HNF-4alpha mutations are common when no HNF-1alpha mutation is found in strictly defined MODY families. The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha MODY and are associated with reduced apolipoprotein A2 levels. We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found.
Eleven Type 2 diabetic subjects (10 male 1 female: age 56.2 ± 9.7 (SD) yr) were treated in random order either with insulin or with sulphonylureas for 8 weeks each, without attempting to alter glycaemic control between the two treatment periods. Insulin treatment was associated with suppression of endogenous insulin secretion (fasting C‐peptide levels ‐35.0 ± 24.2%; p = 0.006), and of intact proinsulin (‐43.1 ± 36.8%; p = 0.03) and 32,33 split proinsulin ‐20.1 ± 27.0%; p = 0.03). Activity of plasminogen activator inhibitor (PAI‐1), a fast acting inhibitor of fibrinolysis, decreased significantly (‐14.3% ± 27.5 %; p = 0.02) but no changes occurred in concentration of lipoproteins or apoproteins between therapies. Changes in concentrations of 32,33 split and intact proinsulin were closely and significantly related (rs = 0.83; p < 0.001) to each other but not with changes in concentrations of C‐peptide (intact proinsulin rs = ‐0.41; p = 0.11) and 32,33 split proinsulin rs = ‐0.27; (p = 0.21). Percentage changes in intact proinsulin concentrations were positively correlated with those in PAI‐1 (rs = 0.51; p = 0.05). There was, however a paradoxical negative relationship between changes in C‐peptide concentrations and those of PAI‐1 (rs = ‐0.73; p = 0.006). These preliminary observations suggest that insulin treatment in Type 2 diabetic subjects without any changes in glycaemic control is associated with a reduced activity of PAI‐1, but is without effect on any other cardiovascular risk factors. Concentrations of insulin precursor molecules may play a role in determining fibrinolytic activity.
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