scholarly journals Changes in Plasma Levels of N-Arachidonoyl Ethanolamine and N-Palmitoylethanolamine following Bariatric Surgery in Morbidly Obese Females with Impaired Glucose Homeostasis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Akhila Mallipedhi ◽  
Sarah L. Prior ◽  
Gareth Dunseath ◽  
Richard M. Bracken ◽  
Jonathan Barry ◽  
...  

Aim. We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance.Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA).Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r=0.55,P=0.01), HOMA-IR (r=0.61,P=0.009), and HOMA %S (r=-0.71,P=0.002). OEA was correlated with weight (r=0.49,P=0.03), waist circumference (r=0.52,P=0.02), fasting insulin (r=0.49,P=0.04), and HOMA-IR (r=0.48,P=0.05). PEA was correlated with fasting insulin (r=0.49,P=0.04). 2-AG had a negative correlation with fasting glucose (r=-0.59,P=0.04).Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

2016 ◽  
Vol 144 (9-10) ◽  
pp. 497-502
Author(s):  
Teodora Beljic-Zivkovic ◽  
Milica Marjanovic-Petkovic ◽  
Miljanka Vuksanovic ◽  
Ivan Soldatovic ◽  
Dobrila Kanlic ◽  
...  

Introduction. A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective. Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods. A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results. Participants were 58.65 ?} 7.62 years of age with a body mass index of 35.06 ?} 5.15 kg/m2, waist circumference of 115.04 ?} 15.5 cm, and the duration of diabetes of 4.11 ?} 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion. Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1813-1813 ◽  
Author(s):  
Racil Zdenek ◽  
Petra Belohlavkova ◽  
Petr Cetkovsky ◽  
Edgar Faber ◽  
Hana Klamova ◽  
...  

Abstract Background: Recently we have published results of pilot study on CML patients demonstrating fast development of hyperinsulinaemia, peripheral insulin resistance, hypoadiponectinaemia and hypercholesterolemia during nilotinib therapy. Aims: To analyze results from follow up multicenter study “ENIGMA 2” with the aim to confirm or to exclude results from the pilot study, as well as to analyze whether these abnormalities are detected in control groups of patients treated with other TKIs - imatinib and dasatinib. Methods: Patients received intensive laboratory workup before the start of TKI and after 3 month of therapy. This included fasting insulin, glucose, adiponectin and lipid serum concentration, HbA1c and oral glucose tolerance test. Patients with TKI treatment interruption for >2 weeks and/or dose reduction for > 25% were excluded. Results: Between 2/2011-6/2014 in 5 centers 37 CML patients initiated therapy with nilotinib, 18 with imatinib and 8 with dasatinib. After 3 months patients treated with nilotinib developed significant hypersinulinaemia and hyperglycaemia as result of fast development of peripheral insulin resistance. This was proved by significant increase in HOMA-2 index during 3 months of nilotinib therapy (mean – 1.4 vs. 1.8; p = 0.0023). Moreover, we have proved significant decrease of adiponectin (major insulin sensitizer) concentration as well as significant increase in total and LDL cholesterol concentration after 3 month of nilotinib treatment. Details are presented in Table. Contrary – none of these abnormalities were detected in the control group of patients treated with imatinib and dasatinib, including any change in insulin resistance measured by HOMA-2 index (means – 0.9 vs. 1.3; p = 0.1046 and 1.1 vs. 1.1; p = 0.9255). Moreover, administration of imatinib (and probably also dasatinib, however only limited data are available at this moment) leads to increase of adiponectin concentration, which serves as major insulin sensitizer in peripheral tissues. Conclusions: Our study proved fast development of peripheral insulin resistance already during the first 3 months of nilotinib therapy as underlying cause of glucose and secondary also lipid metabolism impairment during this treatment. Moreover, this was not proved for patients treated with imatinib and dasatinb and significant increase in adiponectin concentration during imatinib (and probably dasatinib) therapy could at least partly explain observed amelioration of diabetes 2 during its administration described in some studies Supported by the CELL – the Czech Leukemia Study Group – for life Table. NILOTINIB THERAPY (n=37) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.3 (4.5-6.7) 5.7 (4.6-8.2) <0.0001 Fasting insulin [mU/l] 11.2 (2.4-28.3) 14,1 (2.5-32.7) 0.0037 Fasting C-peptide [pmol/ml] 0.73 (0.53-1.78) 0.76 (0.76-3.31) 0.4953 Fasting HbA1c [mmol/mol] 38.9 (24.0-55.0) 38.2 (25.0-57.0) 0.3900 Fasting adiponectin [mg/l] 16.6 (2.1-45.1) 8.6 (2.6-22.4) 0.0019* Total cholesterol [mmol/l] 4.8 (2.5-6.7) 5.9 (4.4-7.9) <0.0001 LDL cholesterol [mmol/l] 2.8 (1.1-4.9) 3.6 (2.1-5.7) <0.0001 IMATINIB THERAPY (n=18) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.5 (4.4-7.7) 5.6 (4.2-6.4) 0.7567 Fasting insulin [mU/l] 6.7 (2.0-19.0) 9.8 (2.0-37.80) 0.1369 Fasting C-peptide [pmol/ml] 0.77 (0.25-1.55) 0.72 (0.27-1.78) 0.4569 Fasting HbA1c [mmol/mol] 44.8 (33.0-59.0) 41.1 (30.0-55.0) 0.005 Fasting adiponectin [mg/l] 10.8 (2.1-25.7) 26.1 (6.0-45.2) <0.0001** Total cholesterol [mmol/l] 5.1 (3.3-7.1) 4,7 (2.6-7.1) 0.1123 LDL cholesterol [mmol/l] 3.1 (1.7-4.7) 2.7 (1.2-4.7) 0.064 DASATINIB THERAPY (n=8) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.8 (4.6-6.8) 5.3 (3.3-6.7) 0.1764 Fasting insulin [mU/l] 8.1 (2.5-19.3) 8.4 (2.6-17.9) 0.8815 Fasting C-peptide [pmol/ml] 0.63 (0.16-1.11) 0.60 (0.24-1.03) 0.8223 Fasting HbA1c [mmol/mol] 38.8 (31.0-51.0) 37.8 (30.0-56.0) 0.684 Fasting adiponectin [mg/l] 17.3 (9.2-26.7) 12.9 (5.5-21.4) 0.0106*** Total cholesterol [mmol/l] 4.0 (3.0-5.0) 4.5 (3.6-5.8) 0.0831 LDL cholesterol [mmol/l] 2.2 (1.6-3.0) 2.5 (1.9-3.3) 0.1140 *number of paired measurements = 24 **number of paired measurements = 12 ***number of paired measurements = 3 Disclosures Zdenek: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Klamova:Novartis and Bristol Myers-Squibb: Consultancy, Honoraria. Mayer:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.


2020 ◽  
Vol 9 (1) ◽  
pp. 196 ◽  
Author(s):  
Carolina Gutierrez-Repiso ◽  
Ailec Ho-Plagaro ◽  
Concepción Santiago-Fernandez ◽  
Sara Garcia-Serrano ◽  
Francisca Rodríguez-Pacheco ◽  
...  

Little is known about the jejunal insulin signalling pathways in insulin resistance/diabetes states and their possible regulation by insulin/leptin. We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM), and the effect of insulin/leptin on intestinal epithelial cells (IEC). Insulin receptor substrate-1 (IRS1) and the catalytic p110β subunit (p110β) of phosphatidylinositol 3-kinase (PI3K) were higher in MO-high-IR than in MO-low-IR. The regulatory p85α subunit of PI3K (p85α)/p110β ratio was lower in MO-high-IR and MO-metf-T2DM than in MO-low-IR. Akt-phosphorylation in Ser473 was reduced in MO-high-IR compared with MO-low-IR. IRS1 and p110-β were associated with insulin and leptin levels. The improvement of body mass index (BMI) and HOMA-IR (homeostasis model assessment of insulin resistance index) after bariatric surgery was associated with a higher IRS1 and a lower p85α/p110β ratio. IEC (intestinal epithelial cells) incubation with a high glucose + insulin dose produced an increase of p85α and p110β. High dose of leptin produced an increase of IRS1, p85α and p110β. In conclusion, despite the existence of insulin resistance, the jejunal expression of genes involved in insulin signalling was increased in MO-high-IR. Their expressions were regulated mainly by leptin. IRS1 and p85α/p110β ratio was associated with the evolution of insulin resistance after bariatric surgery.


Author(s):  
Vivian L. Chin ◽  
Kristen M. Willliams ◽  
Tegan Donnelley ◽  
Marisa Censani ◽  
Rushika Conroy ◽  
...  

Abstract Background Elevated body mass index (BMI) is associated with hypogonadism in men but this is not well described in adolescents. The aim is to evaluate gonadal dysfunction and the effects of weight loss after gastric banding in obese adolescent boys. Methods Thirty-seven of 54 boys (age 16.2±1.2 years, mean BMI 48.2 kg/m2) enrolled at the Center for Adolescent Bariatric Surgery at Columbia University Medical Center had low total testosterone for Tanner 5 <350 ng/dL. Sixteen had long-term hormonal data for analysis at baseline (T0), 1 year (T1) and 2 years (T2) post-surgery. T-tests, chi-squared (χ2) tests, correlation and linear mixed models were performed. Results At T0, the hypogonadal group had higher systolic blood pressure (SBP) (75th vs. 57th percentile, p=0.02), fasting insulin (19 vs. 9 μIU/mL, p=0.0008) and homeostatic index of insulin resistance (HOMA-IR) (4.2 vs. 1.9, p=0.009) compared to control group. Total testosterone was negatively correlated with fasting insulin and HOMA-IR. In the long-term analysis, BMI, weight, waist circumference (WC), and % excess weight decreased at T1 and T2 compared to T0. Mean total testosterone at T0, T1 and T2 were 268, 304 and 368 ng/dL, respectively (p=0.07). There was a statistically significant negative correlation between BMI and testosterone after 2 years (r=−0.81, p=0.003). Conclusions Low testosterone levels but unaltered gonadotropins are common in this group and associated with insulin resistance. While a significant increase in testosterone was not found over time, the negative relationship between BMI and testosterone persisted, suggesting there may be an optimal threshold for testosterone production with respect to BMI. Long-term studies are needed.


2019 ◽  
Vol 32 (7) ◽  
pp. 707-714 ◽  
Author(s):  
Yesim Kutluturk ◽  
Aysehan Akinci ◽  
Ibrahim Halil Ozerol ◽  
Saim Yologlu

Abstract Background Obesity is known to cause metabolic disturbances including insulin resistance, dyslipidemia and alters bone mineralization. The effects of obesity on fibroblast growth factor 23 (FGF-23), which is important in bone mineralization, have not yet been clarified. Our aim was to investigate the association between FGF-23 concentration and obesity-associated dysmetabolism. Methods Subjects comprised 46 obese children and adolescents. The same number of age-matched, healthy controls were recruited. Markers of bone mineralization and glucose metabolism were measured. Thyroid function and insulin resistance were investigated in both groups. In obese subjects; an oral glucose tolerance test (OGTT) was performed and hemoglobin A1c and lipid fractions were measured. Bone mineral density and hepatic steatosis were investigated. Results Serum FGF-23, α-klotho and 1,25(OH)2D3 concentrations were significantly lower while fasting insulin, fasting glucose, C-peptide and alkaline phosphatase (ALP) concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the obese group compared to controls. A significant negative correlation was observed between free tri-iodothyronine (fT3) and both FGF-23 and α-klotho in the obese group. Significant negative correlation was found between FGF-23 and C-peptide and a positive correlation was found between FGF-23 and high density lipoprotein-cholesterol (HDL-c) in the obese subjects with impaired glucose tolerance (IGT). Significant negative correlations were found between FGF-23 and both fasting insulin levels and C-peptide levels in the obese subjects with hepatic steatosis. Conclusions In our study, insulin resistance-associated hyperinsulinism and/or lower 1,25(OH)2D3 levels, both present in obese children and adolescents, may lead to decreased serum FGF-23 concentrations in obese subjects.


2013 ◽  
Vol 80 (5) ◽  
pp. 671-676 ◽  
Author(s):  
José C. Fernández-García ◽  
Mora Murri ◽  
Leticia Coin-Aragüez ◽  
Juan Alcaide ◽  
Rajaa El Bekay ◽  
...  

2021 ◽  
Vol 10 (8) ◽  
pp. 1716
Author(s):  
Idoia Genua ◽  
Núria Puig ◽  
Inka Miñambres ◽  
Sonia Benítez ◽  
Pedro Gil ◽  
...  

The effect of bariatric surgery on lipid profile and the qualitative characteristics of lipoproteins was analyzed in morbidly obese subjects. Thirteen obese patients underwent bariatric surgery. Plasma samples were obtained before surgery and at 6 and 12 months after the intervention. Thirteen healthy subjects comprised the control group. Lipid profile, hsCRP, and the composition and functional characteristics of VLDL, LDL, and HDL were assessed. At baseline, plasma from subjects with obesity had more triglycerides, VLDLc, and hsCRP, and less HDLc than the control group. These levels progressively normalized after surgery, although triglyceride and hsCRP levels remained higher than those in the controls. The main differences in lipoprotein composition between the obese subjects and the controls were increased apoE in VLDL, and decreased cholesterol and apoJ and increased apoC-III content in HDL. The pro-/anti-atherogenic properties of LDL and HDL were altered in the subjects with obesity at baseline compared with the controls, presenting smaller LDL particles that are more susceptible to modification and smaller HDL particles with decreased antioxidant capacity. Bariatric surgery normalized the composition of lipoproteins and improved the qualitative characteristics of LDL and HDL. In summary, patients with obesity present multiple alterations in the qualitative properties of lipoproteins compared with healthy subjects. Bariatric surgery reverted most of these alterations.


2003 ◽  
Vol 149 (4) ◽  
pp. 331-335 ◽  
Author(s):  
JV Silha ◽  
M Krsek ◽  
JV Skrha ◽  
P Sucharda ◽  
BL Nyomba ◽  
...  

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.


2016 ◽  
Vol 7 (8) ◽  
pp. 3390-3401 ◽  
Author(s):  
Damiana D. Rosa ◽  
Łukasz M. Grześkowiak ◽  
Célia L. L. F. Ferreira ◽  
Ana Carolina M. Fonseca ◽  
Sandra A. Reis ◽  
...  

Kefir supplementation in rats with induced metabolic syndrome was able to lower fasting glucose, fasting insulin levels, and reduce insulin resistance.


2021 ◽  
Vol 10 (10) ◽  
pp. 1326-1336
Author(s):  
Nannan Bian ◽  
Xiaomeng Sun ◽  
Biao Zhou ◽  
Lin Zhang ◽  
Qiu Wang ◽  
...  

Objective Bariatric surgery has become the most effective treatment for morbid obesity. Increasing evidence showed that bariatric surgery can alleviate insulin resistance and influence thyroid function. This study aimed to investigate the relationship between changes in thyroid function and adipose tissue insulin resistance (adipo-IR) after bariatric surgery. Methods A total of 287 non-diabetic participants with regular thyroid function were recruited and divided into the lean, overweight and obese groups. Among them, 50 morbidly obese patients submitted to bariatric surgery. Results The obese group had a higher level of adipo-IR, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), FT3/free thyroxine (FT4) and metabolism disorders than the lean and overweight groups. BMI was correlated with TSH, FT3, FT3/FT4 and adipo-IR (r = 0.309, 0.315, 0.322 and 0.651, respectively, all P < 0.001). Adipo-IR was significantly correlated with TSH (r = 0.402, P < 0.001), FT3 (r = 0.309, P < 0.001), and FT3/FT4 (r = 0.228, P < 0.05). Bariatric surgery resulted in a sharp decline in BMI, adipo-IR, TSH, FT3 and FT3/FT4 levels, meanwhile, metabolic disorders improved. The decrease in BMI after bariatric surgery was significantly correlated with reductions in adipo-IR (r = 0.577, P < 0.001) and TSH (r = 0.401, P = 0.005). Interestingly, the fasting blood glucose, fasting insulin, adipo-IR and TSH in the higher TSH group decreased more remarkably than in the lower TSH group. Conclusion Obese individuals with higher TSH levels had an obvious metabolic improvement after bariatric surgery.


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