Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial.

AIMS: To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE). METHODS: The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double-blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events. RESULTS: Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (Pinteraction  = 0.971) or HbA1c category at 1 month. Patients in the combined treatment groups (n = 5380) who experienced serious hypoglycaemia (n = 34) had higher MACE rates than those who did not (35.3% vs 11.4%, adjusted hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.27-4.60; P = .007), although the association was less strong when analysing only events after the hypoglycaemic event (adjusted HR 1.60, 95% CI 0.80, 3.20). CONCLUSIONS: There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post-ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed

Nucleotide sequences of murine intracisternal A-particle gene LTRs have extensive variability within the R region.

Nucleotide sequences of the long terminal repeats (LTRs) of four murine intracisternal A-particle (IAP) genes IAP62, 19, 81 and 14 were determined. Each IAP LTR contains three sequence domains, 5'-U3-R-U5-3', and each is bound by 4 bp imperfect inverted repeats. The transcriptional regulatory sequences, CAAT and TATA, as well as the enhancer core sequence GTGGTAA are conserved and precisely positioned within the U3 region. In the R region, the sequence AATAAA is located twenty base pairs preceding the dinucleotide CA, the polyadenylation site. In IAP19 and IAP81, the 5' and 3' LTRs are flanked by a six nucleotide direct repeat of cellular sequences representing the possible integration sites for these IAP proviruses. Both the size and sequences of different IAP LTRs vary considerably, with the majority of the variation localized within the R regions. The size of R varies from 66 bp in IAP14 to 222 bp in IAP62; in contrast, the U3 and U5 regions are all similar in size. These extra sequences within the R region of large LTRs consist of several unusual directly repeating sequences which account for this variability