Effects of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control: a systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Web of Science, PubMed/MEDLINE and SPORTDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials involving exercise, metformin or their combined treatments in individuals with prediabetes or type 2 diabetes mellitus (T2DM) were included. Outcomes included haemoglobin A1c (HbA1c), 2-hour glucose during oral glucose tolerance test, fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: 407 articles with 410 randomised controlled trials (n=33 802) were included. In prediabetes, the exercise showed greater efficacy than metformin on HbA1c levels (mean difference -0.16%, 95% CI (-0.23 to -0.09) vs -0.10%, 95% CI (-0.21 to 0.02)), 2-hour glucose (-0.68 mmol/L, 95% CI (-0.97 to -0.39) vs 0.01 mmol/L, 95% CI (-0.38 to 0.41)) and HOMA-IR (-0.54, 95% CI (-0.71 to -0.36) vs -0.23, 95% CI (-0.55 to 0.10)), while the efficacy on fasting glucose was comparable (-0.26 mmol/L, 95% CI (-0.32 to -0.19) vs -0.33 mmol/L, 95% CI (-0.45 to -0.21)). In T2DM, metformin was more efficacious than exercise on HbA1c (-0.88%, 95% CI (-1.07 to -0.69) vs -0.48%, 95% CI (-0.58 to -0.38)), 2-hour glucose (-2.55 mmol/L, 95% CI (-3.24 to -1.86) vs -0.97 mmol/L, 95% CI (-1.52 to -0.42)) and fasting glucose (-1.52 mmol/L, 95% CI (-1.73 to -1.31) vs -0.85 mmol/L, 95% CI (-0.96 to -0.74)); exercise+metformin also showed greater efficacy in improving HbA1c (-1.23%, 95% CI (-2.41 to -0.05)) and fasting glucose (-2.02 mmol/L, 95% CI (-3.31 to -0.74)) than each treatment alone. However, the efficacies were modified by exercise modality and metformin dosage. CONCLUSION: Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be superior to exercise in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42023400622.

Continuous Glucose Monitoring in Healthy Adults-Possible Applications in Health Care, Wellness, and Sports.

INTRODUCTION: Continuous glucose monitoring (CGM) systems were primarily developed for patients with diabetes mellitus. However, these systems are increasingly being used by individuals who do not have diabetes mellitus. This mini review describes possible applications of CGM systems in healthy adults in health care, wellness, and sports. RESULTS: CGM systems can be used for early detection of abnormal glucose regulation. Learning from CGM data how the intake of foods with different glycemic loads and physical activity affect glucose responses can be helpful in improving nutritional and/or physical activity behavior. Furthermore, states of stress that affect glucose dynamics could be made visible. Physical performance and/or regeneration can be improved as CGM systems can provide information on glucose values and dynamics that may help optimize nutritional strategies pre-, during, and post-exercise. CONCLUSIONS: CGM has a high potential for health benefits and self-optimization. More scientific studies are needed to improve the interpretation of CGM data. The interaction with other wearables and combined data collection and analysis in one single device would contribute to developing more precise recommendations for users.

Glaucoma Diagnostic Testing: The Influence of Optic Disc Size. / Einfluss der Papillengröße auf die Glaukombildgebung.

BACKGROUND: There are various imaging techniques for the assessment of the optic disc in glaucoma patients. However, anatomically conspicuous, large or small optic discs can be quite challenging for an examiner. OBJECTIVE: The Bruch's membrane opening (BMO) by spectral domain optical coherence tomography (SD-OCT) is a modern approach for the quantitative measures of retinal nerve fibre layer (RNFL). The study focuses on comparison analysis of the BMO method and the widely used Heidelberg retina tomograph (HRT) method - in terms of detection of glaucoma for different optic disc sizes. METHODS: 216 Patients examinations during glaucoma consultation hours. Macro- (Ma) and micro-optic discs (Mi) detected by HRT are analysed via BMO analysis in SD-OCT. Correlation between BMO area and optic disc measured by HRT has been investigated and examined in terms of severity of visual field defect (MD [dB]). RESULTS: The results of study show that for micro and macro-optic discs there is a modest correlation between the size of optic disc measured by BMO and the size of optic disc measured by HRT by applying funduscopic examination (correlation rate r = 0,53; Mi: n = 111, Ma: n = 105). For micro-optic discs with a very small BMO area (< 1.5 mm2), there is a significant tendency (linear trend test p < 0.05) towards deeper visual field defects (MD < - 5 dB). CONCLUSION: The BMO parameter of SD-OCT allows an assessment of glaucoma for a large range of optic disc sizes. BMO area and optic disc size measured by HRT are not correlated. Micro optic discs with a small BMO area lead to a higher risk of deep visual field defects.

No Influence of Nonivamide-nicoboxil on the Peak Power Output in Competitive Sportsmen.

Recent studies have shown that the oxygenated hemoglobin level can be enhanced during rest through the application of nonivamide-nicoboxil cream. However, the effect of nonivamide-nicoboxil cream on oxygenation and endurance performance under hypoxic conditions is unknown. Therefore, the purpose of this study was to investigate the effects of nonivamide-nicoboxil cream on local muscle oxygenation and endurance performance under normoxic and hypoxic conditions. In a cross-over design, 13 athletes (experienced cyclists or triathletes [age: 25.2±3.5 years; VO2max 62.1±7.3 mL·min-1·kg-1]) performed four incremental exercise tests on the cycle ergometer under normoxic or hypoxic conditions, either with nonivamide-nicoboxil or placebo cream. Muscle oxygenation was recorded with near-infrared spectroscopy. Capillary blood samples were taken after each step, and spirometric data were recorded continuously. The application of nonivamide-nicoboxil cream increased muscle oxygenation at rest and during different submaximal workloads as well as during physical exhaustion, irrespective of normoxic or hypoxic conditions. Overall, there were no significant effects of nonivamide-nicoboxil on peak power output, maximal oxygen uptake or lactate concentrations. Muscle oxygenation is significantly higher with the application of nonivamide-nicoboxil cream. However, its application does not increase endurance performance.

Inter-Device Comparison of Blue-Light Autofluorescence in Optic Disc Drusen.

PURPOSE: Monochromatic blue-light fundus autofluorescence has proven to be particularly useful for the detection of optic disc drusen (ODD). The aim of this study was to investigate how accurately novel confocal scanners can detect ODD by means of color fundus and autofluorescence images. METHODS: Images were taken in 20 consecutive patients' eyes with funduscopically visible ODD using the TrueColor Eidon AF (60 × 55°) and the spectral domain Spectralis HRA+OCT (30 × 30°). The features of ODD, including localization, extent, and intensity patterns of autofluorescence were compared and correlated with retinal nerve fiber layer (RNFL) thickness in OCT and perimetry findings. RESULTS: Mean patient age was 46 ± 6 years (6 females, 4 males). The TrueColor Eidon AF enabled accurate localization and extent estimation of the drusen area. Drusen presented as a homogeneous signal. The predilection site of ODD, which was nasally pronounced in >80% of cases, was associated with thinning of the RNFL and corresponding visual field defects. CONCLUSION: The TrueColor Eidon AF allows reliable detection of superficial ODD in nondilated eyes. Extended observational studies are needed to determine the value of this noninvasive, nonmydriatic procedure in terms of follow-up and progression analyses of ODD.

Minimally Invasive Electrochemical Patch-Based Sensor System for Monitoring Glucose and Lactate in the Human Body-A Survey-Based Analysis of the End-User's Perspective.

Background: Wearable electrochemical sensors that detect human biomarkers allow a comprehensive analysis of a person's health condition. The "electronic smart patch system for wireless monitoring of molecular biomarkers for health care and well-being" (ELSAH) project aims to develop a minimally invasive sensor system that is capable of continuously monitoring glucose and lactate in the dermal interstitial fluid in real time. It is the objective of the present study to compare the intended ELSAH-patch specifications with the expectations and requirements of potential end-users at an early stage during the development phase. Methods: A questionnaire addressing different aspects of the ELSAH-patch was filled out by 383 respondents. Results: The participants stated a high general demand for such a system, and they would use the ELSAH-patch in different health care and physical fitness applications. The preferred terminal device for communication with the sensor would be the smartphone. An operating time of 24 hours would be sufficient for 55.8% of the users (95%-CI: 50.3-61.3%), while 43.5% of them (95%-CI: 38.0-48.9%) would prefer a lifetime of several days or more. The software should have a warning function, especially for critical health conditions. Since the measured personal data would be highly sensitive, the participants called for high standards for data security and privacy. Conclusion: In general, the participants' responses on their expectations and requirements were well in line with the intended specifications of the ELSAH-patch system. However, certain technical aspects such as the lifetime, data security and accuracy require special attention during its development.

Effects of Endurance Exercise Bouts in Hypoxia, Hyperoxia, and Normoxia on mTOR-Related Protein Signaling in Human Skeletal Muscle.

Przyklenk, A, Aussieker, T, Gutmann, B, Schiffer, T, Brinkmann, C, Strüder, HK, Bloch, W, Mierau, A, and Gehlert, S. Effects of endurance exercise bouts in hypoxia, hyperoxia, and normoxia on mTOR-related protein signaling in human skeletal muscle. J Strength Cond Res 34(8): 2276-2284, 2020-This study investigated the effects of short-term hypoxia (HY), hyperoxia (PER), and normoxia on anabolic signaling proteins in response to an acute bout of moderate endurance exercise (EEX) before and after an endurance exercise training intervention. Eleven healthy male subjects conducted one-legged cycling endurance exercise (3 × 30 min·wk for 4 weeks). One leg was trained under hypoxic (12% O2) or hyperoxic conditions (in a randomized cross-over design), and the other leg was trained in normoxia (20.9% O2) at the same relative workload. Musculus vastus lateralis biopsies were taken at baseline (T0) as well as immediately after the first (T1) and last (T2) training session to analyze anabolic signaling proteins and the myofiber cross-sectional area (FCSA). No significant differences were detected for FCSA between T0 and T2 under all oxygen conditions (p > 0.05). No significant differences (p > 0.05) were observed for BNIP3, phosphorylated RSK1, ERK1/2, FoxO3a, mTOR, and S6K1 between all conditions and time points. Phosphorylated Akt/PKB decreased significantly (p < 0.05) at T1 in PER and at T2 in HY and PER. Phosphorylated rpS6 decreased significantly (p < 0.05) at T1 only in PER, whereas nonsignificant increases were shown in HY at T2 (p = 0.10). Despite no significant regulations, considerable reductions in eEF2 phosphorylation were detected in HY at T1 and T2 (p = 0.11 and p = 0.12, respectively). Short-term hypoxia in combination with moderate EEX induces favorable acute anabolic signaling responses in human skeletal muscle.

[Exergaming for patients with metabolic syndrome?!] / Exergaming für PatientInnen mit metabolischem Syndrom?!

Due to the tremendous technical progress that has been made in recent years and the increased interest in using new technologies in sports and exercise, the effects of "exergaming" (exercise with video games and the use of an interactive computer-generated virtual reality) on human health have been investigated in numerous research projects. This systematic mini review analyzes the effects of regular exergaming in patients with components of metabolic syndrome. The review indicates that improvements in different variables, e.g., body mass index, body fat, glycemic control and blood lipid/lipoprotein levels, as well as blood pressure, can be achieved through regular exergaming. Future studies should examine whether exergaming can motivate patients with metabolic syndrome to engage in physical activity in the long term. Support from and (initial) supervision by health professionals (sports coaches, physiotherapists) are recommended to increase positive outcomes.

Effects of exercising before breakfast on the health of T2DM patients-A randomized controlled trial.

This is the first study to examine whether training before breakfast in the overnight-fasted state is more effective in improving the health of patients with type 2 diabetes mellitus (T2DM) than after breakfast in the fed state. Thirty T2DM patients (60 ± 8 years, 33.7 ± 4.6 kg/m2 ) were randomly assigned to the F group (training in the overnight-fasted state (n = 15)) and to the C group (training in the fed state (control group, n = 15)). All patients completed an 8-week combined endurance/strength training program. Physical training significantly increased time to physical exhaustion during an endurance test (+10.4%), power output during strength tests (chest presses: +36.7% and seated rows: +37.8%), and fat-free mass (+1.7 kg). Body fat mass (-1.9 kg), glycated hemoglobin (HbA1c) values (absolute change: -0.3%), serum insulin values (-2.5 microU/mL), the homeostatic model assessment for insulin resistance (HOMA-IR) index (-1.1), and circulating triglyceride levels (-31 mg/dL) decreased significantly from pre- to post-training. The training had no effect on body mass index, serum fasting glucose, total cholesterol, low-density lipoprotein/high-density lipoprotein ratio or interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)α levels. Analyses of variance revealed no time × group interaction for any variable (P > .05). The training was effective in improving the health of T2DM patients. However, the preliminary study's data do not provide any evidence that the nutritional state (overnight-fasted or fed) in regular physical training plays a significant role for training-induced adaptations in T2DM patients. Full trials (using other training protocols as well) should be conducted to gain further knowledge about the relevance of pre-exercise breakfast ingestion.

Endurance training alters YKL40, PERM1, and HSP70 skeletal muscle protein contents in men with type 2 diabetes mellitus.

BACKGROUND: The fight against type 2 diabetes mellitus (T2DM) is tremendously challenging. This pilot study investigates whether endurance training (3 times per week for 3 months, moderate intensity) can change the skeletal muscle protein contents of chitinase-3-like protein-1 (YKL40), peroxisome proliferator-activated receptor y coactivator-1 and estrogen-related receptor-induced regulator in muscle-1 (PERM1) and heat-shock protein-70 (HSP70), which have been discussed as novel therapeutically relevant targets. METHODS: Muscle biopsies were obtained from overweight/obese men with T2DM (n = 7, years = 63 ± 9) at T1 (6 weeks pre-training), T2 (1 week pre-training) and T3 (3 to 4 days post-training). The protein levels of YKL40, PERM1, and HSP70 were determined by immunohistochemistry. RESULTS: YKL40, PERM1, and HSP70 were significantly upregulated following endurance training (T2-T3: +103%, +61%, +89%, p = 0.012, p = 0.010, p = 0.028). There was a fiber type-specific distribution of HSP70 with increased protein contents in type I fibers. A significant change in the fiber type distribution with an increase in type I fibers and a decrease in type II fibers was observed post-training. There were no significant differences for YKL40, PERM1, HSP70, or the fiber type distribution between T1 and T2. CONCLUSION: The training-induced upregulation of YKL40, PERM1, and HSP70 could help manage the diabetic disease and reduce its complications.

Design and Baseline Characteristics of the HELP Study: An Extended and Long-Term Observation of Pathological Myopia in Caucasians.

PURPOSE: To assess the natural disease progression of high myopia in Caucasians considered at risk for the development of myopic choroidal neovascularization (mCNV). METHODS: Subjects were recruited in 25 clinical sites between June 2014 and June 2016. Main inclusion criteria included axial length of ≥26 mm, best-corrected visual acuity ≥0.05 decimal equivalent and presence of at least one out of five predefined morphological disease risk criteria. These were (1) subfoveal choroidal thinning < 50 µm, (2) enhanced choroidal curvature length > 6,300 µm, (3) lacquer cracks, (4) patchy atrophy > 5 mm2 and (5) preexisting mCNV in the fellow eye (German Clinical Trial Register DRKS00007761). RESULTS: A total of 150 participants (66% females) with a mean age of 57.2 (±12.7) years (range 21.9-86.2 years) were included. The disease criteria most frequently encountered were choroidal thinning (33.3%) and lacquer cracks (32.7%). Enhanced choroidal curvature length was detected in only 8 subjects and always occurred in combination with other disease criteria. Presence of patchy atrophy was found to be more common in older subjects (p = 0.0012) and also associated with a more severe disease manifestation. CONCLUSION: The baseline data of this study indicate that enhanced choroidal curvature might be less common in Caucasians than in Asian populations. Further, disease severity in patients with high myopia is relatively high in the presence of patchy atrophy.

Influence of endurance training on skeletal muscle mitophagy regulatory proteins in type 2 diabetic men.

BACKGROUND: Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients. METHODS: Muscle biopsies were obtained from eight overweight/obese T2DM men (61±10 years) at T1 (6 weeks pre-training), T2 (1 week pre-training), and T3 (3 to 4 days post-training). Protein contents were determined by Western blotting. RESULTS: The training increased mitochondrial complex II significantly (T2-T3: +29%, p = 0.037). The protein contents of mitophagy regulatory proteins (phosphorylated form of forkhead box O3A (pFOXO3A), mitochondrial E3 ubiquitin protein ligase-1 (MUL1), Bcl-2/adenovirus E1B 19-kD interacting protein-3 (BNIP3), microtubule-associated protein 1 light chain-3B (the ratio LC3B-II/LC3B-I was determined)) did not differ significantly between T1, T2, and T3. CONCLUSIONS: The results imply that training-induced changes in OXPHOS subunits (significant increase in complex II) are not accompanied by changes in mitophagy regulatory proteins in T2DM men. Future studies should elucidate whether acute exercise might affect mitophagic processes in T2DM patients (and whether a transient regulation of mitophagy regulatory proteins is evident) to fully clarify the role of physical activity and mitophagy for mitochondrial health in this particular patient group.

Hypoxia and Hyperoxia Affect Serum Angiogenic Regulators in T2DM Men during Cycling.

Exercise-induced transient increases in pro-angiogenic regulators can promote angiogenesis.This pilot study aims to analyze the potential of exercise to positively affect angiogenic regulators in patients with type 2 diabetes mellitus (T2DM), who often exhibit abnormal angiogenesis, under different environmental conditions. 9 overweight/obese men with uncomplicated T2DM (8 took anti-diabetic drugs) performed submaximal cycling for 40 min in normoxia (≈21 vol%O2), hypoxia (≈14 vol%O2) and during alternating hypoxia/hyperoxia (≈14 vol%O2/≈30 vol%O2, 5-min intervals) (3×3 crossover design). Serum pro-angiogenic vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and anti-angiogenic endostatin were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Non-parametric statistical tests (Wilcoxon, Friedman analysis of variance) were applied. VEGF increased significantly from pre- to post-exercise with hypoxia and hypoxia/hyperoxia. MMP-2 increased significantly in all experimental runs, while MMP-9 only increased significantly with hypoxia and hypoxia/hyperoxia. Endostatin increased significantly with normoxia and hypoxia. However, the magnitude of changes did not differ significantly between conditions. Capillary blood lactate was significantly lower following cycling with hypoxia/hyperoxia than with hypoxia alone. Although differences in subjective ratings of perceived exertion failed significance, 7 subjects were less exerted with hypoxia/hyperoxia than with hypoxia. Submaximal cycling with hypoxia or alternating hypoxia/hyperoxia may induce a more reliable up-regulation of pro-angiogenic regulators compared with normoxia, while hypoxia/hyperoxia may be better tolerated than hypoxia alone.

[Oxidative stress in Masters swimmers following high-intensity (interval) training (HI(I)T)]. / Oxidativer Stress bei Mastersschwimmern nach hochintensivem (Intervall-) Training (HI(I)T).

Increased oxidative stress (OS) can promote diseases in the long term, but it can also trigger cellular adaptations in the short term. The present study aims to analyze whether a 3-month high-intensity (interval) training (HI(I)T) affects OS in 24 Masters swimmers (22-67 years) before (= basal) and after an all-out performance (swimming step-test). Data were analyzed for the entire group and differentiated according to sex and age (under 50 years (U50) and over 50 years (O50)). Prior to the HI(I)T intervention, a significant increase in OS from the basal to the all-out value was observed among the entire group and in the O50-subjects (subgroup analysis). Furthermore, significant increases in basal OS were evident for the entire group post-HI(I)T, but OS was only significantly increased in men in the subgroup analysis. No significant results were observed for women and U50-subjects. The response by Masters swimmers to HI(I)T depends on age and sex.

Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing.

PURPOSE: To describe the directional kinetics of the spread of geographic atrophy (GA) spread in eyes with age-related macular degeneration and foveal sparing. DESIGN: Prospective, noninterventional natural history study: Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM; clinicaltrials.gov identifier, NCT00393692). SUBJECTS: Participants of the FAM study exhibiting foveal sparing of GA. METHODS: Eyes were examined longitudinally with fundus autofluorescence (FAF; excitation wavelength, 488 nm; emission wavelength, >500 nm) and near infrared (NIR) reflectance imaging (Spectralis HRA+OCT or HRA2; Heidelberg Engineering, Heidelberg, Germany). Areas of foveal sparing and GA were measured by 2 independent readers using a semiautomated software tool that allows for combined NIR reflectance and FAF image grading (RegionFinder; Heidelberg Engineering). A linear mixed effect model was used to model GA kinetics over time. MAIN OUTCOME MEASURE: Change of GA lesion size over time (central vs. peripheral progression). RESULTS: A total of 47 eyes of 36 patients (mean age, 73.8±7.5 years) met the inclusion criteria. Mean follow-up time was 25.2±16.9 months (range, 5.9-74.6 months). Interreader agreement for measurements of GA and foveal-sparing size were 0.995 and 0.946, respectively. Mean area progression of GA toward the periphery was 2.27±0.22 mm(2)/year and 0.25±0.03 mm(2)/year toward the center. Analysis of square root-transformed data revealed a 2.8-fold faster atrophy progression toward the periphery than toward the fovea. Faster atrophy progression toward the fovea correlated with faster progression toward the periphery in presence of marked interindividual differences. CONCLUSIONS: The results demonstrate a significantly faster centrifugal than centripetal GA spread in eyes with GA and foveal sparing. Although the underlying pathomechanisms for differential GA progression remain unknown, local factors may be operative that protect the foveal retina-retinal pigment epithelial complex. Quantification of directional spread characteristics and modeling may be useful in the design of interventional clinical trials aiming to prolong foveal survival in eyes with GA.

Endurance training alters basal erythrocyte MCT-1 contents and affects the lactate distribution between plasma and red blood cells in T2DM men following maximal exercise.

Chronic elevated lactate levels are associated with insulin resistance in patients with type 2 diabetes mellitus (T2DM). Furthermore, lactacidosis plays a role in limiting physical performance. Erythrocytes, which take up lactate via monocarboxylate transporter (MCT) proteins, may help transport lactate within the blood from lactate-producing to lactate-consuming organs. This study investigates whether cycling endurance training (3 times/week for 3 months) alters the basal erythrocyte content of MCT-1, and whether it affects lactate distribution kinetics in the blood of T2DM men (n = 10, years = 61 ± 9, body mass index = 31 ± 3 kg/m(2)) following maximal exercise (WHO step-incremental cycle ergometer test). Immunohistochemical staining indicated that basal erythrocyte contents of MCT-1 protein were up-regulated (+90%, P = 0.011) post-training. Erythrocyte and plasma lactate increased from before acute exercise (= resting values) to physical exhaustion pre- as well as post-training (pre-training: +309%, P = 0.004; +360%, P < 0.001; post-training: +318%, P = 0.008; +300%, P < 0.001), and did not significantly decrease during 5 min recovery. The lactate ratio (erythrocytes:plasma) remained unchanged after acute exercise pre-training, but was significantly increased after 5 min recovery post-training (compared with the resting value) (+22%, P = 0.022). The results suggest an increased time-delayed influx of lactate into erythrocytes following an acute bout of exercise in endurance-trained diabetic men.

Skeletal muscle nitric oxide (NO) synthases and NO-signaling in "diabesity"--what about the relevance of exercise training interventions?

Type 2 diabetes mellitus associated with obesity, or "diabesity", coincides with an altered nitric oxide (NO) metabolism in skeletal muscle. Three isoforms of nitric oxide synthase (NOS) exist in human skeletal muscle tissue. Both neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) are constitutively expressed under physiological conditions, producing low levels of NO, while the inducible nitric oxide synthase (iNOS) is strongly up-regulated only under pathophysiological conditions, excessively increasing NO concentrations. Due to chronic inflammation, overweight/obese type 2 diabetic patients exhibit up-regulated protein contents of iNOS and concomitant elevated amounts of NO in skeletal muscle. Low muscular NO levels are important for attaining an adequate cellular redox state--thereby maintaining metabolic integrity--while high NO levels are believed to destroy cellular components and to disturb metabolic processes, e.g., through strongly augmented posttranslational protein S-nitrosylation. Physical training with submaximal intensity has been shown to attenuate inflammatory profiles and iNOS protein contents in the long term. The present review summarizes signaling pathways which induce iNOS up-regulation under pathophysiological conditions and describes molecular mechanisms by which high NO concentrations are likely to contribute to triggering skeletal muscle insulin resistance and to reducing mitochondrial capacity during the development and progression of type 2 diabetes. Based on this information, it discusses the beneficial effects of regular physical exercise on the altered NO metabolism in the skeletal muscle of overweight/obese type 2 diabetic subjects, thus unearthing new perspectives on training strategies for this particular patient group.

The Influence of Acute and Chronic Exercise on Appetite and Appetite Regulation in Patients with Prediabetes or Type 2 Diabetes Mellitus-A Systematic Review.

This systematic review aims to analyze the effects of acute and chronic exercise on appetite and appetite regulation in patients with abnormal glycemic control. PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for eligible studies. The included studies had to report assessments of appetite (primary outcome). Levels of appetite-regulating hormones were analyzed as secondary outcomes (considered, if additionally reported). Seven studies with a total number of 211 patients with prediabetes or type 2 diabetes mellitus (T2DM) met the inclusion criteria. Ratings of hunger, satiety, fullness, prospective food consumption, nausea, and desire to eat, as well as levels of (des-)acylated ghrelin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, pancreatic polypeptide, peptide tyrosine tyrosine, leptin, and spexin were considered. Following acute exercise, the effects on appetite (measured up to one day post-exercise) varied, while there were either no changes or a decrease in appetite ratings following chronic exercise, both compared to control conditions (without exercise). These results were accompanied by inconsistent changes in appetite-regulating hormone levels. The overall risk of bias was low. The present results provide more evidence for an appetite-reducing rather than an appetite-increasing effect of (chronic) exercise on patients with prediabetes or T2DM. PROSPERO ID: CRD42023459322.

[Aflibercept in the clinical routine: the AURIGA study : The 24-month results of the German cohort of treatment-naïve patients with diabetic macular edema receiving intravitreal aflibercept]. / Aflibercept im klinischen Alltag: die AURIGA-Studie : 24-Monats-Ergebnisse der deutschen Kohorte behandlungsnaiver Patienten mit diabetischem Makulaödem unter Therapie mit intravitrealem Aflibercept.

BACKGROUND: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) and macular edema secondary to retinal vein occlusion. This article presents 24-month data from the German cohort of treatment-naïve patients with DME. METHODS: Treatment-naïve patients (≥ 18 years) with DME were treated with IVT-AFL at the discretion of the physician in clinical practice. The primary endpoint was mean change in visual acuity (early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Statistical analyses were descriptive. RESULTS: The analysis included data from 150 DME patients (54.7% male). At months 6, 12 and 24, mean (95% confidence interval) visual acuity gains of 4.6 (2.6; 6.5), 4.0 (2.1; 6.5) and 5.0 (3.0; 6.9) letters from baseline (mean ±SD: 65.0 ± 15.3 letters) and reductions in retinal thickness of 86µm (109; 64µm), 70µm (94; 43µm) and 75µm (103; 47µm) from baseline (mean ±SD: 391 ± 132 µm), respectively, were achieved. At month 24, 54% of patients gained ≥ 5 letters and 22% ≥ 15 letters. Patients received a mean number of 5.0 ± 1.6 injections until month 6, 7.1 ± 3.2 until month 12 and 9.0 ± 5.3 until month 24, 68% of patients received ≥ 5 injections until month 6 and 56% ≥ 7 injections within the first year. The safety profile was consistent with previous studies. DISCUSSION: In the German AURIGA cohort, treatment-naïve DME patients achieved a clinically relevant gain in visual acuity as well as reduction in central retinal thickness following IVT-AFL treatment in clinical practice. From month 6 onwards, improvements were maintained despite a low injection frequency over 24 months. In comparison with previous real-world studies, care of DME patients in clinical practice seems to have improved; however, there is still room for further improvement.