Prediction of CKD Progression and Cardiovascular Events Using Albuminuria and Pulse Wave Velocity.

INTRODUCTION: Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD) and death. Albuminuria is an established risk factor, but additional biomarkers predicting CKD progression or CVD are needed. Arterial stiffness is an easily measurable parameter that has been associated with CVD and mortality. We evaluated the ability of carotid-femoral pulse wave velocity (PWV) and urine albumin-creatinine (UAC) ratio to predict CKD progression, cardiovascular events, and mortality in a cohort of CKD patients. METHODS: In CKD stage 3-5 patients, PWV and UAC were measured at baseline. CKD progression was defined as 50% decline in estimated glomerular filtration rate (eGFR), initiation of dialysis, or renal transplantation. A composite endpoint was defined as CKD progression, myocardial infarction, stroke, or death. Endpoints were analyzed using Cox regression analysis adjusted for possible confounders. RESULTS: We included 181 patients (median age 69 [interquartile range 60-75] years, 67% males) with a mean eGFR of 37 ± 12 mL/min/1.73 m2 and UAC 52 (5-472) mg/g. Mean PWV was 10.6 m/s. Median follow-up until first event was 4 (3-6) years with 44 and 89 patients reaching a CKD progression or composite endpoint, respectively. UAC (g/g) significantly predicted both CKD progression (HR 1.5 [1.2; 1.8]) and composite endpoints (HR 1.4 [1.1; 1.7]) in adjusted Cox regression. In contrast, PWV (m/s) was not associated with neither CKD progression (HR 0.99 [0.84; 1.18]) nor the composite endpoint (HR 1.03 [0.92; 1.15]). CONCLUSION: In an aging CKD population, UAC predicted both CKD progression and a composite endpoint of CKD progression, cardiovascular events, or death, while PWV did not.

Employment of patients with kidney failure treated with dialysis or kidney transplantation-a systematic review and meta-analysis.

BACKGROUND: Patients with kidney failure treated with dialysis or kidney transplantation experience difficulties maintaining employment due to the condition itself and the treatment. We aimed to establish the rate of employment before and after initiation of dialysis and kidney transplantation and to identify predictors of employment during dialysis and posttransplant. METHODS: This systematic review and meta-analysis were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for studies that included employment rate in adults receiving dialysis or a kidney transplant. The literature search included cross-sectional or cohort studies published in English between January 1966 and August 2020 in the PubMed, Embase, and Cochrane Library databases. Data on employment rate, study population, age, gender, educational level, dialysis duration, kidney donor, ethnicity, dialysis modality, waiting time for transplantation, diabetes, and depression were extracted. Quality assessment was performed using the Newcastle-Ottawa Scale. Meta-analysis for predictors for employment, with odds ratios and confidence intervals, and tests for heterogeneity, using chi-square and I2 statistics, were calculated. PROSPERO registration number: CRD42020188853. RESULTS: Thirty-three studies included 162,059 participants receiving dialysis, and 31 studies included 137,742 participants who received kidney transplantation. Dialysis patients were on average 52.6 years old (range: 16-79; 60.3% male), and kidney transplant patients were 46.7 years old (range: 18-78; 59.8% male). The employment rate (weighted mean) for dialysis patients was 26.3% (range: 10.5-59.7%); the employment rate was 36.9% pretransplant (range: 25-86%) and 38.2% posttransplant (range: 14.2-85%). Predictors for employment during dialysis and posttransplant were male, gender, age, being without diabetes, peritoneal dialysis, and higher educational level, and predictors of posttransplant: pretransplant employment included transplantation with a living donor kidney, and being without depression. CONCLUSIONS: Patients with kidney failure had a low employment rate during dialysis and pre- and posttransplant. Kidney failure patients should be supported through a combination of clinical and social measures to ensure that they remain working.

Effects of enhanced versus reduced vasodilating treatment on brachial and central blood pressure in patients with chronic kidney disease: a randomized controlled trial.

BACKGROUND: Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions. METHODS: Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating ß-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison. RESULTS: Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32). CONCLUSION: In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT.

Patient selection for islet or solid organ pancreas transplantation: experiences from a multidisciplinary outpatient-clinic approach.

OBJECTIVE: ß-cell replacement therapy (ßCRT), including pancreas transplantation alone (PTA) and islet transplantation (ITX), is a treatment option for selected type 1 diabetes patients. All potential candidates for ßCRT in Norway are referred to one national transplant centre for evaluation before any pre-transplant workup is started. This evaluation was performed by a transplant nephrologist alone prior to 2015 and by a multidisciplinary team (MDT) from 2015. We have reviewed the allocation of patients to treatment modality and the 1-year clinical outcome for the patients after transplantation. RESEARCH DESIGN AND METHODS: Medical charts of all patients evaluated for ßCRT between 2010 and 2020 in Norway were retrospectively analysed and the outcome of patients receiving ßCRT were studied. RESULTS: One hundred and forty-four patients were assessed for ßCRT eligibility between 2010 and 2020. After MDT evaluation was introduced for ßCRT eligibility in 2015, the percentage of referred patients accepted for the transplant waiting list fell from 84% to 40% (P < 0.005). One year after transplantation, 73% of the PTA and none of the ITX patients were independent of exogenous insulin, 8% of the PTA and 90% of the ITX patients had partial graft function while 19% of the PTA and 10% of the ITX patients suffered from graft loss. CONCLUSION: The acceptance rate for ßCRT was significantly reduced during a 10-year observation period and 81% of the PTA and 90% of the ITX patients had partial or normal graft function 1 year post-transplant.

Influence of Renal Transplantation and Living Kidney Donation on Large Artery Stiffness and Peripheral Vascular Resistance.

BACKGROUND: Vascular status following renal transplantation (RT) may improve while living kidney donation (LKD) is possibly associated with an increased cardiovascular risk. METHODS: We prospectively assessed glomerular filtration rate (mGFR, 51Chrome EDTA clearance) and intermediate vascular risk factors in terms of blood pressure (BP), pulse wave velocity (PWV), central augmentation index (AIx), excess pressure (Pexcess), and forearm vascular resistance in donors (n = 58, 45 ± 13 years) and recipients (n = 51, 50 ± 12 years) before and one year following LKD or RT. RESULTS: After kidney donation, mGFR decreased by 33% to 65 ± 11 ml/min/1.73m2, while recipients obtained a mGFR of 55 ± 9 ml/min/1.73m.2 Ambulatory 24-hour mean arterial BP (MAP) remained unchanged in donors but decreased by 5 mm Hg in recipients (P < 0.05). Carotid-femoral PWV increased by 0.3 m/s in donors (P < 0.05) but remained unchanged in recipients. AIx was unaltered after LKD but decreased following RT (P < 0.01), and Pexcess did not change in either group. Resting forearm resistance (Rrest), measured by venous occlusion plethysmography, increased after LKD (P < 0.05) but was unaffected by RT, while no changes were seen in minimum resistance (Rmin). ΔPWV showed a positive linear association to Δ24-hour MAP in both groups. Multiple linear regression analysis (adjusting for age, gender, and the baseline value of the studied parameter) did not detect independent effects of graft function on 24-hour MAP, PWV, AIx, vascular resistance, or Pexcess, whereas low post-donation GFR was related to higher AIx and Rrest. CONCLUSIONS: RT reduced BP and AIx without affecting PWV, whereas LKD resulted in increased PWV and Rrest, despite unchanged BP.

Aortic Calcification Affects Noninvasive Estimates of Central Blood Pressure in Patients with Severe Chronic Kidney Disease.

BACKGROUND: Central blood pressure (BP) assessed noninvasively considerably underestimates true invasively measured aortic BP in chronic kidney disease (CKD) patients. The difference between the estimated and the true aortic BP increases with decreasing estimated glomerular filtration rates (eGFR). The present study investigated whether aortic calcification affects noninvasive estimates of central BP. METHODS: Twenty-four patients with CKD stage 4-5 undergoing coronary angiography and an aortic computed tomography scan were included (63% males, age [mean ± SD ] 53 ± 11 years, and eGFR 9 ± 5 mL/min/1.73 m2). Invasive aortic BP was measured through the angiography catheter, while non-invasive central BP was obtained using radial artery tonometry with a SphygmoCor® device. The Agatston calcium score (CS) in the aorta was quantified on CT scans using the CS on CT scans. RESULTS: The invasive aortic systolic BP (SBP) was 152 ± 23 mm Hg, while the estimated central SBP was 133 ± 20 mm Hg. Ten patients had a CS of 0 in the aorta, while 14 patients had a CS >0 in the aorta. The estimated central SBP was lower than the invasive aortic SBP in patients with aortic calcification compared to patients without (mean difference 8 mm Hg, 95% CI 0.3-16; p = 0.04). The brachial SBP was lower than the aortic SBP in patients with aortic calcification compared to patients without (mean difference 10 mm Hg, 95% CI 2-19; p = 0.02). CONCLUSION: In patients with advanced CKD the presence of aortic calcification is associated with a higher difference between invasively measured central aortic BP and non-invasive estimates of central BP as compared to patients without calcifications.

Arterial stiffness and peripheral vascular resistance in offspring of hypertensive parents: influence of sex and other confounders.

AIM: Established essential hypertension is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for essential hypertension is uncertain. METHODS: Participants from the Danish Hypertension Prevention Project (DHyPP) (both parents hypertensive) (n = 95, 41 ±â€Š1 years, 53% men) were compared with available spouses (n = 45, 41 ±â€Š1 years) using measurements of ambulatory blood pressure (BP), left ventricular mass index (LVMI), pulse wave velocity, central BP and augmentation index (AIx) in addition to forearm resting and minimal resistance [forearm resting vascular resistance (Rrest) and forearm minimal vascular resistance (Rmin)]. RESULTS: DHyPP patients with participating spouses had higher 24-h mean BP (94 ±â€Š1 vs. 88 ±â€Š1 mmHg, P < 0.01), LVMI (94 ±â€Š3 vs. 80 ±â€Š2 g/m, P < 0.01), central SBP (121 ±â€Š2 vs. 111 ±â€Š2 mmHg, P < 0.01) and AIx (16.0 ±â€Š1.2 vs. 10.5 ±â€Š1.7%, P < 0.01), but similar carotid-femoral pulse wave velocity (7.5 ±â€Š0.2 vs. 7.1 ±â€Š0.2 m/s), Rrest (53 ±â€Š3 vs. 51 ±â€Š3 mmHg/ml/min/100 ml) and log Rmin (0.58 ±â€Š0.02 vs. 0.55 ±â€Š0.02 mmHg/ml/min/100 ml) when compared with spouses. Using multiple linear regression analysis (adjusting for sex, age, BMI, creatinine clearance and 24-h BP, heart rate and sodium excretion) AIx and LVMI remained elevated in DHyPP patients [4.2% (0.7; 7.7), P = 0.02 and 6.3 g/m (0.7; 11.9), P = 0.03]. For the entire DHyPP cohort AIx, Rrest and Rmin were higher in women than men (P < 0.01), and the same was true for AIx and Rmin among spouses (P < 0.05). Furthermore, AIx was linearly associated with Rrest and Rmin. CONCLUSION: Young to middle-aged individuals genetically predisposed for essential hypertension display increased AIx and LVMI, although vascular stiffness and peripheral resistance are still normal.

Early gestational age at preeclampsia onset is associated with subclinical atherosclerosis 12 years after delivery.

INTRODUCTION: Women with a history of preeclampsia have increased risk of cardiovascular disease later in life. However, it is unclear whether early gestational age at preeclampsia onset is associated with higher cardiovascular disease risk. This study aimed to test the association between gestational age at preeclampsia onset (including the early-onset/late-onset preeclampsia distinction) and subclinical atherosclerosis and arterial stiffness in age-matched women 12 years after index pregnancy. MATERIAL AND METHODS: Eligible participants were identified in two Danish registries. Main outcome measures were carotid plaque presence, carotid intima-media thickness, aortic pulse wave velocity, and augmentation index adjusted for heart rate. RESULTS: Twenty-four women with previous early-onset preeclampsia, 24 with previous late-onset preeclampsia and 24 with previous normotensive pregnancies were included after matching on age (±2 years) and time since delivery (±1 year). In all outcome measures, the early-onset group had the highest percentage or mean value. In the adjusted analysis, the early-onset group significantly differed from the late-onset group in all outcome measures except aortic pulse wave velocity. The early-onset group also had significantly higher carotid intima-media thickness (average and left) compared with the normotensive group. Gestational age at preeclampsia onset as a continuous variable was significantly associated to both carotid plaque presence and carotid intima-media thickness (average and right). CONCLUSIONS: Gestational age at preeclampsia onset is negatively associated with markers of subclinical atherosclerosis 12 years after delivery. Potentially, gestational age at preeclampsia onset might be helpful in directing cardiovascular disease prevention after preeclampsia.

Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness.

Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients.

[Hyperbaric oxygen treatment of poisoning]. / Hyperbar iltbehandling af forgiftninger.

Experiments have suggested reduction of neurological sequelae from carbon monoxide (CO) poisoning by treatment with hyper-baric oxygen (HBO). Randomised clinical trials have, however, been ambiguous. The discrepancy may be explained by timing of HBO relative to exposure. For other asphyxiants data are too sparse for a qualified judgement. Until more evidence is available, we suggest that HBO is used exclusively for moderate and severe CO poisoning within a time window of 12 hours.

Glucose homeostasis in adults with Prader-Willi syndrome during treatment with growth hormone: results from a 12-month prospective study.

OBJECTIVES: To investigate glucose homeostasis in relation to body mass index (BMI) in adults with PWS before and after GH therapy. DESIGN: We prospectively investigated the effects of a 12-month GH treatment on body composition and glucose homeostasis in relation to BMI in 39 adults, mean (±SD) age=28.6 (6.5) years with genetically verified PWS. We compared the results for different BMI categories (<25 kg/m²; 25-30 kg/m²; >30 kg/m²) and performed a regression analysis to detect predictors for homeostasis model of assessment-insulin resistance (HOMA-IR). RESULTS: The baseline HOMA-IR was higher, with BMI of >30 kg/m². Our main findings were as follows: i) GH treatment (mean final dose, 0.6 (0.25) mg) was associated with small increases in fasting p-glucose, 2-h p-glucose by oral glucose load tolerance test, HOMA-IR and lean mass, and a reduction in fat mass. ii) Whereas the baseline HOMA-IR was associated with increased BMI (>30 kg/m²), we found no differences in HOMA-IR among the BMI categories after 12 months of GH. iii) Stepwise linear regression identified the triglyceride level as the strongest predictor of HOMA-IR at baseline, whereas an increase in VAT was the strongest predictor of the increase in HOMA-IR after therapy. CONCLUSIONS: GH treatment for 12 months in adults with PWS resulted in an increase in HOMA-IR, irrespective of BMI, confirming that control of HbA1c is essential during GH treatment in PWS.

Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study.

Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1 year followed by 2 years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1 year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P < 0.001) and body composition improved in the GH treated group. Visceral fat decreased by 22.9 ml (P = 0.004), abdominal subcutaneous fat by 70.9 ml (P = 0.003) and thigh fat by 21.3 ml (P = 0.013), whereas thigh muscle increased 6.0 ml (P = 0.005). Lean body mass increased 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). The positive effects on body composition were maintained after 2 years of GH treatment. Peak expiratory flow increased by 12% (P < 0.001) at 2 years of GH treatment. Lipid and glucose metabolism were unchanged, however, three patients developed diabetes at 2 years of GH treatment. In conclusion GH treatment had beneficial effects on the abnormal body composition without serious adverse events making it a logic treatment option in adults with PWS.

Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) shares similarities with the growth hormone (GH) deficiency syndrome in regards to reduced lean body mass and increased fat mass and several short-term trials with GH treatment have demonstrated beneficial effects on body composition. The aim of the present study was to evaluate the effects and safety of two years of GH therapy in adults with PWS. DESIGN: Forty-three adults (24 women) with genetically verified PWS were included. Blood samples, body composition as measured by computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) were performed at baseline and during two years of continued GH treatment. RESULTS: Thirty-nine patients completed treatment for two years. The GH dosage averaged 0.61 mg/day (range 0.2-1.6). Based upon CT, body composition improved at two years; thigh muscle volume increased 6.7 mL (3.7 to 9.7; P<0.001) whereas abdominal subcutaneous fat volume decreased by 53.3 mL (13.8 to 92.9; P=0.01). By DXA, lean body mass improved 2.8 kg (1.9 to 3.6; P<0.001), whereas fat mass decreased by 3.0 kg (1.1 to 4.8; P=0.003). Lung function as evaluated by peak expiratory flow increased 12% (p<0.001) - indicating improved muscle function. Adverse effects were few. Fifteen out of 39 patients had diabetes (DM; n=4) or impaired glucose tolerance (IGT; n=11) prior to GH treatment. Among the 11 patients with IGT, three reverted to normal glucose tolerance, while three progressed to overt DM at two years of GH treatment. CONCLUSION: The known beneficial effects of GH treatment upon body composition in PWS are maintained during two years continuous treatment. With appropriate control, GH is a safe treatment option in adults with PWS.

Normal cortisol response to high-dose synacthen and insulin tolerance test in children and adults with Prader-Willi syndrome.

CONTEXT: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested. OBJECTIVE: The objective of the study was to further explore the HPA axis in PWS by use of routine tests. DESIGN: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness. SETTING: The study was conducted at university hospitals in Denmark and Sweden. PATIENTS: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study. MAIN OUTCOME MEASURES: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response. RESULTS: Fifty-seven PWS patients (median age 22 yr, total range 0.5-48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474-1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16-36) yr] examined with the ITT had a median peak s-cortisol of 668 (502-822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter. CONCLUSION: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

One year of growth hormone treatment in adults with Prader-Willi syndrome improves body composition: results from a randomized, placebo-controlled study.

CONTEXT: Prader-Willi syndrome (PWS) is a multisymptomatic disease that shares many similarities with the GH deficiency syndrome, including altered body composition with more body fat than lean body mass. OBJECTIVE: Our objective was to investigate the effect of GH on body composition in adults with PWS. DESIGN AND PATIENTS: Forty-six adults with PWS were randomized to GH or placebo treatment for 12 months in a double-blind trial. MAIN OUTCOME MEASURES: We evaluated change in regional body composition of the abdomen and thigh as measured by computed tomography and change in total body composition as measured by dual-energy x-ray absorptiometry. RESULTS: Forty patients completed the study. Baseline median IGF-I sd score was -0.4. GH treatment increased IGF-I by 125 µg/liter (1.51 sd score), and based upon computed tomography, body composition improved with a decrease in visceral fat mass of 22.9 ml (P = 0.004), abdominal sc fat mass 70.9 ml (P = 0.003), and thigh fat mass 21.3 ml (P = 0.013), whereas thigh muscle mass increased 6.0 ml (P = 0.005). By dual-energy x-ray absorptiometry, lean body mass improved 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). No major side effects were seen. CONCLUSION: Unrelated to the GH-IGF-I levels at baseline, our results showed that long-term treatment with GH effectively improved body composition and represents a safe, potential treatment option, relieving some of the negative consequences of PWS.

Body composition, endocrine and metabolic profiles in adults with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is a complex genetic disease associated with hypothalamic-pituitary dysfunction and severe obesity. The aim of the present study was to describe the relationships between body composition, metabolic and hormonal profiles in PWS adults. METHOD: Forty six adults with genetically verified PWS, 25 women and 21 men, median age 28 years were studied. Body composition was evaluated by standard anthropometric procedures and with computed tomography (CT) of the abdomen and at the mid-femur level. CT of abdomen was compared to 22 healthy, unmatched adults. Circulating lipids were measured and oral glucose tolerance test (OGTT) and hormonal screening including GH secretory capacity (GHRH/arginine test) was carried out. RESULTS: Median body mass index (BMI) was 27.2 kg/m(2), with women being more obese than men. Sixteen patients had dyslipidaemia, 10 impaired glucose tolerance and seven had diabetes. Fifty percent were hypogonadal and six fulfilled BMI related criteria for growth hormone deficiency (GHD). Visceral to subcutaneous abdominal fat ratio was reduced in PWS. Visceral abdominal fat fraction correlated with both subcutaneous fat, BMI and peak GH-response. Thigh muscle volume was about half of the thigh fat volume. Beneficial effects of sex-steroid replacement on body composition were not observed. CONCLUSIONS: Body fat was primarily located subcutaneously and metabolic consequences of obesity limited. The abnormal body composition similar to that in non-PWS GHD adults increases the interest of GH treatment in the prevention of obesity in adults with PWS.

Assessment of physical function in adults with Prader-Willi syndrome.

PURPOSE: To evaluate implementation of at test battery for assessing physical function in adults with Prader-Willi syndrome (PWS). METHOD: Forty-three adults with PWS, 20 men and 23 women, mean age 29 +/- 9 years. Body mass index (BMI) and body composition were measured. A test battery a.m. Guralnik for standing balance, 2.4 m and 10 m walk and repeated rising from a chair was scored and evaluated. RESULTS: Mean BMI was 29.4 +/- 9.1 kg/m(2), body fat mass (FM) 26.0 +/- 16.1 kg. The adults with PWS managed the test battery well, and high scores were achieved for standing balance and 2.4 m walk. In contrast, only 13 managed maximum score in the repeated rising from a chair and 31 to walk 10 m for 6 s or faster. Significant correlations were seen between 2.4 m walk and FM ( p = 0.041) and between 10 m walk and BMI ( p = 0.001) and FM ( p = 0.019). CONCLUSIONS: Repeated rising from a chair and 10 m walk are useful assessments in clinical practice to identify adults with PWS with reduced physical function. Reduced performance was related to higher BMI and FM emphasising the importance of efforts to keep normal body weight and body composition in adults with PWS. These measures might be useful in monitoring effects of intervention.