This research article shows that a high intensity exercise program compared to a low intensity exercise program of the same session duration and frequency, increases insulin sensitivity to a larger extend in healthy subjects. It also shows that the short insulin tolerance test can be used to detect differences in insulin sensitivity in intervention studies.
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Review of the effects of physical activity on insulin sensitivity
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Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
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(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.
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Background: Weight loss is key to treatment of older adults with obesity and type 2 diabetes, but also a risk for muscle mass loss. This study investigated whether a whey protein drink enriched with leucine and vitamin D could preserve muscle mass and improve glycemic control during combined lifestyle intervention in this population. Methods: 123 older adults with obesity and type 2 diabetes were randomized into a 13-week lifestyle intervention with dietary advice and exercise, receiving either the enriched protein drink (test) or an isocaloric control (control). Muscle mass was assessed with dual-energy X-ray absorptiometry and glycemic control by oral glucose tolerance test. Statistical analyses were performed using a linear mixed model. Results: There was a nonsignificant increase in leg muscle mass (+0.28 kg; 95% CI, −0.01 to 0.56) and a significant increase in appendicular muscle mass (+0.36 kg; 95% CI, 0.005 to 0.71) and total lean mass (+0.92 kg; 95% CI, 0.19 to 1.65) in test vs. control. Insulin sensitivity (Matsuda index) also increased in test vs. control (+0.52; 95% CI, 0.07 to 0.97). Conclusions: Use of an enriched protein drink during combined lifestyle intervention shows beneficial effects on muscle mass and glycemic control in older adults with obesity and type 2 diabetes.
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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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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: The number of obese older adults with diabetes type 2 is increasing worldwide. Weight loss treatment in this group seems beneficial for cardio-metabolic and other health outcomes, but it might reduce muscle mass and bone mineral density (BMD). The association between obesity and BMD is controversial, and the role of muscle mass and dietary protein intake is not fully clear. This study explores the association between body weight, muscle mass, dietary protein intake, and physical activity level on BMD in obese older adults with diabetes type 2. Methods: For this cross-sectional analysis we used baseline data of a 13-week randomized trial evaluating the effect of a multi-modal intervention on muscle preservation and insulin sensitivity during a weight loss program in obese older adults (55-80y) with diabetes type 2 (PROBE). Body weight was measured using a calibrated scale (Life Measurement), appendicular lean mass (ALM) was used as a proxy for muscle mass and was measured by dual-energy X-ray absorptiometry (DXA, Hologic Discovery A), dietary protein intake was estimated by a 3-day food record, Physical Activity Level (PAL) was estimated by a 3-day activity record, and hip BMD was assessed by DXA. After determination of Pearson’s correlation coefficients for body weight, ALM, protein intake, and PAL with BMD, linear regression analysis was performed with significantly correlating determinants (body weight [kg], ALM [kg], protein intake [g/kg/d], and/or PAL [-]) and hip BMD (g/cm2) as outcome variable. Results: Mean age of the 122 included subjects was 67±6y, with a BMI of 33±4kg/m2. 65% of subjects were male. Body weight and ALM correlated significantly with BMD (r=0.34, p<0.001; r=0.43, p<0.001) whereas protein intake and PAL did not (r=0.02, p=0.84; r=0.005, p=0.95). Linear regression analysis with the two determinants body weight and ALM identified ALM as being significantly associated with BMD, whereas body weight was not. Beta for ALM was +0.011 g/cm2 (95% CI: 0.004 – 0.017; p<0.01), meaning that a 1 kg increase in ALM is associated with a +0.011 g/cm2 increase in BMD. Conclusion: In this explorative cross-sectional analysis appendicular muscle mass is positively associated with BMD, rather than body weight, protein intake, and physical activity level.
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Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.
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mHealth 24/7 is een dienst die diabetespatiënten helpt om op eenvoudige wijze toezicht te houden op hun eigen gezondheid. mDiabetes 24/7 is een prototype app binnen de dienst mHealth 24/7. Op dit moment kunnen patiënten met het prototype van de app hun bloedsuikerwaardes, een eetdagboek en de hoeveelheid toegediende insuline bijhouden. mHealth 24/7 heeft de wens geformuleerd om haar informatievoorziening aan diabetespatiënten verder uit te breiden, door gepersonaliseerd inzicht te geven in de oorzaak van stijgingen en dalingen van hun bloedsuikerwaarden. Meer informatie stelt de patiënt in staat om beter gemotiveerde maatregelen te nemen en stimuleert therapietrouw waarmee later complicaties kunnen worden voorkomen. Dit verbetert de kwaliteit van leven en vermindert kosten.In het project is gerealiseerd dat data uit een activity tracker en omgevingstemperatuur ingelezen wordt in de app en wordt geïntegreerd met bestaande data zoals bloedsuikerwaarde. Daarnaast kunnen patiënten handmatig aangeven hoe ze zich voelen. Patiënten krijgen daarmee inzicht in het effect van activiteit, omgevingstemperatuur en stemming op fluctuaties in bloedsuikerwaardes. In een pilot met 25 proefpersonen is de technische werking van de verrijkte app getest evenals de functionaliteit.Er is aangetoond dat de app werkt en dat voor gebruikers de verrijking van de informatie in de app met hartslag, omgevingstemperatuur en stemming van toegevoegde waarde is. Wel blijkt dat een app zoals deze foutloos en realtime moet werken en de gebruiksinterface dusdanig moet werken, dat de gebruikers er uitsluitend gemak van ondervinden. Diabetes is een arbeidsintensieve ziekte en nog meer werk is ongewenst!Als in een volgende pilot meer data kan worden verzameld, kan worden gewerkt aan het voorspellen van fluctuaties in bloedsuikerwaardes waardoor een patiënt ook voortijdig gewaarschuwd kan worden.Vanuit verschillende marktpartijen zoals ziekenhuizen en zorgverzekeraars is interesse getoond voor het project. Gezamenlijk gaan deze partijen aanspraak doen op tijdelijke financiering vanuit de “Beleidsregel Innovatie Kleinschalige Experimenten.
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