Comparisons of visual perception, response-selection, and response-execution performance were made between Type 2 diabetes mellitus patients and a matched nondiabetic control group. 10 well-controlled male patients with Type 2 diabetes without diabetic complications (M age 58 yr.) and an age and IQ-matched non-diabetic control group consisting of 13 male healthy volunteers (M age 57 yr.) were included. Significant differences were found only between the two groups on response-selection performance, which concerns the selection and preparation of an appropriate motor action.
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Proefschrift dat onder andere een tweejarig interventie-onderzoek beschrijft naar het effect van een bewegingsprogramma bij personen met type 2 diabetes.
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Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.
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Sodium-glucose co-transporter 2 (SGLT2) inhibitors, including canagliflozin, reduce the risk of cardiovascular and kidney outcomes in patients with and without type 2 diabetes, albeit with a large interindividual variation. The underlying mechanisms for this variation in response might be attributed to differences in SGLT2 occupancy, resulting from individual variation in plasma and tissue drug exposure and receptor availability. We performed a feasibility study for the use of [18F]canagliflozin positron emission tomography (PET) imaging to determine the association between clinical canagliflozin doses and SGLT2 occupancy in patients with type 2 diabetes. We obtained two 90-minute dynamic PET scans with diagnostic intravenous [18F]canagliflozin administration and a full kinetic analysis in 7 patients with type 2 diabetes. Patients received 50, 100, or 300 mg oral canagliflozin (n = 2:4:1) 2.5 hours before the second scan. Canagliflozin pharmacokinetics and urinary glucose excretion were measured. The apparent SGLT2 occupancy was derived from the difference between the apparent volume of distribution of [18F]canagliflozin in the baseline and post-drug PET scans. Individual canagliflozin area under the curve from oral dosing until 24-hours (AUCP0-24h) varied largely (range 1,715–25,747 μg/L*hour, mean 10,580 μg/L*hour) and increased dose dependently with mean values of 4,543, 6,525, and 20,012 μg/L*hour for 50, 100, and 300 mg, respectively (P = 0.046). SGLT2 occupancy ranged between 65% and 87%, but did not correlate with canagliflozin dose, plasma exposure, or urinary glucose excretion. We report the feasibility of [18F]canagliflozin PET imaging to determine canagliflozin kidney disposition and SGLT2 occupancy. This suggests the potential of [18F]canagliflozin as a tool to visualize and quantify clinically SGLT2 tissue binding.
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The prevalence of type 2 diabetes (T2D) is relatively high among people with a low socioeconomic status (SES). As lifestyle is crucial in T2D management, patients are advised to live healthily, but incorporating lifestyle changes in daily life is not easy. It may be even more difficult for people with a low SES, as they often struggle with more urgent issues in daily life that supersede healthy lifestyle. How to promote a healthy lifestyle such that the needs of low SES patients are met? A boundary condition is a thorough understanding of the target group, and of the differences between individuals in this group. Too often, people with a low SES receive either general advice, or advice targeted to literacy level or ethnic background, whereas the diversity within the low SES population is much wider than that. We developed personas to identify archetypes of the target group, each reflecting a distinct pattern in goals, attitudes and behaviours, to help grasp the diversity of the target group. Ten interviews with low SES T2D-patients revealed their perceptions and experiences related to what is important in life, a healthy lifestyle, living with diabetes, and lifestyle advice. Following Goodwin’s persona development methodology (2011), three groups were qualitatively extracted from the data. In short, the personas are: 1) the worrisome caregiver: wants to live healthier, but is incapable of incorporating advices into one’s life; caring for others is first priority; 2) the conscious self-confident: willing and able to follow up advice in order to reduce medication use; 3) the selfwilled survivor: dealing with multiple (health) issues, and dedicated to solve things one’s own way. Each persona likely responds differently to health promoting strategies. Additional research is needed to enrich the set of personas, for example by verifying them with the target group’s family or health professionals.
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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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Background: Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. Methods: In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). Results: There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. Conclusion: 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.
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Rationale: While combined lifestyle interventions have multiple health benefits, their impact on the oral microbiome is not known. We explored the effects of a lifestyle intervention including protein drink on the oral microbiome in older adults with obesity and type 2 diabetes (T2D).Methods: In a post-hoc analysis of the PROBE study, 87 subjects (66.5±6.1 years, 33% female) with tongue dorsum samples at baseline and week 13 were included. All subjects participated in a 13-week lifestyle intervention with exercise (3x/week) and hypocaloric diet (-600 kcal/day), and had been randomized to receive a test product (21g whey protein enriched with leucine and vitamin D) or isocaloric control (0g protein) 10x/week. T2D was subtyped as muscle insulin resistance (MIR, n=34) or no-MIR (n=36) based on available muscle insulin sensitivity index. Microbiome was analysed by V4 16s rDNA sequencing. Diversity, measured as species richness and Shannon diversity index, was statistically analysed with paired (within group) and independent (between groups) samples t-test.Results: displayed below. Conclusion: Consuming a whey protein drink enriched with leucine and vitamin D during a combined lifestyle intervention increased species richness of the oral microbiome in obese T2D subjects with muscle insulin resistance.
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Aims: This systematic review and meta-analysis evaluates the additional effect of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes. Methods: Embase, Medline, Web of Science and Cochrane Central databases were evaluated, and 11 studies were included. Random-effects meta-analysis was performed on body weight and measures of body composition and glycaemic control, to compare the effect of hypocaloric diet plus exercise with hypocaloric diet alone. Results: Exercise interventions consisted of walking or jogging, cycle ergometer training, football training or resistance training and duration varied from 2 to 52 weeks. Body weight and measures of body composition and glycaemic control decreased during both the combined intervention and hypocaloric diet alone. Mean difference in change of body weight (−0.77 kg [95% CI: −2.03; 0.50]), BMI (−0.34 kg/m2 [95% CI: −0.73; 0.05]), waist circumference (−1.42 cm [95% CI: −3.84; 1.00]), fat-free mass (−0.18 kg [95% CI: −0.52; 0.17]), fat mass (−1.61 kg [95% CI: −4.42; 1.19]), fasting glucose (+0.14 mmol/L [95% CI: −0.02; 0.30]), HbA1c (−1 mmol/mol [95% CI: −3; 1], −0.1% [95% CI: −0.2; 0.1]) and HOMA-IR (+0.01 [95% CI: −0.40; 0.42]) was not statistically different between the combined intervention and hypocaloric diet alone. Two studies reported VO2max and showed significant increases upon the addition of exercise to hypocaloric diet. Conclusions: Based on limited data, we did not find additional effects of exercise to hypocaloric diet in adults with overweight or obesity and type 2 diabetes on body weight, body composition or glycaemic control, while cardio-respiratory fitness improved.
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From the publisher's site: "Trial design: Self-management plays a central role in diabetes management. However, not all patients are able to translate the health care providers’ recommendations for effective self-management in daily life. Diabetes Education and Self-management to Increase Empowerment (DESTINE) primarily investigates the effects of group education program Proactive Interdisciplinary Self-Management (PRISMA) in primary care treated people with Type 2 Diabetes Mellitus (T2DM) on the use of an online care platform. Methods: The DESTINE study has a randomized controlled design (1:1). 200 patients with T2DM using an online care platform called e-Vita will receive either PRISMA in addition to usual care or usual care only. The primary endpoint of this study is usage of the e-Vita platform. The secondary endpoints are participation in the consultation with the care provider, adherence to oral diabetes medications, and a selection of self-reported and clinical measures. After six months, both groups will receive PRISMA in a 6 month extension phase. Discussion: PRISMA focuses on aligning treatment goals from different health care providers while the individual patient remains in the lead. The goal is to shift patients from being an information receiver towards applying self-management and becoming empowered health care participants. Though recognized as important; theoretically based group education is still not routinely offered in the Netherlands. In the future, depending on the study results, e-Vita and PRISMA could be implemented in regular diabetes care. Trial registration: Current Controlled Trials NTR4693. (aut. ref.)"
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