Abstract Objective Type 2 diabetes mellitus (T2DM) is associated with elevated plasma apolipoprotein B and triglycerides levels, reduced HDL cholesterol and the presence of small-dense LDL particles. ...The present study was conducted to investigate the role of plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels, a regulator of LDL-receptor expression, in the occurrence of diabetic dyslipidemia. Methods Plasma PCSK9 was measured in a cohort of subjects with normal glucose metabolism (NGM; n = 288), impaired glucose metabolism (IGM; n = 121) and type 2 diabetes mellitus (T2DM; n = 139) to study whether its relation with plasma apolipoprotein B, triglycerides, total cholesterol, non-HDL cholesterol, LDL cholesterol and HDL cholesterol differed by levels of glucose metabolism status. Results Plasma PCSK9 levels were not different between the three groups (82, 82 and 80 ng/mL in NGM, IGM and T2DM, respectively). PCSK9 was positively associated with total cholesterol, non-HDL cholesterol, LDL cholesterol, apolipoprotein B and triglycerides levels in all subgroups. The regression slopes for the associations with non-HDL cholesterol were steeper among individuals with T2DM than with NGM ( β = 0.016 versus β = 0.009, p -interaction = 0.05). Similar results were obtained for the relation with apolipoprotein B ( β = 0.004 versus β = 0.002, p -interaction = 0.09). Conclusions Although glucose metabolism status per se is not associated with plasma PCSK9 levels, the presence of T2DM may modify the relation between plasma PCSK9 and non-HDL cholesterol and apolipoprotein B. These observations should be regarded as hypothesis generating for further studies aimed at elucidating the role of PCSK9 in the pathogenesis and treatment of diabetic dyslipidemia.
Improvement in the spatial resolution for imaging with fast neutrons Lehmann, E.H.; Mannes, D.; Strobl, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2021, Letnik:
988
Journal Article
Recenzirano
Odprti dostop
We report on the realization of an improved concept for the detection of fast neutrons using a specific setup of scintillators with the aim to overcome limitations in spatial resolution. While fast ...neutron imaging (FNI) is a technique to investigate very thick material layers in transmission mode, currently there is a limit in the spatial resolution at ∼1 mm, which hinders the performance for the detection of features like cracks, material damage or pores in large objects (≫1 cm3). The improved concept presented here is based on the separation of the converter material from the scintillation layer in a suitable way, which was successfully tested and referenced to the standard devices at the NECTAR facility (FRM-2, MLZ, Garching) under realistic beamline conditions. The results imply a break-through in enabling detection of structures on the order of 0.2 to 0.5 mm (a more precise estimation is not possible due to other resolution determining factors in a realistic setup). Potential additional improvements are discussed.
Painful diabetic polyneuropathy (PDP) is associated with high pain scores and is difficult to treat. Therefore, spinal cord stimulation (SCS) has been suggested as second-line treatment. In this ...study, the feasibility and efficacy of SCS in PDP were investigated, as well as the predictive value of clinical sensory testing for the treatment outcome.
Fifteen patients with intractable PDP in the lower limbs were recruited. During lead implantation, the feasibility of achieving adequate paraesthesia coverage using one stimulation lead was investigated. If trial stimulation was successful, a definitive neurostimulator was implanted. Pain intensity was scored using an 11-point numeric rating scale and patients’ global impression of change scale. Additionally, neuropathic pain characteristics, quality of life, sleep quality and mood were assessed. The predictive value of clinical sensory testing for the treatment outcome was analysed.
Adequate paraesthesia coverage was achieved in 14 out of 15 patients. Clinically relevant pain relief was present in 11 patients after trial stimulation and 10 patients at 12 months. The quality of life was significantly increased at 2 weeks and 3 months in patients with successful SCS treatment. Several neuropathic pain characteristics and quality of sleep were improved at 2 weeks and 12 months. Preoperative clinical sensory testing did not differentiate between treatment responders from non-responders.
SCS seems to be an efficacious and feasible treatment for intractable PDP. In this exploratory study, it was not possible to predict the treatment outcome using clinical sensory testing. These results justify performing a randomized clinical trial.
Reactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney ...disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown.
Subjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO.
Fasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h fasting: 1.12 (95% CI: 0.97–1.29); post-OGTT: 1.19 (1.01–1.41), eGFR<60mL/min/1.73 m2 fasting: 1.58 (95% CI: 1.38–1.82), post-OGTT: 1.57 (1.34–1.83) and retinopathy fasting: 1.59 (95% CI: 1.01–2.53), post-OGTT: 1.38 (0.77–2.48). No associations with prior CVD were found.
Fasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.
Aims
To estimate the societal costs and quality of life of people with type 2 diabetes and to compare these results with those of people with normal glucose tolerance or prediabetes.
Methods
Data ...from 2915 individuals from the population‐based Maastricht Study were included. Costs were assessed through a resource‐use questionnaire completed by the participants; cost prices were based on Dutch costing guidelines. Quality of life was expressed in utilities using the Dutch EuroQol 5D‐3L questionnaire and the SF‐36 health survey. Based on normal fasting glucose and 2‐h plasma glucose values, participants were classified into three groups: normal glucose tolerance (n = 1701); prediabetes (n = 446); or type 2 diabetes (n = 768).
Results
Participants with type 2 diabetes had on average 2.2 times higher societal costs than those with normal glucose tolerance (€3,006 and €1,377 per 6 months, respectively) and had lower utilities (0.77 and 0.81, respectively). No significant differences were found between participants with normal glucose tolerance and those with prediabetes. Subgroup analyses showed that higher age, being female and having two or more diabetes‐related complications resulted in higher costs (P < 0.05) and lower utilities.
Conclusions
This study showed that people with type 2 diabetes have substantially higher societal costs and lower quality of life than people with normal glucose tolerance. The results provide important input for future model‐based economic evaluations and for policy decision‐making.
What's new?
The high costs of type 2 diabetes, together with its impact on quality of life, place a great burden on both the individual affected and society as a whole.
People with type 2 diabetes have, on average, 2.2 times higher societal costs and experience a lower quality of life than people without type 2 diabetes.
The total societal costs for people with ≥2 diabetes complications are 4.4 times higher than total societal costs for people without complications.
Abstract Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to ...this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62 ± 7.5 years, 44% women) was used. Participants were classified as insulin user (n = 13) or non-insulin user (n = 37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (β):− 0.56 (95% CI:− 0.89 to − 0.24)), trabecular vBMD (β:− 0.58 (95% CI:− 0.87 to − 0.30)), trabecular thickness (β:− 0.55 (95% CI:− 0.87 to − 0.23)), cortical thickness (β:− 0.41 (95% CI:− 0.74 to − 0.08)), log cortical pore volume (β:− 0.43 (95% CI:− 0.73 to − 0.13)), bone stiffness (β:− 0.39 (95% CI:− 0.62 to − 0.17)) and failure load (β:− 0.39 (95% CI:− 0.60 to − 0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
P-type point contact (PPC) high-purity germanium detectors are an important technology in astroparticle and nuclear physics due to their superb energy resolution, low noise, and pulse shape ...discrimination capabilities. Analysis of data from the Majorana Demonstrator, a neutrinoless double-β decay experiment deploying PPC detectors enriched in 76Ge, has led to several novel improvements in the analysis of PPC signals. In this work we discuss charge trapping in PPC detectors and its effect on energy resolution. Small dislocations or impurities in the crystal lattice result in trapping of charge carriers from an ionization event of interest, attenuating the signal, and degrading the measured energy. We present a modified digital pole-zero correction to the signal energy estimation that counters the effects of charge trapping and improves the energy resolution of the Majorana Demonstrator by approximately 30 % to around 2.4 keV full width at half-maximum at 2039 keV, the 76Ge Q value. An alternative approach achieving similar resolution enhancement is also presented.
Context:
The BclI polymorphism in the glucocorticoid receptor (GR) gene is associated with enhanced glucocorticoid (GC) sensitivity.
Objective:
Our objective was to investigate the association of the ...BclI polymorphism with body fatness and insulin resistance.
Design and Setting:
We conducted an observational cohort study, combining data from 2 cohort studies enriched with individuals with impaired glucose metabolism and/or diabetes mellitus type 2 (DM2).
Patients and Methods:
We examined 1228 participants (mean age 64.7 years, 45% women) from the Cohort Study on Diabetes and Atherosclerosis Maastricht (CODAM, n = 543) and the Hoorn Study (n = 685). Body mass index (BMI), waist and hip circumferences, and waist-to-hip ratio (WHR) were obtained; insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA2-IR).
Results:
We identified 519 noncarriers (CC), 540 heterozygous (CG) carriers, and 169 homozygous (GG) carriers of the G-allele of the BclI polymorphism. Homozygous carriers had a higher BMI (28.9 vs 27.9 kg/m2) and waist (99.6 vs 97.2 cm) and hip (105.5 vs 103.2 cm) circumference compared with noncarriers, also after adjustment for age, sex, cohort, glucose tolerance, and lifestyle risk factors: β = 0.94 kg/m2 (95% confidence interval, 0.24–1.63), β = 2.84 cm (0.95;4.73) and β = 2.38 cm (0.88–3.87), respectively. Similar results were obtained when comparing homozygous carriers with heterozygous carriers: β = 1.03 kg/m2 (0.34–1.72), β = 2.20 cm (0.31–4.08) and β = 1.99 cm (0.51–3.48), respectively. There were no differences in WHR. Ln-HOMA2-IR was higher in GG carriers compared with CG carriers; 0.29 vs 0.17 β = 0.09 (0.01–0.17), but this effect was attenuated after adjustment for BMI β = 0.04 (−0.04 to 0.11).
Conclusion:
Homozygous carriers of the BclI polymorphism of the GR gene have significantly greater total body fatness, contributing to higher HOMA2-IR, compared with heterozygous carriers and noncarriers.
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