Effect of continuous positive airway pressure therapy on sexual function and serum testosterone in males with type 2 diabetes and obstructive sleep apnoea.

OBJECTIVE: There have been no studies of the effect of continuous positive airway pressure (CPAP) therapy on erectile dysfunction (ED) and serum testosterone in men with type 2 diabetes and obstructive sleep apnoea (OSA), a patient group at increased risk of ED and hypogonadism. The aim of this study was to determine whether CPAP improves sexual and gonadal function in males with type 2 diabetes and a pre-CPAP apnoea-hypopnoea index >15/h. DESIGN: Substudy of a trial assessing the effect of 3 months of CPAP on cardiovascular risk in type 2 diabetes. PATIENTS: Of 35 males starting CPAP, 27 (mean ± SD age 65.4 ± 9.6 years, median [interquartile range] diabetes duration 12.1 [5.2-15.3] years) completed the trial. MEASUREMENTS: Serum total and free testosterone, responses to the Androgen Deficiency in the Aging Aale (ADAM) and Sexual Health Inventory for Men (SHIM) questionnaires. RESULTS: There were no significant changes in mean total or free testosterone (baseline concentrations 12.7 ± 4.5 nm and 0.26 ± 0.07 pm, respectively), or SHIM score (baseline 13 [5-17]), after 3 months of CPAP (P > 0.20). The ADAM score (baseline 6.2 ± 2.1) fell after 1 month (to 5.0 ± 2.6) and was maintained at this level at 3 months (P = 0.015). The Epworth Sleepiness Scale score decreased and self-reported physical activity increased over 3 months (P ≤ 0.017) without a change in body mass index (P = 1.00). CONCLUSIONS: These findings imply that CPAP therapy improves somnolence and promotes exercise in men with type 2 diabetes, but that there is no direct benefit for gonadal or sexual function.

Effect of continuous positive airway pressure therapy on cardiovascular risk factors in patients with type 2 diabetes and obstructive sleep apnea.

CONTEXT: Few prospective intervention studies have examined the effect of continuous positive airway pressure (CPAP) therapy on cardiovascular disease (CVD) risk factors in diabetes. OBJECTIVE: Our objective was to determine whether CPAP improves CVD risk factors in patients with type 2 diabetes and obstructive sleep apnea (OSA). DESIGN AND SETTING: This was a randomized parallel group intervention trial in an urban Australian community. PATIENTS: Fifty-nine participants of the Fremantle Diabetes Study Phase II at high risk for OSA consented to confirmatory polysomnography followed by randomization to a 3-month CPAP intervention initiated early (<1 wk) or late (1-2 months). MAIN OUTCOME MEASURES: Patients were assessed before and 1 and 3 months after CPAP started. Tests for repeated measures were used to compare variables of interest over time. RESULTS: Forty-four patients (75%) completed the study. Their mean ± sd age was 66.1 ± 8.8 yr, and 61.4% were male. Completers and noncompleters had similar age, sex, diabetes duration, apnea-hypopnea index, and Epworth Sleepiness Scale (P ≥ 0.29). There were no differences in outcome between early and late randomization, and the data were pooled. The Epworth Sleepiness Scale decreased between entry and 1 month [-4.8 (-6.5 to -3.1), P < 0.001]. Blood pressure improved between entry and 3 months (from 149 ± 23/80 ± 12 to 140 ± 18/73 ± 13 mm Hg; P ≤ 0.007). Pulse rate declined within the first month [-6 (-10 to -2) beats/min, P = 0.002]. Glycemic control and serum lipids, which were mostly within recommended target ranges at entry, did not change. CONCLUSIONS: Three months of CPAP in community-based people with type 2 diabetes significantly decreased blood pressure and pulse rate but did not influence metabolic control.

Dyslipidemic diabetic serum increases lipid accumulation and expression of stearoyl-CoA desaturase in human macrophages.

Type 2 diabetes and dyslipidemia are risk factors for cardiovascular disease. However, mechanisms by which hypertriglyceridemia influences atherogenesis remain unclear. We examined effects of dyslipidemic diabetic serum on macrophage lipid accumulation as a model of foam cell formation. Normal human macrophages were cultured in media supplemented with 10% serum from non-diabetic normolipidemic or non-diabetic hypercholesterolemic adults versus adults with Type 2 diabetes; diabetes and hypertriglyceridemia; or diabetes and hypercholesterolemia. Exposure to diabetic sera resulted in increased macrophage fatty acids (2-3 fold higher, both saturated and unsaturated). Macrophage expression of CD36, scavenger receptor A (SR-A) and stearoyl-CoA desaturase (SCD) was increased, most prominently in macrophages exposed to hypertriglyceridemic diabetic serum (twofold increase in CD36 and fourfold increase in SCD, p < 0.05). In these conditions, RNA inhibition of CD36 reduced macrophage free cholesterol (163.9 ± 10.5 vs. 221.9 ± 26.2 mmol free cholesterol/g protein, p = 0.04). RNA inhibition of SCD decreased macrophage fatty acid content, increased ABCA1 level and enhanced cholesterol efflux (18.0 ± 3.9 vs. 8.0 ± 0.8% at 48 h, p = 0.03). Diabetic dyslipidemia may contribute to accelerated atherosclerosis via alterations in macrophage lipid metabolism favoring foam cell formation. Increased expression of CD36 and SR-A would facilitate macrophage lipid uptake, while increased expression of SCD could block compensatory upregulation of ABCA1 and cholesterol efflux. Further studies are needed to clarify whether modulation of macrophage lipid metabolism might reduce progression of diabetic atherosclerosis.