effects on microvascular behaviour.
Lee
B C
BC
Department of Vascular Medicine, Postgraduate Medical School, University of Exeter, UK.
Appleton
M
M
Shore
A C
AC
Tooke
J E
JE
Hattersley
A T
AT
D000328:Adult; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D005260:Female; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D006940:Hyperemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
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