[Show abstract][Hide abstract] ABSTRACT: Background
Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice.
We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level.
Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83–3.60), 1.50 (0.72–3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23–3.10), 1.35 (0.93–1.94) and 1.70 (1.14–2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small.
Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesis:
The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome.
We included 2,497 participants (mean age 60.0 ± 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (≥30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses.
Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome.
An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings.
[Show abstract][Hide abstract] ABSTRACT: As accelerometers are commonly used for 24-h measurements of daily activity, methods for separating waking from sleeping time are necessary for correct estimations of total daily activity levels accumulated during the waking period. Therefore, an algorithm to determine wake and bed times in 24-h accelerometry data was developed and the agreement of this algorithm with self-report was examined. One hundred seventy-seven participants (aged 40-75 years) of The Maastricht Study who completed a diary and who wore the activPAL3™ 24 h/day, on average 6 consecutive days were included. Intraclass correlation coefficient (ICC) was calculated and the Bland-Altman method was used to examine associations between the self-reported and algorithm-calculated waking hours. Mean self-reported waking hours was 15.8 h/day, which was significantly correlated with the algorithm-calculated waking hours (15.8 h/day, ICC = 0.79, P = < 0.001). The Bland-Altman plot indicated good agreement in waking hours as the mean difference was 0.02 h (95% limits of agreement (LoA) = -1.1 to 1.2 h). The median of the absolute difference was 15.6 min (Q1-Q3 = 7.6-33.2 min), and 71% of absolute differences was less than 30 min. The newly developed automated algorithm to determine wake and bed times was highly associated with self-reported times, and can therefore be used to identify waking time in 24-h accelerometry data in large-scale epidemiological studies.
No preview · Article · Feb 2016 · Journal of Sports Sciences
[Show abstract][Hide abstract] ABSTRACT: Objective:
The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosing acute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche) and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds for hs-cTnT and hs-cTnI were derived from different reference cohorts it is unclear whether they are biologically equivalent. We directly assessed sex-specific and age-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort, to investigate whether current divergent thresholds of hs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohort variation.
A healthy reference population was derived from a population-based cohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals with diabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG, N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerular filtration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits.
1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits of hs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limits were higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age.
Direct comparison reveals numerically similar thresholds for hs-cTnT and hs-cTnI assays. This finding is in line with recently reported underdiagnosis of AMI with the current decision limit of 26 ng/L for hs-cTnI, especially among women. Downwards adjustment of the hs-cTnI threshold, differentiated for sex, would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI.
[Show abstract][Hide abstract] ABSTRACT: Background/objectives:
Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity.
This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used.
Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUVMean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039).
Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT.
[Show abstract][Hide abstract] ABSTRACT: A previous study by Savelberg et al. indicated higher plantar flexion moments at 40% of the stance phase and simultaneously an increase in plantar loading in people with diabetic polyneuropathy. It was hypothesised that muscle weakness in the lower extremity caused by polyneuropathy can affect the ability to generate enough momentum during the first part of the stance phase to counter the forward momentum of the body and the roll off of the foot. This could lead to a faster forward transfer of the centre of pressure of the foot (COP) and consequently a higher forefoot loading. The current study sought to test this hypothetical cascade.
[Show abstract][Hide abstract] ABSTRACT: Diabetic polyneuropathy (DPN) is a common co morbidity in diabetic patients. It has been associated with diminished muscle strength, impaired mobility and decreased quality of life (QoL). The purpose of this study was to evaluate the acute and long term effect of a moderate intensive intervention on muscle strength, mobility and QoL in patients with DPN.
[Show abstract][Hide abstract] ABSTRACT: Background:
Type D personality - the combination of negative affectivity (NA) and social inhibition (SI) - has been associated with depression but little is known about underlying mechanisms. We examined whether (1) Type D is a vulnerability factor for depression in general, (2) Type D is associated with inflammation or endothelial dysfunction, and (3) these biomarkers alter the possible association between Type D and depression.
In the Maastricht Study, 712 subjects underwent assessment of NA, SI and Type D personality (DS14), depressive disorder (Mini-International Neuropsychiatric Interview) and depressive symptoms (Patient Health Questionnaire-9). Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, vWF) were measured with sandwich immunoassays or ELISA and combined into standardized sumscores.
Regarding personality, 49% of the study population was low in NA and SI, 22% had SI only, 12% NA only and 17% had Type D. Depressive disorder and depressive symptoms were significantly more prevalent in Type D versus the other three personality subgroups. Multivariable regression analyses showed that Type D was associated with inflammation (β=0.228, p=0.014) and endothelial dysfunction (β=0.216, p=0.022). After adjustment for these biomarkers, Type D remained independently associated with increased vulnerability to depressive disorder (OR=13.20, p<0.001) and depressive symptoms (β=3.87, p<0.001).
The cross-sectional design restrained us to draw any conclusions on causality. The relatively low prevalence of depressive disorder restrained us to adjust for more potential confounders.
Type D personality may be a vulnerability factor for depression, irrespective of levels of inflammation or endothelial dysfunction. Future research should examine possible underlying mechanisms.
No preview · Article · Oct 2015 · Journal of Affective Disorders
[Show abstract][Hide abstract] ABSTRACT: The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be introduced to T2DM patients. Recently, genome-wide association studies (GWASs) have shown that variants in the gene encoding GKRP protect against T2DM and kidney disease but predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These genetic data, together with previous experience with systemic and hepatospecific glucokinase activators, provide insight into the anticipated efficacy and safety of small-molecule disruptors in humans. Interestingly, they suggest that the opposite - enhanced GKRP-glucokinase binding - could be beneficial in selected patients. Disruption of the GKRP-glucokinase complex is a promising new antidiabetic target, since it results in lower plasma glucose levels without inducing hypoglycemia.Missense variants in the gene encoding GKRP (. GCKR) allow us to gain an impression of the safety and efficacy of GKRP-glucokinase disruptors, as the biological effects of these variants are similar to those of exogenous disruptors.The GCKR minor allele is associated not only with protection against T2DM but also with predisposition to dyslipidemia, gout, and NAFLD.The relationship between GCKR and cardiovascular disease has been inconclusive.
No preview · Article · Oct 2015 · Trends in Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Foot problems complicating diabetes are a source of major patient suffering and societal costs. Investing in evidence-based, internationally appropriate diabetic foot care guidance is likely among the most cost-effective forms of healthcare expenditure, provided it is goal-focused and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has been publishing and updating international Practical Guidelines since 1999. The 2015 updates are based on systematic reviews of the literature, and recommendations are formulated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. As such, we changed the name from "Practical Guidelines" to "Guidance". In this article we describe the development of the 2015 IWGDF Guidance documents on prevention and management of foot problems in diabetes. This Guidance consists of five documents, prepared by five working groups of international experts. These documents provide guidance related to foot complications in persons with diabetes on: prevention; footwear and offloading; peripheral artery disease; infections; and, wound healing interventions. Based on these five documents, the IWGDF Editorial Board produced a summary guidance for daily practice. The resultant of this process, after review by the Editorial Board and by international IWGDF members of all documents, is an evidence-based global consensus on prevention and management of foot problems in diabetes. Plans are already under way to implement this Guidance. We believe that following the recommendations of the 2015 IWGDF Guidance will almost certainly result in improved management of foot problems in persons with diabetes and a subsequent worldwide reduction in the tragedies caused by these foot problems. This article is protected by copyright. All rights reserved.
Full-text · Article · Sep 2015 · Diabetes/Metabolism Research and Reviews
[Show abstract][Hide abstract] ABSTRACT: Background and aims: Observational studies suggest an inverse association between total dairy intake
and diabetes risk. However, there is a lack of information on the relation of specific dairy products with
impaired glucose metabolism (IGM) and type 2 diabetes (T2DM).
Materials and methods: Individuals aged 40-75 y were recruited for The Maastricht Study. All
participants filled out a 254-food item food frequency questionnaire (FFQ), covering 41 specific dairy
items that captured differences between full fat, semi-skimmed, and skimmed products, as well as
fermented and non-fermented products. Glucose metabolism status was assessed by an oral glucose
tolerance test and participants were informed on their glucose metabolism status after returning the FFQ.
2,508 Individuals were available to estimate odds ratios (ORs (95%CI)) for IGM (n=501) and newly
diagnosed (ND) T2DM (n=129), with adjustment for BMI, physical activity, smoking, education, energy
intake, and intake of vegetables, fruits, meat, and fish.
Results: For IGM, fully adjusted analyses revealed inverse associations, with ORs (95% CI) comparing
the highest with the lowest tertile of intake of 0.73 (0.55 - 0.96) for skimmed products and 0.74 (0.54 -
0.99) for fermented products. These dairy products were not associated with ND T2DM. In contrast, full
fat products were positively associated with ND T2DM (OR (95%CI): 2.01 (1.16-3.47)), whereas total
dairy intake was inversely associated with ND T2DM (OR (95%CI): 0.46 (0.24-0.86)).
Conclusion: Individuals with a high consumption of skimmed and fermented products had a lower odds
of having IGM, and individuals with a high consumption of total dairy products had a lower odds of
having ND T2DM. High intake of full fat products was not related to IGM, but increased the odds of ND
Supported by: European Regional Development Fund, Economic Affairs(NL), CARIM, NUTRIM, FC
[Show abstract][Hide abstract] ABSTRACT: Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus (DM) are important to estimate the risk of amputation, ulceration, wound healing and presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another. To evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction-angiography, colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies (QUADAS) instrument. Of 6629 studies identified, 10 met the criteria for inclusion. In these studies the patients had a median age of 60-74 years and a median duration of diabetes of 9-24 years. Two studies reported exclusively on patients with symptomatic (ulcerated/ infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of an ABI threshold <0.9 ranged from 2 to 25 (median 8) and <0.1 to 0.7 (median 0.3), respectively. In patients with neuropathy the NLR of the ABI was generally higher (2 out of 3 studies) indicating poorer performance, and ranged between 0.3-0.5. A toe brachial index (TBI) <0.75 was associated with a median PLR and NLR of 3 and ≤0.1, respectively, and was less affected by neuropathy in one study. Also, in two separate studies pulse oximetry used to measure the oxygen saturation of peripheral blood and Doppler wave form analyses had NLRs of 0.2 and <0.1. The reported performance of ABI for the diagnosis of PAD in patients with DM is variable and is adversely affected by the presence of neuropathy. Limited evidence suggests that TBI, pulse oximetry and wave form analysis may be superior to ABI for diagnosing PAD in patients with neuropathy with and without foot ulcers. There was insufficient data to support the adoption of one particular diagnostic modality over another and no comparisons existed with clinical examination. The quality of studies evaluating diagnostic techniques for the detection of PAD in individuals with diabetes is poor. Improved compliance with guidelines for methodological quality is needed in future studies. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Full-text · Article · Sep 2015 · Diabetes/Metabolism Research and Reviews
[Show abstract][Hide abstract] ABSTRACT: Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/ or major amputation among patients with active diabetic foot ulceration. Two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies (QUIPS) instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥45 mmHg), and TcPO2 ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ABI < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Full-text · Article · Sep 2015 · Diabetes/Metabolism Research and Reviews