Gastric Bypass for Insulin Resistance due to Lipodystrophy

We report a 41-year-old woman with severe insulin resistance due to partial lipodystrophy, who was successfully treated with gastric bypass surgery.     

Gene Expression of Leptin, Resistin, and Adiponectin in the White Adipose Tissue of Obese Patients with Non-Alcoholic Fatty Liver Disease and Insulin Resistance

Background: Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Methods: Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 ± 40.56 mg/dL; serum insulin 8.28 ± 3.52 μU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 ± 8.43 mg/dL; serum insulin 3.431 ± 1.162 μU/mL). Results: Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Conclusions: Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.     

Changes in Insulin Resistance Following Bariatric Surgery: Role of Caloric Restriction and Weight Loss

The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increasing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass procedures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and biliopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resistance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms.     

Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.     

Insulin Resistance in the Severely Obese and Links with Metabolic Co-morbidities

Background: The association between insulin resistance (IR) and obesity and its causal relationship with type 2 diabetes is well recognized.The possibility of an association, causal or otherwise, with other obesity-related co-morbidities warrants consideration. Methods: IR was calculated pre-operatively in 80 patients undergoing gastric bypass surgery for severe obesity, using the homeostasis model assessment (HOMA) method, and again in 70 patients on at least one occasion post-operatively within 12 months. Correlations with weight parameters and pre-existing co-morbidities including diabetes, hypertension, dyslipidemia and hepatic steatosis were made. Results: 78/80 patients had IR pre-operatively which did not correlate with pre-operative weight or BMI. As expected, there were positive correlations between pre-operative IR and abnormal glucose tolerance and diabetes. A positive correlation was also found between IR and hepatic steatosis, but no correlation was noted between IR and hypertension or fasting levels of cholesterol, triglycerides or Chol/HDL cholesterol ratios. Improvement in IR was uniformly seen after gastric bypass, sooner than would be accounted for by weight loss alone. The degree of pre-operative IR was not a predictor of weight loss after gastric bypass in these patients. Conclusions: While IR is an almost universal accompaniment of severe obesity, it does not correlate with the degree of obesity in this group of patients. A number of important co-morbidities show a clear association with IR, and improvement in these after gastric bypass may well be related to striking and rapid changes in IR.     

Predictors of Nonalcoholic Steatohepatitis (NASH) in Obese Patients Undergoing Gastric Bypass

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions gaining increasing recognition in hepatology as a potential cause of cirrhosis and end-stage liver disease. Obesity is one of the main risk factors. The aims of this study were to determine the frequency of NAFLD in obese patients and to identify variables that predict NASH. Methods: A prospective study was conducted of obese patients undergoing gastric bypass over a 20-month period. Assessment included liver function tests and evaluation of insulin resistance with the homeostatic model assessment (HOMA-IR). Liver biopsy was performed in all patients at the time of surgery. Clinical and biochemical variables were analyzed using a multivariate analysis to identify independent predictors of NASH. Results: 127 consecutive patients were included (62% female, 38% male, mean age 40±11 years, mean body mass index 42±6 kg/m²). Arterial hypertension was present in 52 patients (41%) and type 2 diabetes in 18 (14%). NAFLD was confirmed in 80 patients (63%), 47 (37%) had simple steatosis, and 33 (26%) had NASH. Cirrhosis was found in 2 patients corresponding to 1.6% of the total population. On multivariate analysis, AST >31 (IU/L) (OR 3.38, CI 1.17-9.8) and HOMA-IR >5.8 (OR 4.18, CI 1.39-12.49) independently predicted NASH. Conclusions: NAFLD is highly prevalent in morbidly obese patients. A high proportion of these patients exhibit NASH on histological examination. Insulin resistance represents the main predictor of NASH.     

Changes in Insulin Resistance Following Bariatric Surgery and the Adipoinsular Axis: Role of the Adipocytokines,Leptin, Adiponectin and Resistin

The fat mass participates in the regulation of glucose and insulin metabolism through the release of adipocytokines in a mechanism called the adipoinsular axis. Putative adipocytokines include leptin, adiponectin and resistin. Obesity plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). Bariatric surgery for morbidly obese patients leads to rapid and prolonged improvement in insulin resistance and T2DM in the vast majority of patients. We have previously proposed that the rapid improvement in insulin resistance observed following bariatric surgery is mediated by changes in incretin levels of the entero-insular axis and that long-term improvement is modulated by fat mass loss and changes in adipocytokine levels of the adipoinsular axis. In this review, we examine the information that supports a role of leptin, adiponectin and resistin in the development of insulin resistance and T2DM. Increasing levels of leptin and decreasing levels of adiponectin correlate with worsening insulin resistance in obese individuals. We also explore the relationship between changes in adipocytokines following bariatric surgery and long-term improvement in insulin resistance and T2DM. Leptin levels drop and adiponectin levels rise following laparoscopic adjustable gastric banding, gastric bypass and biliopancreatic diversion. These changes correlate with weight loss and improvement in insulin. Although resistin may play an important role in explaining insulin resistance, animal and human studies currently show conflicting results.     

Leptin and Insulin Action in Severely Obese Women

Background: The authors investigated the interrelationships between the components of the metabolic syndrome in severe obesity. Methods: In non-diabetic, severely obese women, the degree of obesity (BMI), the insulin sensitivity (from the Homeostatic Model of Assessment, HOMA), the serum leptin concentration and the presence of dyslipidemia and arterial hypertension were evaluated. Results: In insulin-resistant patients, an overall impaired metabolic status and a greater cardiovascular risk were observed, while serum leptin concentration was higher than in the insulin-sensitive ones. Leptin levels and HOMA data correlated independent of BMI findings, while the presence of dyslipidemia and hypertension was unrelated to the other metabolic syndrome factors. Conclusion: In severely obese women, although other factors independently intervene, serum leptin has a role in developing the metabolic syndrome.     

Short-term Changes in Insulin Resistance following Weight Loss Surgery for Morbid Obesity: Laparoscopic Adjustable Gastric Banding versus Laparoscopic Roux-en-Y Gastric Bypass

Background: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGBP) both effectively treat the insulin resistance associated with type 2 diabetes mellitus (T2DM). Restriction of caloric consumption, alterations in the entero-insular axis or weight loss may contribute to lowering insulin resistance after these procedures. The relative importance of these mechanisms, however, following LAGB and LRYGBP remain unclear. The aim of this study was to compare directly the short-term changes in insulin resistance following LAGB and LRYGBP in similar populations of patients. Methods: Patient preference determined operation type. The Homeostasis Model Assessment for Insulin Resistance (HOMA IR) was used to measure insulin resistance. Preoperative values were compared to postoperative levels obtained within 90 days of surgery. Significant differences between groups were tested by ANOVA. Results: There were no significant preoperative differences between groups. The 56 LAGB patients had a mean age of 42.5 years (25.7-63), BMI of 45.5 kg/m² (35-66) and preoperative HOMA IR of 4.1 (1.4-39.2). 75% of LAGB patients were female and 43% had T2DM. The 61 LRYGBP patients had a median age of 39.9 years (22.1-64.3), BMI of 45.0 kg/m² (36-62), and preoperative HOMA IR of 5.0 (0.6-56.5). 79% of LRYGBP patients were women and 44.3% had T2DM. Median follow-up for LAGB patients was 45 days (18-90) and for LRYGBP patients 46 days (8-88 days). LAGB patients had a median of 14.8% excess weight loss (6.9%-37.0%) and LRYGB patients 24.2% (9.8%-51.4%). Postoperative HOMA IR was significantly less after LRYGBP, 2.2 (0.7-12.2), than LAGB, 2.6 (0.8-29.6), although change in HOMA IR was not significantly different. Change in HOMA IR for both groups did not vary with length of follow-up or weight loss but correlated best with preoperative HOMA IR (LAGB r=0.8264; LRYGBP r=0.9711). Conclusions: Both LAGB and LRYGBP significantly improved insulin resistance during the first 3 months following surgery. Both operations generated similar changes in HOMA IR, although postoperative HOMA IR levels were significantly lower after LRYGBP. These findings suggest that caloric restriction plays a significant role in improving insulin resistance after both LAGB and LRYGBP.     

Effect of Abdominal Obesity on Insulin Resistance and the Components of the Metabolic Syndrome: Evidence Supporting Obesity as the Central Feature

Background: Metabolic syndrome includes abdominal obesity, diabetes type 2, hypertension, dyslipidemia, derangements of fibrinolysis, and atherosclerosis. Since abdominal obesity is one of the major components of the insulin resistance syndrome (IRS), an attempt was made to evaluate the interrelationships between the magnitude of obesity and the components of the syndrome. Methods: A cross-sectional study of 123 subjects with type 2 diabetes, of whom 31 were normal body weight and 92 had varying degrees of obesity was conducted. The participants were investigated in terms of clinical and laboratory findings of IRS. Fasting and 30-min (early) plasma glucose and serum insulin excursions in response to oral glucose challenge (75 g) were determined. The peripheral and hepatic insulin resistance (insensitivity) was calculated by homeostasis model assessment (HOMA). Results: Clinical and biochemical findings were compared with the components of the IRS, and demonstrated that a rise in fasting as well as 30-min insulin secretion increases as abdominal body fat (obesity) increases. There was also a significant and proportional correlation between the magnitude of abdominal obesity and the components of metabolic syndrome. Conclusion: Abdominal adiposity appears to have a pivotal role in the development of IRS.     

Morbidly Obese Individuals with Impaired Fasting Glucose have a Specific Pattern of Insulin Secretion and Sensitivity: Effect of Weight Loss after Bariatric Surgery

Background: Obesity is often associated with hyper-secrection of insulin. Impaired fasting glucose (IFG) has recently been redefined as a fasting plasma glucose of 5.6-6.9 mmol/L. The aim of this study was to determine whether changes in insulin secretion in morbidly obese persons also commence with normal serum glucose levels. Methods: 32 morbidly obese subjects were studied before and after bariatric surgery. Measurements were made of glucose tolerance (K_G), insulin sensitivity (SI), first-phase insulin release and the disposition index (DI) from a frequently sampled intravenous glucose tolerance test. Result: In morbidly obese subjects, the SI (P<0.01), DI (P<0.01) and first-phase insulin release (P<0.02) started changing with serum glucose levels considered to be normal (5.00-5.28 mmol/L). K_G showed a clear slope according to the baseline glycemia status (P<0.05), and it was significantly related with the DI, both before (r=0.76, P<0.001) and after (r=0.57, P=0.002) surgery. Following surgery, all the variables significantly associated with insulin secretion and insulin sensitivity recovered significantly. The most significant changes occurred in morbidly obese individuals with IFG. Conclusions: Morbidly obese subjects show slopes of insulin sensitivity and insulin secretion in accordance with their baseline serum glucose levels. The fall in first-phase insulin release begins when serum glucose values are considered normal. Morbidly obese persons with the IFG phenotype have a specific pattern of insulin sensitivity and insulin secretion. K_G clearly discriminates the clinical phenotypes, depending on baseline serum glucose levels.     

Changes in Insulin Sensitivity in Morbidly Obese Patients with or without Metabolic Syndrome after Gastric Bypass

Background: We evaluated the medium term changes in insulin sensitivity in morbidly obese patients with and without metabolic syndrome before and after Roux-en-Y gastric bypass (RYGBP) with silastic ring (Capella-Fobi). Methods: A longitudinal, clinical intervention study was conducted in 40 patients between 18 and 65 years old, with obesity class II and III (BMI ≥35-52 kg/m²), divided into 2 groups: no metabolic syndrome (NMS, n=21) and metabolic syndrome (MS, n=19). Anthropometric measurements, biochemical tests and classification of MS according to the NCEP criteria, were performed pre-operatively and at 3 and 6 months postoperatively. Results: In the preoperative period, 87% of the patients presented obesity class III (BMI 47±5 kg/m²) while 13% of the patients had obesity class II (37±2 kg/m²), and 19 patients (47.5%) presented MS. In the preoperative period, there were no differences among patients with MS and NMS in relation to the anthropometrics and body composition measurements. However, triglyceridemia, glycemia and insulinemia were higher in the MS group compared to the NMS group (P<0.05), although there was no difference in HOMA between the groups. HDL-cholesterol was lower in the MS group (p<0.05). In both postoperative study periods, all patients had significant reduction of anthropometric variables, body composition and biochemical variables. There were no differences between MS and NMS (p>0.05) groups. However, insulinemia decreased more in the postoperative period in the MS group compared to the NMS group (p<0.05). MS frequency in the MS group diminished to 26% after 3 postoperative months and no patient presented features of MS after 6 months postoperatively. Conclusions: Based on these observation: 1) patients of class II and III obesity present peripheral resistance to hyperinsulinemia without hyperglycemia; 2) RYGBP is able to reduce anthropometric measurements and body composition in a similar way for patients who have, or have not, MS; 3) there is rapid normalization of biochemistry of carbohydrates and lipids; 4) patients with previous MS lose the criteria needed for this diagnosis after 6 postoperative months.     

Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Background:This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. Methods: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. Results: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. Conclusion: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.     

The Prevalence of Nonalcoholic Steatohepatitis is Greater in Morbidly Obese Men Compared to Women

Background: Nonalcoholic steatohepatitis (NASH) is a form of liver injury that is common in morbidly obese subjects. It has been shown that gender differences exist in the spectrum of nonalcoholic fatty liver disease (NAFLD). The focus of this study was to further characterize these gender differences based on ATP III criteria used to diagnose the metabolic syndrome (MS). Methods: We retrospectively assessed NAFLD 58 men and 307 women who underwent gastric bypass, for the presence of NASH, MS, and positive predictors of NASH. Results: There was no statistical difference in age, gender, or the presence of diabetes. The prevalence of NASH in men and women was 60.3% and 30.9%, respectively (P<0.001). Multivariate logistic analysis showed an association of male gender with NASH (2.7; 95% CI, 1.3-5.6, P=0.006) as well as age, AST, and diabetes. MS was diagnosed in 91.4% and 76.2% of men and women (P=0.008), and men tended to have more criteria for MS compared to women. The only positive predictor of MS that was statistically significant between genders was high triglycerides (P=0.003). Controlling for BMI and excess body weight produced similar results. Conclusions: Gender differences do exist within NAFLD and MS, that may be associated with free fatty acid flow to the liver.     

Some Hormonal Changes Before and After Vertical Banded Gastroplasty for Severe Obesity

Background: Hormonal disturbances play a role in the development of obesity, but may be a consequence of obesity itself. In this study we assessed the influence of the surgically-induced weight loss on some important hormonal abnormalities in the morbidly obese patients. Material and Methods: Fasting serum prolactin, insulin, cortisol and thyroid hormones: free thyroxin (FT4),free triiodothyronine (FT3) and thyrotropin (TTH), have been studied by radioimmune methods before vertical banded gastroplasty (VBG) and after operation in the early (10-14 days) and late period when excess weight loss (EWL) 51.7-57.1% had been achieved. Results: On the 10-14 day after VBG, prolactin increased significantly in women (p<0.05), but decreased after weight loss (p<0.01). Fasting insulin was lowered significantly (p<0.05) soon after VBG in the hyperinsulinemic (51.7 % of the total group) and diabetic (n-9) patients. After weight loss, insulin decreased significantly (p< 0.0001) vs. preoperative. Concentration of cortisol was unchanged both in the early and in the late postoperative period. On the days 10-14, significant elevation of TTH and decrease of FT3 (p<0.05) have been noted. After essential weight loss TTH dropped significantly vs. preoperative (p< 0.05) with no changes in FT3 and FT4 concentration. Conclusions: VBG and consequent weight loss favorably influence the hormonal abnormalities in the morbidly obese. Further studies are needed to make clear a relationship between this and other parameters of metabolic syndrome. The hormonal abnormalities may influence the indications for surgery in less than morbidly obese patients with metabolic syndrome.     

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25‐hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal‐weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high‐performance liquid chromatography (HPLC) and body composition by dual‐energy X‐ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty‐six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.     

Comparison of IL-8, IL-6 and PGE2 Formation by Visceral (Omental) Adipose Tissue of Obese Caucasian Compared to African-American Women

Background: One of the key consequences of obesity is an enhanced release of cytokines such as IL-8 and IL-6 by adipose tissue. There may be differences in adiposity, inflammatory markers, and medical co-morbidity between morbidly obese African-American (AA) and Caucasian (CA) women. We hypothesized that there are ethnic differences in inflammatory markers and medical co-morbidities. Methods: We compared the mRNA content in omental fat and the release of IL-8, IL-6 and PGE₂ after a 4-hour incubation of explants of adipose tissue in women undergoing bariatric surgery. In addition, medical co-morbidities and fat measurements were examined and compared. Results: Medication usage differed, with CA women being three times more likely to report taking medication for depression compared to AA women (P≤0.001). IL-8 and PGE₂ release over 4 hours by omental fat in vitro was the same in CA and AA women. Similar results were seen with respect to the COX-2 mRNA and IL-8 mRNA values at the start and at the end of the incubation. In CA and AA women, the IL-6 mRNA content in fat immediately after removal from the patients was the same. Conclusions: In morbidly obese women seeking bariatric surgery, there are little ethnic differences between cytokine release by omental adipose tissue explants in vitro, or the mRNA content in omental adipose tissue of IL-6, IL-8 or COX-2. The only noted difference between AA and CA morbidly obese women was the greater use of antidepressants by CA women.     

Effect of Massive Weight Loss induced by Bariatric Surgery on Serum Levels of Interleukin-18 and Monocyte-Chemoattractant-Protein-1 in Morbid Obesity

Background: Morbid obesity is associated with insulin resistance (IR), chronic inflammation and premature atherosclerosis. Since vascular inflammation may contribute to the increased risk of cardiovascular morbidity and mortality of these patients, we studied circulating Interleukin-18 (L-18) and monocyte-chemoattractant-protein-1 (MCP-1) levels in 37 patients with morbid obesity before and after significant weight loss induced by bariatric surgery and their preoperative and postoperative associations with C-reactive protein (CRP) and IR-associated factors. Methods: High sensitivity assays were used to measure concentrations of fasting CRP, IL-18 and MCP-1. Differences between patients before and after bariatric surgery were analyzed by Student's paired t-test. To investigate the associations of the observed reductions of values, delta of parameters were calculated and preoperative, postoperative and delta data were tested by univariate and multivariate linear regression. Results: After a mean follow-up period of 26.5 months and a massive weight loss of 35 kg induced by bariatric surgery, circulating IL-18 levels decreased by 37% (P<0.001) and circulating MCP-1 levels by 47% (P<0.001). Multiple linear regression of delta values of IL-18 showed that only 2-hour glucose (P=0.008) remained independently and significantly associated with IL-18, whereas multiple linear regression analysis of delta values of MCP-1 revealed that only delta of HOMA-IR (P<0.001) remained independently and significantly associated with MCP-1, respectively. Conclusions: Because both biomarkers have been shown to play an important role in the development and progression of atherosclerosis, the observations presented in this study could be of clinical relevance for morbidly obese patients undergoing bariatric surgery.