Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial

AimsTo investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.MethodsData were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D.ResultsAt baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.ConclusionsFibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD

Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study

Aims: The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE). Methods: We examined the predictive discrimination of lifestyle measures using C-index and R2 in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol). Results: The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all–cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007–0.020) and 0.022 (0.017–0.028) respectively for all-cause mortality; and by 0.023 (0.005–0.042) and 0.034 (0.020–0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003–0.012) and 0.013 (0.009–0.017) for all-cause mortality; and 0.012 (–0.001–0.025) and 0.024 (0.013–0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2 mirrored those for C-index. Conclusion: A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.</div

Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes

Introduction Trimethylamine N-oxide (TMAO) has been identified as a novel gut-derived molecule that is associated with the risk of cardiometabolic diseases. However, the relationship between TMAO and physical activity is not well understood. This study prospectively investigates the association between TMAO and objectively assessed physical activity in a population at high risk of type 2 diabetes mellitus. Research design and methods Baseline and 12-month follow-up data were used from the Walking Away from Type 2 Diabetes trial, which recruited adults at high risk of type 2 diabetes from primary care in 2009-2010. TMAO was analyzed using targeted mass spectrometry. Generalized estimating equation models with an exchangeable correlation structure were used to investigate the associations between accelerometer-Assessed exposures (sedentary time, light physical activity, moderate to vigorous physical activity (MVPA)) and TMAO, adjusting for demographic, clinical and lifestyle factors in varying degrees. Results Overall, 483 individuals had plasma samples available for the analysis of TMAO (316 (65.4%) men, 167 (34.6%) women), contributing 886 observations to the analysis. MVPA (min/day) was associated with TMAO in all models. In the fully adjusted model, each 30 min or SD difference in MVPA was associated with 0.584 μmol/L (0.070, 1.098) and 0.456 μmol/L (0.054, 0.858) lower TMAO, respectively. Sedentary time and light physical activity were not associated with TMAO in any model. Conclusions Engagement with MVPA was associated with lower TMAO levels, suggesting a possible new mechanism underlining the inverse relationship between physical activity and cardiometabolic health

Evaluation of an 8-Week vegan diet on plasma Trimethylamine-N-Oxide and postchallenge glucose in Adults with dysglycemia or obesity

ABSTRACT Background Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health. Objectives We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia. Methods This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39–64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight. Results TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61–17.3) μmol/L to 5.66 (97.5% CI, 4.56–7.02) μmol/L and 6.38 (97.5% CI, 5.25–7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98–38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24–8.90) mmol/L to 7.14 (97.5% CI, 6.30–7.98) mmol/L and 7.34 (97.5% CI, 6.63–8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8. Conclusions These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988

Evaluation of an 8-Week Vegan Diet on Plasma Trimethylamine-N-Oxide and Postchallenge Glucose in Adults with Dysglycemia or Obesity

BackgroundTrimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health.ObjectivesWe investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia.MethodsThis interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight.ResultsTMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8.ConclusionsThese findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988

Sedentary time is independently related to adipose tissue insulin resistance in adults with or at risk of type 2 diabetes

Introduction: This cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high-risk of type 2 diabetes (T2DM). Methods: Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (IQR) age 66.2 (66.0 – 70.8) years, body mass index (BMI) 31.1 (28.0 – 34.4) kg.m-2, 62% male, n = 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and non-esterified fatty acids (ADIPO-IR), while sedentary time and MVPA were determined from wrist-worn accelerometery. Generalised linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (white European vs. south Asian), BMI, age, and sex. Results: In finally-adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30-min of sedentary time associated with a 1.80 (95% CI: 0.51 to 3.06; P = 0.006) unit higher ADIPO-IR. This relationship strengthened as BMI increased (β= 3.48 [95%CI=1.50 to 5.46], P=0.005 in the upper BMI tertile [≥ 33.2 kg.m-2]). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin (n = 126) and when separated into the participants with T2DM (n = 32) and those at-high-risk (n = 147). Conclusions: Sedentary time is positively related to adipose tissue insulin sensitivity in people with or at high-risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycaemia.</p

sj-docx-1-tae-10.1177_20420188231193231 – Supplemental material for Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans

Supplemental material, sj-docx-1-tae-10.1177_20420188231193231 for Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans by Lavanya Athithan, Gaurav S. Gulsin, Joseph Henson, Loai Althagafi, Emma Redman, Stavroula Argyridou, Kelly S. Parke, Jian Yeo, Thomas Yates, Kamlesh Khunti, Melanie J. Davies, Gerry P. McCann and Emer M. Brady in Therapeutic Advances in Endocrinology and Metabolism</p

Sedentary time is independently related to adipose tissue insulin resistance in adults with or at risk of type 2 diabetes

Introduction: This cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high-risk of type 2 diabetes (T2DM). Methods: Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (IQR) age 66.2 (66.0 – 70.8) years, body mass index (BMI) 31.1 (28.0 – 34.4) kg.m-2, 62% male, n = 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and non-esterified fatty acids (ADIPO-IR), while sedentary time and MVPA were determined from wrist-worn accelerometery. Generalised linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (white European vs. south Asian), BMI, age, and sex. Results: In finally-adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30-min of sedentary time associated with a 1.80 (95% CI: 0.51 to 3.06; P = 0.006) unit higher ADIPO-IR. This relationship strengthened as BMI increased (β= 3.48 [95%CI=1.50 to 5.46], P=0.005 in the upper BMI tertile [≥ 33.2 kg.m-2]). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin (n = 126) and when separated into the participants with T2DM (n = 32) and those at-high-risk (n = 147). Conclusions: Sedentary time is positively related to adipose tissue insulin sensitivity in people with or at high-risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycaemia.</p

Sedentary Time is Independently Related to Adipose Tissue Insulin Resistance in Adults with or at Risk of Type 2 Diabetes

Introduction  This cross-sectional study examined associations of device-measured sedentary time and moderate-to-vigorous physical activity (MVPA) with adipose tissue insulin resistance in people with or at high-risk of type 2 diabetes (T2DM). Methods  Data were combined from six previous experimental studies (within our group) involving patients with T2DM or primary risk factors (median (IQR) age 66.2 (66.0 – 70.8) years, body mass index (BMI) 31.1 (28.0 – 34.4) kg.m-2, 62% male, n = 179). Adipose tissue insulin resistance was calculated as the product of fasted circulating insulin and non-esterified fatty acids (ADIPO-IR), while sedentary time and MVPA were determined from wrist-worn accelerometery. Generalised linear models examined associations of sedentary time and MVPA with ADIPO-IR with interaction terms added to explore the moderating influence of ethnicity (white European vs. south Asian), BMI, age, and sex. Results  In finally-adjusted models, sedentary time was positively associated with ADIPO-IR, with every 30-min of sedentary time associated with a 1.80 (95% CI: 0.51 to 3.06; P = 0.006) unit higher ADIPO-IR. This relationship strengthened as BMI increased (β = 3.48 [95%CI = 1.50 to 5.46], P = 0.005 in the upper BMI tertile [≥ 33.2 kg.m-2]). MVPA was unrelated to ADIPO-IR. These results were consistent in sensitivity analyses that excluded participants taking statins and/or metformin (n = 126) and when separated into the participants with T2DM (n = 32) and those at-high-risk (n = 147). Conclusions  Sedentary time is positively related to adipose tissue insulin sensitivity in people with or at high-risk of T2DM. This relationship strengthens as BMI increases and may help explain established relationships between greater sedentary time, ectopic lipid, and hyperglycaemia.</p

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: a secondary analysis of the DIASTOLIC randomised controlled trial

To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D. Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: 1) exercise training, 2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or 3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre-and post-intervention in T2D. At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53 % male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training. Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.</p