NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609 FTO Risk Allele.

Context: The FTO gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by FTO has not been rigorously tested for in a uniformly obese study population comprising both sexes. Objective: To test for associations of the rs9939609 FTO risk allele with NEFA suppression. Methods: We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression. Results: No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation (P > .7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression. Conclusion: In a gender-mixed adult population of obese individuals, an FTO obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance.

Oral health problems are associated with malnutrition in hospitalised adult patients.

BACKGROUND & AIMS: Hospitalised patients are especially vulnerable to malnutrition, which is associated with an increased risk of complications, leading to longer hospital stays, increased healthcare costs, and with a potentially negative effect on the prognosis. Poor oral health may make food intake difficult and contribute to poor nutritional status. The aim of the present cross-sectional study was to assess the occurrence of poor oral health and malnutrition in adult hospitalised patients, and further to investigate associations between oral health problems and malnutrition. METHODS: The Patient-Generated Subjective Global Assessment (PG-SGA) determined the patients' nutritional status. The oral health condition was evaluated according to the Revised Oral Assessment Guide-Jönköping (ROAG-J) and unstimulated salivary flow rate. Clinical information was collected from medical records. RESULTS: The study population included 118 patients from 15 somatic and 3 psychiatric wards at a University Hospital in Norway. Nearly half the patients (46%) were categorised as malnourished and in need of symptom alleviation or nutritional intervention. Malnutrition was found in all diagnostic conditions. According to ROAG-J, at least one oral health problem was identified in 93% of the patients. Severe oral health problems were more frequent in malnourished patients. Overall, both the number and total score of oral health problems were associated with malnutrition (OR 1.57, 95% CI 1.20-2.06 and OR 1.47, 95% CI 1.17-1.83, respectively). Of specific oral health items, problems with lips and mucous membranes were significantly associated with malnutrition. One-fifth of all patients had hyposalivation, but this was not associated with malnutrition. CONCLUSIONS: Oral health problems and malnutrition are commonly seen in hospitalised adult patients. The association between the two calls for raised awareness of oral health issues in assessing patients' nutritional status. Further study is required to clarify whether oral health problems constitute a causal factor in malnutrition.

Exploring Dietary Intake in Adults with Severe Obesity and Associations with the FTO rs9939609 Genotypes.

Background: Few have studied the associations between rs9939609 genotypes in the obesity candidate locus FTO and energy and nutrient intakes and meal frequencies in adults with severe obesity. We are unaware of studies that have assessed adherence to key dietary recommendations in this population, at least in Norway. Increased knowledge of genotype associations with dietary factors could improve personalized obesity therapy. Objectives: The present study aimed to explore how the rs9939609 genotypes associate with dietary variables and adherence to key dietary recommendations in a sample of adults with severe obesity. Methods: A cross-sectional observation study designed to have similar numbers of participants with genotypes TT, AT, and AA included 100 patients (70% women) with median (25th, 75th percentile) age 42 (32, 50) y and BMI 42.8 (39.5, 46.4) kg/m2. We assessed intakes of food groups, energy, and macro- and micronutrients from three 24-h dietary recalls and meal frequencies. Genotype associations were analyzed using regression analyses. Reported intakes were evaluated against national diet recommendations. Results: Using a significance level of 0.01, we found no genotype associations with energy intake, energy density, adherence to recommendations, or meal frequency but tendencies of associations with energy adjusted protein intake (AA > AT, P = 0.037; AT > TT, P = 0.064), food groups milk and cream (AT > TT, P = 0.029), and Mixed dishes (AA > TT, P = 0.039). Few participants complied with recommendations for intakes of whole grains (21%), fruits and vegetables (11%), and fish (37%); however, 67% followed the recommendation to limit added sugar. Less than 20% had recommended intakes of vitamin D and folate. Conclusions: In our patients with severe obesity, we found tendencies of associations between the FTO rs9939609 genotypes and diet but no significant associations at the 0.01 level and below. Few met key food-based diet recommendations, suggesting that the food habits in this population pose an increased risk of nutrient deficiencies. Curr Dev Nutr 2023;xx:xx.

The fat mass and obesity-associated (FTO) gene allele rs9939609 and glucose tolerance, hepatic and total insulin sensitivity, in adults with obesity.

The objective of the study was to assess associations of the rs9939609 FTO allele to glucose tolerance, hepatic and total insulin sensitivity (IS) in individuals with obesity. From a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer, hepatic IS was assessed by rates of basal and suppressed glucose appearance (Ra), a measure of endogenous glucose production (EGP), and the hepatic insulin resistance index (HIR). Total IS was assessed by rates of glucose infusion (GIR), disappearance (Rd), and metabolic clearance (MCR). From a meal test we assessed IS by the Matsuda index and glucose tolerance by glucose and insulin measurements in the fasted state and postprandially for 2.5 h. The meal test was performed in 97 healthy individuals with BMI ≥35 in similar-sized risk-allele groups (n = 32 T/T, 31 A/T, and 34 A/A), and 79 of them performed the clamp. We analyzed outcomes separately for males and females, and adjusted glucose Ra, Rd, MCR, GIR, and HIR for fat mass. We did not find genotype effects on EGP. Among males, genotype A/A was associated with a significantly lower glucose Rd, MCR, and Matsuda index score relative to genotype T/T. Glucose tolerance was significantly lower in males with genotype A/T vs. T/T and A/A. For females, there were no genotype effects on hepatic or total IS, or on glucose tolerance. Independently of genotypes, females displayed a significantly better hepatic and total IS, and better glucose tolerance than males. We conclude that in subjects with similar obesity we did not register any FTO risk-allele effect on hepatic IS. A FTO risk-allele effect on total IS was registered in males only, findings which need to be reproduced in further studies. Results confirm marked differences in IS between the biological sexes and extend present knowledge by demonstrating a lower endogenous glucose production in females vs. males in uniformly obese individuals.

Impact of a FTO gene risk variant on variables of energy metabolism in adults with obesity class 2 and 3.

PURPOSE: The metabolic consequences of carrying a FTO obesity-promoting risk allele have not been fully elucidated and may be confounded by obesity per se. Against this background, we investigated the impact of FTO allele (SNP rs9939609) on fasting and postprandial energy expenditure and fasting substrate expenditure in a study population of uniformly and similarly obese individuals. PROCEDURES: We studied a similar number of participants with BMI classes 2-3 (median BMI 42.8 kg/m2) who were either homozygote for the non-risk allele TT (n = 33, numbers increased by enrichment), heterozygote (AT) (n = 32), or homozygote for the risk allele AA (n = 35). MAJOR FINDINGS: Basal metabolic rate and postprandial energy expenditure did not differ between FTO-groups. However, fasting respiratory quotient (RQ) was increased in those carrying ≥1 risk allele (p = 0.008), whereas postprandial RQ was not. CONCLUSION: In this study population, the FTO-risk allele associates with fasting reduced fat and increased carbohydrate oxidation.

Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study.

BACKGROUND: Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. METHODS: The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). RESULTS: Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. CONCLUSIONS: In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.

Central obesity is associated with lower intake of whole-grain bread and less frequent breakfast and lunch: results from the HUNT study, an adult all-population survey.

All-population and area-based investigations of diet in central obesity are scarce. We used cross-sectional data from 50 339 individuals who responded to the HUNT3 survey of 2006-2008, which recruited from all county-residing adults 20 years and older, to investigate whether those with central obesity eat and drink differently than others. Answers to dietary questions were recoded and analyzed with multiple linear regression, using waist/hip ratio (WHR), age, and sex as explanatory variables. Frequencies of consumption or amounts of food, beverages, and meals were compared among WHR quartiles. Central obesity was present in the quartile with the highest WHR, WHR4 (WHR ≥ 0.917 for women and 0.981 for men) but not in the quartile with the lowest WHR, WHR1 (WHR < 0.817 for women and 0.895 for men). Dietary variables differed markedly by age and sex. After adjustment for these factors and for multiple testing, we found significant differences between WHR4 and WHR1 for 19 of 30 dietary variables. Central obesity was associated with a lower intake of any bread, and of whole-grain bread in particular. Intake of fruits and berries, vegetables, and pasta and rice was less, and intake of sausages and hamburgers and boiled potatoes was more frequent. Intake of alcohol, tea, and fruit juice was lower in those with central obesity, whereas intake of sugar-free soft drinks and coffee was higher. The frequency of breakfast and lunch was lower and of nightly meals was higher in those with central obesity. In conclusion, in this large area-based population, central obesity was associated with differences in dietary habits, some of which (such as decreased consumption of whole-grain bread and increased intake of sugar-free drinks) are of possible clinical significance.