Long-term aircraft noise exposure may increase the risk of cardiovascular disease, but no study has investigated chronic effects on the metabolic system.
The aim of this study was to investigate ...effects of long-term aircraft noise exposure on body mass index (BMI), waist circumference, and type 2 diabetes. Furthermore, we explored the modifying effects of sleep disturbance.
This prospective cohort study of residents of Stockholm County, Sweden, followed 5,156 participants with normal baseline oral glucose tolerance tests (OGTT) for up to 10 years. Exposure to aircraft noise was estimated based on residential history. Information on outcomes and confounders was obtained from baseline and follow-up surveys and examinations, and participants who developed prediabetes or type 2 diabetes were identified by self-reported physician diagnosis or OGTT at follow-up. Adjusted associations were assessed by linear, logistic, and random-effects models.
The mean (± SD) increases in BMI and waist circumference during follow-up were 1.09 ± 1.97 kg/m2 and 4.39 ± 6.39 cm, respectively. The cumulative incidence of prediabetes and type 2 diabetes was 8% and 3%, respectively. Based on an ordinal noise variable, a 5-dB(A) increase in aircraft noise was associated with a greater increase in waist circumference of 1.51 cm (95% CI: 1.13, 1.89), fully adjusted. This association appeared particularly strong among those who did not change their home address during the study period, which may be a result of lower exposure misclassification. However, no clear associations were found for BMI or type 2 diabetes. Furthermore, sleep disturbances did not appear to modify the associations with aircraft noise.
Long-term aircraft noise exposure may be linked to metabolic outcomes, in particular increased waist circumference.
The protein nucleobindin-2 (NUCB2, also known as nesfatin) was recently implicated as a mediator of anorexia and catabolism in the central nervous system, and has been suggested to act as a cleaved ...and secreted messenger. Given the overlap of signalling molecules between the brain and pancreas, we have explored the presence of NUCB2 in the islets of Langerhans. We also performed an investigation of the dynamic regulation of pancreatic NUCB2 in different metabolic states. NUCB2-like immunoreactivity was detected by immunofluorescence in all human and rat islet beta-cells (as detected by co-localization with insulin), but not in other islet cells or in the exocrine pancreas. Islet NUCB2 content, as measured by enzyme immunoassay, did not change significantly following an overnight fast, but was substantially lower in islets isolated from an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rats (48% of non-diabetic Wistar rat control). Serum levels, however, were not different between Wistar and GK rats. The release of NUCB2 from isolated rat islets was significantly elevated following glucose challenge (123%), but this effect was substantially lower than that observed for insulin (816%). In contrast, serum levels of NUCB2 showed a reversible decrease in an i.p. glucose tolerance test. These data suggest a role for NUCB2 in beta-cell function and a potential involvement in diabetic pathology. However, our findings, together with previous reports, appear more compatible with intracellular actions rather than with endocrine/paracrine communication, and suggest that NUCB2 in serum derives primarily from non-islet sources.
Here, we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the ...potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis, we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy.
Mobile health, mHealth is recognized as a strategy to improve lifestyle behaviors. Research targeting specific lifestyle behaviors has shown that interventions using smartphones can be effective. ...However, few studies have evaluated solutions with multicomponent interventions, tailoring the intervention to the specific needs of the participant using a combination of mHealth and conventional treatment. To accomplish this, we developed Health Integrator, an mHealth platform with services and offers in the areas of diet, physical activity, sleeping habits, stress, alcohol and tobacco use. In the system, the user selects an area of intervention together with a health coach and set weekly goals. This study protocol presents the design and methodology of the Health Integrator Study, a randomized controlled trial to promote improved lifestyle behaviors.
A three-arm parallel randomized controlled trial (1:1:1) is conducted in the Stockholm County, Sweden. In total, 209 employees at a four different companies representing both white and blue collar workers, have been recruited. Participants are randomized to either a control group or to one of two intervention groups receiving a 3-month lifestyle behavior change program including either 1) use of Health Integrator and monthly health coaching sessions or 2) only Health Integrator. At baseline and follow-up after 3- and 6-months, all participants answer questionnaires assessing lifestyle behaviors and quality of life. At baseline and the 3-month follow-up (end of intervention period), weight, height, waist circumference and blood pressure are measured, and all participants wear an Actigraph accelerometer for 7 days to assess physical activity. Blood lipid profile and HbA1c are measured among all participants at baseline. If baseline measures fall outside the normal range, a second measurement is done after 3 months.
The Health Integrator Intervention Study will evaluate if a personalized intervention combining mHealth and conventional programs for lifestyle change, with or without additional health coach sessions, can improve lifestyle behaviors and quality of life. Based on the results from this trial, Health Integrator can easily be implemented within a broad public.
ClinicalTrials.gov Identifier: NCT03579342 . Retrospectively registered, first submitted May 8, 2018.
To investigate the prospective influence of work stress on type 2 diabetes (T2D).
This population-based cohort included 3,205 women and 2,227 men, aged 35-56 years, with baseline normal glucose ...tolerance measured with oral glucose tolerance test. At follow-up 8-10 years later, T2D was diagnosed in 60 women and 111 men. Work stress factors evaluated by questionnaire (i.e., demands, decision latitude, job strain, shift work, overtime work, and also sense of coherence) were studied in association with T2D. Odds ratios (ORs) and 95% CIs adjusted for age, education, BMI, physical activity, smoking, family history of diabetes, and psychological distress were calculated.
In women, low decision latitude was associated with T2D on its own (OR 2.4 95% CI 1.1-5.2) and combined with high demands: job strain (OR 4.2 2.0-8.7), adjusted for all available potential confounders. Also, shift work increased the risk of T2D in women (OR 2.2 1.0-4.7) when adjusted for age, education, and psychological distress, although this risk was diluted after multifactor adjustment (OR 1.9 0.8-4.4). In men, high work demands and high strain decreased the risk of T2D (OR 0.5 0.3-0.9) for both measures, as did an active job (high demands and high decision latitude, OR 0.4 0.2-0.9).
Work stress and shift work may contribute to the development of T2D in women. In men, the risk was decreased by high work demands, high strain, and an active job.
The burden of type 2 diabetes is increasing rapidly, not least in Sub-Saharan Africa, and disadvantaged populations are disproportionally affected. Self-management is a key strategy for people at ...risk of or with type 2 diabetes, but implementation is a challenge. The objective of this study is to assess the determinants of self-management from an implementation perspective in three settings: two rural districts in Uganda, an urban township in South Africa, and socio-economically disadvantaged suburbs in Sweden. Data collection followed an exploratory multiple-case study design, integrating data from interviews, focus group discussions, and observations. Data collection and analysis were guided by a contextualized version of a transdisciplinary framework for self-management. Findings indicate that people at risk of or with type 2 diabetes are aware of major self-management strategies, but fail to integrate these into their daily lives. Depending on the setting, opportunities to facilitate implementation of self-management include: improving patient-provider interaction, improving health service delivery, and encouraging community initiatives supporting self-management. Modification of the physical environment (e.g. accessibility to healthy food) and the socio-cultural environment (i.e. norms, values, attitudes, and social support) may have an important influence on people's lifestyle. Regarding the study methodology, we learned that this innovative approach can lead to a comprehensive analysis of self-management determinants across different settings. An important barrier was the difficult contextualization of concepts like perceived autonomy and self-efficacy. Intervention studies are needed to confirm whether the pathways suggested by this study are valid and to test the proposed opportunities for change.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by intestinal cells and stimulates insulin secretion from the pancreas in a glucose-dependent manner. Exogenously supplied GLP-1 ...analogues are used in the treatment of type 2 diabetes. An anti-diabetic effect of Lactobacillus in lowering plasma glucose levels and its use as a vehicle for delivery of protein and antibody fragments has been shown previously. The aim of this study was to employ lactobacilli as a vehicle for in situ production and delivery of GLP-1 analogue to normalize blood glucose level in diabetic GK (Goto-Kakizaki) rats. In this study, we designed pentameric GLP-1 (5×GLP-1) analogues which were both expressed in a secreted form and anchored to the surface of lactobacilli. Intestinal trypsin sites were introduced within 5×GLP-1, leading to digestion of the pentamer into an active monomeric form. The E. coli-produced 5×GLP-1 peptides delivered by intestinal intubation to GK rats resulted in a significant improvement of glycemic control demonstrated by an intraperitoneal glucose tolerance test. Meanwhile, the purified 5×GLP-1 (trypsin-digested) from the Lactobacillus cultures stimulated insulin secretion from HIT-T15 cells, similar to the E. coli-produced 5×GLP-1 peptides. When delivered by gavage to GK rats, non-expressor L. paracasei significantly lowered the blood glucose level but 5×GLP-1 expression did not provide an additional anti-diabetic effect, possibly due to the low levels produced. Our results indicate that lactobacilli themselves might be used as an alternative treatment method for type 2 diabetes, but further work is needed to increase the expression level of GLP-1 by lactobacilli in order to obtain a significant insulinotropic effect in vivo.
Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common ...substrate arginine, resulting in diminished production of NO. The aim of this study was to evaluate coronary microvascular function in type 2 diabetic Goto-Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA), l-arginine, and the NOS inhibitor N(G)-monomethyl -l-arginine (l-NMMA). GK rats had impaired CFVR compared with Wistar rats (1.31 ± 0.09 vs. 1.87 ± 0.05, P < 0.001). CFVR was restored by nor-NOHA treatment compared with vehicle in GK rats (1.71 ± 0.13 vs. 1.23 ± 0.12, P < 0.05) but remained unchanged in Wistar rats (1.88 ± 0.10 vs. 1.79 ± 0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine compared with vehicle. Arginase II expression was increased in the aorta and myocardium from GK rats compared with Wistar rats. Citrulline-to-ornithine and citrulline-to-arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats after nor-NOHA treatment, suggesting a shift of arginine utilization from arginase to NOS. In conclusion, coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability.
Background The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups ...based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes. Methods Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and beta-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes. Results Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low beta-cell function (LRLB), low-risk high beta-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk beta-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years. Conclusions Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions. Keywords: Precision medicine, Data-driven analysis, Type 2 diabetes, Prevention, Public health, Epidemiology
Adiponectin (APM1) is an adipocyte-derived peptide. The APM1 gene is located on chromosome 3q27 and linked to type 2 diabetes. In patients with type 2 diabetes, the adiponectin level in plasma is ...decreased in comparison to healthy subjects. To identify genetic defects of the APM1 gene that contribute to the development of type 2 diabetes, we genotyped 13 single nucleotide polymorphisms (SNPs) in 106 patients with type 2 diabetes, 325 patients with impaired glucose tolerance (IGT), and 497 nondiabetic control subjects in Swedish Caucasians by using dynamic allele-specific hybridization (DASH). We found that SNPs -11426(A/G) and -11377(G/C) in the proximal promoter region had significant differences of allele frequencies between type 2 diabetic patients and nondiabetic control subjects (P = 0.02 and P = 0.04, respectively). SNP-11426(A/G) was significantly associated with fasting plasma glucose in type 2 diabetic patients (P = 0.02) and in IGT subjects (P = 0.04), while the patients carrying CC and CG genotypes for SNP-11377(G/C) had a higher BMI than the patients with the GG genotype (P = 0.03). Haplotype analysis of 13 SNPs in the APM1 gene showed that estimates of haplotype frequencies in Swedish Caucasians are similar to those estimated in French Caucasians. However, no significant association of haplotypes with type 2 diabetes and IGT was detected in our study. The present study provides additional evidence that SNPs in the proximal promoter region of the APM1 gene contribute to the development of type 2 diabetes.
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