The prevention of type 2 diabetes mellitus (T2DM) is a target priority for the WHO and the United Nations and is a key priority in the 2018 Berlin Declaration, which is a global call for early actions related to T2DM. Health-care policies advocate that individuals at high risk of developing T2DM undertake lifestyle modification, irrespective of whether the prediabetes phenotype is defined by hyperglycaemia in the postprandial state (impaired glucose tolerance) and/or fasting state (impaired fasting glucose) or by intermediate HbA1c levels. However, current evidence indicates that diabetes prevention programmes based on lifestyle change have not been successful in preventing T2DM in individuals with isolated impaired fasting glucose. We propose that further research is needed to identify effective lifestyle interventions for individuals with isolated impaired fasting glucose. Furthermore, we call for the identification of innovative approaches that better identify people with impaired glucose tolerance, who benefit from the currently available lifestyle-based diabetes prevention programmes.

Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype.

Aims: To identify profiles of type 2 diabetes from continuous glucose monitoring (CGM) data using ambulatory glucose profile (AGP) indicators and examine the association with prevalent complication...

Profiles of Intraday Glucose in Type 2 Diabetes and Their Association with Complications: An Analysis of Continuous Glucose Monitoring Data.

Weight loss induced by decreased energy intake (diet) or exercise generally has favorable effects on insulin sensitivity and cardiometabolic risk. The variation in these responses to diet-induced weight loss with or without exercise, particularly in older obese adults, is less clear. The objectives of our study were to (1) examine the effect of weight loss with or without exercise on the variability of responses in insulin sensitivity and cardiometabolic risk factors and (2) to explore whether baseline phenotypic characteristics are associated with response. Sedentary older obese (BMI 36.3 ± 5.0 kg/m2) adults (68.6 ± 4.7 years) were randomized to one of 3 groups: health education control (HED); diet-induced weight loss (WL); or weight loss and exercise (WL + EX) for 6 months. Composite Z-scores were calculated for changes in insulin sensitivity (C_IS: rate of glucose disposal/insulin at steady state during hyperinsulinemic euglycemic clamp, HOMA-IR, and HbA1C) and cardiometabolic risk (C_CMR: waist circumference, triglycerides, and fasting glucose). Baseline measures included body composition (MRI), cardiorespiratory fitness, in vivo mitochondrial function (ATPmax; P-MRS), and muscle fiber type. WL + EX groups had a greater proportion of High Responders in both C_IS and C_CMR compared to HED and WL only (all p < 0.05). Pre-intervention measures of insulin (r = 0.60) and HOMA-IR (r = 0.56) were associated with change in insulin sensitivity (C_IS) in the WL group (p < 0.05). Pre-intervention measures of glucose (r = 0.55), triglycerides (r = 0.53), and VLDL (r = 0.53) were associated with change in cardiometabolic risk (C_CMR) in the WL group (p < 0.05), whereas triglycerides (r = 0.59) and VLDL (r = 0.59) were associated with C_CMR (all p < 0.05) in WL + EX. Thus, the addition of exercise to diet-induced weight loss increases the proportion of older obese adults who improve insulin sensitivity and cardiometabolic risk. Additionally, individuals with poorer metabolic status are more likely to experience greater improvements in cardiometabolic risk during weight loss with or without exercise.

/pdf/individual-response-variation-in-the-effects-of-weight-loss-2pirnp27t8.pdf

Individual Response Variation in the Effects of Weight Loss and Exercise on Insulin Sensitivity and Cardiometabolic Risk in Older Adults.

Physical exercise is a powerful measure to prevent cardiometabolic diseases. However, the individual response to lifestyle interventions is variable and cannot, to date, be predicted. N-Lactoylphenylalanine (Lac-Phe) produced during exercise has recently been shown to mediate weight loss in obese mice. Lac-Phe could also contribute to, and potentially explain differences in, the effectiveness of exercise interventions in humans. Sedentary overweight and obese subjects completed an 8-week supervised endurance exercise intervention (n = 22). Before and after the intervention, plasma levels of Lac-Phe were determined by UHPLC-MS in the resting state and immediately after an acute bout of endurance exercise. Adipose tissue volume was quantified using MRI. Acute exercise caused a pronounced increase in Lac-Phe, both before and after the intervention. Higher levels of Lac-Phe after acute exercise were associated with a greater reduction in abdominal subcutaneous and, to a lower degree, visceral adipose tissue during the intervention. Lac-Phe produced during physical activity could contribute to weight loss by acting as a signaling molecule that regulates food intake, as previously shown in mice. Quantification of Lac-Phe during an exercise test could be employed as a tool to predict and potentially improve the individual response to exercise-based lifestyle interventions in overweight humans and those with obesity.

/pdf/exercise-induced-n-lactoylphenylalanine-predicts-adipose-2vx7fuzl.pdf

Exercise-Induced N-Lactoylphenylalanine Predicts Adipose Tissue Loss during Endurance Training in Overweight and Obese Humans

Current studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them.The baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI < 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG.During an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08-1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27-1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39-3.54).In China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage. 

/pdf/relationship-between-bmi-and-risk-of-impaired-glucose-270cna7z.pdf

Relationship between BMI and risk of impaired glucose tolerance and impaired fasting glucose in Chinese adults: a prospective study

Serum OPG/TRAIL ratio predicts the presence of cardiovascular disease in people with Type 2 Diabetes Mellitus.

With the global escalation of type 2 diabetes and evidence consistently showing that its onset can be prevented or delayed by changing lifestyle behaviours, there is an urgent need to translate practical, affordable and acceptable interventions from the research setting into the real world. One such approach to lifestyle interventions might be the introduction of a programme in which the individual is provided with choice and facilitated to ‘self-select’ an exercise programme. Previous research has shown that this is likely to be less resource intensive, an essential requirement for success outside the controlled research environment, while at the same time promoting positive responses relating to adherence, competence and self-efficacy, essential attributes for long-term success. Through a two-group parallel-randomised controlled trial, this study aims to assess the clinical and psychological impact of the DEXLIFE ‘self-selected’ lifestyle modification programme in adults at risk of developing type 2 diabetes. A total of 360 subjects at risk of developing type 2 diabetes are randomly assigned in a 1:3 ratio to a control (n = 90) or intervention arm (n = 270). Randomization is stratified by age, sex and body mass index. The control arm receives general information on lifestyle and diabetes risk. The intervention group participate in a 12 week ‘self-selected’ supervised exercise training programme accompanied with dietary advice to improve food choices. Participants are given access to Dublin City University Sport (an on-campus gym) and asked to perform four exercise classes per week. Dublin City University Sport offers over 50 classes per week, many of which are medically supervised. If weight loss is indicated, reduction in total calorie intake by 600 kcal/day is advised. Common to all food plans is 15 g/1000 kcal. Insulin sensitivity is the primary outcome measure. Secondary outcome measures include glucose function, fitness, body composition, anthropometrics, heart rate variability, lipid profiles, blood pressure, physical activity levels, dietary intake and quality of life. "Self-selected" lifestyle intervention has not previously been evaluated in type 2 diabetes prevention and if shown to be successful could be implemented in practice immediately. Current Controlled Trials: ISRCTN66987085
 .

/pdf/an-evaluation-of-the-dexlife-self-selected-lifestyle-4sqv56eas5.pdf

An evaluation of the DEXLIFE ‘self-selected’ lifestyle intervention aimed at improving insulin sensitivity in people at risk of developing type 2 diabetes: study protocol for a randomised controlled trial

Pulse Wave Velocity And Pulmonary Function Testing As Markers Of Cardiovascular Disease In Females: 3271 Board #92 May 29 2:30 PM - 4:00 PM

Background: Lifestyle interventions have been shown to delay or prevent the onset of type 2 diabetes among high risk adults. A better understanding of the variability in physiological responses would support the matching of individuals with the best type of intervention in future prevention programmes, in order to optimize risk reduction. The purpose of this study was to determine if phenotypic characteristics at baseline or following a 12 weeks lifestyle intervention could explain the inter-individual variability in change in glucose tolerance in individuals with high risk for type 2 diabetes. Methods: In total, 285 subjects with normal glucose tolerance (NGT, FINDRISC score > 12), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were recruited for a 12 weeks lifestyle intervention. Glucose tolerance, insulin sensitivity, anthropometric characteristics and aerobic fitness were measured. Variability of responses was examined by grouping participants by baseline glycemic status, by cluster analysis based on the change in glucose tolerance and by Principal Component Analysis (PCA). Results: In agreement with other studies, the mean response to the 12 weeks intervention was positive for the majority of parameters. Overall, 89% improved BMI, 80% waist circumference, and 81% body fat while only 64% improved fasting plasma glucose and 60% 2 h glucose. The impact of the intervention by glycaemic group did not show any phenotypic differences in response between NGT, IFG, and IGT. A hierarchical cluster analysis of change in glucose tolerance identified four sub-groups of "responders" (high and moderate) and "non-responders" (no response or deteriorated) but there were few differences in baseline clincal and physiological parameters or in response to the intervention to explain the overall variance. A further PCA analysis of 19 clinical and physiological univariables could explain less than half (48%) of total variability. Conclusion: We found that phenotypic characteristics from standard clinical and physiological parameters were not sufficient to account for the inter-individual variability in glucose tolerance following a 12 weeks lifestyle intervention in inidivuals at high risk for type 2 diabetes. Further work is required to identify biomarkers that complement phenotypic traits and better predict the response to glucose tolerance.

/pdf/phenotypic-responses-to-a-lifestyle-intervention-do-not-1qobezar9e.pdf

Phenotypic Responses to a Lifestyle Intervention Do Not Account for Inter-Individual Variability in Glucose Tolerance for Individuals at High Risk of Type 2 Diabetes.

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Serum OPG/TRAIL ratio predicts the presence of cardiovascular disease in people with Type 2 Diabetes Mellitus.

An evaluation of the DEXLIFE ‘self-selected’ lifestyle intervention aimed at improving insulin sensitivity in people at risk of developing type 2 diabetes: study protocol for a randomised controlled trial

Pulse Wave Velocity And Pulmonary Function Testing As Markers Of Cardiovascular Disease In Females: 3271 Board #92 May 29 2:30 PM - 4:00 PM

Phenotypic Responses to a Lifestyle Intervention Do Not Account for Inter-Individual Variability in Glucose Tolerance for Individuals at High Risk of Type 2 Diabetes.