Emmanuel Disse

A lipid-parameter-based index for estimating insulin sensitivity and identifying insulin resistance in a healthy population

AIM Insulin resistance needs to be identified as early as possible in its development to allow targeted prevention programmes. Therefore, we compared various fasting surrogate indices for insulin sensitivity using the euglycaemic insulin clamp in an attempt to develop the most appropriate method for assessing insulin resistance in a healthy population. METHODS Glucose, insulin, proinsulin, glucagon, glucose tolerance, fasting lipids, liver enzymes, blood pressure, anthropometric parameters and insulin sensitivity (Mffm/I) using the euglycaemic insulin clamp were obtained for 70 normoglycaemic non-obese individuals. Spearmans rank correlations were used to examine the association between Mffm/I and various fasting surrogate indices of insulin sensitivity. A regression model was used to determine the weighting for each variable and to derive a formula for estimating insulin resistance. The clinical value of the surrogate indices and the new formula for identifying insulin-resistant individuals was evaluated by the use of receiver operating characteristic (ROC) curves. RESULTS The variables that best predicted insulin sensitivity were the HDL-to-total cholesterol ratio, the fasting NEFA and fasting insulin. The use of the lipid-parameter-based formula Mffm/I=12x[2.5x(HDL-c/total cholesterol)-NEFA] - fasting insulin appeared to have high clinical value in predicting insulin resistance. The correlation coefficient between Mffm/I and the new fasting index was higher than those with the most commonly used fasting surrogate indices for insulin sensitivity. CONCLUSION A lipid-parameter-based index using fasting samples provides a simple means of screening for insulin resistance in the healthy population.

Need for Intensive Nutrition Care After Bariatric Surgery Is Mini Gastric Bypass at Fault

Severe nutrition complications after bariatric surgery remain poorly described. The aim of this case series was to identify specific factors associated with nutrition complications after bariatric surgery and to characterize their nutrition disorders. We retrospectively reviewed all people referred to the clinical nutrition intensive care unit of our university hospital after bariatric surgery from January 2013 to June 2015. Twelve persons who required artificial nutrition supplies (ie, enteral nutrition or parenteral nutrition) were identified. Seven persons underwent a “one-anastomosis gastric bypass” (OAGB) or “mini gastric bypass,” 2 underwent a Roux-en-Y gastric bypass, 2 had a sleeve gastrectomy, and 1 had an adjustable gastric band. This case series suggests that OAGB could overexpose subjects to severe nutrition complications requiring intensive nutrition care and therefore cannot be considered a “mini” bariatric surgery. Even if OAGB is often considered a simplified surgical technique, it obviously requires as the other standard bariatric procedures a close follow-up by experimented teams aware of its specific complications.

Increased TSH in obesity: Evidence for a BMI-independent association with leptin

AIM This study aimed to determine whether the association between thyroid-stimulating hormone (TSH) and body mass index (BMI) is related to leptin concentration in obese individuals. METHODS Plasma TSH and leptin assays were performed in 800 consecutive patients, hospitalized for a nutritional checkup, with a BMI ≥ 30 kg/m(2). Various anthropometric, hormonal and metabolic parameters, including age, weight, BMI, insulin, leptin and TSH, were measured or calculated. Univariate and multivariate regression analyses were performed to identify any significant relationships between these parameters. Also, characteristics of the patients in the lowest and highest quartiles of TSH distribution were compared. RESULTS TSH was positively correlated with both BMI and leptin. When multiple regression analysis was performed, TSH and leptin maintained a significant association independent of BMI. Patients in the fourth quartile of TSH distribution displayed higher BMI and higher leptin levels in comparison to the first quartile. CONCLUSION Our study has confirmed an increase in TSH in conjunction with BMI in obese subjects. This increase was correlated with leptin independently of BMI. It is hypothesized that the increase in TSH observed in obese subjects was the consequence of both fat mass accumulation and a positive energy-balance.

Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?

AIM This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated. RESULTS Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) μg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. CONCLUSION Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).

Should we wait for metabolic complications before operating on obese patients? Gastric bypass outcomes in metabolically healthy obese individuals.

BACKGROUND A subgroup of obese patients without metabolic disorders has been identified and defined as metabolically healthy but morbidly obese (MHMO). OBJECTIVES To compare Roux-en-Y gastric bypass (RYGB) outcomes between MHMO and metabolically unhealthy morbidly obese (MUMO) patients to assess whether the obesity phenotype could affect the results. SETTING A university-affiliated tertiary care center. METHODS One hundred nineteen consecutive patients underwent RYGB; 102 completed the 2-year follow-up and were divided into 2 groups (MHMO and MUMO) according to Wildman criteria, including blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood sugar, C-reactive protein (CRP), and homeostasis model assessment of insulin resistance (HOMA-IR). Weight loss and metabolic parameter changes were analyzed. RESULTS Twenty-one of 102 (20.6%) patients were identified as MHMO; they were mostly women (90.5%) and were significantly younger than MUMO patients (39.4 ± 9.1 yr versus 47.2 ± 10, P = .001); 12.6% were lost to follow-up. MHMO phenotype was significantly associated with a greater percentage of excess body mass index loss (P = .03), independent of gender, age, and redo procedures. All metabolic parameters were significantly improved 2 years after surgery in the MUMO group. HOMA-IR, CRP, and triglycerides were significantly lower 2 years after surgery in the MHMO group, whereas fasting blood sugar and HDL-C were unchanged. At 2 years of follow-up, 92.3% of the population was metabolically healthy. CONCLUSIONS RYGB is an effective procedure to achieve weight loss and had a strong positive metabolic effect in both MHMO and MUMO phenotypes. RYGB led to an increase of the metabolically healthy status and may prevent or delay the onset of metabolic disorders.

Relevance of Roux-en-Y gastric bypass volumetry using 3-dimensional gastric computed tomography with gas to predict weight loss at 1 year

BACKGROUND Causes of Roux-en-Y gastric bypass (RYGB) failures are still controversial. Literature data suggest that gastric pouch or gastrojejunal anastomosis distentions over time could be a key factor. Making the hypothesis that progressive distention of RYGB volumes is 1 of the main factors of weight loss failure, the aim of our study was to evaluate bypass volumes changes using repeated 3-dimensional gastric computed tomography with gas and the possible negative correlation with weight loss results at 1 year. METHODS Thirty-nine patients eligible for RYGB were prospectively included. Gastric bypass volumes were assessed at 3 and 12 months postsurgery performing 3-dimensional gastric computed tomography with gas and weight loss outcomes were recorded during the first postoperative year. RESULTS There was no loss to follow up. Mean % excess body mass index lost (%EBMIL) at 1 year was 66.7%. Seven patients (17.9%) did not reach Reinhold criteria and were considered as RYGB failures. We found no linear correlation between the 1 year %EBMIL and mean values of the gastric pouch (r=.01; P=.94), and the neo stomach (r=.09 ; P=.57) at 3 months. Revisional surgery was correlated negatively with %EBMIL at 1 year. CONCLUSION Weight loss at 1 year does not seem to be correlated to RYGB volume changes. Behavioral factors probably play a major role in weight loss failure.

Deep brain stimulation as a therapeutic option for obesity: A critical review

Despite a better understanding of obesity pathophysiology, treating this disease remains a challenge. New therapeutic options are needed. Targeting the brain is a promising way, considering both the brain abnormalities in obesity and the effects of bariatric surgery on the gut-brain axis. Deep brain stimulation could be an alternative treatment for obesity since this safe and reversible neurosurgical procedure modulates neural circuits for therapeutic purposes. We aimed to provide a critical review of published clinical and preclinical studies in this field. Owing to the physiology of eating and brain alterations in people with obesity, two brain areas, namely the hypothalamus and the nucleus accumbens are putative targets. Preclinical studies with animal models of obesity showed that deep brain stimulation of hypothalamus or nucleus accumbens induces weight loss. The mechanisms of action remain to be fully elucidated. Preclinical data suggest that stimulation of nucleus accumbens reduces food intake, while stimulation of hypothalamus could increase resting energy expenditure. Clinical experience with deep brain stimulation for obesity remains limited to six patients with mixed results, but some clinical trials are ongoing. Thus, drawing clear conclusions about the effectiveness of this treatment is not yet possible, even if the results of preclinical studies are encouraging. Future clinical studies should examine its efficacy and safety, while preclinical studies could help understand its mechanisms of action. We hope that our review will provide ways to design further studies.

Ghrelin concentration as an indicator of eating-disorder risk in obese women

AIM Eating disorders (EDs), disordered eating (DE) and obesity are thought to have overlapping aetiological processes. DE in obesity can jeopardize weight-loss results, and acyl ghrelin (AG) is a hormone that stimulates food intake and reward processes. The main study objective was to determine whether higher-than-expected concentrations of AG in common obesity are associated with DE symptoms. METHODS The study population included 84 women, aged 20-55 years, free of established EDs: 55 were severely obese (OB) and 29 were of normal weight (NW). OB participants were stratified into two groups according to their median concentration of fasting AG distribution. The OB women with a high fasting plasma ghrelin concentration (HGC) were compared with both OB women with a low fasting plasma ghrelin concentration (LGC) and NW women. Participants were assessed by the Eating Disorder Inventory (EDI-2), Three-Factor Eating Questionnaire (TFEQ) and Hospital Anxiety and Depression Scale (HADS). Fasting glucose, insulin, leptin and ghrelin plasma concentrations were also quantified. RESULTS Between the two AG groups of OB women, there was no statistical difference in either anthropometric or metabolic parameters, HADS, TFEQ or fasting hunger scores. However, the HGC group scored significantly higher than the LGC group on the drive-for-thinness subscale of EDI-2 (9.30±0.99 vs. 6.46±0.83, respectively; P=0.033). CONCLUSION Results support the hypothesis of a potential relationship between fasting plasma AG concentrations and ED risk, regardless of mood and anxiety. AG may be considered a potential biomarker of vulnerability for developing EDs.

P220 Bien qu’il n’inclut pas la glycémie dans son équation, l’index simple d’évaluation d’insulinorésistance (index Disse) est fiable chez les patients diabétiques de type 2

Introduction Le but de cette etude etait de comparer l’evaluation de la sensibilite a l’insuline a l’aide d’un nouvel index a jeun pour lequel l’equation n’inclue pas la glycemie (index Disse = 12 X [2,5 X (HDL-c/ Total cholesterol) – acides gras non esterifies] – insuline), avec les donnees du clamp hyperinsulinemique euglycemique chez des patients diabetiques de type 2. Cet index a ete valide pour les populations saines et obeses non diabetiques. Patients et Methodes Les donnees de clamp de 25 sujets presentant un diabete de type 2 (IMC = 30,2 ± 0,9 kg/m2, duree diabete : 34 ± 3 mois ; HbA1c : 9,1 ± 0,5 %) ont ete analysees. Les patients etaient traites par metformine (n = 11), sulfamide (n = 1), insuline (n = 1), dietetique seule (n = 2), insuline + metformine (n = 1) et metformine + sulfamides (n = 8). Les parametres biologiques mesures a jeun (glucose, insuline, cholesterol total et HDL, acides gras non esterifies) ont ete utilises pour calculer differents index simples (rapport glycemie/insulinemie, HOMA, QUICKI, Revised-QUICKI et index Disse). Les correlations et comparaisons entre les index et les donnees du clamp ont ete analysees par le test de correlation de Spearman et le diagramme des differences de Bland-Altman. Resultats Les index Disse, HOMA, QUICKI et Revised-QUICKI etaient significativement correles (p Conclusion Ces resultats etendent la validite de l’index Disse aux patients diabetiques de type 2. Ces resultats suggerent que l’index Disse peut etre utilise pour apprecier l’insulinoresistance dans la population generale et ce, quelque soit la tolerance au glucose des sujets.