License, which permits unrestricted use, distribution, and reproduction in any medium, provided t... more License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Type 2 diabetesmellitus (T2D) is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT) has the power to combatmetabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limitedmechanistic insight into how these adaptations occur.This review provides an overview of the intervention data on the impact of RT on glucosemetabolism. In addition, themolecularmechanisms that lead to adaptation in skeletalmuscle in response to RT and that are associatedwith possible beneficialmetabolic responses are ...
High intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impa... more High intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impact on metabolism remains unclear. We hypothesized that 12-week HIIT improves insulin sensitivity in people with or without type 2 diabetes (T2D, NDM). However, despite identically improved VO2max, mainly insulin-resistant persons (T2D, IR NDM) responded with improved insulin sensitivity and circulating small extracellular vesicles (SEV), along with reduced myocellular protein kinase Cε activity (T2D) or inflammation (IR NDM). These changes related to the SEV proteome, characterized by downregulated phospholipase C pathway (T2D) and upregulated antioxidant capacity (IR NDM). Thus, SEV cargo likely contributes to modulating exercise responsiveness in humans.
Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Althou... more Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Although aging is associated with declining endurance performance and muscle function, these components can favorably be modified by regular physical activity and especially by exercise training at all ages in both sexes. In addition, age-related changes in body composition and metabolism, which affect even highly trained masters athletes, can in part be compensated for by higher exercise metabolic efficiency in active individuals. Accordingly, masters athletes are often considered as a role model for healthy aging and their physical capacities are an impressive example of what is possible in aging individuals. In the present review, we first discuss physiological changes, performance and trainability of older athletes with a focus on sex differences. Second, we describe the most important hormonal alterations occurring during aging pertaining regulation of appetite, glucose homeostasis and en...
Adipose dysfunction may drive the development of insulin resistance, type 2 diabetes (T2D) and no... more Adipose dysfunction may drive the development of insulin resistance, type 2 diabetes (T2D) and nonalcoholic (NA) fatty liver disease (NAFLD), comprising NA fatty liver and steatohepatitis (NAFL and NASH). Possible underlying mechanism comprise impaired lipid storage or mitochondrial oxidation favoring increased fatty acid flux to other tissues. Thus, we examined subcutaneous (SAT) and visceral adipose tissue (VAT) mitochondrial capacity in humans with different degrees of insulin resistance and histologically proven NAFLD. Obese people without NAFL (OBE-CON, n=20, 38±8 years, body mass index 53±6 kg/m2, 10% T2D), with NAFL (OBE-NAFL, n=20, 40±8 years, 51±5 kg/m2, 25% T2D) or NASH (OBE-NASH, n=20, 42±10 years, 51±6 kg/m2, 40% T2D) underwent metabolic phenotyping and tissue biopsies. O2 flux rates from different substrates were measured with high resolution respirometry in SAT and VAT. In VAT, maximal uncoupled respiration was lower in OBE-NAFL (least square means (LSM): 0.46 pmol*mg ...
Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in h... more Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in heart failure and triggers inflammatory pathways. NFkB can be induced by damaged mitochondria. Its association with myocardial mitochondrial respiratory function in non-ischemic diabetes-related heart failure in humans is yet unclear. We hypothesized that human ventricular myocardial NFkB expression (i) is increased by type 2 diabetes mellitus (T2DM), and (ii) relates to reduced myocardial mitochondrial respiration. Heart transplant recipients with or without T2DM (as determined by oral glucose tolerance test), about to undergo post-transplant surveillance endomyocardial biopsies, were included, if they had received hearts from donors without T2DM. Thus, time since transplantation equaled diabetes-exposure of the transplanted hearts (2.9±2.4 years). We assessed normalized NFkB p105 subunit (NFkB1) mRNA expression using real-time PCR and myocardial mitochondrial respiration using high-reso...
Small extracellular vesicles (SEV) are secreted into circulation after acute exercise suggesting ... more Small extracellular vesicles (SEV) are secreted into circulation after acute exercise suggesting a new mode of tissue crosstalk. High intensity interval training (HIIT) leads to improved insulin sensitivity and oxidative capacity in patients with type 2 diabetes. As the impact of HIIT on SEV release is unknown, this study examined its effects on number and proteome of SEV in insulin sensitive (IS) and insulin resistant (IR) humans to identify biomarkers for the early prediction of individual responses of insulin sensitivity to exercising. Eight T2D, 8 glucose tolerant IR and 6 IS humans with similar age and BMI (HbA1c in %: 7.4 ± 0.4, 5.3 ± 0.1, 5.5 ± 0.1; M-value in mg*kg-1*min-1: 1.8 ± 0.4, 4.1 ± 0.4, 7.2 ± 0.5) performed a 12-weeks HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last exercise bout, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps and serum samples were collected to isolate SEV by size exclusion chromatography. SEV size and number were measured by Nanoparticle Tracking Analysis and proteomic profiling was done by mass spectrometry using data independent acquisition. After 12 weeks of HIIT, T2D and IR improved their insulin sensitivity (M-value: T2D 3.5 ± 0.8, IR 6.2 ± 0.7; p In conclusion, HIIT increases SEV number, but differently affects SEV mass and proteome in IS and IR humans, suggesting that SEV cargo could contribute to the individual response of insulin sensitivity to HIIT. Detailed characterization of SEV cargo can help to better understand the mechanisms of tissue crosstalk in the adaptation to exercise training and to develop novel exercise mimetics. Disclosure L. Mastrototaro: None. M. Apostolopoulou: None. S. Hartwig: None. D. Pesta: None. K. Strassburger: None. E. DeFilippo: None. Y. Karusheva: None. S. Gancheva: None. D.F. Markgraf: None. S. Lehr: None. K. Mussig: None. H. Al-Hasani: Consultant; Self; Bayer AG. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.
Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transpor... more Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transporters are required and whether hormonal changes due to hypophosphatemia contribute to muscle function is unknown. To address these questions we generated a series of conditional knockout mice lacking one or both house-keeping Pi transporters Pit1 and Pit2 in skeletal muscle (sm), using the postnatally expressed human skeletal actin-cre. Simultaneous conditional deletion of both transporters caused skeletal muscle atrophy, resulting in death by postnatal day P13. smPit1−/−, smPit2−/− and three allele mutants are fertile and have normal body weights, suggesting a high degree of redundance for the two transporters in skeletal muscle. However, these mice show a gene-dose dependent reduction in running activity also seen in another hypophosphatemic model (Hyp mice). In contrast to Hyp mice, grip strength is preserved. Further evaluation of the mechanism shows reduced ERK1/2 activation and stim...
High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogen... more High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogenesis in healthy populations. We hypothesized that HIIT would increase skeletal muscle insulin sensitivity due to improved muscle mitochondrial function in type 2 diabetes (T2D) patients and age- and BMI-matched controls (CON). We examined 18 sedentary male patients with T2D and 23 healthy male CON (age: 58±5 vs. 57±4 years, BMI: 31.4±2.4 vs. 30.4±2.3 kg.m-2) that were enrolled in a 12-week HIIT cycling protocol. CON were further grouped in insulin-sensitive (IS) and -resistant (IR) (baseline M in mg.kg-1.min-1; 7.4 ± 1.3 vs. 4.2 ± 1.1, p Disclosure M. Apostolopoulou: None. D. Pesta: None. Y. Karusheva: None. S. Gancheva: None. T. Jelenik: None. A. Bierwagen: None. K. M ssig: None. J. Szendroedi: None. M. Roden: Speaker9s Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.
Recent controlled trials have demonstrated that type 2 diabetes (T2D) remission is possible with ... more Recent controlled trials have demonstrated that type 2 diabetes (T2D) remission is possible with significant weight loss in people with newly diagnosed T2D. However, current programs focus on face-to-face education and behavior change, which limit scalability and inclusivity. We examined the effect of a digital education and behavior change program targeting a very low-calorie diet on metabolic control, insulin sensitivity as well as liver fat and fibrosis. Patients with diet/metformin controlled T2D (n=8, 50% male, 52±12 years, BMI 33±4 kg/m2) were remotely supported to undertake a very low-calorie (800 kcal/day) diet using digital education, behavior change and tracking with one-to-one tele-coaching for 12 weeks. Insulin sensitivity index was calculated using a mixed-meal tolerance test, liver fat content by 1H-magnetic resonance spectroscopy and liver fibrosis by elastography. After 12 weeks, participants had reduced their body weight by 9.0±3.6 kg and HbA1c (6.6±1.2% vs. 6.0±0.6...
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, Jan 24, 2018
Impaired lung function associates with deterioration of glycemic control and diabetes-related oxi... more Impaired lung function associates with deterioration of glycemic control and diabetes-related oxidative stress in long-standing type 2 diabetes. We hypothesized that recent-onset type 2 diabetes patients exhibit abnormal pulmonary function when compared to glucose-tolerant controls and that the frequencies of single-nucleotide polymorphisms (SNPs), known to associate with lung dysfunction, are different between both groups. Type 2 diabetes patients with a known disease duration<1 year (n=34) had similar age, sex distribution and BMI as overweight controls (n=26). Lung function was assessed by spirometry comprising predicted forced vital capacity (FVC%), predicted forced expiratory volume in one second (FEV1%) and the FEV1/FVC ratio. Multivariable linear regressions were performed to investigate group differences, which were adjusted for potential confounders such as age, sex, BMI, height and smoking status. SNP genotyping was conducted using real-time polymerase chain reaction-ba...
Oxidative stress describes an imbalance between production and degradation of reactive oxygen spe... more Oxidative stress describes an imbalance between production and degradation of reactive oxygen species (ROS), which can damage macromolecules. However, ROS may also serve as signaling molecules activating cellular pathways involved in cell proliferation and adaptation. This review describes alterations in metabolic diseases including obesity, insulin resistance, and/or diabetes mellitus as well as responses to acute and chronic physical exercise. Chronic upregulation of oxidative stress associates with the development of insulin resistance and type 2 diabetes (T2D). While single bouts of exercise can transiently induce oxidative stress, chronic exercise promotes favorable oxidative adaptations with improvements in muscle mitochondrial biogenesis and glucose uptake. Although impaired antioxidant defense fails to scavenge ROS in metabolic diseases, chronic exercising can restore this abnormality. The different metabolic effects are likely due to variability of reactive species and disc...
Importance of Determining Maximal Heart Rate for Providing a Standardized Training Stimulus To th... more Importance of Determining Maximal Heart Rate for Providing a Standardized Training Stimulus To the Editor We read with interest the Original Investigation in a recent issue of JAMA Internal Medicine by Zhang et al1 who conducted a large, long-term randomized clinical trial to study the effects of moderate and vigorous exercise on nonalcoholic fatty liver disease (NAFLD). The authors conclude that moderate and vigorous exercise programs have similar effects on reduction of liver fat among patients with central obesity and NAFLD. Their data generally underline the significant role of exercise for mediating health benefits and improving the condition of NAFLD, which is becoming the most common liver disease worldwide. However, we are not really convinced of their conclusion and would like to provide a few comments. For the standardization of the training load, in our opinion it would have been important to conduct cardiopulmonary exercise testing or at least determine maximal heart rate (HRmax) among the patients with NAFLD as the agepredicted HRmax is not always a valid measure of effort.2 The well-known variation of HRmax in this cohort justifies individual determination of HRmax. If these gold standards were not available, the formula 208−(0.7 × age) = HRmax would have been better suited, especially for obese patients.3 An adrenergic overdrive often observed in this cohort contributes to alterations in cardiovascular function and further complic ates determination of exercise intensity.4 These issues should at least have been addressed in the limitations of the study. It further seems that the exercise training was not adjusted to account for progression of physical condition of the individuals. This blurs the transition from vigorous to moderate training. In addition, reporting the results of heart rate monitoring over the course of exercise training would enable a rough evaluation of progress and differences in exercise intensities between groups. Due to the different training stimuli over the first 6 months in the 2 groups (vigorous and moderate, respectively), cardiovascular adaptations and hence target heart rates will most likely be different for the following 6 months.
Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life s... more Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2'-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2'-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P=0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly red...
License, which permits unrestricted use, distribution, and reproduction in any medium, provided t... more License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Type 2 diabetesmellitus (T2D) is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT) has the power to combatmetabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limitedmechanistic insight into how these adaptations occur.This review provides an overview of the intervention data on the impact of RT on glucosemetabolism. In addition, themolecularmechanisms that lead to adaptation in skeletalmuscle in response to RT and that are associatedwith possible beneficialmetabolic responses are ...
High intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impa... more High intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impact on metabolism remains unclear. We hypothesized that 12-week HIIT improves insulin sensitivity in people with or without type 2 diabetes (T2D, NDM). However, despite identically improved VO2max, mainly insulin-resistant persons (T2D, IR NDM) responded with improved insulin sensitivity and circulating small extracellular vesicles (SEV), along with reduced myocellular protein kinase Cε activity (T2D) or inflammation (IR NDM). These changes related to the SEV proteome, characterized by downregulated phospholipase C pathway (T2D) and upregulated antioxidant capacity (IR NDM). Thus, SEV cargo likely contributes to modulating exercise responsiveness in humans.
Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Althou... more Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Although aging is associated with declining endurance performance and muscle function, these components can favorably be modified by regular physical activity and especially by exercise training at all ages in both sexes. In addition, age-related changes in body composition and metabolism, which affect even highly trained masters athletes, can in part be compensated for by higher exercise metabolic efficiency in active individuals. Accordingly, masters athletes are often considered as a role model for healthy aging and their physical capacities are an impressive example of what is possible in aging individuals. In the present review, we first discuss physiological changes, performance and trainability of older athletes with a focus on sex differences. Second, we describe the most important hormonal alterations occurring during aging pertaining regulation of appetite, glucose homeostasis and en...
Adipose dysfunction may drive the development of insulin resistance, type 2 diabetes (T2D) and no... more Adipose dysfunction may drive the development of insulin resistance, type 2 diabetes (T2D) and nonalcoholic (NA) fatty liver disease (NAFLD), comprising NA fatty liver and steatohepatitis (NAFL and NASH). Possible underlying mechanism comprise impaired lipid storage or mitochondrial oxidation favoring increased fatty acid flux to other tissues. Thus, we examined subcutaneous (SAT) and visceral adipose tissue (VAT) mitochondrial capacity in humans with different degrees of insulin resistance and histologically proven NAFLD. Obese people without NAFL (OBE-CON, n=20, 38±8 years, body mass index 53±6 kg/m2, 10% T2D), with NAFL (OBE-NAFL, n=20, 40±8 years, 51±5 kg/m2, 25% T2D) or NASH (OBE-NASH, n=20, 42±10 years, 51±6 kg/m2, 40% T2D) underwent metabolic phenotyping and tissue biopsies. O2 flux rates from different substrates were measured with high resolution respirometry in SAT and VAT. In VAT, maximal uncoupled respiration was lower in OBE-NAFL (least square means (LSM): 0.46 pmol*mg ...
Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in h... more Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in heart failure and triggers inflammatory pathways. NFkB can be induced by damaged mitochondria. Its association with myocardial mitochondrial respiratory function in non-ischemic diabetes-related heart failure in humans is yet unclear. We hypothesized that human ventricular myocardial NFkB expression (i) is increased by type 2 diabetes mellitus (T2DM), and (ii) relates to reduced myocardial mitochondrial respiration. Heart transplant recipients with or without T2DM (as determined by oral glucose tolerance test), about to undergo post-transplant surveillance endomyocardial biopsies, were included, if they had received hearts from donors without T2DM. Thus, time since transplantation equaled diabetes-exposure of the transplanted hearts (2.9±2.4 years). We assessed normalized NFkB p105 subunit (NFkB1) mRNA expression using real-time PCR and myocardial mitochondrial respiration using high-reso...
Small extracellular vesicles (SEV) are secreted into circulation after acute exercise suggesting ... more Small extracellular vesicles (SEV) are secreted into circulation after acute exercise suggesting a new mode of tissue crosstalk. High intensity interval training (HIIT) leads to improved insulin sensitivity and oxidative capacity in patients with type 2 diabetes. As the impact of HIIT on SEV release is unknown, this study examined its effects on number and proteome of SEV in insulin sensitive (IS) and insulin resistant (IR) humans to identify biomarkers for the early prediction of individual responses of insulin sensitivity to exercising. Eight T2D, 8 glucose tolerant IR and 6 IS humans with similar age and BMI (HbA1c in %: 7.4 ± 0.4, 5.3 ± 0.1, 5.5 ± 0.1; M-value in mg*kg-1*min-1: 1.8 ± 0.4, 4.1 ± 0.4, 7.2 ± 0.5) performed a 12-weeks HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last exercise bout, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps and serum samples were collected to isolate SEV by size exclusion chromatography. SEV size and number were measured by Nanoparticle Tracking Analysis and proteomic profiling was done by mass spectrometry using data independent acquisition. After 12 weeks of HIIT, T2D and IR improved their insulin sensitivity (M-value: T2D 3.5 ± 0.8, IR 6.2 ± 0.7; p In conclusion, HIIT increases SEV number, but differently affects SEV mass and proteome in IS and IR humans, suggesting that SEV cargo could contribute to the individual response of insulin sensitivity to HIIT. Detailed characterization of SEV cargo can help to better understand the mechanisms of tissue crosstalk in the adaptation to exercise training and to develop novel exercise mimetics. Disclosure L. Mastrototaro: None. M. Apostolopoulou: None. S. Hartwig: None. D. Pesta: None. K. Strassburger: None. E. DeFilippo: None. Y. Karusheva: None. S. Gancheva: None. D.F. Markgraf: None. S. Lehr: None. K. Mussig: None. H. Al-Hasani: Consultant; Self; Bayer AG. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.
Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transpor... more Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transporters are required and whether hormonal changes due to hypophosphatemia contribute to muscle function is unknown. To address these questions we generated a series of conditional knockout mice lacking one or both house-keeping Pi transporters Pit1 and Pit2 in skeletal muscle (sm), using the postnatally expressed human skeletal actin-cre. Simultaneous conditional deletion of both transporters caused skeletal muscle atrophy, resulting in death by postnatal day P13. smPit1−/−, smPit2−/− and three allele mutants are fertile and have normal body weights, suggesting a high degree of redundance for the two transporters in skeletal muscle. However, these mice show a gene-dose dependent reduction in running activity also seen in another hypophosphatemic model (Hyp mice). In contrast to Hyp mice, grip strength is preserved. Further evaluation of the mechanism shows reduced ERK1/2 activation and stim...
High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogen... more High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogenesis in healthy populations. We hypothesized that HIIT would increase skeletal muscle insulin sensitivity due to improved muscle mitochondrial function in type 2 diabetes (T2D) patients and age- and BMI-matched controls (CON). We examined 18 sedentary male patients with T2D and 23 healthy male CON (age: 58±5 vs. 57±4 years, BMI: 31.4±2.4 vs. 30.4±2.3 kg.m-2) that were enrolled in a 12-week HIIT cycling protocol. CON were further grouped in insulin-sensitive (IS) and -resistant (IR) (baseline M in mg.kg-1.min-1; 7.4 ± 1.3 vs. 4.2 ± 1.1, p Disclosure M. Apostolopoulou: None. D. Pesta: None. Y. Karusheva: None. S. Gancheva: None. T. Jelenik: None. A. Bierwagen: None. K. M ssig: None. J. Szendroedi: None. M. Roden: Speaker9s Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.
Recent controlled trials have demonstrated that type 2 diabetes (T2D) remission is possible with ... more Recent controlled trials have demonstrated that type 2 diabetes (T2D) remission is possible with significant weight loss in people with newly diagnosed T2D. However, current programs focus on face-to-face education and behavior change, which limit scalability and inclusivity. We examined the effect of a digital education and behavior change program targeting a very low-calorie diet on metabolic control, insulin sensitivity as well as liver fat and fibrosis. Patients with diet/metformin controlled T2D (n=8, 50% male, 52±12 years, BMI 33±4 kg/m2) were remotely supported to undertake a very low-calorie (800 kcal/day) diet using digital education, behavior change and tracking with one-to-one tele-coaching for 12 weeks. Insulin sensitivity index was calculated using a mixed-meal tolerance test, liver fat content by 1H-magnetic resonance spectroscopy and liver fibrosis by elastography. After 12 weeks, participants had reduced their body weight by 9.0±3.6 kg and HbA1c (6.6±1.2% vs. 6.0±0.6...
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, Jan 24, 2018
Impaired lung function associates with deterioration of glycemic control and diabetes-related oxi... more Impaired lung function associates with deterioration of glycemic control and diabetes-related oxidative stress in long-standing type 2 diabetes. We hypothesized that recent-onset type 2 diabetes patients exhibit abnormal pulmonary function when compared to glucose-tolerant controls and that the frequencies of single-nucleotide polymorphisms (SNPs), known to associate with lung dysfunction, are different between both groups. Type 2 diabetes patients with a known disease duration<1 year (n=34) had similar age, sex distribution and BMI as overweight controls (n=26). Lung function was assessed by spirometry comprising predicted forced vital capacity (FVC%), predicted forced expiratory volume in one second (FEV1%) and the FEV1/FVC ratio. Multivariable linear regressions were performed to investigate group differences, which were adjusted for potential confounders such as age, sex, BMI, height and smoking status. SNP genotyping was conducted using real-time polymerase chain reaction-ba...
Oxidative stress describes an imbalance between production and degradation of reactive oxygen spe... more Oxidative stress describes an imbalance between production and degradation of reactive oxygen species (ROS), which can damage macromolecules. However, ROS may also serve as signaling molecules activating cellular pathways involved in cell proliferation and adaptation. This review describes alterations in metabolic diseases including obesity, insulin resistance, and/or diabetes mellitus as well as responses to acute and chronic physical exercise. Chronic upregulation of oxidative stress associates with the development of insulin resistance and type 2 diabetes (T2D). While single bouts of exercise can transiently induce oxidative stress, chronic exercise promotes favorable oxidative adaptations with improvements in muscle mitochondrial biogenesis and glucose uptake. Although impaired antioxidant defense fails to scavenge ROS in metabolic diseases, chronic exercising can restore this abnormality. The different metabolic effects are likely due to variability of reactive species and disc...
Importance of Determining Maximal Heart Rate for Providing a Standardized Training Stimulus To th... more Importance of Determining Maximal Heart Rate for Providing a Standardized Training Stimulus To the Editor We read with interest the Original Investigation in a recent issue of JAMA Internal Medicine by Zhang et al1 who conducted a large, long-term randomized clinical trial to study the effects of moderate and vigorous exercise on nonalcoholic fatty liver disease (NAFLD). The authors conclude that moderate and vigorous exercise programs have similar effects on reduction of liver fat among patients with central obesity and NAFLD. Their data generally underline the significant role of exercise for mediating health benefits and improving the condition of NAFLD, which is becoming the most common liver disease worldwide. However, we are not really convinced of their conclusion and would like to provide a few comments. For the standardization of the training load, in our opinion it would have been important to conduct cardiopulmonary exercise testing or at least determine maximal heart rate (HRmax) among the patients with NAFLD as the agepredicted HRmax is not always a valid measure of effort.2 The well-known variation of HRmax in this cohort justifies individual determination of HRmax. If these gold standards were not available, the formula 208−(0.7 × age) = HRmax would have been better suited, especially for obese patients.3 An adrenergic overdrive often observed in this cohort contributes to alterations in cardiovascular function and further complic ates determination of exercise intensity.4 These issues should at least have been addressed in the limitations of the study. It further seems that the exercise training was not adjusted to account for progression of physical condition of the individuals. This blurs the transition from vigorous to moderate training. In addition, reporting the results of heart rate monitoring over the course of exercise training would enable a rough evaluation of progress and differences in exercise intensities between groups. Due to the different training stimuli over the first 6 months in the 2 groups (vigorous and moderate, respectively), cardiovascular adaptations and hence target heart rates will most likely be different for the following 6 months.
Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life s... more Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2'-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2'-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P=0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly red...
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