Objectives To describe the range of collaborative approaches to shared decision-making (SDM) observed in clinical encounters of patients with diabetes and their clinicians.Design A secondary... Show moreObjectives To describe the range of collaborative approaches to shared decision-making (SDM) observed in clinical encounters of patients with diabetes and their clinicians.Design A secondary analysis of videorecordings obtained in a randomised trial comparing usual diabetes primary care with or without using a within-encounter conversation SDM tool.Setting Using the purposeful SDM framework, we classified the forms of SDM observed in a random sample of 100 video-recorded clinical encounters of patients with type 2 diabetes in primary care.Main outcome measures We assessed the correlation between the extent to which each form of SDM was used and patient involvement (OPTION12-scale).Results We observed at least one instance of SDM in 86 of 100 encounters. In 31 (36%) of these 86 encounters, we found only one form of SDM, in 25 (29%) two forms, and in 30 (35%), we found ≥3 forms of SDM. In these encounters, 196 instances of SDM were identified, with weighing alternatives (n=64 of 196, 33%), negotiating conflicting desires (n=59, 30%) and problemsolving (n=70, 36%) being similarly prevalent and developing existential insight accounting for only 1% (n=3) of instances. Only the form of SDM focused on weighing alternatives was correlated with a higher OPTION12-score. More forms of SDM were used when medications were changed (2.4 SDM forms (SD 1.48) vs 1.8 (SD 1.46); p=0.050).Conclusions After considering forms of SDM beyond weighing alternatives, SDM was present in most encounters. Clinicians and patients often used different forms of SDM within the same encounter. Recognising a range of SDM forms that clinicians and patients use to respond to problematic situations, as demonstrated in this study, opens new lines of research, education and practice that may advance patient-centred, evidence-based care. Show less
The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)-mediated beta -cell destruction in type 1 diabetes (T1D). Among them, the... Show moreThe signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)-mediated beta -cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human beta -cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1 alpha /miR-17-5p axis and demonstrate that inhibition of the IRE1 alpha activity impairs processing of preproinsulin signal peptide antigen and its recognition by specific autoreactive CTLs during inflammation. These results underscore the impact of ER stress in the increased visibility of beta -cells to the immune system and position the IRE1 alpha /miR-17 pathway as a central component in beta -cell destruction processes and as a potential target for the treatment of autoimmune T1D. Show less
Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in... Show moreDysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased insulin secretion. In isolated human islets treated with antagomir-132, insulin secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in insulin secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve insulin secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function. Show less
BackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the... Show moreBackgroundThis study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).MethodsData from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65-85years). At baseline and 12-18months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12-18months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6months follow-up and 12-18months follow-up.ResultsOf all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio=0.95, 95% CI=0.90-0.99), but not in men (Ratio=0.99, 95% CI=0.85-1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio=0.94, 95% CI=0.89-0.99), but not in men (Ratio=1.00, 95% CI=0.87-1.11). Greater pain variability over 12-18months was associated with more PA at follow-up in men (Ratio=1.18, 95% CI=1.01-1.38), but not in women (Ratio=0.94, 95% CI=0.86-1.03).ConclusionsGreater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research. Show less
Conclusions/interpretation Taken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.
Left ventricular (LV) diastolic dysfunction and increased arterial stiffness are common in patients with diabetes mellitus (DM). However, the relation between these two pathophysiological factors... Show moreLeft ventricular (LV) diastolic dysfunction and increased arterial stiffness are common in patients with diabetes mellitus (DM). However, the relation between these two pathophysiological factors remains unclear. The aim of this study was to investigate the relationship between LV diastolic function and arterial stiffness as assessed with applanation tonometry. In 142 asymptomatic patients with DM (mean age 48 years, 75 (53 %) men, 72 (51 %) patients with type 2 DM) LV diastolic function was assessed with echocardiography. Arterial stiffness was evaluated measuring the aortic pulse wave velocity (PWV) whereas wave reflection was assessed measuring central systolic blood pressure (cSBP), central pulse pressure (cPP), and augmentation index (AIx) with applanation tonometry. Mean E/A ratio, E' and E/E' ratio were 1.1 ± 0.3, 8.1 ± 2.3 and 9.2 ± 3.3 cm/s, respectively. Mean PWV, mean cSBP, median cPP and mean AIx were 7.9 ± 2.4 m/s, 122 ± 17 mmHg, 40 [35-51] mmHg and 17.9 ± 12.1 %, respectively. PWV was independently associated with LV diastolic dysfunction grade (β = 0.76, p = 0.03). In contrast, measures of wave reflection, cPP, cSBP and AIx were independently related with E/A ratio, but not with the LV diastolic dysfunction grade. Parameters of arterial stiffness and wave reflection are associated with echocardiographic indices of LV diastolic function in asymptomatic patients with DM. Therapies that prevent progression of arterial stiffness and reduce late-systolic pressure overload may help to reduce the prevalence of LV diastolic dysfunction in this population. Show less
Purpose: In diabetes, generalised microvascular disease and coronary artery disease (CAD) are likely to occur in parallel. We used a sidestream dark field (SDF) handheld imaging device to determine... Show morePurpose: In diabetes, generalised microvascular disease and coronary artery disease (CAD) are likely to occur in parallel. We used a sidestream dark field (SDF) handheld imaging device to determine the relation between the labial microcirculation parameters and CAD in asymptomatic patients with diabetes.Methods: SDF imaging was validated for assessment of labial capillary density and tortuosity. Thereafter, mean labial capillary density and tortuosity were evaluated and compared in non-diabetic controls, and in asymptomatic patients with type 1 and type 2 diabetes. In diabetic patients, mean capillary density and tortuosity were compared according to the presence of CAD.Results: Both type 1 and type 2 diabetes were associated with increased capillary density and tortuosity. In diabetes, mean capillary density was an independent predictor of elevated coronary artery calcium (CAC) (p = 0.03) and obstructive CAD on computed tomography angiography (p = 0.01). Using a cut-off mean capillary density of 24.9 (per 0.63 mm(2)) the negative predictive value was 84% and 89% for elevated CAC and obstructive CAD. Likewise, capillary tortuosity was an independent predictor of increased CAC (p = 0.01) and obstructive CAD (p = 0.04).Conclusion: Assessment of labial microcirculation parameters using SDF imaging is feasible and conveys the potential to estimate vascular morbidity in patients with diabetes, at bedside. Show less
