Achieving a healthy weight balance has been a central focus of care for people who have cystic fibrosis (CF). Over the years, the emphasis has primarily been on promoting weight gain to optimize ...pulmonary outcomes. With continued improvements in CF care, including highly effective CF modulators available for many people, the CF community is now experiencing a new challenge: addressing the concern that some people are gaining weight excessively. While at this time, we do not know to what extent overweight and obesity will affect health outcomes for people with CF, it is likely that excessive weight gain may have negative health impacts similar to those seen in the general population. In this paper, we review the history of nutritional guidelines for people with CF, as well as more recent trends toward overweight and obesity for some. A multidisciplinary approach is needed to collaboratively start the oftentimes difficult conversation regarding excessive weight gain, and to identify resources to help people achieve and maintain a healthy weight through diet, exercise, and behavioral modification.
Abstract
Objective
We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of ...latent autoimmune diabetes in adults (LADA) and type 2 diabetes.
Methods
We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP).
Results
The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data). Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO.
Conclusions
Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.
Although a higher prevalence of overweight/obesity was reported in clinical samples of patients with Attention-Deficit/Hyperactivity Disorder (ADHD), an association between overweight and ADHD has ...yet not been established in the general population in childhood. As both disorders are common and significantly affect psychosocial functioning, we investigated the prevalence of ADHD in overweight/obese youth and vice versa. In a cross-sectional nationally representative and community based survey 2,863 parents and their children aged 11–17 years rated symptoms on the Diagnostic and Statistical Manual of Mental Disorders-based German ADHD Rating scale. Weight and height were assessed by professionals. Body mass index was categorized according to national age and sex specific reference values. Overall, 4.2% of the respondents met criteria for ADHD. The prevalence of ADHD was significantly higher for overweight/obese (7%) than for normal weight (3.5%) and underweight (4.9%) children. In a logistic regression analysis controlling for age, gender, and socio-economic status, overweight/obese children were twice as likely to have an ADHD diagnosis (OR = 2.0). Vice versa, adjusting for all covariates, children with ADHD had an OR of 1.9 for overweight/obesity status. For all weight-status groups, children with ADHD more frequently reported eating problems as compared to their non-clinical counterparts. Overweight/obese respondents with ADHD displayed the highest level of health services utilization. A clinician should be aware of the significant risk for a child with ADHD to become overweight and for an overweight child to have ADHD. Longitudinal studies are needed to better understand the mechanisms underlying the association between ADHD and overweight/obesity.
The growing concern about the impact of overweight on health has led to studies that shed light on types of obesity other than the classic model based on body mass index. Normal-weight obesity ...syndrome is characterized by excess body fat in individuals with adequate body mass index (18.5–24.9 kg/m2). This condition increases the risk of cardiovascular morbidity and mortality and other conditions associated with chronic diseases, such as insulin resistance, hypertension, and dyslipidemia. The aims of this review are to define the diagnostic criteria for normal-weight obesity syndrome and to examine the risks associated with this condition in order to promote preventive measures and early treatment for affected individuals.
Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory ...biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.
Children from families who immigrated to the United States may consume a lower-quality diet compared with their US-born peers. However, specific features of their dietary patterns, which could be a ...focus for improving diet quality, are not well-studied.
The aim of this study was to examine dietary patterns that distinguish interpersonal variability in dietary intake and explore the association of dietary patterns with nutrient intake and weight status.
This study was a cross-sectional analysis of baseline data from the Live Well randomized controlled trial collected between 2009 and 2010.
Study participants included 313 children (3-12 years) whose mothers immigrated to the United States from Latin America and resided in Somerville, Massachusetts.
Dietary patterns (derived using principal component analysis); nutrient intake (derived from dietary data collected using the Block Food Screener); and weight status (categorized using body mass index z score based on measured height and weight).
Nutrient intake levels were compared across quartiles for dietary patterns using analysis of covariance. Multivariable logistic or linear regression models were used to determine the associations between dietary pattern scores and odds of overweight or obesity or z scores.
Two dietary patterns emerged: “fruits and vegetables” and “meat and sweets.” Highest adherence to the fruits and vegetables pattern was associated with more healthful nutrient intake and lower odds of having overweight or obesity (odds ratio 0.37; 95% CI 0.16 to 0.98), but not body mass index z score (β = –.07; 95% CI –.51 to 0.36) compared with the lowest adherence. Adherence to the meat and sweets pattern was associated with less healthful nutrient intake but not with the odds of experiencing overweight or obesity (odds ratio 0.48; 95% CI 0.16 to 1.46).
A healthful dietary pattern in children of families who immigrated to the United States from Latin America may include a variety of fruits and vegetables. Longitudinal studies should be conducted to further assess the role of dietary intake patterns on the health of these children.
The existence of a paradoxical association between overweight/obesity and survival benefits, the so-called obesity paradox, in heart failure (HF) as well as coronary artery disease (CAD) remains ...contentious. Previously, we reported that a past history of CAD negated the obesity paradox in the general population with acute HF. Herein, we further focused on HF complicating acute myocardial infarction (AMI) and compared the prognostic effects of overweight/obesity with respect to the severity of HF.
We conducted a multicenter retrospective study of 7265 consecutive patients with AMI. The severity of HF was categorized according to the Killip classification. Overweight/obesity was defined as a body mass index (BMI) of ≥25 kg/m2. The interaction between overweight/obesity and the Killip classification for in-hospital mortality was tested in the entire cohort. Multivariable logistic regression analyses were performed to examine the effects of overweight/obesity on in-hospital mortality.
Across the entire study cohort, 1931 patients had HF. Overweight/obesity had a significant association with reductions in in-hospital mortality in patients with mild HF (Killip class II; odds ratio OR, 0.284; P = 0.019). Conversely, overweight/obesity was a significant risk factor for in-hospital mortality in patients with severe HF (Killip class IV; OR, 2.152; P = 0.001). The effects of overweight/obesity on in-hospital mortality in patients with moderate HF (Killip class III) were intermediate between those with mild HF and severe HF.
Opposing effects of overweight/obesity on in-hospital mortality in patients with mild HF versus severe HF were demonstrated, suggesting a balance between beneficial and deleterious effects of overweight/obesity may be inclined toward the latter with the severity of HF complicating AMI.
To evaluate the associations of body mass index (BMI) with all-cause, cardiovascular disease (CVD), and expanded CVD mortality in the elderly.
Observational cohort study.
Annual physical examination ...program for the elderly from 2006 to 2010.
We included 77,541 Taipei residents aged ≥ 65 years (39,365 men and 38,176 women).
BMI was categorized as underweight (BMI<18.5), normal weight (18.5 ≤ BMI<25), overweight (25 ≤ BMI<30), grade 1 obesity (30 ≤ BMI<35), or grade 2-3 obesity (BMI ≥ 35). Mortality was ascertained by national death files.
Underweight (hazard ratios HRs of all-cause, CVD, and expanded CVD mortality: 1.92, 1.74, and 1.77, respectively), grade 2-3 obesity (HRs: 1.59, 2.36, and 2.22, respectively), older age, male sex, smoking, and high fasting blood sugar were significant predictors of mortality. Meanwhile, being married/cohabitating, higher education, alcohol consumption, more regular exercise, and high total cholesterol were inversely associated with mortality. Multivariate stratified subgroup analyses verified smokers (HRs of all-cause, CVD, and expanded CVD mortality: 3.25, 10.71, and 7.86, respectively, for grade 2-3 obesity), the high triglyceride group (HRs: 5.82, 10.99, and 14.22, respectively for underweight), and patients with 3-4 factors related to metabolic syndrome (HRs: 4.86, 12.72, and 11.42, respectively, for underweight) were associated with mortality.
The associations of BMI with all-cause, CVD, expanded CVD mortality in the elderly are represented by U-shaped curves, suggesting unilateral promotions or interventions in weight reduction in the elderly may be inappropriate. Heterogeneous effects of grades 1 and 2-3 obesity on mortality were observed and should be treated as different levels of obesity.
A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) ...cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse.
We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79).
Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (∼0.84 MJ/d).
Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R(2) = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein α activity (z = 2.0, P = 6.6 × 10(-7)), liver X receptor α/β agonism (z = 2.1, P = 2.8 × 10(-7)), and inhibition of leptin-like signaling (z = -2.6, P = 3.9 × 10(-5)).
We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction-mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype.
Aims
To determine the effects of glucagon‐like peptide (GLP)‐1 receptor agonists (RA) on uric acid (UA) levels and kidney UA clearance.
Material and methods
This study involved post‐hoc analyses of 4 ...controlled clinical trials, which assessed actions of GLP‐1RA administration on kidney physiology. The immediate effects of GLP‐1RA exenatide infusion vs placebo were determined in 9 healthy overweight men (Study‐A) and in 52 overweight T2DM patients (Study‐B). The effects of 12 weeks of long‐acting GLP‐1RA liraglutide vs placebo in 36 overweight T2DM patients (Study‐C) and of 8 weeks of short‐acting GLP‐1RA lixisenatide vs once‐daily titrated insulin glulisine in 35 overweight T2DM patients (Study‐D) were also examined. Plasma UA, fractional (inulin‐corrected) and absolute urinary excretion of UA (UEUA) and sodium (UENa), and urine pH were determined.
Results
Median baseline plasma UA level was 5.39 to 6.33 mg/dL across all studies (17%‐22% of subjects were hyperuricaemic). In Study‐A, exenatide infusion slightly increased plasma UA (+0.07 ± 0.02 mg/dL, P = .04), and raised absolute‐UEUA (+1.58 ± 0.65 mg/min/1.73 m2, P = .02), but did not affect fractional UEUA compared to placebo. Fractional UEUA and absolute UEUA correlated with increases in urine pH (r:0.86, P = .003 and r:0.92, P < .001, respectively). Fractional UEUA correlated with increased fractional UENa (r:0.76, P = .02). In Study‐B, exenatide infusion did not affect plasma UA, but increased fractional UEUA (+0.76 ± 0.38%, P = .049) and absolute UEUA (+0.75 ± 0.27 mg/min/1.73 m2, P = .007), compared to placebo. In regression analyses, both parameters were explained by changes in urine pH and, in part, by changes in UENa. In Study‐C, liraglutide treatment did not affect plasma UA, UEUA, UENa or urine pH, compared to placebo. In Study‐D, lixisenatide treatment increased UENa and urine pH from baseline, but did not affect plasma UA or UEUA.
Conclusion
Immediate exenatide infusion increases UEUA in overweight healthy men and in T2DM patients, probably by inhibiting Na+/H+‐exchanger type‐3 in the renal proximal tubule. Prolonged treatment with a long‐acting or short‐acting GLP‐1RA does not affect plasma UA or UEUA in T2DM patients with normal plasma UA levels and at relatively low cardiovascular risk. Our results suggest that the cardio‐renal benefits of GLP‐1RA are not mediated through changes in UA.
PDF
