The LifeLines Cohort Study is a large population-based cohort study and biobank that was established as a resource for research on complex interactions between environmental, phenotypic and genomic ...factors in the development of chronic diseases and healthy ageing. Between 2006 and 2013, inhabitants of the northern part of The Netherlands and their families were invited to participate, thereby contributing to a three-generation design. Participants visited one of the LifeLines research sites for a physical examination, including lung function, ECG and cognition tests, and completed extensive questionnaires. Baseline data were collected for 167 729 participants, aged from 6 months to 93 years. Follow-up visits are scheduled every 5 years, and in between participants receive follow-up questionnaires. Linkage is being established with medical registries and environmental data. LifeLines contains information on biochemistry, medical history, psychosocial characteristics, lifestyle and more. Genomic data are available including genome-wide genetic data of 15 638 participants. Fasting blood and 24-h urine samples are processed on the day of collection and stored at -80 °C in a fully automated storage facility. The aim of LifeLines is to be a resource for the national and international scientific community. Requests for data and biomaterials can be submitted to the LifeLines Research Office LLscience@umcg.nl.
There is ongoing debate on the association between eosinophil count and diseases, as previous studies were inconsistent. We studied the relationship of eosinophil count with 22 complex metabolic, ...cardiac, and pulmonary traits and diseases. From the population-based LifeLines Cohort Study (N = 167,729), 13,301 individuals were included. We focused on relationship of eosinophil count with three classes of metabolic (7 traits, 2 diseases), cardiac (6 traits, 2 diseases), and pulmonary (2 traits, 2 diseases) outcomes. Regression analyses were applied in overall, women and men, while adjusted for age, sex, BMI and smoking. A p-value of <0.00076 was considered statistically significant. 58.2% of population were women (mean±SD 51.3±11.1 years old). In overall, one-SD higher of ln-eosinophil count was associated with a 0.04 (±SE ±0.002;p = 6.0×10-6) SD higher levels in ln-BMI, 0.06 (±0.007;p = 3.1×10-12) SD in ln-TG, 0.04 (±0.003;p = 7.0×10-6) SD in TC, 0.04 (±0.004;p = 6.3×10-7) SD in LDL, 0.04 (±0.006;p = 6.0×10-6) SD in HbA1c; and with a 0.05 (±0.004;p = 1.7×10-8) SD lower levels in HDL, 0.05 (±0.007;p = 3.4×10-23) SD in FEV1, and 0.09 (±0.001;p = 6.6×10-28) SD in FEV1/FVC. A higher ln-eosinophil count was associated with 1.18 (95%CI 1.09-1.28;p = 2.0×10-5) odds ratio of obesity, 1.29 (1.19-1.39;p = 1.1×10-10) of metabolic syndrome, 1.40 (1.25-1.56;p = 2.7×10-9) of COPD and 1.81 (1.61-2.03;p = 1.0×10-23) of asthma. Similar results were found in women. We found no association between ln-eosinophil count either with blood pressure indices in overall, women and men; or with BMI, LDL, HbA1c and obesity in men. In a large population based cohort, we confirmed eosinophil count as a potential factor implicated in metabolic and pulmonary outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the ...association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome.
The main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity.
The final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08-1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08-2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity.
In the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent studies have reported hemoglobin A1c (HbA1c) differences across ethnic groups that could limit its use in clinical practice. The authors of the A1C-Derived Average Glucose study have advocated ...to report HbA1c in estimated average glucose (AG) equivalents. The aim of this study was to assess the relationships between HbA1c and the mean of three 7-point self-monitored blood glucose (BG) profiles, and to assess whether estimated AG is an accurate measure of glycemia in different ethnic groups.
We evaluated 1,879 participants with type 2 diabetes in the DURABLE trial who were 30 to 80 years of age, from 11 countries, and, according to self-reported ethnic origin, were Caucasian, of African descent (black), Asian, or Hispanic. We performed logistic regression of the relationship between the mean self-monitored BG and HbA1c, and estimated AG, according to ethnic background.
Baseline mean (SD) HbA1c was 9.0% (1.3) (75 SD, 14 mmol/mol), and mean self-monitored BG was 12.1 mmol/L (3.1) (217 SD, 55 mg/dL). In the clinically relevant HbA1c range of 7.0-9.0% (53-75 mmol/mol), non-Caucasian ethnic groups had 0.2-0.5% (2-6 mmol/mol) higher HbA1c compared with Caucasians for a given BG level. At the mean self-monitored BG levels≤11.6 mmol/L, estimated AG overestimated the actual average BG; at levels>11.6 mmol/L, estimated AG underestimated the actual BG levels.
For a given degree of glycemia, HbA1c levels vary among different ethnic groups. Ethnicity needs to be taken into account when using HbA1c to assess glycemic control or to set glycemic targets. Estimated AG is not a reliable marker for mean glycemia and therefore is of limited clinical value.
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and ...become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.
Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This ...study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration.
In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day).
Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro.
Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.
The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its ...individual components.
64,046 participants aged 18-80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25-30, overweight; BMI≥30 kg/m2, obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis.
Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7-71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks.
Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Skin autofluorescence, a biomarker for advanced glycation end products (AGEs) accumulation, has been shown to predict diabetes-related cardiovascular complications and is associated with several ...environmental and lifestyle factors. In the present study, we examined the association between various smoking behaviors and skin autofluorescence, as well as the association between several cotinine biomarkers and skin autofluorescence, using both epidemiological and metabolomics data.
In a cross-sectional study, we evaluated participants from the LifeLines Cohort Study and the Qatar Metabolomics Study on Diabetes (QMDiab). In the LifeLines Cohort Study smoking behavior and secondhand smoking were assessed in 8,905 individuals including 309 individuals (3.5%) with type 2 diabetes. In QMDiab, cotinine biomarkers were measured in saliva, plasma and urine in 364 individuals of whom 188 (51%) had type 2 diabetes. Skin autofluorescence was measured non-invasively in all participants using the AGE Reader.
Skin autofluorescence levels increased with a higher number of hours being exposed to secondhand smoking. Skin autofluorescence levels of former smokers approached levels of never smokers after around 15 years of smoking cessation. Urinary cotinine N-oxide, a biomarker of nicotine exposure, was found to be positively associated with skin autofluorescence in the QMDiab study (p = 0.03).
In the present study, we have demonstrated that secondhand smoking is associated with higher skin autofluorescence levels whereas smoking cessation has a beneficial effect on skin autofluorescence. Finally, urinary cotinine N-oxide might be used as an alternative way for questionnaires to examine the effect of (environmental) tobacco smoking on skin autofluorescence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Health-related quality of life (HR-QoL) may be compromised in obese individuals, depending on the presence of other complications. The aim of this study is to assess the effect of obesity-related ...conditions on HR-QoL. These conditions are i) grade of obesity with and without type 2 diabetes (T2D), ii) metabolic syndrome (MetS), and iii) level of inflammation.
From the Dutch LifeLines Cohort Study we included 13,686 obese individuals, aged 18-80 years. HR-QoL was measured with the RAND 36-Item Health Survey which encompasses eight health domains. We calculated the percentage of obese individuals with poor HR-QoL, i.e. those scoring below the domain and sex specific cut-off value derived from the normal weight population. Logistic regression analysis was used to calculate the probability of having poor domain scores according to the conditions under study.
Higher grades of obesity and the additional presence of T2D were associated with lower HR-QoL, particularly in the domains physical functioning (men: odds ratios (ORs) 1.48-11.34, P<0.005, and women: ORs 1.66-5.05, P<0.001) and general health (men: ORs 1.44-3.07, P<0.005, and women: ORs 1.36-3.73, P<0.001). A higher percentage of obese individuals with MetS had a poor HR-QoL than those without MetS. Furthermore, we observed a linear trend between inflammation and the percentage of obese individuals with poor scores on the HR-QoL domains. Individuals with MetS were more likely to have poor scores in the domains general health, vitality, social functioning and role limitations due to emotional problems. Obese women with increased inflammation levels were more likely to have poor scores on all domains except role limitations due to emotional problems and mental health.
The impact of obesity on an individual's quality of life is enhanced by grade of obesity, T2D, MetS and inflammation and are mainly related to reduced physical health. The mental well-being is less often impaired.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/hypothesis
We aimed to assess and contextualise 134 potential risk variables for the development of type 2 diabetes and to determine their applicability in risk prediction.
Methods
A total of ...96,534 people without baseline diabetes (372,007 person-years) from the Dutch Lifelines cohort were included. We used a risk variable-wide association study (RV-WAS) design to independently screen and replicate risk variables for 5-year incidence of type 2 diabetes. For identified variables, we contextualised HRs, calculated correlations and assessed their robustness and unique contribution in different clinical contexts using bootstrapped and cross-validated lasso regression models. We evaluated the change in risk, or ‘HR trajectory’, when sequentially assigning variables to a model.
Results
We identified 63 risk variables, with novel associations for quality-of-life indicators and non-cardiovascular medications (i.e., proton-pump inhibitors, anti-asthmatics). For continuous variables, the increase of 1 SD of HbA
1c
, i.e., 3.39 mmol/mol (0.31%), was equivalent in risk to an increase of 0.53 mmol/l of glucose, 19.8 cm of waist circumference, 8.34 kg/m
2
of BMI, 0.67 mmol/l of HDL-cholesterol, and 0.14 mmol/l of uric acid. Other variables required an increase of >3 SD, which is not physiologically realistic or a rare occurrence in the population. Though moderately correlated, the inclusion of four variables satiated prediction models. Invasive variables, except for glucose and HbA
1c
, contributed little compared with non-invasive variables. Glucose, HbA
1c
and family history of diabetes explained a unique part of disease risk. Adding risk variables to a satiated model can impact the HRs of variables already in the model.
Conclusions
Many variables show weak or inconsistent associations with the development of type 2 diabetes, and only a handful can reliably explain disease risk. Newly discovered risk variables will yield little over established factors, and existing prediction models can be simplified. A systematic, data-driven approach to identify risk variables for the prediction of type 2 diabetes is necessary for the practice of precision medicine.
Graphical abstract
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