Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes.

AIM: This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin. METHODS: In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored. RESULTS: In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week). CONCLUSION: BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.

Factors determining residual volume in normal and asthmatic subjects.

We have studied the mechanisms determining the residual volume (RV), by inducing temporary changes in RV through respiratory manoeuvres and bronchodilation. Four asthmatic and 5 normal subjects inhaled placebo, salbutamol, and ipratropium bromide, and performed maximum expiratory manoeuvres after partial and maximal inspiration. RV and static lung pressure-volume measurements were made in each experiment. After bronchodilation, RV increased in both groups after a maximal inspiration, while bronchodilatation, as such, decreased RV in both groups. We also found unexpectedly that in the asthmatic patients, the static transpulmonary pressure (Pst) at low lung volumes increased after bronchodilatation. Our findings can be explained if bronchodilators open-up closed airways, and if a preceding maximal inspiration decreases the elastic recoil pressure of the lungs causing a change of the lung volume at which airway closure occurs. The results also support that Pst at low lung volume is influenced by airway closure and underestimates the elastic recoil pressure of the lungs, even in normal subjects. We postulate that the increase in Pst at low lung volumes after bronchodilatation is due to smaller amounts of trapped gas.

A device for evaluation of flow recording equipment.

We have constructed a calibration device which simulates a maximum expiratory flow, and which can also be used to determine quantitatively the frequency response and linearity of flow recording equipment. It consists of a pressure chamber full of copper chips serving as a heat exchanger. When inflated to twice the atmospheric pressure, it delivers 8.2 l of air during deflation. Deflation is released by a falling weight. The time tS between 10% and 90% of the peak expiratory flow out of the chamber (PEFR) can be varied between 10 ms and 90 ms. PEFR up to 19 l X s-1 can be obtained by changing the size of an orifice in the outlet line. The calibrator was tested with a Fleisch no 4 pneumotachograph linear up to 15 l X s-1. The coefficient of variation of PEFR (12.2 l X s-1) and FVC (8.2 l) was 2% and 1% respectively for 10 consecutive deflations. The frequency response in terms of tS of the tested equipment can be evaluated from the flow-volume curve produced by the calibrator. Examination of tS in 50 medical students shows that tS of the equipment should be less than about 20 ms in order to correctly measure PEFR. By means of a single deflation, the linearity of the total recording system can be tested over a range of flows because the flow signal of the calibrator is declining almost linearly with time.

Lipopolysaccharide-induced activation of suppressor cells: reversal by an agent which alters cyclic nucleotide metabolism.

The effects of bacterial lipopolysaccharides (LPS) on the suppressor activity of mouse spleen cells were examined. Pretreatment with LPS was shown to induce suppressor activity in vivo and in vitro. Concurrent treatment of spleen cells with LPS and imidazole, an agent which increases the activity of cyclic nucleotide phosphodiesterases and hastens the degradation of cyclic AMP, reversed the suppressor-inducing effects of LPS. In vitro treatment of spleen cells with aminophylline, an agent which inhibits phosphodiesterase activity, had no effect on suppressor activity. The reversal of LPS-induced suppressor activity by imidazole was time-dependent and addition of this agent 20 hr after LPS treatment did not reverse suppression. These data are consistent with the hypothesis that LPS-induced suppressor activity may be mediated via cyclic AMP-dependent pathways.

Inhibition of graft rejection by LPS: further evidence for effects on T lymphocytes.

The effects of bacterial lipopolysaccharides (LPS) on the growth of allografted lymphoma cells in Balb/c mice were studied. It was determined that the injection of LPS at the time of graft implantation resulted in a transient proliferation and a delay in the rejection of the graft. This effect was not attributable to any enhancement of proliferation of the lymphoma cells by LPS nor to any activity of LPS as a competing antigen or as a polyclonal activator of antibody formation. The in vitro cytotoxicity of peritoneal macrophages from LPS-treated animals against allogeneic lymphoma cells was equal to that of mice not treated with LPS. In vitro proliferation responses of splenic lymphocytes from LPS-treated animals indicated that LPS treatment produced a differential depression of Concanavalin A (Con A) responses but phytohemagglutinin (PHA)-induced responses were elevated significantly. These results suggest that the LPS-induced impairment of cell-mediated immunity involves a subset of Con A reactive T cells whose function is important in allograft rejection.