Igor Alexander Harsch

The Effect of Continuous Positive Airway Pressure Treatment on Insulin Sensitivity in Patients with Obstructive Sleep Apnoea Syndrome and Type 2 Diabetes

Background: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. Objectives: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. Methods: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 ± 21.3; body mass index (BMI) 37.3 ± 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 ± 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. Results: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 ± 2.94 vs. 2.74 ± 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 ± 0.6%; not significant). Fasting leptin levels showed no significant changes. Conclusions: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Prevalence of sleep apnoea in diabetic patients

Background:  Diabetes and obstructive sleep apnoea (OSA) syndrome share a high prevalence in industrialized nations. The presence of OSA seems to promote the development of diabetes mellitus (DM) and vice versa.

Adiponectin in patients with obstructive sleep apnea syndrome: Course and physiological relevance

Background: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS). Objectives: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS. Methods: Thirty nondiabetic, obese patients with OSAS (mean age 56.4 ± 11.1 years; apnoea-hypopnoea index (AHI) 46.03 ± 19.57) underwent CPAP treatment. Adiponectin levels and the levels of proinflammatory cytokines and proteins reflecting platelet activation [regulated on activation normally T cell expressed and secreted (RANTES) and soluble P-selectin (sCD62p)], as well as the insulin sensitivity index were measured before, and after 2 days and 3 months of CPAP treatment. Results: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase in insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p = 0.021) after adjustment for body fat (p = 0.003). During treatment, changes in adiponectin levels were highly predictable by the insulin sensitivity index. Conclusions: We found a significant relation between adiponectin and the insulin sensitivity index in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of the body mass index on adiponectin secretion, which was unchanged during nCPAP treatment.

Initiation of CPAP therapy for OSA: does prophylactic humidification during CPAP pressure titration improve initial patient acceptance and comfort?

Background: Heated humidifiers (HH) enable effective treatment of upper airway dryness during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA), but the role of prophylactic use of HH during the initiation of nCPAP treatment has not been studied so far. Objectives: The aim of the present study was to investigate whether prophylactic HH during the initiation of CPAP would result in improved initial patient comfort and acceptance. Methods: In 44 consecutive, previously untreated OSA patients with no history of upper airway dryness, CPAP titration with and without HH was performed on two consecutive nights in a randomised order. The patients were interviewed after each treatment night in order to establish the comfort of the treatment, and, after the second treatment, they were asked which of the two nights they considered more pleasant, and which treatment they would prefer for long-term use. Results: Following CPAP titration with HH, 32 patients (73%) claimed to have had a better night’s sleep than usual (i.e. without CPAP treatment) compared with 33 patients (75%) saying the same following CPAP treatment without HH. For 21 patients (47.7%) treatment with HH was more pleasant, 23 (52.3%) saw no difference or said that treatment without HH was more pleasant. Nineteen patients (43.2%) gave preference to treatment with HH for long-term use, while 25 patients (56.8%) had no preference or said they would prefer treatment without HH. Conclusions: The use of HH during the initiation phase of CPAP treatment was associated neither with an initial improvement in comfort nor with greater initial treatment acceptance.

Leptin, Obestatin and Apelin levels in patients with obstructive sleep apnoea syndrome

Summary Background Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. Material/Methods Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. Results Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. Conclusions In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

Diabetes mellitus negatively affects peri-implant bone formation in the diabetic domestic pig

AIM Diabetes mellitus is classified as a relative contraindication for implant treatment, and higher failure rates have been seen in diabetic patients. The aim of the present study was to investigate the effect of diabetes on peri-implant bone formation in an animal model of human bone repair. MATERIALS AND METHODS Diabetes was induced by an intra-venous application of streptozotocin (90 mg/kg) in 15 domestic pigs. Implants were placed after significant histopathological changes in the hard and soft tissues were verified. The bone-implant contact (BIC), peri-implant bone mineral density (BMD), and expression of collagen type-I and osteocalcin proteins were qualitatively evaluated 4 and 12 weeks after implantation. Fifteen animals served as healthy controls. RESULTS Diabetes caused pathological changes in the soft and hard tissues. The BIC and BMD were significantly reduced in the diabetic group after 4 and 12 weeks. Collagen type-I was increased in the diabetic group at both time points, whereas osteocalcin was reduced in the diabetic group. CONCLUSIONS Poorly controlled diabetes negatively affects peri-implant bone formation and bone mineralization. These findings have to be taken into consideration for diabetic patients with an indication for implant therapy.

Reproducibility of a Standardized Titration Procedure for the Initiation of Continuous Positive Airway Pressure Therapy in Patients with Obstructive Sleep Apnoea

Background: Manual titration of continuous positive airway pressure (CPAP) under polysomnographic control is the method most commonly employed to establish the minimal effective pressure (Peff) for the treatment of the obstructive sleep apnoea syndrome (OSA). To date, however, the reproducibility of Peff titrated in this way has not been investigated in any detail. Objectives: The present study aims to establish the reproducibility of Peff determined by manual titrations of CPAP under polysomnographic control in the sleep lab. Methods: In a group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3 (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6), with newly diagnosed OSA, manual titration of CPAP was performed on two consecutive nights using the following standard titration protocol: starting at 4 mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until no signs of airway obstruction could be seen, and arousals were no longer elicited. When no airway obstruction was detected over a period of 30 min, the pressure was lowered once during the night in steps of 1 mbar at intervals of at least 10 min, until obstructive events reappeared, whereupon the pressure was again increased as described above, until, once more, no signs of airway obstruction and no arousals occurred. The second titration was carried out in a blind manner, that is the lab technician did not know the results of the first pressure titration. Results: The mean (SD) Peff for all titrations was 8.1 mbar (2.9). A high level of correlation was found between the Peff titrated on the first night and that titrated on the second night (Spearman correlation coefficient = 0.89). In a few individual cases, however, differences of up to 3 mbar were found between Peff on the first night and Peff on the second night. On average, the Peff measured on the second night was 0.5 mbar (SD = 1.3, range: –2.0 to 3.0 mbar) higher than that of the first night. Conclusions: With standardization of the manual titration of CPAP, Peff is readily reproducible. In individual cases, however, a difference of as much as 3.0 mbar between the two titrations is possible.

Establishment of a streptozotocin‐induced diabetic domestic pig model and a systematic evaluation of pathological changes in the hard and soft tissue over a 12‐month period

OBJECTIVE The number of diabetic patients in need of medical treatment is growing steadily. Therefore, a diabetic animal model with high degree of similarities with humans, which is suitable for the systematic evaluation of biomaterials and medical devices, is needed. MATERIALS AND METHODS Twenty domestic pigs were used for the study. Fifteen received Streptozotocin (STZ) to induce diabetes mellitus. Internal parameters were measured and bone as well as soft tissues biopsies were taken after 0, 6 and 12 months and evaluated qualitatively and quantitatively by means of scanning electronic microscopy, light microscopy and microradiography. RESULTS The results of the clinical internal parameters, determined by the American Diabetes Association for the definition of diabetes mellitus could be fulfilled. Pathological changes of the skin vasculatures were already visible after 6 months with a significant wall thickening in the diabetic group. The bone mineralization was lower in the diabetic group after 6 months and with a significant difference after 12 months. CONCLUSION From the present results, it can be concluded that a STZ dosage of 90 mg/kg body weight in the domestic pig is suitable for the induction of an apparent diabetes, leading to histolopathological changes in the hard and soft tissues already after 6 months. The high degree of similarities with humans makes it an interesting diabetic animal model for biomaterial research in a compromised animal model.

Sensitivity of a simplified forced oscillation technique for detection of upper airway obstruction

The sensitivity of a simplified variant of forced oscillation technique (FOT) was studied for assessment of dynamic upper airway obstruction during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA). The airway impedance P[FOT] was measured by FOT and the oesophageal pressure (P(oes)) was recorded during stable stage II sleep in 11 patients with OSA. The CPAP level was initially set high enough to completely abolish upper airway obstruction. To induce gradually increasing upper airway re-obstruction, the CPAP pressure was then lowered stepwise. Thirty six such manoeuvres were analysed, blind, to define the first inspiration at which upper airway re-obstruction was detectable by analysis of P[FOT](t(FOT)) and by P(oes)(t(oes)), respectively. On seven occasions t(FOT) and t(oes) occurred together, in the remaining 29 cases t(FOT) preceded t(oes) with a mean latency of 6.0+/-7.7 (0-32) breath cycles. In no case did t(oes) preceed t(FOT). FOT is a highly sensitive tool for the assessment of incipient upper airway obstruction during nCPAP therapy.

Effect of Helicobacter pylori on delay in ulcer healing induced by aspirin in rats

Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major pathogenic factors in peptic ulcer disease but whether these two factors exert synergistic or antagonistic effects on ulcer healing has been a subject of controversy. We compared the effect of aspirin alone with that of aspirin combined with H. pylori on gastric acid secretion and healing of acetic acid gastric ulcers in rats. The H. pylori colonization of gastric mucosa was determined by viable H. pylori culture, histology and assessment of bacterial DNA using polymerase chain reaction (PCR). The area of ulcers, gastric blood flow, mucosal generation of prostaglandin E(2) and plasma gastrin levels and expression of cyclooxygenase-1, cyclooxygenase-2 and growth factors was determined. Aspirin delayed significantly the healing of chronic gastric ulcers, decreased the gastric blood flow at the ulcer margin and gastric mucosal prostaglandin E(2) generation being without significant influence on gastric acid output. H. pylori acquisition that produced moderate gastric inflammation at the ulcer margin delayed significantly the healing of gastric ulcers, decreased significantly both the gastric blood flow at the ulcer margin and the gastric secretion while raising significantly the gastric mucosal prostaglandin E(2) generation and plasma gastrin levels. H. pylori infection attenuated the aspirin-induced inhibition of ulcer healing and accompanying fall in the gastric blood flow. Both aspirin and H. pylori up-regulated significantly cyclooxygenase-2 messenger RNA (mRNA) and protein but not that of cyclooxygenase-1 at the ulcer margin. Aspirin reduced significantly the transforming growth factor alpha- and vascular endothelial growth factor mRNAs, but these effects were significantly attenuated by H. pylori. We conclude that H. pylori antagonizes, in part, aspirin-induced delay of ulcer healing due to suppression of acid secretion, the enhancement in prostaglandin E(2) possibly derived from cyclooxygenase-2 and the overexpression of transforming growth factor alpha and vascular endothelial growth factor in the ulcer area.