Hyperinsulinemia and insulin resistance are commonly observed in essential hypertension, which is part of the metabolic syndrome. The aim of this study was to examine whether insulin secretion ...abnormalities or alterations in insulin sensitivity and glucose tolerance are also present in healthy men, offspring of patients with essential hypertension. Twelve young (27 ± 3.6 years), lean normotensive offspring were compared with 14 age-, sex-, and body mass index (BMI)-matched controls without a family history of hypertension, diabetes mellitus, and coronary heart disease. We studied glucose tolerance, insulin secretion, and sensitivity using 10-hour hyperglycemic and 10-hour hyperinsulinemic-euglycemic clamps (HIC). Glucose tolerance was comparable in the offspring and controls. However, the offspring had higher insulin and C-peptide levels during the hyperglycemic clamp (HGC) compared with controls (
P < .05). There was no difference in the early phase of insulin secretion between the groups. The insulin sensitivity index (glucose infusion rate/serum insulin) was significantly lower in the offspring during both clamps. Moreover, the offspring had higher systolic (
P < .001) and diastolic (
P < .001) blood pressure and had higher serum cholesterol (
P < .01) and triglyceride (
P < .05) levels. Apparently healthy, young, lean individuals with a genetic predisposition to essential hypertension and with normal glucose tolerance had higher insulin secretion and lower insulin sensitivity than controls. These abnormalities, together with higher blood pressure and altered lipid metabolism, may play a role in the development of hypertension and an increased risk of cardiovascular morbidity and mortality in these individuals.
Abstract Objective The aim of the study is to compare the course and severity of narcolepsy in relation to different ages at the disease onset. Methods Clinical interviews with the completion of the ...Stanford questionnaire, Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT) were evaluated in 105 patients (44 males, 61 females, mean age 45.4 ± 19.2, BMI 29.2 ± 5.8) suffering from narcolepsy. Results The severity of the disease was judged by clinical complaints, ESS value and MSLT results. No relations with the age at onset and clinical tetrad were found, however, smoking may be associated with an increased risk of hypnagogic hallucinations. There was no correlation between the number of sleep and cataplectic attacks and the age at onset, nor did subjective ESS show any significant dependence. However, earlier onset of the disease correlated with shorter MSLT mean latency. A correlation was found between the BMI and narcolepsy sleepiness rating in the elderly and between degree of education attained and subjective complaints. Conclusions The clinical severity of narcolepsy does not depend on the age at onset.
Introduction. The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic ...metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the production of proinflammatory and profibrotic factors secreted from adipose tissue, which can in turn directly impair kidney cells and potentiate insulin resistance. In this study, we investigated the manifestation of renal lipid accumulation and its effect on renal dysfunction in a model of metabolic syndrome—the hereditary hypertriglyceridemic rat (HHTg)—by assessing microalbuminuria and targeted urinary proteomics. Male Wistar control rats and HHTg rats were fed a standard diet and observed over the course of ageing at 3, 12, and 20 months of age. Results. Chronically elevated levels of triglycerides in HHTg rats were associated with increased levels of NEFA during OGTT and over a period of 24 hours (+80%, P<0.01). HHTg animals exhibited qualitative changes in NEFA fatty acid composition, represented by an increased proportion of saturated fatty acids (P<0.05) and a decreased proportion of n-3 PUFA (P<0.01). Ectopic lipid deposition in the kidneys of HHTg rats—triglycerides (+30%) and cholesterol (+10%)—was associated with markedly elevated microalbuminuria as ageing increased, despite the absence of microalbuminuria at the young age of 3 months in these animals. According to targeted proteomic analysis, 3-month-old HHTg rats (in comparison to age-matched controls) exhibited increased urinary secretion of proinflammatory parameters (MCP-1, IL-6, IL-8, P<0.01) and decreased urinary secretion of epidermal growth factor (EGF, P<0.01) before manifestation of microalbuminuria. Elevation in the urinary secretion of inflammatory cytokines can be affected by increased relative expression of MCP-1 in the renal cortex (P<0.05). Conclusions. Our results confirm dyslipidemia and ectopic lipid accumulation to be key contributors in the development of metabolic syndrome-associated renal dysfunction. Assessing urinary secretion of proinflammatory cytokines and epidermal growth factor can help in detecting early development of metabolic syndrome-associated renal dysfunction.
Charcot's or neuropathic osteoarthropathy is one of the most debilitating orthopedic sequelae of diabetes mellitus. Distinguishing Charcot's neuroarthropathy from clinically similar conditions may be ...challenging. The neurovascular theory postulates that Charcot's neuroarthropathy may be secondary to sympathetic denervation of the lower-extremity vasculature. A convenient method for assessing autonomic neuropathy in patients with Charcot's neuroarthropathy is needed. Short-term power spectral analysis (PSA) of heart rate variability (HRV), a noninvasive and quantitative method for assessing autonomic neuropathy, may be advantageous compared with the traditionally used Ewing's cardiovascular reflex tests. However, there are limitations to the clinical use of PSA of HRV because of poor standardization. We standardized PSA of HRV and assessed autonomic neuropathy in 17 people with acute Charcot's neuroarthropathy using PSA of HRV versus Ewing's tests. More patients with Charcot's neuroarthropathy were diagnosed as having autonomic neuropathy with PSA of HRV than with Ewing's tests (94% versus 82%); however, no significant difference between the two methods was found. The results of this study suggest that PSA of HRV requires minimal patient collaboration and time expenditure compared with Ewing's tests and may be useful in detecting autonomic neuropathy in patients with Charcot's neuroarthropathy.
Sleep-related rhythmic movements (SRRMs) are common in young children and become less prevalent with increasing age. When SRRMs significantly interfere with sleep and/or affect daytime functioning, ...potentially resulting in injury, rhythmic movement disorder (SRRMD) is diagnosed.
The aim of our study was to assess clinical comorbidities, types of SRRMs, sleep stage/wakefulness distribution during night, and age-dependence of these parameters.
In sum, 45 patients (age range 1–26 years, mean age 10.56 ± 6.4 years, 29 men) were clinically examined for SRRMs or SRRMD. Nocturnal polysomnography (PSG) was recorded in 38 patients. To evaluate clinical and sleep comorbidity, the cohort of 38 patients was divided according to age into four groups: (1) younger than 5 years (N = 7), (2) 5–9 years (N = 12), (3) 10–14 years (N = 11), and (4) ≥ 15 years (N = 8).
A clear relationship between perinatal risk factors and developmental disorders (attention deficit hyperactivity disorder - ADHD, specific learning disability) was found which extended population prevalence at least five times. A total of 62 recordings were evaluated in 38 patients; SRRMs were found in PSG in 31 of 38 patients (82%). No age-dependent correlation between type of SRRMs and sleep stage/wakefulness distribution during the night was observed. However, when all recordings were correlated together, rolling stereotypes occurred more frequently in REM sleep, and rocking stereotypes in superficial NREM sleep.
Developmental disorders and perinatal risk factors were connected with SRRMs and SRRMD in children and young adults. Rolling movements were significantly associated with REM stage and rocking stereotypes with superficial NREM sleep, independent of age.
•Sleep-related rhythmic movements are frequently associated with perinatal risk factors and developmental disorders.•No correlation between rhythmic movements and sleep stages/wakefulness and/or dependence on their type was detected in different age groups.•A tendency toward rolling movements in REM sleep, and rocking movements in superficial NREM sleep was found.
The aim of the study was the comparison of a simple standardized noninvasive examination of neuropathy and angiopathy with routine diagnostic practice in community diabetes clinics for the ...identification of patients at risk of foot ulceration. Consecutive patients (
n=322), aged 30 years and more, with a diabetes duration of more than 5 years, were examined by trained podiatric nurses in six diabetes clinics over a 1-year period; 44 of these patients had active or previous foot ulcerations. We evaluated the differences between the routine diagnostic practice (based on the patient's medical history and a physical examination) and noninvasive testing of peripheral neuropathy vibration perception threshold (VPT) and the Semmes-Weinstein 10-g monofilament wire system and angiopathy Doppler ankle/brachial index (ABI). Using receiver operating characteristic (ROC) analysis, we evaluated the sensitivity and specificity of noninvasive testing methods for identifying patients at risk and selecting the optimal diagnostic cutoff points. Patients with severe neuropathy, as determined by noninvasive testing (VPT ≥30 V and/or insensitivity to 10 g monofilament), had been diagnosed to have neuropathy in diabetes clinics in 54% of cases. Patients with angiopathy at risk of developing diabetic foot ulcers (ABI ≤0.8) had been diagnosed, in diabetes clinics, to have peripheral arterial disease in 50% (they reported claudications in 41%, had femoral artery bruits detected in 29% and nonpalpable peripheral pulsations in 12%). Our findings stress the importance of using standardized simple noninvasive testing methods to increase the accuracy of identifying patients at risk for the diabetic foot at the community level.
SUMMARY
The best overall index of renal function is considered to be glomerular filtration rate (GFR) and the gold standard for its assessment is renal inulin clearance (Cin) Unfortunately, Cin ...cannot be routinely used in daily practice due to its complexity as a test. The most often used ones are the Cockcroft‐Gault (CG) formula and the recently developed Modification of Diet in Renal Disease (MDRD) prediction equation. Calculation of MDRD (estimated GFR) according to this formula is simple but it requires a computer program. The following table is prepared for parts of the world where the computer program is not available as yet.
It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper ...investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.
Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate ...whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful ( n = 61 ) and failed ( n = 98 ) islet isolations. Samples of donor pancreatic tissue ( n = 78 ) were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m2 ( P < 0.001 ), cold ischemia time more than 8 hours ( P < 0.01 ), hospitalization longer than 96 hours ( P < 0.05 ), higher catecholamine doses ( P < 0.05 ), and edematous pancreases ( P < 0.01 ) all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas ( P < 0.001 ). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation ( P < 0.001 ). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection.
BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%–80% of kidney transplant recipients resulting in BK ...virus-related nephropathy in 1%–10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n=11), infected asymptomatic patients (n=9), and patients with BK virus nephropathy (n=10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P<0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P<0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.
PDF
