Aims/hypothesis
Earlier studies have shown that skin autofluorescence measured with an AGE reader estimates the accumulation of AGEs in the skin, which increases with ageing and is associated with ...the metabolic syndrome and type 2 diabetes. In the present study, we examined whether the measurement of skin autofluorescence can predict 4 year risk of incident type 2 diabetes, cardiovascular disease (CVD) and mortality in the general population.
Methods
For this prospective analysis, we included 72,880 participants of the Dutch Lifelines Cohort Study, who underwent baseline investigations between 2007 and 2013, had validated baseline skin autofluorescence values available and were not known to have diabetes or CVD. Individuals were diagnosed with incident type 2 diabetes by self-report or by a fasting blood glucose ≥7.0 mmol/l or HbA
1c
≥48 mmol/mol (≥6.5%) at follow-up. Participants were diagnosed as having incident CVD (myocardial infarction, coronary interventions, cerebrovascular accident, transient ischaemic attack, intermittent claudication or vascular surgery) by self-report. Mortality was ascertained using the Municipal Personal Records Database.
Results
After a median follow-up of 4 years (range 0.5–10 years), 1056 participants (1.4%) had developed type 2 diabetes, 1258 individuals (1.7%) were diagnosed with CVD, while 928 (1.3%) had died. Baseline skin autofluorescence was elevated in participants with incident type 2 diabetes and/or CVD and in those who had died (all
p
< 0.001), compared with individuals who survived and remained free of the two diseases. Skin autofluorescence predicted the development of type 2 diabetes, CVD and mortality, independent of several traditional risk factors, such as the metabolic syndrome, glucose and HbA
1c
.
Conclusions/interpretation
The non-invasive skin autofluorescence measurement is of clinical value for screening for future risk of type 2 diabetes, CVD and mortality, independent of glycaemic measures and the metabolic syndrome.
Anemia is a major and currently poorly understood clinical manifestation of hematopoietic aging. Upon aging, hematopoietic clones harboring acquired leukemia-associated mutations expand and become ...detectable, now referred to as clonal hematopoiesis (CH). To investigate the relationship between CH and anemia of the elderly, we explored the landscape and dynamics of CH in older individuals with anemia. From the prospective, population-based Lifelines cohort (n = 167 729), we selected all individuals at least 60 years old who have anemia according to World Health Organization criteria (n = 676) and 1:1 matched control participants. Peripheral blood of 1298 individuals was analyzed for acquired mutations at a variant allele frequency (VAF) of 1% or higher in 27 driver genes. To track clonal evolution over time, we included all available follow-up samples (n = 943). CH was more frequently detected in individuals with anemia (46.6%) compared with control individuals (39.1%; P = .007). Although no differences were observed regarding commonly detected DTA mutations (DNMT3A, TET2, ASXL1) in individuals with anemia compared with control individuals, other mutations were enriched in the anemia cohort, including TP53 and SF3B1. Unlike individuals with nutrient deficiency (P = .84), individuals with anemia of chronic inflammation and unexplained anemia revealed a higher prevalence of CH (P = .035 and P = .017, respectively) compared with their matched control individuals. Follow-up analyses revealed that clones may expand and decline, generally showing only a subtle increase in VAF (mean, 0.56%) over the course of 44 months, irrespective of the presence of anemia. Specific mutations were associated with different growth rates and propensities to acquire an additional hit. In contrast to smaller clones (<5% VAF), which did not affect overall survival, larger clones were associated with increased risk for death.
•Specific mutations, including TP53 and SF3B1, but not DNMT3A, TET2, and ASXL1, were enriched in older individuals with anemia.•In general, clones only confer a limited selective advantage over time, which is differentially affected by specific driver genes.
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The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified ...by smoking behavior. Apolipoproteins (apo) associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) may be altered in MetS. This study aimed to examine the association between smoking and the following parameters: MetS and its components, levels of apolipoproteins and estimated lipoprotein particle size, separately for men and women, and in different body mass index (BMI) classes.
We included 24,389 men and 35,078 women aged between 18 and 80 years who participated in the LifeLines Cohort Study between December 2006 and January 2012; 5,685 men and 6,989 women were current smokers. Participants were categorized into three different body mass index (BMI) classes (BMI <25; BMI 25 to 30; BMI ≥30 kg/m²). MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP:ATPIII) criteria. Blood pressure, anthropometric and lipid measurements were rigorously standardized, and the large sample size enabled a powerful estimate of quantitative changes. The association between smoking and the individual MetS components, and apoA1 and apoB, was tested with linear regression. Logistic regression was used to examine the effect of smoking and daily tobacco smoked on risk of having MetS. All models were age adjusted and stratified by sex and BMI class.
Prevalence of MetS increased with higher BMI levels. A total of 64% of obese men and 42% of obese women had MetS. Current smoking was associated with a higher risk of MetS in both sexes and all BMI classes (odds ratio 1.7 to 2.4 for men, 1.8 to 2.3 for women, all P values <0.001). Current smokers had lower levels of HDL cholesterol and apoA1, higher levels of triglycerides and apoB, and higher waist circumference than non-smokers (all P <0.001). Smoking had no consistent association with blood pressure or fasting blood glucose. In all BMI classes, we found a dose-dependent association of daily tobacco consumption with MetS prevalence as well as with lower levels of HDL cholesterol, higher triglyceride levels and lower ratios of HDL cholesterol/apoA1 and, only in those with BMI <30, LDL cholesterol/apoB (all P <0.001).
Smoking is associated with an increased prevalence of MetS, independent of sex and BMI class. This increased risk is mainly related to lower HDL cholesterol, and higher triglycerides and waist circumference. In addition, smoking was associated with unfavorable changes in apoA1 and apoB, and in lipoprotein particle size. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/196.
Objective
Insulin‐like growth factor 1 (IGF‐1) measurements play a central role in the diagnosis and follow‐up of acromegaly and growth hormone deficiency. However, improving health care outcomes for ...these patients involves an intricate process of laboratory diagnostics and skilled health care professionals. The integrated effects of IGF‐1 reports on diagnosis and treatment decisions are yet unknown.
Design, Patients and Measurements
Extended quality assessment, distributing the description of five (real) patient cases with accompanying blood samples. Patients suspected or during follow up for acromegaly or adult onset of growth hormone deficiency were included. Laboratory specialists and endocrinologists in the same centre were asked to interpret their centre‐specific IGF‐1 results by using a laboratory and medical questionnaire. This way, insight could be obtained into the combined effects of different assays, assay harmonisation, reference value sets, and individual physician interpretation in relation to guidelines, thus reviewing the entire diagnostic and management process.
Results
Limited variation (CV 13.8 ± 2.8) was found in IGF‐1 concentrations despite different use of the harmonization sample and factor among laboratories. This interlaboratory variation increased upon conversion to SD scores (CV 15.7 ± 40.7) as a consequence of the use of different reference value sets. Furthermore, there was a lack of adherence to international guidelines among endocrinologists.
Conclusions
Highly variable diagnostic and treatment outcomes in acromegaly and AGHD in the Netherlands can be attributed to increased variability of IGF‐1 upon conversion to SD scores and low adherence to clinical guidelines.
Anemia is highly prevalent, especially in older individuals. In selected populations, anemia has been reported to be associated with impaired survival and health-related quality of life. However, ...data on this impact in the general population are rare. Furthermore, discussions on the optimal definition of anemia have not been conclusive. We investigated these issues using survival data, scores from a health-related quality of life questionnaire (RAND-36), and hemoglobin concentration from 138670 subjects, aged 18-93 years, participating in the Lifelines cohort. Anemia was defined according to World Health Organization criteria and was further subclassified in participants over 60 years old. Anemia was present in 5510 (4.0%) of all 138670 subjects and 516 (2.8%) in the 18667 individuals older than 60 years. Anemia had no impact on overall survival and limited impact on health-related quality of life in individuals less than 60 years old. In contrast, in individuals over 60 years old anemia significantly impaired overall survival and health-related quality of life. The lower health-related quality of life was mainly observed in subscales representing physical functioning. Although consensus on the subclassification of anemia is lacking, our data suggest that particularly anemia of chronic inflammation was associated with worse overall survival and decreased health-related quality of life. Multivariate models confirmed that anemia was an independent risk factor for decreased health-related quality of life in older individuals. Finally, women with a hemoglobin concentration between 12.0-13.0 g/dL (considered anemia in men, but not in women) experienced a significantly lower health-related quality of life. This large, prospective, population-based study indicates that anemia is associated with worse overall survival and health-related quality of life in older individuals, but not in younger individuals. The findings of this study challenge the definition of anemia in women over 60 years old, and suggest that the optimal definition of anemia, in the perspective of health-related quality of life, in women over 60 years old should be altered to a hemoglobin concentration below 13.0 g/dL (8.0 mmol/L), which is comparable to that in men.
Our aim was to study the effect of secondary carnitine deficiency (SCD) and carnitine supplementation on important outcome measures for persons with medium‐chain Acyl–CoA dehydrogenase deficiency ...(MCADD). We performed a large retrospective observational study using all recorded visits of persons with MCADD in the University Medical Center Groningen, the Netherlands, between October 1994 and October 2019. Frequency and duration of acute unscheduled preventive hospital visits, exercise tolerance, fatigue, and muscle pain were considered important clinical outcomes and were studied in relation to (acyl)carnitine profile and carnitine supplementation status. The study encompassed 1228 visits of 93 persons with MCADD. >60% had SCD during follow‐up. This included only persons with severe MCADD. Carnitine supplementation and SCD were unrelated to the frequency and duration of the acute unscheduled preventive hospital visits (P > 0.05). The relative risk for fatigue, muscle ache, or exercise intolerance was equal between persons with and without SCD (RR 1.6, 95% CI 0.48–5.10, P = 0.4662). No episodes of metabolic crisis were recorded in non‐carnitine‐supplemented persons with MCADD and SCD. In some persons with MCADD, SCD resolved without carnitine supplementation. There is absence of real‐world evidence in favor of routine carnitine analysis and carnitine supplementation in the follow‐up of persons with MCADD.
Continuous glucose monitoring (CGM) systems have great potential for real‐time assessment of glycemic variation in patients with hepatic glycogen storage disease (GSD). However, detailed descriptions ...and in‐depth analysis of CGM data from hepatic GSD patients during interventions are scarce. This is a retrospective in‐depth analysis of CGM parameters, acquired in a continuous, real‐time fashion describing glucose management in 15 individual GSD patients. CGM subsets are obtained both in‐hospital and at home, upon nocturnal dietary intervention (n = 1), starch loads (n = 11) and treatment of GSD Ib patients with empagliflozin (n = 3). Descriptive CGM parameters, and parameters reflecting glycemic variation and glycemic control are considered useful CGM outcome parameters. Furthermore, the combination of first and second order derivatives, cumulative sum and Fourier analysis identified both subtle and sudden changes in glucose management; hence, aiding assessment of dietary and medical interventions. CGM data interpolation for nocturnal intervals reduced confounding by physical activity and diet. Based on these analyses, we conclude that in‐depth CGM analysis can be a powerful tool to assess glucose management and optimize treatment in individual hepatic GSD patients.
Background
Skin autofluorescence (SAF) is a noninvasive marker of advanced glycation end products (AGEs). In diabetes, higher SAF levels have been positively associated with long‐term complications, ...cardiovascular morbidity and mortality. Because little is known about the factors that influence SAF in nondiabetic individuals, we assessed the association of clinical and lifestyle parameters with SAF as well as their interactions in a large‐scale, nondiabetic population and performed the same analysis in a type 2 diabetic subgroup.
Methods
In a cross‐sectional study in participants from the LifeLines Cohort Study, extensive clinical and biochemical phenotyping, including SAF measurement, was assessed in 9009 subjects of whom 314 (3·5%) subjects with type 2 diabetes.
Results
Mean SAF was 2·04 ± 0·44 arbitrary units (AU) in nondiabetic individuals and 2·44 ± 0·55 AU in type 2 diabetic subjects (P < 0·0001). Multivariate backward regression analysis showed that in the nondiabetic population, SAF was significantly and independently associated with age, BMI, HbA1c, creatinine clearance, genetic polymorphism in NAT2 (rs4921914), current smoking, pack‐years of smoking and coffee consumption. In the type 2 diabetic group, a similar set of factors was associated with SAF, except for coffee consumption.
Conclusions
In addition to the established literature on type 2 diabetes, we have demonstrated that SAF levels are associated with several clinical and lifestyle factors in the nondiabetic population. These parameters should be taken into consideration when using SAF as a screening or prediction tool for populations at risk for cardiovascular disease and diabetes.
Diversity in the reported prevalence of metabolically healthy obesity (MHO), suggests that modifiable factors may be at play. We evaluated differences in dietary patterns and physical activity ...between MHO and metabolically unhealthy obesity (MUO).
Cross-sectional data of 9270 obese individuals (30-69 years) of the Lifelines Cohort Study was used. MHO was defined as obesity and no metabolic syndrome risk factors and no cardiovascular disease history. MUO was defined as obesity and ≥2 metabolic syndrome risk factors. Sex-specific associations of dietary patterns (identified by principal component analysis) and physical activity with MHO were assessed by multivariable logistic regression (reference group: MUO). Analyses were adjusted for multiple covariates.
Among 3442 men and 5828 women, 10.2% and 24.4% had MHO and 56.9% and 35.3% MUO, respectively. We generated four obesity-specific dietary patterns. Two were related to MHO, and in women only. In the highest quartile (Q) of 'bread, potatoes and sweet snacks' pattern, odds ratio (OR) (95% CI) for MHO was 0.52 (0.39-0.70). For the healthier pattern 'fruit, vegetables and fish', an OR of 1.36 (1.09-1.71) in Q3 and 1.55 (1.21-1.97) in Q4 was found for MHO. For physical activity, there was a positive association between moderate physical activity and vigorous physical activity in the highest tertile and MHO in women and men, respectively (OR 1.19 (1.01-1.41) and OR 2.02 (1.50-2.71)).
The healthier diet -characterized by 'fruit, vegetables and fish'- and moderate physical activity in women, and vigorous physical activity in men may be related to MHO. The (refined) carbohydrate-rich 'bread, potatoes and sweet snacks' dietary pattern was found to counteract MHO in women.
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