Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women

The endogenous nitric oxide-synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is elevated in patients with increased risk for arteriosclerosis. Obesity is a risk factor for cardiovascular disease. We measured plasma ADMA concentrations in morbidly obese women before and after weight loss following gastroplastic surgery. ADMA and symmetrical dimethyl-L-arginine concentrations were analyzed by HPLC from 34 female patients (age 41 +/- 7 yr) with a body mass index (BMI) of 49 +/- 1 kg/m2 before and 14 months after vertical ring gastroplasty. Age-matched healthy women (BMI < 25 kg/m2; n = 24) were studied as controls. After gastroplastic surgery, BMI decreased to 34 +/- 1 kg/m2 in obese women (P < 0.00001), and ADMA concentrations were reduced from 1.06 +/- 0.06 micromol/liter at baseline to 0.81 +/- 0.04 micromol/liter after weight loss (P < 0.00001). Symmetrical dimethyl-L-arginine plasma levels were not affected. ADMA correlated with high-sensitivity C-reactive protein at baseline (r = 0.42; P < 0.05) and after weight loss (r = 0.56; P < 0.005). No association with blood pressure or plasma lipids could be observed. ADMA concentrations were lower in controls (0.68 +/- 0.04 micromol/liter; P < 0.05) compared with obese patients before or after weight reduction. The decrease of highly elevated ADMA concentrations in morbidly obese patients is paralleled by improvement of parameters associated with the metabolic syndrome after weight loss.     

Elevated production and metabolic clearance rates of androgens in morbidly obese women

Blood production rates of testosterone, dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-diol) were found to be approximately 2-fold elevated in morbidly obese, nonhirsute, normally menstruating women. Values were intermediate between those found in normal women and those in a group of nonobese normally menstruating women with idiopathic hirsutism. Elevated androgen production rates in obese women were associated with 2- to 3-fold increases in MCRs, presumably due to decreased levels of sex hormone-binding globulin. Thus, increased production rates were offset by increased MCRs, resulting in plasma testosterone, DHT, and 3 alpha-diol concentrations that were similar in the obese and normal women. By contrast, women with hirsutism had increased production rates associated with elevated plasma androgens as well as increased MCRs. Urinary excretion of testosterone glucuronide and 3 alpha-diol glucuronide (3 alpha-diol G) were elevated in both obese and hirsute women, paralleling the increased androgen production rates. Despite increased production rates and excretion of androgens, obese women exhibited no menstrual abnormalities, hirsutism, or other signs of virilism. To explore the apparent ineffectiveness of increased androgen production to produce virilizing symptoms, we measured plasma 3 alpha-diol G levels as a measure of peripheral androgen action. The mean +/- SE plasma 3 alpha-diol G was 53 +/- 8 ng/dl in obese women and 36 +/- 6 in normal women; by contrast, women with idiopathic hirsutism had levels of 440 +/- 99, a 12-fold elevation. Plasma testosterone glucuronide in obese and hirsute women were only 2- to 3-fold elevated, while plasma DHT glucuronide was not increased in obese women and was only 2-fold elevated in hirsute women. Thus, obesity is a state of increased androgen production and accelerated clearance. 3 alpha-diol G levels in obese women were only minimally elevated, in contrast to values in the hirsute women, perhaps reflecting the apparent androgen ineffectiveness.     

Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.     

Prevalence and severity of sleep disordered breathing in a group of morbidly obese patients.

BACKGROUND: Obesity may be complicated by sleep disordered breathing (SDB). The presence of SDB is associated with increased morbidity and mortality. Patient characteristics, pulmonary function tests and daytime arterial blood gas analyses may help to identify patients with SDB. These variables and the prevalence and severity of sleep disordered breathing were studied in a group morbidly obese patients. METHODS: Forty-eight patients, 19 men and 29 women who were referred to our clinic of internal medicine because of their obesity were included. Characteristics, pulmonary function tests and daytime arterial blood gas analyses of groups with different grades of SDB were compared. RESULTS: Male subjects had significantly more apnoeas/hypopnoeas per hour (AHI) (18.4 +/- 20.9 versus 4.8 +/- 9.4) with more desaturation, a lower mean saturation (92.6 +/- 4.1 versus 96.1 +/- 1.6) and a lower saturation nadir (73.8 +/- 12.0 versus 83.1 +/- 6.7). Five (26%) of the male subjects and none of the female subjects had severe SDB (AHI > or = 25). Subjects were divided into three groups according to the severity of their SDB: twenty-nine subjects (23 women and 6 men) with AHI < 5, 14 subjects (6 women and 8 men) with AHI > or = 5 and < 25 and 5 subjects, all men, with AHI > or = 25. Except for gender no significant differences were found between the three groups. CONCLUSION: Our study confirms the findings that morbidity obese men have SDB more frequently and more severely than obese women. Patient characteristics other than gender, pulmonary function tests and daytime blood gas analyses have no predictive value.     

Prevalence and associated factors of obstructive sleep apnea in morbidly obese patients undergoing bariatric surgery

Sleep and Breathing - Our goal in this study is to determine the prevalence and associated factors of obstructive sleep apnea (OSA) in morbidly obese patients undergoing bariatric surgery. This...     

Thromboxane production in morbidly obese subjects

Postmortem studies have demonstrated that morbidly obese subjects, surprisingly, have less coronary atherosclerosis than obese subjects. However, the reasons for this apparent protection from atherosclerosis are not yet clear. Thromboxane A2, a marker of platelet activation, is greater in obese subjects than in lean subjects, and this might be a clue to their increased cardiovascular risk. However, data on thromboxane A2 in morbidly obese subjects are lacking; therefore, we hypothesized that lower levels of thromboxane A2 in morbidly obese subjects might play a role in their lower atherothrombotic burden. We measured the serum levels of thromboxane B2 (TxB2), a stable metabolite of thromboxane A2, high-sensitivity C-reactive protein (hs-CRP) and leptin in 17 lean subjects (body mass index [BMI] 22.9 ± 1.6 kg/m(2)), 25 obese subjects (BMI 32.6 ± 2.4 kg/m(2)), and 23 morbidly obese subjects (BMI 48.6 ± 7.1 kg/m(2)), without insulin resistance, diabetes, or overt cardiovascular disease. The serum TxB2 levels were lower in the lean subjects than in the obese subjects (p = 0.046) and in the morbidly obese subjects than in the lean and obese subjects (p = 0.015 and p <0.001, respectively). In contrast, the hs-CRP and leptin levels were greater in the obese than in the lean subjects (hs-CRP, p <0.001; leptin, p <0.001) and in the morbidly obese subjects than in the lean subjects (p <0.001 for both). Leptin was also higher in the morbidly obese subjects than in the obese subjects (p <0.001). TxB2 negatively correlated with leptin and BMI. hs-CRP correlated with leptin, and both also correlated with waist circumference, BMI, and homeostasis model assessment of insulin-resistance. In conclusion, insulin-sensitive morbidly obese subjects had lower levels of TxB2 than the obese subjects and lean subjects, suggesting that reduced platelet activation could play a role in the paradoxical protection of morbidly obese subjects from atherosclerosis, despite the greater levels of leptin.     

Thrombolytic therapy in morbidly obese patients

Most of the concern about dosing thrombolytic agents as presented in the literature is related to the lower weight groups and the increased incidence of bleeding in this patient population. Not much is known or written about what dose of thrombolytic therapy should be used in the grossly obese patient with an AMI. Although it may be uncommon to have a morbidly obese patient with an AMI, it does occur. Perhaps body weight doesn't matter since we are really dosing the clot and not the body, but, as far as I can discern, there are no data regarding dosing of thrombolytic drugs to guide the clinician managing these patients.     

SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women

Background and aims. Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity-related complications in the mouse model. To date, SFRP5 expression in non-alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women.Material and methods. Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral).Results. Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006). Conclusion. This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans.     

Psychiatric evaluation of morbidly obese patients

Psychiatric consultation should be integral to the overall evaluation of morbidly obese patients prior to any treatment but particularly before surgery. In addition to clarifying the presence or absence of diagnosable psychiatric illness, which then may affect the decision to proceed to surgery, psychiatric consultation can elicit data on psychological disturbances that are neurotic or indicative of a personality disorder or trait that may affect treatment. Important developmental and life history data contribute to an understanding of the patient and the role of eating behavior in the patient's life, which in turn aids the entire treatment team in establishing a more effective and mutually cooperative approach to treatment.     

Impact of insulin resistance on lipoprotein subpopulation distribution in lean and morbidly obese nondiabetic women

The purpose of this study was to examine the effects of insulin resistance on the lipoprotein subpopulation distribution of very-low-density, low-density, and high-density lipoproteins (VLDL, LDL, and HDL) in lean and morbidly obese nondiabetic women. Lean women (body mass index [BMI], 20 to 27 kg/m2) stratified by BMI were divided into insulin-sensitive (SL, n = 12) and insulin-resistant (RL, n = 8) groups according to Bergman's minimal model, SI. A group of obese women (BMI, 30 to 53 kg/m2), also stratified by BMI, were divided into insulin-sensitive (SO, n = 10) and insulin-resistant (RO, n = 11) groups in a similar fashion. Resistant groups were similar to sensitive groups (SL v RL and SO vRO) in age, weight, percent body fat, and waist circumference, ie, total and regional adiposity. VLDL, LDL, and HDL subpopulation distributions were determined in fasting plasma samples by nuclear magnetic resonance (NMR) spectroscopy. The average particle sizes of all 3 classes of lipoproteins were similar for the SL and RL groups. In contrast, RO subjects had larger VLDL, smaller LDL, and smaller HDL, than SO subjects (P < .05). Lower concentrations of large LDL and large HDL were found in RO compared with SO subjects (P < .05). In obese women, but not in lean women, VLDL size was associated with plasma insulin (r = .60, P < .005), while LDL size and HDL size were negatively correlated with plasma insulin (r = -.39, P < .05 and r = -.38, P < .05) and positively correlated with SI (r = .54, P < .01 and r = .42, P < .05). These results suggest that in obese women, insulin resistance may be involved in the formation of lipoprotein subpopulation distributions that are associated with vascular disease.     

Effect of a satiating meal on the concentrations of procolipase propeptide in the serum and urine of normal and morbidly obese subjects.

The effect of a satiating meal on the serum and urinary concentrations of procolipase propeptide (Ala-Pro-Gly-Pro-Arg, APGPR) immunoreactivity, as measured by enzyme linked immunosorbent assay (ELISA) specific for free APGPR, has been studied in normal and morbidly obese human subjects. The normal subjects displayed a biphasic response with coordinate increases in both serum and urine APGPR immunoreactivity both occurring within the first two hours after the meal. In two of three of the morbidly obese subjects, this early rise in APGPR concentration in urine was not seen but was followed by a slow rise in urinary APGPR immunoreactivity at four to six hours. In both the normal and obese groups, the urinary immunoreactive signal was found to coelute with synthetic APGPR on gel chromatography. In rats, procolipase propeptide (Val-Pro-Asp-Pro-Arg, VPDPR) specifically inhibits fat intake early in the postprandial period when given peripherally or centrally. This study suggests that in humans APGPR reaches the circulation shortly after feeding and is excreted in the urine. These findings are consistent with the hypothesis that human procolipase propeptide may also act as a satiety signal. In addition the late appearance of the peptide in some of the morbidly obese patients could be associated with perturbation of appetite control in these subjects.     

Steatohepatic cirrhosis in a morbidly obese patient

Sixty to ninety percent of obese subjects show histological abnormalities of the liver. The hepatic lesion can be classified into one of the four following groups: steatosis, steatohepatitis, fibrosis and cirrhosis. The incidence of cirrhosis among patients with fatty liver changes ranges from 1.5% to 8%. The now abandoned surgery procedures performed for the treatment of morbid obesity (jejunoileal bypass) had left a negative experience: the onset of acute hepatic failure in subjects with no previous hepatic disease or the development of cirrhosis within one year of the bypass. Very low formula diets leading to precipitous weight loss in morbidly obese people induce metabolic changes similar to those observed after jejunoileal bypass. We report the case of a morbidly obese patient who had lost 40 kg of weight during the 6 months previous to his hospitalization. He came with signs of hepatic failure. He worsened rapidly and died in a month-time. The hepatic tissue obtained post-mortem showed a non alcoholic steatohepatitic cirrhosis.     

Abdominal wall cellulitis in the morbidly obese

Currently, almost two-thirds of the US population is either overweight or obese. In addition to non-infectious complications, obesity predisposes to infections, including lower extremity cellulitis. Although cases of abdominal wall cellulitis in the morbidly obese occur, to date there has been no formal address of this syndrome in the literature. We therefore reviewed our clinical experience of abdominal wall cellulitis complicating morbid obesity. A retrospective database search was performed to identify patients with both cellulitis and morbid obesity who were seen at the Mayo Clinic between January 1998 and August 2003. Clinical and microbiologic data were collected for these patients. Of the 260 cases of cellulitis identified, 24 (9.2%) had morbid obesity and abdominal wall cellulitis. The mean age of the 24 patients was 47 (range 22-70) y and over two-thirds of them were females. Their mean body mass index (BMI) was 62.3 (range 39.6-108.6). 17 (70.8%) had a remote history of abdominal surgery. 16 patients required 23 hospitalizations. Five patients developed cellulitis complications and 7 (29.1%) patients had recurrent bouts of cellulitis during the study period. Abdominal wall cellulitis is a unique infectious complication in patients with morbid obesity. Further study is needed to better define the pathogenesis of this illness to develop strategies in treatment and prevention.