Obese Veterans Enrolled in a Veterans Affairs Medical Center Outpatient Weight Loss Clinic Are Likely to Experience Disordered Sleep and Posttraumatic Stress.

STUDY OBJECTIVES: This cross-sectional study aimed to characterize sleep patterns, the quality and duration of sleep, and estimate the prevalence of common sleep disorders and posttraumatic stress disorder (PTSD) in a hospital-based Veterans Affairs MOVE! (Managing Overweight Veterans Everywhere) clinic. METHODS: Participants completed five instruments: the Pittsburgh Sleep Quality Index (PSQI), Smith's Measure of Morningness/Eveningness, Restless Legs Syndrome Rating Scale, the STOP Questionnaire, and the Posttraumatic Stress Disorder (PTSD) Checklist - Civilian Version (PCL-C). RESULTS: Enrolled Veterans (n = 96) were mostly male (78%), African American (49%), mean age 58 (standard deviation [SD] 10.6) years, and mean body mass index (BMI) 38.4 kg/m(2) (SD 8.4). By PSQI, 89% rated sleep quality as "poor" (mean = 11.1, SD = 5.1), consistent with severely impaired sleep. Most were at high risk for sleep disorders including restless leg syndrome (53%), obstructive sleep apnea (66%), and circadian sleep disorders (72%). Forty-seven percent endorsed clinically significant symptoms of PTSD. Hypotheses-generating regression models suggest sleep latency (minutes before falling asleep) was associated with BMI (p = 0.018). Bedtime, getting up time, hours of sleep, waking up in the middle of the night or early morning, having to get up to use the bathroom, inability to breathe comfortably, cough or snore loudly, feeling too cold or too hot, having bad dreams, pain, and frequency of having trouble sleeping, were not significantly associated with BMI. CONCLUSIONS: Our cross-sectional study suggests that sleep difficulties are common among Veterans referred to a weight loss program at a Veterans Affairs Hospital. Controlled studies are needed to investigate whether the results are generalizable and whether obesity among veterans is a risk factor for sleep disorders and PTSD. COMMENTARY: A commentary on this article appears in this issue on page 943.

Comparison of different metabolic syndrome definitions and risks of incident cardiovascular events in the elderly.

The metabolic syndrome is associated with increased cardiovascular risk, and its prevalence increases with age. Various definitions of the metabolic syndrome exist, but whether some definitions are more predictive of future cardiovascular events in the elderly is unclear. We compared the risk of incident cardiovascular events in elderly individuals at least 65 years old from the Cardiovascular Health Study with and without the metabolic syndrome as defined by the European Group for the Study of Insulin Resistance (EGIR), National Cholesterol Education Program (NCEP)/American Heart Association (AHA), American Association of Clinical Endocrinologists, International Diabetes Federation (IDF), and modified World Health Organization (WHO) criteria (n = 3390). Participants were without baseline diabetes or cardiovascular disease. Except for EGIR, all definitions of the metabolic syndrome were significantly associated with increased risk of incident cardiovascular (coronary or cerebrovascular) events. Adjusted hazard ratios (HRs) for risk of incident cardiovascular events as defined by the modified WHO, NCEP/AHA, American Association of Clinical Endocrinologists, and IDF criteria ranged from 1.153 (P = .045) for NCEP/AHA to 1.314 (P < .001) for IDF, with 95% confidence interval (CI) ranging from 1.003 to 1.503. Adjusted HR for EGIR was 1.087 (95% CI, 0.908-1.301; P = .362). Similarly, all definitions of the metabolic syndrome were significantly associated with incident coronary events except for the EGIR definition. Only the modified WHO definition was associated with increased risk for cerebrovascular events (adjusted HR, 1.301; 95% CI, 1.038-1.631; P = .022). Although all metabolic syndrome definitions except EGIR were associated with total cardiovascular events and coronary events, only the modified WHO definition was also associated with risk of cerebrovascular events.

Depression, stress, and heart disease in earthquakes and Takotsubo cardiomyopathy.

The preponderance of evidence links depressive disorder and coronary heart disease (CHD). Despite this evidence, multiple clinical trials have failed to show that effective treatment of depression favorably modifies the development, clinical course, or outcome of comorbid CHD. Possible reasons for these failures include the heterogeneity of depression, limitations of assessment instruments, limited understanding of the biology of depressive disorders, lack of biological markers, and the observation that depression may be more a product of CHD than a true risk factor for it. In this commentary, to better address the effects of externally provoked stress on physical health, we examine evidence about 2 specific examples of stress and subsequent heart disease: earthquake-induced adverse cardiac events among individuals with coronary artery disease, and stress-induced Takotsubo cardiomyopathy. In the former case, existing studies suggest that the stress and distress of earthquakes accelerate the development of poor cardiac outcomes for individuals with established coronary artery disease. In the latter example, existing case studies indicate that the profound left ventricular dysfunction of Takotsubo cardiomyopathy tends to quickly normalize once the acute stress is relieved. Together, these examples indicate that the presence or absence of prestress medical illness and its severity may better determine the outcome of the medical illness than the nature and severity of the stress, including depression. That is, any effort to look at depression among individuals with medical illness must look carefully at the medical illness itself and consider depression a possible nonspecific stress. In patients with comorbid depression and CHD, we propose using the more firmly established CHD outcome measurements to better understand how depression or other stressors and their associated treatments influence the prognosis and outcome of this medical illness.

Psychotropic drug considerations in depressed patients with metabolic disturbances.

Depression, obesity, diabetes mellitus, and the metabolic syndrome are conditions commonly treated in primary care. The prevalence of each condition separately does not explain the frequency of their co-occurrence. Depression may lead to or exacerbate these endocrine and metabolic conditions. Conversely, these medical conditions may lead to or exacerbate depression. Psychotropic drugs that treat depression may increase appetite with resultant weight gain. Rarely, such agents may be associated with weight loss. We review the potential for psychotropic drugs to alter body weight and provide a table as a guide to drug selection. Unless circumstances dictate otherwise, clinicians should select psychotropic drugs least likely to induce weight gain when treating depressed patients with obesity, diabetes mellitus, or the metabolic syndrome. Even drugs generally thought to be "weight neutral" may occasionally be associated with weight gain. Thus, alerting patients to this potential and due diligence form the cornerstone of weight management in the depressed patient.

Effect of macronutrient composition on postprandial peptide YY levels.

BACKGROUND: Peptide YY (PYY) is released from the distal small intestine and colon after meals and reduces appetite by increasing satiety. The amount of PYY released is proportional to calories ingested. Fat ingestion has also been reported to stimulate PYY release. OBJECTIVE: The objective of the study was to determine whether macronutrient composition influences postprandial serum PYY levels by comparing 1 wk of a weight-maintenance low-carbohydrate, high-fat (LCHF) diet with a low-fat, high-carbohydrate (LFHC) diet. METHODS: In this randomized crossover study, 18 obese subjects (14 females, 4 males, mean body mass index 35.6 +/- 2.9 kg/m(2)) were randomly assigned initially to 1 wk of a weight-maintenance LCHF or LFHC diet, after which a test meal of identical composition was given and serum PYY levels were assessed for 2.5 h postprandially. After a 1-wk washout period, subjects were crossed over and retested. RESULTS: After 1 wk, mean postprandial area under the curve PYY after the LCHF test meal was 1.5-fold greater than after the LFHC test meal (P < 0.001). The LCHF diet led to 55% higher levels of postprandial serum PYY levels, compared with the LFHC diet (P = 0.005). CONCLUSIONS: These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals.

Safety of an immune-enhancing nutrition supplement in cirrhotic patients with history of encephalopathy.

Malnutrition in advanced cirrhosis may worsen liver function and increase susceptibility to infections. Immune-enhancing nutrition supplements (IENS) may be of value, but their safety in patients with decompensated cirrhosis and history of encephalopathy is unknown. We assessed the safety of Impact Recover (Novartis, St. Louis Park, MN), an orally palatable IENS, in 12 men with hepatic cirrhosis of Child-Turcotte-Pugh (CTP) class B or C, ages 40-60. On day 0, patients were evaluated serially for 6 hours after ingestion of 2 packets of Impact Recover. Despite a transient doubling of the blood ammonia, no cognitive abnormalities were noted on clinical assessment or psychometric testing. Subsequently, patients were instructed to ingest 3 packets per day of Impact Recover for 56 days, after which supplements were stopped. Patients were evaluated in a fasting state on days 0 (baseline), 56 (end of treatment), and 112 (follow-up). One patient was transplanted on day 21, and another died after an urgent cholecystectomy on day 30. The remaining 10 patients completed the study. Mean value of CTP score was 9 (range, 7-11) and mean value of model for end-stage liver disease (MELD) score was 14 (7-21), and there was no change after 8 weeks of IENS. Only 1 experienced transient worsening of encephalopathy after omitting lactulose. Performances on psychometric tests did not change. Transferrin levels increased rapidly with IENS, then returned toward baseline after IENS was stopped. Fasting insulin and peptide YY (PYY) levels also increased, but fasting glucose and hemoglobin A1C did not change. Trends in other nutrition and immune parameters did not reach significance. We conclude that acute and chronic administration of Impact Recover was well tolerated in cirrhotic patients with controlled encephalopathy. Further studies are justified to assess potential efficacy of long-term IENS in preventing infection and slowing progression in advanced cirrhosis.

Plasma hyperosmolality stimulates leptin secretion acutely by a vasopressin-adrenal mechanism.

Glucose administration to rodents acutely stimulates leptin secretion. To investigate the mechanism, rats were infused intravenously with various concentrations of glucose, and plasma leptin concentrations were measured with time. The osmolality of the infusates was equalized with various concentrations of carbohydrates that are not metabolized. Hyperosmolar glucose stimulates leptin secretion in a dose-dependent manner, with peak plasma leptin concentrations occurring approximately 3 h after the end of the glucose infusion. Hypertonic infusions of galactose, mannitol, and sodium chloride independently stimulate leptin secretion with approximately one-half the strength of equivalent osmolar concentrations of glucose. Peak plasma leptin concentrations occur approximately 4 h after the end of the hypertonic solution infusion. Hypertonic solutions of mannitol do not stimulate leptin secretion in vasopressin-deficient or in adrenalectomized animals. In conclusion, intravenous infusions of hypertonic glucose and hypertonic mannitol independently stimulate leptin secretion. Hyperosmolality stimulates leptin secretion by a vasopressin-adrenal mechanism.

Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans.

Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects. (2)H(2)O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-(2)H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 +/- 47.4 to 939.3 +/- 61.3 micromol/l, P < 0.01) and safflower oil (588.2.0 +/- 43.0 to 857.8 +/- 68.7 micromol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 +/- 1.8 vs. 11.2 +/- 1.0 micromol x kg FFM(-1) x min(-1)). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 +/- 50.7 vs. 377.8 +/- 38.0 micromol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 +/- 1.4 vs. 6.5 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism.

Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats.

Dietary fatty acid composition modifies hepatic lipid metabolism. To determine the effects of fatty acids on hepatic triglyceride storage, rats were fed diets enriched in carbohydrates (control), fish oil, or lard. After 4 weeks, the animals were fasted overnight. In the morning, the animals were either sacrificed or fed 8 g of their respective diets before sacrifice. Animals ingested more food calories with diets containing fish oil than with other diets. However, fish oil-fed animals weighed less and had less body fat. In fish oil-fed animals, liver triglyceride was lower by 27% (P <.05) and 73% (P <.01) than in control- and lard-fed animals, respectively. Fish oil altered the postprandial gene expression of hepatic regulators of fatty acid degradation and synthesis. Fish oil feeding blunted the normal postprandial decline in fatty acid degradation genes (PPARalpha, CPT1, and ACO) and blunted the normal postprandial rise in triglyceride synthesis genes (SREBP1-c, FAS, SCD-1). Therefore, the direct postprandial effect of fish oil ingestion decreases the propensity for hepatic triglyceride storage. In conclusion, n-3 polyunsaturated fatty acids decrease total body weight, total body fat, and hepatic steatosis.

An unusual cause of autonomic dysreflexia: pheochromocytoma in an individual with tetraplegia.

BACKGROUND: Autonomic dysreflexia (AD) is a frequent, serious acute syndrome that occurs in patients with spinal cord lesions at level T6 and above. The syndrome is caused by massive sympathetic discharge that is triggered by a noxious stimulus below the level of the spinal cord lesion. Pheochromocytomas are rare tumors that present with symptoms similar to AD. METHODS: Case Report. FINDINGS: A 50-year-old man with C7 American Spinal Injury Association scale A tetraplegia presented with episodes of severe headaches and paroxysmal hypertension. He was diagnosed with AD. Despite resolving bladder and bowel problems, he continued to have hypertensive episodes. A CT scan of the abdomen revealed a heterogeneous left adrenal mass. Further workup revealed significantly elevated serum and 24-hour urinary catecholamines. Clonidine failed to fully suppress the markedly elevated concentrations of serum catecholamines. These biochemical findings were consistent with the diagnosis of pheochromocytoma. Prior to surgery, the patient was treated with alpha-receptor blockers and volume expansion with intravenous fluids. A left adrenalectomy was performed. The surgical specimen revealed that the adrenal gland was expanded by a spherical mass. The pathologic report was benign pheochromocytoma of the left adrenal gland. CONCLUSION: Clinical symptoms and hypertensive episodes resolved following adrenalectomy. To our knowledge, this is the first reported case of a pheochromocytoma in an individual with spinal cord injury.

Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats.

The interrelationship between insulin and leptin resistance in young Fischer 344 (F344) rats was studied. Young F344 and Sprague-Dawley (SD) rats were fed regular chow. F344 animals had two- to threefold higher insulin and triglyceride concentrations and increased stores of triglycerides within liver and muscle. F344 animals gained more body fat. Both acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I gene expression were 20-50% less in F344 animals than in age-matched SD animals. Peroxisome proliferator-activated receptor-alpha gene expression was reduced in 70-day-old F344 animals. Finally, resistin gene expression was similar in 70-day-old SD and F344 animals. Resistin gene expression increased fivefold in F344 animals and twofold in SD animals from 70 to 130 days, without a change in insulin sensitivity. We conclude that young F344 animals have both insulin and leptin resistance, which may lead to diminished fatty oxidation and accumulation of triglycerides in insulin-sensitive target tissues. We did not detect a role for resistin in the etiology of insulin resistance in F344 animals.