Camilla Verdich

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects.OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake.METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal.SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1–43.8 kg/m2) and 12 lean (BMI 20.4–24.7 kg/m2) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4–23.2).RESULTS: Total area under the GLP-1 response curve (AUCtotal, GLP-1) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUCtotal, GIP and AUCincremental, GIP were lowered (P<0.05). An inverse correlation was observed between AUCincremental, GIP and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r 2=0.67, P=0.001).CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.

Associations between postprandial insulin and blood glucose responses, appetite sensations and energy intake in normal weight and overweight individuals: a meta-analysis of test meal studies

It is unclear whether postprandial blood glucose or insulin exerts a regulatory function in short-term appetite regulation in humans. The aim of this study was to investigate, by use of meta-analysis, the role of blood glucose and insulin in short-term appetite sensation and energy intake (EI) in normal weight and overweight participants. Data from seven test meal studies were used, including 136 healthy participants (ALL) (92 normal weight (NW) and 44 overweight or obese (OW)). All meals were served as breakfasts after an overnight fast, and appetite sensations and blood samples were obtained frequently in the postprandial period. Finally, an ad libitum lunch was served. Data were analysed by fixed effects study level (SL) meta-regression analysis and individual participant data (IPD) regression analysis, using STATA software. In SL analysis, postprandial insulin response was associated with decreased hunger in ALL, NW and OW (P < 0.019), and with increased satiety in NW (P = 0.004) and lower subsequent EI in OW (P = 0.022). Multivariate IPD analysis showed similar associations, but only in NW for hunger, satiety and EI (P < 0.028), and in ALL for EI (P = 0.016). The only association involving blood glucose was the multivariate IPD analysis showing an inverse association between blood glucose and EI in ALL (P = 0.032). Our results suggest that insulin, but not glucose, is associated with short-term appetite regulation in healthy participants, but the relationship is disrupted in the overweight and obese. We conclude that the postprandial insulin response may be an important satiety signal, and that central nervous system insulin resistance in overweight might explain the blunted effect on appetite.

Effect of obesity and major weight reduction on gastric emptying.

BACKGROUND: An enhanced gastric emptying rate might reduce the satiating effect of food and thereby promote obesity. Gastric emptying rate has previously been compared between obese and lean subjects with conflicting outcome.OBJECTIVE: Comparison of gastric emptying rate in lean and obese subjects before and after a major weight reduction.DESIGN: The study was designed as a case–control study comparing obese and lean subjects and a subsequent comparison of obese subjects before and after a dietary induced major weight reduction.METHOD: Gastric emptying rate following a solid test meal was estimated scintigraphically for 3 h using the left anterior oblique projection.SUBJECTS: Nineteen non-diabetic obese (mean BMI=38.7 kg/m2) and 12 lean (mean BMI=23.1 kg/m2) males matched for age and height. All obese subjects were re-examined after a mean weight loss of 18.8 kg (95% CI, 14.4–23.2) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability.RESULTS: When comparing obese and lean subjects no differences were seen in overall 3 h emptying rate (30.3% per hour vs 30.5% per hour). However, a trend towards a higher percentage gastric emptying during the initial 30 min was seen in the obese when compared to lean subjects (24.0% vs 17.8% of the test meal; P=0.08). Weight loss was associated with a reduction in percentage gastric emptying during the initial 30 min (from 24.0% to 18.3% of the test-meal; P<0.02), whereas the overall 3 h emptying rate was unaffected (30.3% vs 30.9% per hour). Neither initial or overall emptying rate differed between reduced-obese and lean subjects.CONCLUSION: Overall 3 h gastric emptying rate was similar in obese and normal weight males, and unaffected by a major weight loss. However, percentage gastric emptying during the initial 30 min for a solid meal appeared to be increased in obese males and was normalized after a major weight reduction.

Genetic Polymorphisms and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets

Objectives: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. Design: Randomised, parallel, two-arm, open-label multi-centre trial. Setting: Eight clinical centres in seven European countries. Participants: 771 obese adult individuals. Interventions: 10-wk dietary intervention to hypo-energetic (−600 kcal/d) diets with a targeted fat energy of 20%–25% or 40%–45%, completed in 648 participants. Outcome Measures: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. Results: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from −0.6 to 0.8 kg, and homozygotes, from −0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to −1.6 kg in heterozygotes, and from 3.8 kg to −2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. Conclusions: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.

Randomized, multi-center trial of two hypo-energetic diets in obese subjects: high- versus low-fat content

Objective:To investigate whether a hypo-energetic low-fat diet is superior to a hypo-energetic high-fat diet for the treatment of obesity.Design:Open-label, 10-week dietary intervention comparing two hypo-energetic (−600 kcal/day) diets with a fat energy percent of 20–25 or 40–45.Subjects:Obese (BMI ⩾30 kg/m2) adult subjects (n=771), from eight European centers.Measurements:Body weight loss, dropout rates, proportion of subjects who lost more than 10% of initial body weight, blood lipid profile, insulin and glucose.Results:The dietary fat energy percent was 25% in the low-fat group and 40% in the high-fat group (mean difference: 16 (95% confidence interval (CI) 15–17)%). Average weight loss was 6.9 kg in the low-fat group and 6.6 kg in the high-fat group (mean difference: 0.3 (95% CI −0.2 to 0.8) kg). Dropout was 13.6% (n=53) in the low-fat group and 18.3% (n=70) in the high-fat group (P=0.001). Among completers, more subjects lost >10% in the low-fat group than in the high-fat group ((20.8%, n=70) versus (14.7%, n=46), P=0.02). Fasting plasma total, low-density lipoprotein- and high-density lipoprotein-cholesterol decreased in both groups, but more so in the low-fat group than in the high-fat group. Fasting plasma insulin and glucose were lowered equally by both diets.Conclusions:The low-fat diet produced similar mean weight loss as the high-fat diet, but resulted in more subjects losing >10% of initial body weight and fewer dropouts. Both diets produced favorable changes in fasting blood lipids, insulin and glucose.

Changes in body composition during weight loss in obese subjects in the NUGENOB study: comparison of bioelectrical impedance vs. dual-energy X-ray absorptiometry.

AIM We studied the accuracy of bioelectrical impedance analysis (BIA) to assess changes in body composition during moderate weight loss in obese subjects. METHODS Estimates of changes in fat mass (FM) and fat-free mass (FFM) by BIA were compared with those by dual-energy X-ray absorptiometry (DXA) as the reference method during a 10-week standardized weight-loss intervention. In obese women (age: 20-50 years, mean BMI: 33.8 kg/m(2)) participating in a European multicentre trial (nutrient-gene interactions in human obesity [NUGENOB]), body composition was assessed by BIA (Bodystat QuadScan 4000) and DXA (Lunar DPX-IQ at two centres, Hologic QDR 2000 at another centre) at baseline (n=131) and at week 10 (n=105) after a mean weight loss of -5.7 kg. RESULTS At baseline, BIA significantly overestimated FFM and underestimated FM (by 1-3 kg on average) compared with DXA, and the limits of agreement were wide (mean ± 7-8.5 kg). For body-composition changes, although biases were generally non-significant, the limits of agreement were also wide (mean ± 3.7-4.6 kg). An FFM prediction equation for BIA data was developed in subjects scanned with Lunar instruments and cross-validated in an independent sample of 31 obese women undergoing similar weight loss. However, no major improvement in limits of agreement was found. CONCLUSION During moderate diet-induced weight loss, the use of BIA leads to estimates of changes in body composition at the individual level that can differ substantially from those assessed by DXA, indicating that BIA and DXA cannot be used interchangeably. However, BIA in this context may be used for assessing changes in body composition at group level.

Total adiponectin and adiponectin multimeric complexes in relation to weight loss-induced improvements in insulin sensitivity in obese women: the NUGENOB study

AIM Adiponectin increases insulin sensitivity, protects arterial walls against atherosclerosis, and regulates glucose metabolism, and is decreased in obese, insulin resistant, and type 2 diabetic patients. Adiponectin circulates in plasma as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW form was suggested to be closely associated with insulin sensitivity. This study investigated whether diet-induced changes in insulin sensitivity were associated with changes in adiponectin multimeric complexes. SUBJECTS Twenty obese women with highest and twenty obese women with lowest diet induced changes in insulin sensitivity (responders and non-responders respectively), matched for weight loss (body mass index (BMI)=34.5 (s.d. 2.9) resp. 36.5 kg/m(2) (s.d. 4.0) for responders and non-responders), were selected from 292 women who underwent a 10-week low-caloric diet (LCD; 600 kcal/d less than energy requirements). Plasma HMW, MMW, and LMW forms of adiponectin were quantified using Western blot method. RESULTS LCD induced comparable weight reduction in responders and non-responders by 8.2 and 7.6 kg. Homeostasis model assessment insulin resistance index decreased by 48.1% in responders and remained unchanged in non-responders. Total plasma adiponectin and the quantity of HMW and MMW remained unchanged in both groups, while LMW increased by 16.3% in non-responders. No differences between both groups were observed at baseline and after the study. Total plasma adiponectin, MMW, and LMW were negatively associated with fasting insulin levels at baseline. CONCLUSION No differences in total plasma adiponectin, HMW, MMW, and LMW forms were observed between responders and non-responders following 10-week LCD, suggesting that adiponectin is not a major determinant of weight loss-induced improvements in insulin sensitivity.

Impaired Fat-induced Thermogenesis in Obese Subjects: The NUGENOB Study

Objectives: To study energy expenditure before and 3 hours after a high‐fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113).

Obese male subjects show increased resting forearm venous plasma noradrenaline concentration but decreased 24-hour sympathetic activity as evaluated by thrombocyte noradrenaline measurements

OBJECTIVE: To study resting forearm venous plasma noradrenaline (NA) and 24 h sympathoadrenal activity evaluated by measurements of thrombocyte NA and adrenaline (A) in obese male subjects before and after weight reduction.DESIGN: Blood samples were collected in obese subjects and in controls after an overnight fast.MEASUREMENTS: Fatness and fat distribution parameters, plasma and thrombocyte NA and A, lymphocyte β β2-adrenoceptor mRNA, cAMP and lymphocyte subset composition.RESULTS: Forearm venous plasma NA at rest was significantly elevated in the obese subjects and correlated to the body mass index and diastolic blood pressure. Thrombocyte NA and A correlated, however, negatively to the body fat % in obese subjects. Further analysis showed that thrombocyte NA and A were reduced in obese subjects with body fat % above 40% but not in the other groups. Weight reduction normalized both forearm venous plasma NA and thrombocyte NA and A. ββ2-adrenoceptor mRNA correlated positively to the frequency of CD3−CD56+ and CD3+CD8+ cells in the blood and negatively to plasma A, but there was no difference in the mRNA level, cyclic AMP and lymphocyte subset composition between obese and controls.CONCLUSIONS: Sympathetic activity at rest as evaluated by forearm venous plasma NA was increased in the obese male subjects and this abnormality was related to the increase in body mass index and the arterial blood pressure. Thrombocyte NA and A, which is likely to reflect 24 h plasma catecholamine concentrations were reduced in obese subjects with a body fat % above 40%, probably due to a reduced physical activity in these subjects. Both catecholamine parameters were normalized by weight reduction.