Increased liver echogenicity and liver enzymes are associated with extreme obesity, adolescent age and male gender: analysis from the German/Austrian/Swiss obesity registry APV.

BACKGROUND: Childhood obesity is often associated with non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in pediatrics. METHODS: This multi-center study analyzed liver echogenicity and liver enzymes in relation to obesity, age, gender and comorbidities. Data were collected using a standardized documentation software (APV) from 1.033 pediatric patients (age: 4-18 years, body mass index = BMI: 28-36 kg/m2, 50% boys) with overweight (BMI >90th percentile), obesity (BMI >97th percentile) or extreme obesity (BMI > 99.5th percentile) and obesity related comorbidities, especially NAFLD from 26 centers of Germany, Austria and Switzerland. Liver enzymes aspartate aminotransferase (AST), alanine-aminotransferase (ALT) and gamma glutamyltransferase (gammaGT) were evaluated using 2 cut-off values a) > 25 U/L and b) > 50 U/L. Multiple logistic regression models were used for statistical analysis. RESULTS: In total, 44% of the patients showed increased liver echogenicity. Liver enzymes > 25 U/L were present in 64% and > 50 U/L in 17%. Increased liver echogenicity was associated with elevated liver enzymes (> 25 U/L: odds ratio (OR) = 1.4, 95% CI: 1.1-1.9, P < 0.02; > 50 U/L: OR = 3.5, 95% CI: 2.4-5.1, P < 0.0001). Extreme obesity, adolescence and male gender were associated with increased liver echogenicity (extreme obesity vs overweight OR = 3.5, 95% CI: 1.9-6.1, P < 0.0001; age > 14 years vs age < 9 years OR = 2.2, 95% CI: 1.4-3.5, P < 0.001; boys vs girls OR = 1.6, 95% CI: 1.2-2.0, P < 0.001) and elevated liver enzymes (extreme obesity vs overweight > 25 U/L: OR = 4.1, 95% CI: 2.4-6.9, P < 0.0001; > 50 U/L: OR = 18.5, 95% CI: 2.5-135, P < 0.0001; age > 14 years vs age < 9 years > 50 U/L: OR = 1.9, 95% CI: 1.0-3.7, P > 0.05; boys vs girls > 25 U/L: OR = 3.1, 95% CI: 2.4-4.1, P < 0.0001; > 50 U/L: OR = 2.1, 95% CI: 1.5-2.9, P < 0.0001). Impaired glucose metabolism showed a significant correlation with elevated liver enzymes > 50 U/L (OR = 4.4, 95% CI: 1.6-11.8, P < 0.005). Arterial hypertension seemed to occur in patients with elevated liver enzymes > 25 U/L (OR 1.6, 95% CI: 1.2-2.0, P < 0.005). CONCLUSIONS: NAFLD is strongly related to extreme obesity in male adolescents. Moreover impaired glucose tolerance was observed in patients with elevated liver enzymes > 50 U/L, but arterial hypertension was only present in patients with moderately elevated liver enzymes > 25 U/L.

Effect on Liver Enzymes of Biliopancreatic Diversion: 4 Years of Follow-Up.

BACKGROUND: Elevated serum aminotransferase levels are commonly associated with obesity and with a progression to chronic liver disease. Bariatric surgery is the most effective strategy to achieve weight loss. METHODS: We conducted the present study with the aim of evaluating the influence of biliopancreatic diversion (BPD) on liver enzymes levels during 4 years in morbid obese patients with normal aminotransferase (n = 65) and in morbid obese patients with high aminotransferase basal levels (n = 50). RESULTS: A decrease in alanine aminotransferase and aspartate aminotransferase activities was significant after biliopancreatic diversion. The basal percentage of high aminotransferase levels and percentage of ratio ALT/AST <1 also decreased significantly at 1-, 2-, 3- and 4-years of follow-up in both groups. ALT (52 to 20%), AST (42 to 10%) and ALT/AST (80 to 22%) in patients with normal aminotransferase. ALT (82 to 20%), AST (70 to 6%) and ALT/AST (90 to 20%) in patients with elevated transaminase basal levels. Bariatric surgery was associated with a significant and sustained decrease in body weight in both groups. Serum trasnaminases level changes were positively correlated to body weight changes during follow-up. CONCLUSION: BPD is an effective method of achieving sustainable weight loss and reduced aminotransferase levels and enzyme ratios of liver damage.

What distinguishes adipose tissue of severely obese humans who are insulin sensitive and resistant?

PURPOSE OF REVIEW: Despite a strong correlation between obesity and insulin resistance, 25% of severely obese (BMI >40) individuals are insulin sensitive. In this review, we will examine the factors in adipose tissue that distinguish the two groups, as well as reasons for believing the insulin-sensitive group will be less disease prone. RECENT FINDINGS: Obesity has been linked to the metabolic syndrome with an increase in visceral (intra-abdominal) compared to subcutaneous fat. Recent studies in which adipose tissue of insulin-sensitive and insulin-resistant patients with severe obesity were compared indicate that the insulin-resistant group is also distinguished by increases in oxidative stress and decreases in AMP-activated protein kinase (AMPK) activity. In contrast, changes in the expression of genes for SIRT1, inflammatory cytokines, mitochondrial biogenesis and function, and the two α-isoforms of AMPK showed more depot variation. Studies of how these and other changes in adipose tissue respond to bariatric surgery are still in their infancy. SUMMARY: Available data suggest that increases in oxidative stress, decreases in AMPK activity and SIRT1 gene expression, depot-specific changes in inflammatory, mitochondrial and other genes distinguish adipose tissue of insulin resistant from insulin-sensitive individuals with severe obesity.

Effects of laparoscopic Roux-en-Y gastric bypass on glucose-6 phosphate dehydrogenase activity in obese type 2 diabetics.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that provides the majority of NADPH required for lipid biosynthesis. G6PD overexpression has been implicated in insulin resistance, hyperlipidemia, and increased oxidative stress in animals. This study examines G6PD expression in obese diabetic and nondiabetic subjects pre- and post-laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Patients undergoing LRYGB were recruited for the IRB-approved study and placed in either the diabetic (n = 11) or nondiabetic group (n = 16) (diabetic, HbA1c > 6.5%; nondiabetic, HbA1c < 6.0%). Blood samples were collected at baseline and throughout the first 3 postoperative months. Liver, adipose, and omental samples were taken during surgery. Results are expressed as mean ± SEM and were compared statistically using the Mann-Whitney test. RESULTS: The two groups were not significantly different at baseline except for fasting glucose and HbA1c. G6PD activity (nm/min/mg protein) was significantly higher in red blood cells (RBCs) (3.12 ± 1.39 vs. 0.67 ± 0.14) and liver (17.23 ± 2.40 vs. 9.74 ± 2.18) in diabetics compared to nondiabetics. There was good correlation between increased liver G6PD activity and the severity of diabetes as measured by HbA1c (r (2) = 0.525) and fasting glucose (r (2) = 0.542). No significant difference was found in the adipose or omental G6PD expression. Both groups experienced a significant increase in G6PD blood activity shortly following surgery (1 week) followed by a reduction 3 months after surgery. CONCLUSION: These results are the first ever seen in human subjects and demonstrate increased G6PD activity in diabetics compared to nondiabetics. These results suggest a correlation between G6PD activity and the severity of type 2 diabetes. The early increases in G6PD activity after LRYGB were unexpected and longer follow-up is needed to determine the effects of LRYGB on G6PD activity.

Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects.

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

Gamma-glutamyl transferase is strongly associated with degree of overweight and sex.

Gamma-glutamyl transferase (GGT) is a marker for cardiovascular risk and an independent predictor of long-term outcome in adults. Epidemiological data from pediatric cohorts are rare. We studied the association of GGT to body mass index as a standard deviation score, sex, and age in 68,415 children (age 11.7 ± 4.4 years; 48% boys; body mass index 27.2 ± 7.4 kg/m2; GGT measured in n = 23,955). GGT >50 U/L is strongly associated with extreme obesity (odds ratio 27.13, 95% confidence interval 15.07-48.85) and male sex (odds ratio 2.60, 95% confidence interval 2.03-3.31). GGT seems to be of clinical relevance and may be marketable as a surrogate in risk profiling for children with obesity.

Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis is a key event in non-alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. METHODS: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82+/-1.41; age: 45+/-10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis-related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. RESULTS: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: x 11.56; FATP-5: x 1.33; CD95/Fas: x 3.18; NOXA: x 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72+/-2.32 mg/dl vs. patients: 23.03+/-1.24 mg/dl) and M30 levels (control: 83.12+/-7.46 U/L vs. patients: 212.61+/-22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. CONCLUSIONS: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis.

11beta-hydroxysteroid dehydrogenase type 1 is overexpressed in subcutaneous adipose tissue of morbidly obese patients.

BACKGROUND: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme catalyzes interconversion of inactive cortisone to active cortisol. Its expression in adipose tissue has been associated with obesity and some of its metabolic disorders. Controversies regarding which fat depots [subcutaneous adipose tissue (SAT) or visceral adipose tissue (VAT)] have higher expression still remain. The aim of this work was to evaluate 11beta-HSD1 expression in SAT and VAT of obese patients and evaluate its association to metabolic features of metabolic syndrome. METHODS: In 32 morbidly obese patients, paired samples of SAT and VAT were collected. All patients, 40.2+/-12.3 years and 36.7+/-3.8 body mass index (BMI), underwent sleeve gastrectomy or laparoscopic gastric bypass. Gene expression of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction. Spearman correlation test was used to evaluate relationships between 11beta-HSD1 levels and clinical and biochemical parameters. RESULTS: 11beta-HSD1 mRNA levels were higher in SAT than in VAT, with median expression levels of 11.4 arbitrary units (AU) and 7.8 AU, respectively (p=0.03). SAT 11beta-HSD1 mRNA were correlated with VAT mRNA levels (r=-0.6, p=0.018) and hip circumference (r=0.66, p=0.018). SAT 11beta-HSD1 levels increase parallel according to BMI category. We did not find a correlation between SAT or VAT with fasting glucose (r=0.15, p=NS), total cholesterol (r=0.13, p=NS), triglycerides (r=0.04, p=NS), and high-density lipoprotein (r=-0.16, p=NS). However, SAT expression in patients with features of MS was higher than those without features of MS. CONCLUSIONS: Our results demonstrate that SATs express higher 11beta-HSD1 mRNA levels than VAT. This finding highlights the importance of SAT in obesity and its possible role on metabolic disorders associated with obesity.

Lipoprotein lipase expression in livers of morbidly obese patients could be responsible for liver steatosis.

BACKGROUND: Most patients with morbid obesity develop non-alcoholic fatty liver disease (NAFLD). The origins of lipid deposition in the liver and the effects of bariatric surgery in the obese with NAFLD are controversial. METHODS: We analyzed lipids and lipoprotein lipase (LPL) in both plasma and liver biopsies performed before and 12-18 months after Roux-en-Y gastric bypass surgery in 26 patients. RESULTS: In the livers of morbidly obese patients, the levels of LPL messenger RNA (mRNA) were higher (4.5-fold) before surgery than afterwards than control livers. In these patients, LPL activity was also significantly higher (91 +/- 7 mU/g) than in controls (51 +/- 3 mU/g, p = 0.0026) and correlated with the severity of the liver damage. All hepatic lipids were significantly increased in obese patients; however, after bariatric surgery, these lipids, with the exception of NEFA, tended to recover to normal levels. CONCLUSIONS: The liver of obese patients presented higher LPL activity than controls, and unlike the controls, this enzyme could be synthesized in the liver because it also present LPL mRNA. The presence of the LPL activity could enable the liver to capture circulating triacylglycerides, thus favoring the typical steatosis observed in these patients.

A single-nucleotide polymorphism in the p110beta gene promoter is associated with partial protection from insulin resistance in severely obese adolescents.

OBJECTIVE: Severe juvenile obesity causes metabolic and cardiovascular complications in adulthood. The catalytic p110beta subunit of phosphatidyl-inositol-3 kinase is a major effector of insulin action. We studied the p110beta gene as a candidate gene for association with insulin resistance (IR) and fasting glycemia in severely obese children. METHODS: We conducted an association study in 580 severely obese European children (body mass index > 99.6th centile) and 606 nonobese control children, in whom glucose and insulin were measured in the fasting state. The homeostasis model assessment insulin resistance index was used to estimate IR. RESULTS: We found that a single-nucleotide polymorphism (rs361072) located in the promoter of the p110beta gene was associated with fasting glucose (P = 0.0002), insulin (P = 2.6 10(-8)), and homeostasis model assessment insulin resistance index (P =1 10(-9)) in the severely obese children. The effect of rs361072 was marginal or not significant in nonobese children. CONCLUSIONS: The C allele of rs361072 attenuates IR in superobese children.

Stimulation of human omental adipose tissue lipolysis by growth hormone plus dexamethasone.

Growth hormone [GH] administration results in a reduction in adiposity of humans that is attributed to stimulation of lipolysis. We examined the effect of direct addition of human GH, in both the absence and presence of dexamethasone [Dex], as well as that of interferon beta on lipolysis by omental adipose tissue explants from obese women incubated for 48h in primary culture. There was a significant stimulation of lipolysis by GH in the presence of Dex but not by Dex or GH alone. There was also a significant further stimulation by GH in the presence of Dex of hormone-sensitive lipase, perilipin, lipoprotein lipase and beta1 adrenergic receptor mRNA. We conclude that the direct lipolytic effect of GH is accompanied by an increase in HSL mRNA in the presence of DEX, but GH also increased the mRNAs for other proteins that could explain all or part of its lipolytic action.

Association of raised liver transaminases with physical inactivity, increased waist-hip ratio, and other metabolic morbidities in severely obese children.

OBJECTIVE: To identify factors associated with raised alanine transaminase, aspartate transaminase, and gamma-glutaryl transferase in severely obese children PATIENTS AND METHODS: In all, 201 children with early-onset obesity and greater than 140% ideal weight for height were recruited. Anthropometric and body fat measurements, fasting blood tests, and oral glucose tolerance tests were performed. RESULTS: The mean and standard deviation (SD) for age was 11.1 (3.0) years, for weight for height 170.5% (22.7%), and for percentage body fat was 40.7% (5.2%). Elevated liver transaminases were present in 53 subjects (26.4%), who were therefore at risk for nonalcoholic fatty liver disease, and was associated with male sex (odds ratio [OR] 2.144, 95% confidence interval [CI] 1.033-4.448), Chinese ethnicity (OR 2.062, 95% CI 1.038-4.096), reduced physical activity (OR 2.389, 95% CI 1.163-4.909), insulin resistance (P < 0.05), elevated triglyceride levels (P = 0.029), and increased waist-hip ratio (P = 0.005). Stepwise logistic regression analysis of the main factors as covariates revealed Chinese ethnicity, waist-hip ratio, reduced physical activity, and homeostasis model assessment index were significant predictors. Alanine transaminase/aspartate transaminase were not well correlated with percentage body fat and weight for height. Subjects with type 2 diabetes mellitus and impaired glucose tolerance were more likely to have raised hepatic transaminases (OR 6.176, 95% CI 1.326-28.754). The severity of metabolic syndrome correlated with increasing aspartate transaminase, alanine transaminase, and gamma-glutaryl transferase (P < 0.01). CONCLUSIONS: Insulin resistance, truncal adiposity, and physical inactivity are major determinants potentially modifiable to reduce risk of nonalcoholic fatty liver disease. Increasing physical activity levels were associated with decreasing insulin resistance and transaminases, despite lack of correlation with waist-hip ratio, which supports the direct benefit of regular physical activity in preventing nonalcoholic fatty liver disease.

Perforated appendicitis masquerading as acute pancreatitis in a morbidly obese patient.

Diagnosis and treatment of common conditions in morbidly obese patients still pose a challenge to physicians and surgeons. Sometimes too much reliance is put on investigations that can lead to a misdiagnosis. This case demonstrates an obese woman admitted under the medical team with a presumed diagnosis of pneumonia, who was later found to have an acute abdomen and raised amylase, which led to an assumed diagnosis of pancreatitis. She died within 24 h of admission and post mortem confirmed the cause of death as systemic sepsis due to perforated appendicitis, with no evidence of pancreatitis. Significantly elevated serum amylase level may occur in non-pancreatitic acute abdomen.

γ-Glutamyltransferase Fractions in Obese Subjects with Type 2 Diabetes: Relation to Insulin Sensitivity and Effects of Bariatric Surgery.

BACKGROUND/OBJECTIVES: Gamma-glutamyltranspeptidase (GGT) levels are an independent risk marker for the development of type 2 diabetes (T2DM). We investigated the relationship between the newly identified serum GGT fractions and glucose metabolism in obese subjects before and after bariatric surgery. SUBJECTS/METHODS: Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a 5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365). Insulin sensitivity was assessed by the OGIS index and ß-cell function by C-peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed by gel-filtration chromatography. RESULTS: At T15, total GGT activity decreased by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all patients showed a reduction in total GGT, in particular b-GGT (≥ 60%) and m-GGT (≥ 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-, and m-GGT fractions at T0 were significantly higher than in patients with low-grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was a significant fall in total GGT as well as in each fraction in both groups. In a multiple regression model, b-GGT was the only fraction related to insulin sensitivity (p = 0.016; ß coeff. = - 14.0) independently of BMI, fasting glucose, and triglycerides. CONCLUSIONS: While GGT activity is generally associated with impaired glucose metabolism, fractional GGT analysis showed that the b-GGT fraction specifically and independently tracks with insulin resistance.

A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index.

Background Proopiomelanocortin (POMC) is a complex polypeptide that produces a variety of biologically active substances via cleavage in a tissue-specific manner [Challis BG, Millington GW. Proopiomelanocortin deficiency. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 1993-2018], yielding several products including adrenocorticotrophic (ACTH) and melanocyte stimulating hormones (MSH). These peptides have roles in the regulation of food intake, energy homeostasis, adrenal steroidogenesis, melanocyte stimulation and immune modulation. Rare mutations in the POMC gene can lead to ACTH deficiency and thus isolated hypocortisolism. The first cases of POMC mutation were documented by Krude et al. in 1998 [Krude H, Biebermann H, Luck W, Horn R, Brabant G, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155-7]. Mutations in the POMC gene were linked with a clinical phenotype of adrenal insufficiency, red hair pigmentation, early onset and rapidly progressive obesity, early onset type 2 diabetes, hypothyroidism, hypogonadism and growth hormone deficiency. Case presentation We describe a prepubertal Hispanic boy with a novel homozygous POMC mutation with severe obesity, hypothyroidism, adrenal insufficiency and abnormal reddish hair pigmentation. The patient presented as a 2-year-old with exponential weight gain, abnormal thyroid labs and speech delay. Laboratory testing demonstrated central adrenal insufficiency and genetic testing confirmed a homozygous mutation (nucleotide change c.20_21ins25) in exon 3 of the POMC gene. Replacement therapy with thyroid hormone and hydrocortisone was coupled to a slight decrease in the rate of weight gain, although hyperphagia persisted. Parent-directed nutrition and activity education as well as attempts to restrict access to food resulted in a plateau of the body mass index (BMI). At 4 years of age, metformin treatment was initiated with the patient showing evolving signs of insulin resistance and failure of lifestyle/dietary intervention to adequately decrease the BMI. Over a 3-year metformin treatment span, the BMI decreased from 34.9 kg/m2 to 32.9 kg/m2. Conclusions We demonstrate a possible role for metformin in stemming progressive weight gain, thereby impacting the early onset obesity due to hyperphagia.

Surgical caloric restriction ameliorates mitochondrial electron transport dysfunction in obese females.

BACKGROUND: The authors examine the mitochondrial electron transport system (ETS) with regard to caloric restriction and body size in humans. METHODS: The study population included 59 morbidly obese (MO) female subjects with mean body mass index (BMI) 49.6 +/- 1.7 and 40 age-matched previously morbidly obese patients with surgically-induced caloric restriction (SCR) and mean BMI 28.9 +/- 1.1. ETS function in the 2 study groups were made by measuring their lymphocyte mitochondrial ETS complexes I-IV activities and complex III binding kinetics. Linear regression analyses were used to analyze the interactions between ETS function and BMI, energy intake, and metabolic status. RESULTS: The MO, as compared to SCR, subjects had significantly (P < 0.01) higher ETS complexes II-IV activities (complex II = 20.4 +/- 1.9 vs 15.3 +/- 1.1, complex III = 129.4 +/- 10.1 vs 72.3 +/- 4.9, complex IV = 3.1 +/- 0.3 vs 1.4 +/- 0.1 nmol/mg/min for the MO vs SCR, respectively). ETS complexes activities were positively and significantly correlated with subjects' BMI, carbohydrate caloric intake, and fasting plasma insulin levels. Michaelis-Menten kinetic analysis showed that the Km for ubiquinol-2 in complex III of MO patients was 2-fold greater than SCR values, reflecting an apparent reduction in substrate binding capacities producing a resistance to electron flow in the MO population. Caloric consumption, carbohydrate calories, insulin levels, and BMI were also each significantly (P < 0.05) and positively correlated with the Km of Complex III. CONCLUSIONS: ETS function and efficiency are compromised by increasing BMI and caloric consumption in morbidly obese women, and caloric restriction may reduce the potential for excessive oxidative free radical generation via the ETS.

Relationship between obstructive sleep apnea and liver abnormalities in morbidly obese patients: a prospective study.

BACKGROUND: Morbid obesity is a risk factor of nonalcoholic steatohepatitis (NASH). Obstructive sleep apnea (OSA) could also be an independent risk factor for elevated liver enzymes and NASH. The relationships between liver injuries and OSA in morbidly obese patients requiring bariatric surgery were studied prospectively. METHODS: Every consecutive morbidly obese patient (BMI > or =40 kg/m2 or > or =35 kg/m2 with severe comorbidities) requiring bariatric surgery was included between January 2003 and October 2004. Polygraphic recording, serum aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT) and liver biopsy were systematically performed. OSA was present when the apnea-hypopnea index (AHI) was >10/h. RESULTS: 62 patients (54 F; age 38.5 +/- 11.0 (SD) yrs; BMI 47.8 +/- 8.4 kg/m2) were included. Liver enzymes (AST, ALT or GGT) were increased in 46.6%. NASH was present in 34.4% and OSA in 84.7%. Patients with OSA were significantly older (P = 0.015) and had a higher BMI (P = 0.003). In multivariate analysis, risk factors for elevated liver enzymes were the presence of OSA and male sex. The presence of NASH was similar in patients with or without OSA (32.7% vs 44.4% of patients, P = 0.76). CONCLUSION: In this cohort of morbidly obese patients requiring bariatric surgery, one-third of patients had NASH, a prevalence similar to previous studies. OSA was found to be a risk factor for elevated liver enzymes but not for NASH.

Aminotransferase activity in morbid and uncomplicated obesity: predictive role of fasting insulin.

BACKGROUND AND AIMS: An elevation in liver enzymes and, most notably, high serum alanine aminotransferase (ALT) activity, has been correlated with metabolic syndrome and obesity. However, whether obesity per se or obesity-related co-morbidities affect aminotransferase activity is still unclear. In this study we sought to evaluate serum aminotransferase activity in morbid and uncomplicated obese subjects METHODS: In this cross-sectional study, serum aminotransferase activity, anthropometric and metabolic parameters were assessed in 290 morbid and 105 uncomplicated consecutive obese subjects matched for body mass index (BMI) (40.1+/-6.8 vs. 39.9+/-8.3 kg/m(2), respectively), age (35.9+/-10 vs. 34.8+/-9.6 years, respectively), sex distribution and duration of obesity. RESULTS: Uncomplicated obese subjects showed significantly lower serum ALT activity (17.58+/-6.3 (range 10-39) vs. 23.43+/-16 (range 12-89) U/l, (p<0.001)), and lower aspartate aminotransferase (AST), AST/ALT ratios and gamma-glutamyltranspeptidase (gammaGT) (p<0.01 for all) than morbid obese subjects. Only 11% women and 19% men in the uncomplicated obese group showed high ALT levels, while ALT activity was high in 48% women and 51% men in the morbid obese group. Fasting insulin was the best correlate of ALT activity (R(2)=0.21, p=0.003). CONCLUSIONS: Our findings show that elevated ALT and AST activity are associated with increased fasting insulin and not with obesity per se, suggesting that the presence of insulin resistance, rather than BMI alone, plays a role in mediating the increased aminotransferase activity.

Impact of bariatric surgery on non-alcoholic fatty liver disease.

Introduction; p to 300 million people have the body mass index (BMI) greater than 30 kg/m2. Obesity is the cause of many serious diseases, such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD). Bariatric surgery is the only effective method of achieving weight loss in patients with morbid obesity. OBJECTIVES: The aim of the study was to assess the impact of bariatric surgery on non-alcoholic fatty liver disease in patients operated on due to morbid obesity. MATERIAL AND METHODS: We included 20 patients who were qualified for bariatric procedures based on BMI > 40 kg/ m2 or BMI > 35kg/m2 with the presence of comorbidities. The average body weight in the group was 143.85kg, with an average BMI of 49.16kg/m2. Before the procedure, we evaluated the severity of non-alcoholic fatty liver disease in each patient using the Sheriff-Saadeh ultrasound scale. We also evaluated the levels of liver enzymes. Follow-up evaluation was performed twelve months after surgery. RESULTS: Twelve months after surgery, the average weight was 102.34 kg. The mean %WL was 33.01%, %EWL was 58.8%, and %EBMIL was 61.37%. All patients showed remission of fatty liver disease. Liver damage, evaluated with ultrasound imaging, decreased from an average of 1.85 on the Sheriff-Saadeh scale, before surgery, to 0.15 twelve months after surgery (p < 0.001). As regards liver enzymes, the level of alanine aminotransferase decreased from 64.5 (U/l) to 27.95 (U/l) (p < 0.001), and the level of aspartate aminotransferase decreased from 54.4 (U/l) to 27.2 (U/l). CONCLUSIONS: Bariatric procedures not only lead to a significant and lasting weight loss, but they also contribute to the reduction of fatty liver disease and improve liver function.

Rhabdomyolysis after gastric bypass: severity and outcome patterns.

BACKGROUND: Rhabdomyolysis (RML) is a recently recognized complication of bariatric operations, but it is not known whether creatine kinase (CK) levels along with clinical markers are able to define the course and outcome. METHODS: Bariatric patients (n=324) were reviewed retrospectively. Substantially elevated plasma CK after operation was identified in 4.9% (16/324). The affected population was divided into Group I (n=11, 68.8%) with CK 1050-8000 IU/L and no conspicuous muscle pain, weakness or swelling, and Group II (n=5, 31.2%) displaying CK >8000 IU/L and severe pain and dysfunction. The main outcome measures were CK concentration, frequency of renal failure, need for hemodialysis and mortality. RESULTS: Group I subjects compared to Group II were younger (37.7 +/- 10.9 vs 44.0 +/- 5.5 years, P<0.05) and predominantly females (72.7% vs 40.0%, P<0.05). Peak CK values were definitely lower (2811 +/- 952 vs 28136 +/- 19000 IU/L, P<0.001), and none progressed to renal failure (0% vs 40.0%, P<0.05). No difference was detected regarding preoperative BMI (50.8 +/- 8.1 vs 54.6 +/- 7.0 kg/m(2), NS), duration of operation (5.3 +/- 1.6 vs 5.6 +/- 2.1 hours, NS) or types of anesthetic drugs (basically fentanyl, nitrogen oxide and halothane/isoflurane). CONCLUSIONS: 1) Demographic features, nominally gender and age, were different between the two degrees of RML; 2) Renal failure and hemodialysis were a danger only in patients with massive CK elevation and muscle pain; 3) Moderate CK increase was very well tolerated and rarely entailed major clinical symptoms; 4) Early diagnosis, fluid replenishment and general supportive therapy probably contributed to avert mortality.