Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae.

Elevated dosage of the GAC1 gene from the yeast Saccharomyces cerevisiae causes hyperaccumulation of glycogen whereas a gene disruption of GAC1 results in reduced glycogen levels. Glycogen synthase is almost entirely in the active, glucose 6-phosphate-independent, form in cells with increased gene dosage of GAC1 whereas the enzyme is mostly in the inactive form in strains lacking GAC1. GAC1 encodes an 88 kDa protein that is similar to the regulatory subunit (RG1) of phosphoprotein phosphatase type 1 (PP-1) from skeletal muscle that targets PP-1 to glycogen particles. Taken together, these results suggest that GAC1 encodes a regulatory subunit of PP-1. As previously shown for glycogen phosphorylase (GPH1), GAC1 RNA accumulates concomitantly with the appearance of glycogen. A strain with a mutation in the regulatory subunit of the cAMP-dependent protein kinase (bcy1) fails to accumulate GPH1 and GAC1 RNA. These results point to coordinate regulation of enzymes involved in glycogen metabolism at the level of RNA accumulation and indicate that at least part of this control is exerted by the RAS-cAMP pathway.