Acute haemodynamic response to sleeping head-up at 6 inches in older inpatients.

OBJECTIVE: Our aim was to investigate the effect of monotherapy of sleeping head-up (SHU) at 6 in. in a group of older inpatients with OH from all causes. METHODS: We recruited nine consecutive inpatients (mean age (SD) 76(5) years) with persistent, symptomatic OH with a mean systolic blood pressure (SBP) drop on standing and nadir SBP of 68 (27.8) and 94 (19.2) mmHg respectively. All patients underwent SHU for 1 week. Beat-to-beat haemodynamics during lying and standing, 24-hour ambulatory blood pressure, supine haematocrit, urea/electrolytes, plasma renin activity and aldosterone were measured before and after intervention. RESULTS: One week after SHU, SBP, stroke volume and cardiac output increased significantly (all P < 0.05) by 12 mmHg, 15 ml and 1.3 l/minutes respectively while heart rate and total peripheral resistance were significantly reduced by 3.6 bpm and 0.355 dynes/s/cm(5) respectively during 2 minute of standing. Serum creatinine was also significantly lower. Five patients improved in their mobility following SHU. INTERPRETATIONS: SHU for 1 week at 6 in. was well tolerated by older in-patients with OH, associated with improved orthostatic tolerance, and with haemodynamic changes in keeping with increased extracellular volume. SHU at 6 in. has a role in the acute treatment of OH for patients in hospital, but its longer-term effects and in the out-patient setting require further study.

Vascular inflammatory markers in early-onset obese and type 2 diabetes subjects before and after three months' aerobic exercise training.

Early-onset type 2 diabetes (T2DM) may lead to very early vascular complications. Cardiovascular mortality is two to five times higher in adults with diabetes than in people without diabetes. The cardiovascular risk of young people with T2DM is unknown. T2DM in young people is associated with marked visceral obesity, insulin resistance and microalbuminuria. We recently showed that these subjects did not improve in either fitness (maximum volume of oxygen consumption, VO2max) or glucose disposal after exercise training. Seven subjects with early-onset T2DM (aged 26.1+/-0.9 years, body mass index [BMI] 35.6+/-1.2 kg/m2) and 14 age-matched obese subjects with normal glucose tolerance (aged 25.6+/-0.9 years, BMI 34.3+/-1.4 kg/m2) underwent aerobic training for 12 weeks. Serum vascular inflammatory markers (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM-1], soluble vascular cell adhesion molecule [sVCAM-1], E-Selectin and P-Selectin) were measured before and after the training programme. At baseline, plasma concentrations of vascular inflammatory markers were significantly elevated in both groups. They did not improve after exercise.

In vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype.

The purpose of this study was to determine if immune mechanisms in GAD positive patients' contribute to the pathogenesis of a specific sub-type of Type 2 diabetes. GAD positive (n=8) and GAD negative (n=8) subjects diagnosed with Type 2 diabetes were matched for age, gender, body mass index, duration of diabetes and glycaemic control. All subjects underwent an insulin-modified frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and insulin secretory function with minimal model analysis. In addition, BRIN-BD11 clonal beta-cells were supplemented with patients' sera to determine basal and alanine-stimulated insulin secretion and terminal complement complex (TCC) formation. Both groups were severely insulin resistant (0.56+/-0.17 vs. 0.99+/-0.3310(-4)min(-1)/(microUml(-1)) for GADneg and GADpos, respectively) but the GAD negative subjects had a higher basal (87+/-11 vs. 58+/-14pmoll(-1), p<0.05) and glucose-stimulated insulin secretion (DeltaAUCins 0.96+/-0.12 vs. 0.60+/-0.12pmol/(l(-1)min), p<0.05). In vivo measures of insulin secretion were negatively correlated with TCC formation, independent of antibody status. In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced beta-cell impairment. TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes.