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71.
Koren D Levitt Katz LE Brar PC Gallagher PR Berkowitz RI Brooks LJ 《Diabetes care》2011,34(11):2442-2447
OBJECTIVE
Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis.RESEARCH DESIGN AND METHODS
This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A1c (HbA1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables.RESULTS
We found significant U-shaped (quadratic) associations between sleep duration and both HbA1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures.CONCLUSIONS
Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents.Sleep deprivation is endemic; 9.3% of U.S. adults sleep <6 h per night (1), and 75% of high-school seniors report getting insufficient sleep (2). This cumulative societal sleep curtailment is significant, as sleep deprivation is associated with a number of metabolic consequences: increased predisposition to obesity (3) and insulin resistance (IR) (4) in both adults and children, increased risk of type 2 diabetes mellitus (T2DM) in adults (5), and higher fasting glucose in young adults with preexisting diabetes (6). The metabolic consequences of insufficient sleep may be the result of a lack of total sleep or insufficiency of a certain sleep component. The American Academy of Sleep Medicine recognizes four different sleep stages indicated as follows: stage 1 (N1), a brief transition between wake and sleep; stage 2 (N2); stage 3 (N3), “slow-wave” or “deep” sleep; and rapid eye movement (REM) (dream) sleep. In adult studies, cerebral glucose utilization declines (7) and plasma glucose rises (8) in N3 sleep. One pediatric study found a negative association between REM sleep duration and obesity (9), but there is little pediatric data on sleep architecture and glucose and insulin homeostasis. A potential confounding factor is obstructive sleep apnea (OSA), a syndrome more common in obesity in which upper airway obstruction leads to sleep fragmentation and desaturation (10). OSA has been associated with T2DM risk in adults (10) and with IR in children (11,12). We hypothesized that in obese adolescents (who are at risk for T2DM), altered sleep architecture is associated with abnormalities of insulin secretion and sensitivity and of glucose homeostasis independently of confounding factors (e.g., degree of obesity, presence of OSA, sex, and pubertal stage). Therefore, the aim of our study was to investigate the relationship between sleep architecture and insulin secretion and sensitivity and overall glycemia in this population. 相似文献72.
N-nitrosopyrrolidine (NPYR) is an important carcinogen, frequently present in the environment and food chain. Oral administration of NPYR to experimental rats evoked severe biochemical and pathological changes. In the present investigation, the protective role of dietary fibre on NPYR-induced toxicity in hypercholesterolemic rats was studied. Supplementation of chickpea seed coat fibre in the diet reduced the hepato-toxic effects of NPYR, as evident from the decreased hepatic degeneration and improved liver weight index compared to control. Administration of NPYR resulted in an increase in the osmotic fragility of erythrocytes in the experimental animals. The antioxidant potential of experimental animals decreased in the NPYR-fed group, which was evident from the increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NPYR. Administration of NPYR resulted in a substantial and significant increase in LPO in all tissues, to a varying degree, though the effect was maximum in the case of the liver. Inclusion of chickpea seed coat fibre considerably reduced the peroxidative damage caused by NPYR in all tissues. The effect of NPYR administration on antioxidant potential was variable in different tissues, but the effect was reduced considerably on inclusion of chickpea seed coat fibre in the diet, providing reasonable protection against NPYR-induced oxidative stress, and, hence, its toxicity. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups. However, the pathological effects of NPYR administration were markedly reduced with the addition of chickpea seed coat fibre in the diet. 相似文献
73.
Brar P Kwon GY Holleran S Bai D Tall AR Ramakrishnan R Green PH 《The American journal of medicine》2006,119(9):786-790
Purpose
Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease.Subjects and methods
We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids.Results
There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P = .06). The LDL/HDL ratio decreased by 0.36 ± 0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P = .02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy.Conclusions
Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio. 相似文献74.
75.
Chen A Brar B Choi CS Rousso D Vaughan J Kuperman Y Kim SN Donaldson C Smith SM Jamieson P Li C Nagy TR Shulman GI Lee KF Vale W 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(44):16580-16585
Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and is a major site of peripheral insulin resistance. Urocortin 2 (Ucn 2), a member of the corticotropin-releasing factor (CRF) family, and its cognate type 2 CRF receptor (CRFR2) are highly expressed in skeletal muscle. To determine the physiological role of Ucn 2, we generated mice that are deficient in this peptide. Using glucose-tolerance tests (GTTs), insulin-tolerance tests (ITTs), and hyperinsulinemic euglycemic glucose clamp studies, we demonstrated that mice lacking Ucn 2 exhibited increased insulin sensitivity and were protected against fat-induced insulin resistance. Administration of synthetic Ucn 2 to mutant mice before the GTTs and ITTs restored blood glucose to WT levels. Administration of a CRFR2 selective antagonist to WT mice resulted in a GTT profile that mirrored that of Ucn 2-null mice. Body composition measurements of Ucn 2-null mice on a high-fat diet demonstrated decreases in fat and increases in lean tissue compared with WT mice. We propose that null mutant mice display increased glucose uptake in skeletal muscle through the removal of Ucn 2-mediated inhibition of insulin signaling. In keeping with these data, Ucn 2 inhibited insulin-induced Akt and ERK1/2 phosphorylation in cultured skeletal muscle cells and C2C12 myotubes. These data are consistent with the hypothesis that Ucn 2 functions as a local negative regulator of glucose uptake in skeletal muscle and encourage exploration of the possibility that suppression of the Ucn 2/CRFR2 pathway may provide benefits in insulin-resistant states such as type 2 diabetes. 相似文献
76.
Gavin H. Harris Shiela M. Strauss Carina Katigbak Bhupinder S. Brar Lawrence S. Brown Jr. Steven S. Kipnis Steven A. Kritz Mark W. Parrino 《Journal of substance abuse treatment》2010
In view of their role in licensing opioid treatment programs (OTPs), state opioid treatment authorities (SOTAs) are in a unique position to influence how OTPs address their patients' alcohol abuse. Using data from a telephone survey of SOTAs from the District of Columbia and states that have at least one OTP (n = 46), this study examines the extent to which SOTAs address alcohol abuse in their respective state policies and guidelines for OTPs. Findings indicate that 27 states have overall measures on how to address patients' problematic alcohol use, 23 states require or recommend alcohol education to be provided to all patients, and 17 states have stipulations that address specific actions to be taken if patients present at daily dosing under the influence of alcohol. Although SOTAs generally rate alcohol of at least moderate importance in formulating regulations, many of their policies and guidelines do not deal with various alcohol-related services and issues. 相似文献
77.
In the present investigation, the behavioral, morphological, and histopathological effects of cypermethrin, a widely used synthetic pyrethroid insecticide, was ascertained in male and female albino rats (Rattus norvegicus). Cypermethrin administered at repeated oral doses of 5 and 20 mg/kg/day for 30 days produced varying degree of mild to moderate toxic symptoms and behavioral changes in both male and female rats. The lower dose produced very mild toxicosis characterized by intermittent diarrhea, decreased feed intake, and thick eye discharge, whereas higher dose displayed mild to moderate toxicosis with diarrhea, decreased feed intake, loss of body weight, dyspnoea, ataxia, eye discharge, and salivation. Two female and one male albino rats died between 23 to 28 days after displaying signs of incoordination and tremors. Repeated oral doses of cypermethrin for 30 days enhanced the relative weight of liver and heart, but significantly decreased that of brain, kidneys, and testes. Microscopically, cypermethrin produced neuronal degeneration and increase in glial cells in brain, and disorganization of hepatic laminae, increase in sinusoid, and necrosis of hepatocytes in liver. Section of kidney displayed hemorrhage and sloughing off renal epithelial cell in the convoluted tubules, shrinkage of glomeruli, and necrosis of renal tubules. Repeated administration of cypermethrin also produced hemorrhages within myocardium, disruption of branching structure, and loss of striation of cardiac tissue; thickening of alveolar septa in lungs, partial to extensive loss of various stages of spermatogenesis in testes, and loss of follicular cells and oocytes in ovaries. The study suggested that repeated oral exposure of cypermethrin has considerable harmful effects on body organs in R. norvegicus. 相似文献
78.
Background
Hyponatremia is frequently detected as a cause in patients admitted to command Hospital Kolkata with altered sensorium. We evaluated these patients to rule out two common endocrine causes as etiological factors i.e. hypothyroidism and hypoadrenalism.Method
We studied 100 patients over a period of two years in all seasons who were admitted to hospital with altered sensorium and found to have hyponatremia as a cause, after ruling out other causes of altered sensorium as per inclusion and exclusion criteria. They were subjected to thyroid and adrenal evaluation in addition to detailed history, clinical examination and lab evaluation as per study protocol.Results
Total 100 patients were enrolled in the study. The age of patients varied from 31 years to more than 70 years. Majority of patients were between the age group of 41–60 years (49 patients. Males were predominant in the study. Only 8 patients were detected to have hypothyroidism requiring replacement therapy and only 2 patients had adrenal insufficiency. 48 patients had drug induced hyponatremia and 42 idiopathic hyponatremia. No seasonal variation was noted.Conclusion
Thiazide diuretic intake as antihypertensive drug was found to be a major cause of hyponatremia. Most of the patients in this group were using thiazide diuretics. In idiopathic group the cause of hyponatremia can be hypothesized as multifactorial. The hot and humid climate of Kolkata and other coastal regions made them more vulnerable to develop hyponatremia. Hypothyroidism and hypoadrenalism were not found to be major causes of unexplained hyponatremia. 相似文献79.
80.