Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids ...(SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (
H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our
H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.
Body fat distribution is, next to overall obesity, an important risk factor for cardiometabolic outcomes in the general population. In particular, visceral adipose tissue (VAT) is strongly associated ...with cardiometabolic risk factors. Since it is unclear whether body fat distribution is also important in men and women with obesity we investigated the associations between measures of body fat distribution and cardiometabolic risk factors in men and women with obesity.
In this cross-sectional analysis of obese men and women (BMI≥30 kg/m2) included in the Netherlands Epidemiology of Obesity Study, waist:hip ratio(WHR), waist circumference, and MRI-based abdominal subcutaneous adipose tissue (aSAT) and VAT were determined. Associations between measures of body fat distribution and presence of ≥1 risk factor, such as hypertension or hypertriglyceridemia, were examined using logistic regression analyses; stratified by sex and adjusted for age, ethnicity, education, tobacco smoking, alcohol consumption, physical activity and depending on the association additionally for total body fat or VAT.
We included 2,983 obese individuals (57% women) with a mean age of 56 and standard deviation (SD) of 6 and mean BMI of 34.0 kg/m2 (4.0), after exclusion of individuals with missing values of cardiometabolic risk factors (n = 33). 241 individuals were obese without other cardiometabolic risk factors. In obese women, all measures of body fat distribution except aSAT (OR per SD:0.76, 95%CI: 0.53, 1.10) were associated with having ≥1 cardiometabolic risk factor, of which VAT most strongly associated (5.77; 3.02, 11.01). In obese men, associations of body fat distribution and the presence of cardiometabolic risk factors were attenuated. (e.g. VAT:1.42; 0.84, 2.41).
In obese women, but less so in men, measures of body fat distribution, of which VAT most strongly, are associated with cardiometabolic risk factors.
The relative importance of overweight after childhood and excess weight gain during adulthood remains unclear. In 39,909 male participants of the Health Professionals Follow-Up Study who were 40-75 ...years of age in 1986 and were followed until 2008, we documented 8,755 incident cases of obesity-related chronic diseases (type 2 diabetes mellitus, cardiovascular diseases, and colorectal, renal, pancreatic, and esophageal cancers). We calculated composite and cause-specific hazard ratios using a model that included body mass index (BMI; weight (kg)/height (m)(2)) at 21 years of age, weight change since age 21 years, smoking, alcohol consumption, and family histories of myocardial infarction, colon cancer, and diabetes. Compared with a BMI at 21 years of 18.5-22.9, the composite hazard ratio for a BMI of 23-24.9 was 1.22 (95% confidence interval (CI): 1.16, 1.29), that for a BMI of 25.0-27.4 was 1.57 (95% CI: 1.48, 1.67), that for a BMI of 27.5-29.9 was 2.40 (95% CI: 2.17, 2.65), and that for a BMI ≥30.0 was 3.15 (95% CI: 2.76, 3.60). The composite hazard ratios for adult weight gain compared with a stable weight were 1.12 (95% CI: 1.03, 1.22) for a gain of 2.5-4.9 kg, 1.41 (95% CI: 1.31, 1.52) for a gain of 5-9.9 kg, 1.72 (95% CI: 1.59, 1.86) for a gain of 10-14.9 kg, and 2.45 (95% CI: 2.27, 2.63) for a gain ≥15 kg. Adiposity in early adulthood and adult weight gain were both associated with marked increases in the risk of major chronic diseases in middle-aged and older men, and these associations were already apparent at modest levels of overweight and weight gain.
Fatty liver is the leading cause of chronic liver diseases and increases the risk of cardiovascular disease. Besides alcohol consumption, energy-containing nonalcoholic beverages may contribute to ...liver fat accumulation.
We aimed to study the consumption of alcoholic and nonalcoholic beverages and their mutual replacement in relation to hepatic triglyceride content (HTGC) in middle-aged men and women.
In this cross-sectional analysis, HTGC was assessed by proton magnetic resonance spectroscopy. Habitual consumption of alcoholic and nonalcoholic beverages was assessed using a validated food-frequency questionnaire. All beverages were converted to standard servings and to percentage of total energy intake (En%). We performed linear regression to examine the association of alcoholic and nonalcoholic beverages with HTGC, adjusted for age, sex, smoking, education, ethnicity, physical activity, total energy intake, and total body fat. We studied replacement of alcoholic beverages with nonalcoholic beverages per 1 serving/d and per 5 En%/d.
After exclusion of individuals with missing values, 1966 participants (47% men) were analyzed, with a mean ± SD age of 55 ± 6 y, BMI of 26 ± 4 kg/m2, and HTGC of 5.7% ± 7.9%. Each extra alcoholic serving per day was associated with more liver fat (1.09 times; 95% CI: 1.05, 1.12). Replacing 5 En% of alcoholic beverages with milk was associated with less liver fat (0.89 times; 95% CI: 0.81, 0.98), whereas replacement with 5 En% of sugar-sweetened beverages was associated with liver fat to an extent similar to alcoholic beverages (1.00 times; 95% CI: 0.91, 1.09).
In a population-based cohort, consumption of each extra daily alcoholic beverage was associated with more liver fat. In isocaloric replacement of alcoholic beverages, milk was associated with less liver fat, whereas sugar-sweetened beverages were equally associated with liver fat. This suggests that intake of alcohol and sugars may contribute to liver fat accumulation. This trial was registered at clinicaltrials.gov as NCT03410316.
Visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) are major risk factors for cardiometabolic diseases.
We aimed to investigate the association of dietary intake of the main food ...groups with VAT and HTGC in middle-aged men and women.
We used data from the Netherlands Epidemiology of Obesity study, a population-based study including 6671 participants aged 45–65 y at baseline. In this cross-sectional analysis, VAT and HTGC were assessed by magnetic resonance imaging and spectroscopy, respectively, as the primary outcomes. Habitual intake of main food groups (dairy, meat, fish, fruits and vegetables, sweet snacks, and fats and oils) was estimated through the use of a food-frequency questionnaire. We examined associations of intake of different food groups with VAT and HTGC by linear regression analysis stratified by sex and adjusted for age, smoking, education, ethnicity, physical activity, basal metabolic rate, energy-restricted diet, menopausal state, and total energy intake.
In women, a 100-g/d higher intake of dairy was associated with 2.0 cm2 less VAT (95% CI: −3.4, −0.7 cm2) and a 0.95-fold lower HTGC (95% CI: 0.90-, 0.99-fold). Moreover, a 100-g/d higher intake of fruit and vegetables was associated with 1.6 cm2 less VAT (95% CI: −2.9, −0.2 cm2) in women. Fruit and vegetables were negatively associated (0.95; 95% CI: 0.91, 1.00) with HTGC, and sweet snacks were positively associated (1.29; 95% CI: 1.03, 1.63). Patterns were weaker but similar in men. Fish intake was not associated with VAT or HTGC and plant-based fat and oil intake were only associated with VAT after adjustment for total body fat.
Despite some variation in the strength of the associations between men and women, dietary intake of sweet snacks was positively associated with HTGC, and fruit and vegetable intake were negatively associated with visceral and liver fat content. Prospective studies are needed to confirm these results. The Netherlands Epidemiology of Obesity study is registered at clinicaltrials.gov with identifier NCT03410316.
To understand how individuals (self-)manage obesity, insight is needed into how patients perceive their condition and how this perception translates into health outcomes (e.g., health-related quality ...of life, HRQOL). Our objectives were (1) to examine illness perceptions in individuals with overweight and obesity, and (2) to investigate associations of these perceptions with physical and mental HRQOL.
In a cross-sectional analysis of the Netherlands Epidemiology of Obesity Study (n = 6432; 52% women), illness perceptions were assessed using the Brief Illness Perception Questionnaire, and HRQOL was assessed using the 36-Item Short-Form Health Survey. Illness perceptions were calculated for different categories of overall, abdominal, and metabolically unhealthy obesity. We investigated associations of illness perceptions with HRQOL using BMI-stratified multivariable linear regression analyses.
Compared to individuals with normal weight, individuals with obesity believed to a higher extent that their condition had more serious consequences Mean Difference (95%CI): 1.8 (1.6-2.0), persisted for a longer time 3.4 (3.2-3.6), manifested in more symptoms 3.8 (3.6-4.0), caused more worry 4.2 (3.9-4.4) and emotional distress 2.0 (1.8-2.2), but was more manageable with medical treatment 3.1 (2.9-3.4). They perceived to a lesser extent that they had personal control -2.2 (-2.4, -2.0) and understanding -0.3 (-0.5, -0.1) regarding their condition. These negative perceptions were less pronounced in individuals with abdominal obesity. Behaviour/Lifestyle was attributed by 73% of participants to be the cause of their obesity. Stronger negative illness perceptions were associated with impaired HRQOL, particularly the physical component.
Individuals with obesity perceived their conditions as threatening, and this seemed somewhat stronger in individuals with overall obesity than those with abdominal obesity. Behaviour/Lifestyle is a crucial target intervention and empowering self-management behaviour to achieve a healthy body weight may deliver promising results. In addition, strategies that aim to change negative perceptions of obesity into more adaptive ones may improve HRQOL.
In trans women receiving hormone therapy, body fat and insulin resistance increases, with opposite effects in trans men. These metabolic alterations may affect the risk of developing type 2 diabetes ...in trans women and trans men.
We aimed to compare the incidence of type 2 diabetes of adult trans women and trans men during hormone therapy with rates from their birth-assigned sex in the general population.
Retrospective data from the Amsterdam Cohort of Gender Dysphoria with transgender individuals on hormone therapy between 1972 and 2018 were linked to a nationwide health data registry. Because no central registry of diabetes is available, the occurrence of diabetes was inferred from the first dispense of a glucose-lowering agent. Standardized incidence ratios (SIR) were computed for trans women and trans men in comparison with the same birth sex from the general population.
Compared with their birth-assigned sex in the general population, no difference in the incidence of type 2 diabetes mellitus was observed in trans women (N = 2585, 90 cases; SIR 0.94; 95% CI, 0.76-1.14) or trans men (N = 1514, 32 cases; SIR 1.40; 95% CI, 0.96-1.92).
Despite studies reporting an increase in insulin resistance in feminizing hormone therapy and a decrease in insulin resistance in masculinizing hormone therapy, the incidence of diabetes in transgender individuals after initiation of hormone therapy was not different compared with the general population.
The effects of endocrinological treatment on cardiovascular risk profile in transgender adolescents are unknown. In this retrospective cohort study, we aim to investigate these effects and assess ...obesity and dyslipidemia prevalence in transgender adolescents at 22 years compared with peers.
Changes in BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and lipid values during treatment, along with the prevalence of obesity and dyslipidemia at 22 years, were recorded in 71 transwomen and 121 transmen who started gonadotropin-releasing hormone agonists in their adolescence (15 years), with a subsequent addition of sex hormones (17 years).
In transwomen, changes in BMI (+3.0; 95% confidence interval CI 1.6 to 4.4), SBP (-2 mm Hg; 95% CI -7 to 3), DBP (+10 mm Hg; 95% CI 7 to 14), glucose (0.0 mmol/L; 95% CI -0.2 to 0.2), HOMA-IR (+0.6; 95% CI -0.6 to 1.9), and lipid values were similar or more favorable compared with peers. The same was true for transmen regarding changes in BMI (+2.3; 95% CI 1.7 to 2.9), SBP (+7 mm Hg; 95% CI 3 to 10), DBP (+7 mm Hg; 95% CI 5 to 10), glucose (+0.1 mmol/L; 95% CI -0.1 to 0.3), HOMA-IR (-0.2; 95% CI -0.8 to 0.3), and lipid values. At age 22, obesity prevalence was 9.9% in transwomen, 6.6% in transmen, 2.2% in ciswomen, and 3.0% in cismen.
Generally, endocrinological treatment in transgender adolescents is safe regarding cardiovascular risk. Because obesity is more prevalent in transgender adolescents compared with peers, body weight management should be important during the medical trajectory.
Obesity is a well-established risk factor for many chronic diseases. Incomplete insight exists in the causal pathways responsible for obesity-related disorders and consequently, in the identification ...of obese individuals at risk of these disorders. The Netherlands Epidemiology of Obesity (NEO) study is designed for extensive phenotyping to investigate pathways that lead to obesity-related diseases. The NEO study is a population-based, prospective cohort study that includes 6,673 individuals aged 45–65 years, with an oversampling of individuals with overweight or obesity. At baseline, data on demography, lifestyle, and medical history have been collected by questionnaires. In addition, samples of 24-h urine, fasting and postprandial blood plasma and serum, and DNA were collected. Participants underwent an extensive physical examination, including anthropometry, electrocardiography, spirometry, and measurement of the carotid artery intima-media thickness by ultrasonography. In random subsamples of participants, magnetic resonance imaging of abdominal fat, pulse wave velocity of the aorta, heart, and brain, magnetic resonance spectroscopy of the liver, indirect calorimetry, dual-energy X-ray absorptiometry, or accelerometry measurements were performed. The collection of data started in September 2008 and completed at the end of September 2012. Participants are followed for the incidence of obesity-related diseases and mortality. The NEO study investigates pathways that lead to obesity-related diseases. A better understanding of the mechanisms underlying the development of disease in obesity may help to identify individuals who are susceptible to the detrimental metabolic, cardiovascular and other consequences of obesity and has implications for the development of prevention and treatment strategies.
The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ...ratio adjusted for body mass index WHRadjBMI) and general adiposity (body mass index BMI) with cardiometabolic disease.
Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis CARDIoGRAM plus The Coronary Artery Disease C4D Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.
Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio OR for CHD, 1.48; 95% confidence interval CI, 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m
; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD).
Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
PDF
