ABSTRACT
INTRODUCTION: Obstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. METHODS: Severely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis-Mass Spectrometry (CE-MS). RESULTS: Twenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7 kg/m(2)) and 25 controls without OSA (age 52±9years, BMI 39±4 kg/m(2)) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. CONCLUSIONS: The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA.
ABSTRACT
Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and predispose to gout. The evidence for the effects of OSA on serum urate in severe obesity is limited. This study investigated whether OSA was associated with serum urate in severe obesity and whether continuous positive airway pressure (CPAP) treatment was associated with a fall in urate. Severely obese subjects without known OSA or gout were recruited. Baseline assessments included urate, metabolic parameters, spirometry and overnight polysomnography. OSA patients were initially naive to treatment and were offered CPAP. At follow-up, change in urate was compared between CPAP-treated and non-CPAP-treated subjects. A high urate was defined as greater than the median. Logistic regression was performed to identify associations between (1) OSA and high urate at baseline and (2) use of CPAP and change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA and 31 (34%) non-OSA). Median urate was 345 µmol/L. OSA was associated with high urate in females at baseline after adjusting for confounders (adjusted odds ratio ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with a fall to a low urate category at follow-up ( = 0.017). Regression revealed a trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95% CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and CPAP may reduce levels in patients with OSA. There may be a need to consider and assess for OSA in obese patients with hyperuricaemia and recurrent attacks of gout.
Subject(s)
Continuous Positive Airway Pressure , Obesity, Morbid/blood , Obesity, Morbid/complications , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/therapy , Uric Acid/blood , Adult , Blood Pressure , C-Reactive Protein/metabolism , Female , Follow-Up Studies , Humans , Male , Metabolic Syndrome/complications , Middle Aged , Severity of Illness Index , Sex Factors , Sleep Apnea, Obstructive/complicationsABSTRACT
BACKGROUND: Obstructive sleep apnoea (OSA) may independently increase cardiovascular risk in obesity. Although there is evidence that arterial stiffness is altered in OSA, knowledge of these effects with continuous positive airway pressure (CPAP) in severe obesity (body mass index (BMI) ≥ 35 kg/m(2)) is limited. This study aimed to explore how arterial stiffness, as measured by the augmentation index (Aix), changed in severely obese patients with OSA who were treated with CPAP and in patients without OSA. METHODS: Forty-two patients with severe obesity-22 with OSA, 20 without OSA-were recruited at baseline and followed-up after a median of 13.5 months. Pulse wave analysis (PWA) was performed using applanation tonometry at the radial artery to measure augmentation index (Aix), augmentation pressure (AP) and subendocardial viability ratio (SEVR). Cardiovascular parameters and body composition were also measured. RESULTS: There were significant improvements in Aix, AP (both P < 0.001) and SEVR (P = 0.021) in OSA patients on CPAP compared with subjects without OSA. Epworth scores (P < 0.001), systolic (P < 0.001) and mean arterial pressures (P = 0.002) improved with CPAP. Regression showed that CPAP was significantly associated with change in arterial stiffness from baseline. However, patients with OSA on CPAP continued to have increased arterial stiffness (Aix) (P < 0.001), AP (P = 0.028) and reduced SEVR (P = 0.002) relative to non-OSA patients. CONCLUSION: Although sleepiness and blood pressure improve with CPAP in severe obesity, CPAP alone is not sufficient to modify PWA measures to levels comparable with non-OSA patients. This supports a need for a multifaceted approach when managing cardiovascular risk in patients with severe obesity and obstructive sleep apnoea receiving CPAP therapy.
Subject(s)
Continuous Positive Airway Pressure , Obesity, Morbid/physiopathology , Obesity, Morbid/therapy , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapy , Vascular Stiffness/physiology , Adult , Case-Control Studies , Cohort Studies , England , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity, Morbid/complications , Polysomnography , Pulse Wave Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Obstructive sleep apnoea (OSA) is a common complication of obesity and can have a substantial negative impact on a patient's quality of life and risk of cardiovascular disease. The aim of this case-control study was to undertake discovery profiling of urinary peptides using capillary electrophoresis-mass spectrometry (CE-MS) in obese subjects with and without OSA, without a history of coronary artery disease. MATERIALS AND METHODS: Urinary samples were analysed by CE-MS. Body composition and blood pressure measurements were recorded. Overnight polysomnography was conducted to confirm or refute OSA. OSA patients were naïve to continuous positive airway pressure treatment. RESULTS: Sixty-one subjects with OSA (age 47 ± 9 years, BMI 43 ± 8 kg/m(2)) and 31 controls (age 49 ± 10 years, BMI 40 ± 5 kg/m(2)) were studied; P = ns for age and BMI. Apnoea-hypopnoea Index was higher in patients with OSA (24 ± 18·6) than controls without OSA (non-OSA) (2·6 ± 1·1; P < 0·0001). Metabolic syndrome was present in 35 (57%) of those with OSA compared with 4 (13%) of controls (P < 0·0001). Twenty-four polypeptides were candidates for differential distribution (P < 0·01), although these differences did not reach significance after multiple testing. Sequences were determined for eight peptides demonstrating origins from collagens and fibrinogen alpha. CONCLUSIONS: In this study, we report for the first time, urinary proteomic profile analyses using CE-MS in OSA and non-OSA obese groups. The differences in urinary proteomic profiles prior to adjustment for multiple testing, with increased metabolic syndrome in obese OSA subjects, suggest that there may be a role for CE-MS in characterising urinary profiles in severely obese populations with OSA.
Subject(s)
Obesity/urine , Proteomics/methods , Sleep Apnea, Obstructive/urine , Case-Control Studies , Electrophoresis, Capillary/methods , Female , Humans , Male , Mass Spectrometry/methods , Middle Aged , Obesity/complications , Peptides/urine , Sleep Apnea, Obstructive/etiologyABSTRACT
Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non-invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy-two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m(-2) ), without obstructive sleep apnea (non-OSA) 25 (body mass index 40 ± 5 kg m(-2) )] were characterised using anthropometric, respiratory and cardio-metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non-OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea-hypopnea index; P < 0.001). apnea-hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.
Subject(s)
Cardiovascular Diseases/complications , Cardiovascular Diseases/physiopathology , Obesity, Morbid/complications , Obesity, Morbid/physiopathology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Vascular Stiffness , Adiposity , Blood Glucose/analysis , Blood Pressure , Body Mass Index , Case-Control Studies , Fasting/blood , Female , Humans , Lipids/blood , Male , Metabolic Syndrome/complications , Middle Aged , Pulse Wave Analysis , Risk Factors , Waist-Hip RatioABSTRACT
In a meta-analysis that investigated the effects of dietary sodium restriction in diabetes nephropathy, although blood pressure fell, there were significant increases in plasma renin and aldosterone levels. In this article, we hypothesise that in diabetic nephropathy, ACE-I or ARB treatment attenuates any rise in RAS hormones that might result from dietary salt restriction and that the beneficial effects of the salt restriction such as a lower blood pressure outweigh any potentially negative consequences of RAS activation such as a rise in intraglomerular pressure because of the synergistic effects of sodium restriction and RAS antagonist therapy.
Subject(s)
Diabetic Nephropathies/etiology , Sodium, Dietary/administration & dosage , Humans , Models, Theoretical , Renin-Angiotensin System/drug effects , Sodium, Dietary/pharmacologyABSTRACT
OBJECTIVE: Fasting is not routinely recommended for renal function tests, despite the known effects of cooked meat on creatinine. We therefore studied variation in creatinine and estimated glomerular filtration rate (eGFR) after a standardized cooked meat meal in 80 subjects: healthy volunteers and diabetic patients with chronic kidney disease (CKD) stages 1 and 2, 3a, 3b, and 4 (n = 16/group). RESEARCH DESIGN AND METHODS: The interventions were a standardized cooked meat and a nonmeat meal, each providing â¼54 g protein, together with 250 mL water, on separate days. Fasting and postprandial blood samples at 1, 2, and 4 h were drawn for creatinine measurement using a kinetic alkaline picrate assay on an Olympus AU640 analyzer. The modified four-variable Modification of Diet in Renal Disease equation traceable to isotope dilution mass spectrometry creatinine was used to calculate eGFR. RESULTS: Consumption of a standardized cooked meat meal significantly increased serum creatinine and resulted in significant fall in eGFR in all stages of CKD studied; 6 of 16 CKD 3a patients were misclassified as CKD 3b. This effect of cooked meat on serum creatinine disappears after 12 h of fasting in all study participants. CONCLUSIONS: Creatine in meat is converted to creatinine on cooking, which is absorbed, causing significant increases in serum creatinine. This could impact management, as threshold for commencing and withdrawing certain medications and expensive investigations is defined by eGFR. eGFR calculated using fasting serum creatinine would be a better reflection of kidney function in these patients.
Subject(s)
Cooking , Creatinine/blood , Diabetic Nephropathies/physiopathology , Glomerular Filtration Rate , Meat Products , Renal Insufficiency, Chronic/physiopathology , Adult , Aged , Diabetic Nephropathies/blood , Female , Humans , Kidney Function Tests , Male , Middle Aged , Renal Insufficiency, Chronic/bloodABSTRACT
People with diabetes may be hospitalised for the condition or another reason. Either way, they need special care to avoid diabetes-related complications. General ward nurses and trainee doctors were tested on their knowledge of diabetes, with poor results in some areas. The questionnaire used could prove a useful tool for identifying and addressing these problems.
Subject(s)
Diabetes Mellitus , Medical Staff, Hospital/education , Nursing Staff, Hospital/education , beta Karyopherins , Clinical Competence , Diabetes Mellitus/nursing , Educational Measurement , Humans , Medical Staff, Hospital/standards , Nursing Staff, Hospital/standards , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
This study was designed to assess the frequency of the dawn phenomenon in patients with type 2 diabetes. A secondary aim was to examine the influence of varying treatment regimens on the frequency of the dawn phenomenon. The dawn phenomenon was defined as a rise in plasma glucose levels of > or = 0.5 mmol/L (10 mg/dL) between 0500 and 0900 h occurring after a growth hormone surge of > or = 5 microg/L. Sixteen subjects (six men, 10 women) with type 2 diabetes were studied overnight on their current mode of therapy in the General Clinical Research Center. Additionally, six of these subjects were restudied in random order after each of the following three therapeutic regimens: (1) 6 weeks of glipizide, (2) 6 weeks of bedtime NPH insulin, and (3) 3 days of intensive insulin therapy with multiple injections of regular insulin followed by assessment during overnight intravenous infusion of insulin. Thus, a total of 34 overnight studies were performed under various treatment conditions to provide an approximate frequency of the dawn phenomenon in type 2 diabetes. Blood was drawn every 30 min between midnight and 0800 h for measurement of glucose, insulin, C-peptide, and growth hormone levels. Additional counterregulatory hormone levels were determined during 24 of the studies, and the integrity of growth hormone secretion in response to insulin-induced hypoglycemia was assessed in 12 of the 16 patients. The subjects were aged 51 +/- 15 years with a body mass index of 31 +/- 5 kg/m(2) and a mean glycosylated hemoglobin of 8.1 +/- 1.2%. The dawn phenomenon occurred in only one of 34 (3%) studies. Moreover, the four different treatment regimens did not affect the frequency of occurrence of the dawn phenomenon. Ten of the 12 patients tested failed to secrete growth hormone in response to insulin-induced hypoglycemia. These data suggest that the dawn phenomenon is unusual in type 2 diabetes. Previously reported high prevalence rates in studies using similar sample size may be attributable to a Biostator-induced artifact. Decisions regarding therapies for type 2 diabetes should not be based on the assumption that the dawn phenomenon routinely causes early morning hyperglycemia.
Subject(s)
Blood Glucose/metabolism , Circadian Rhythm/physiology , Diabetes Mellitus, Type 2/blood , Blood Glucose/analysis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Hormones/blood , Human Growth Hormone/blood , Humans , Hyperglycemia/blood , Hyperglycemia/etiology , Hypoglycemic Agents/blood , Hypoglycemic Agents/therapeutic use , Insulin/blood , Insulin/therapeutic use , Male , Middle AgedABSTRACT
OBJECTIVE: To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l. RESULTS: Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide. CONCLUSIONS: Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.