Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.

Exercise improves quality of life in indigenous Polynesian peoples with type 2 diabetes and visceral obesity.

BACKGROUND: To evaluate the differential effect of 2, group-based exercise modalities on quality of life (QoL) in indigenous Polynesian peoples with type 2 diabetes (T2DM) and visceral obesity. METHODS: Participants were randomized to resistance training or aerobic training performed 3 times per for 16 weeks. The Short-Form 36 was administered at baseline and post intervention to assess 8 domains and physical and mental component scales (PCS and MCS) of QoL. RESULTS: With the exception of Mental Health and MCS, all scores were lower at baseline than general population norms. Significant improvements were documented in several QoL scores in each group post intervention. No group x time interactions were noted. Pooled analyses of the total cohort indicated significantly improved Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Role-Emotional, PCS and MCS. Adaptation ranged from 5%-22%, and demonstrated a moderate-to-large effect (Cohen's d = 0.64-1.29). All measures of QoL increased to near equivalent, or greater than general norms. CONCLUSION: Exercise, regardless of specific modality, can improve many aspects of QoL in this population. Robust trials are required to investigate factors mediating improvements in QoL, and create greater advocacy for exercise as a QoL intervention in this and other indigenous populations with T2DM.

Exercise intervention in New Zealand Polynesian peoples with type 2 diabetes: Cultural considerations and clinical trial recommendations.

The Maori and Pacific Islands peoples of New Zealand suffer a greater burden of type 2 diabetes mellitus (T2DM) and associated comorbidities than their European counterparts. Empirical evidence supports the clinical application of aerobic and resistance training for effective diabetes management and potential remission, but few studies have investigated the effectiveness of these interventions in specific ethnic cohorts. We recently conducted the first trial to investigate the effect of prescribed exercise training in Polynesian people with T2DM. This article presents the cultural considerations undertaken to successfully implement the study. The research procedures were accepted and approved by cultural liaisons and potential participants. The approved methodology involved a trial evaluating and comparing the effects of two, 16-week exercise regimens (i.e. aerobic training and resistance training) on glycosylated haemoglobin (HbA1c), related diabetes markers (i.e. insulin resistance, blood lipids, relevant cytokines and anthropometric and hemodynamic indices) and health-related quality of life. Future exercise-related research or implementation strategies in this cohort should focus on cultural awareness and techniques to enhance participation and compliance. Our approach to cultural consultation could be considered by researchers undertaking trials in this and other ethnic populations suffering an extreme burden of T2DM, including indigenous Australians and Americans.

Targeting the type 2 diabetes epidemic in Polynesia: historical perspective and rationale for exercise intervention trials.

The Polynesian people of New Zealand are particularly vulnerable to type 2 diabetes mellitus (T2DM) and related comorbidities, including obesity and cardiovascular disease. T2DM could potentially be managed and abated with appropriate and targeted exercise prescriptions; however, the uptake of such interventions by this cohort remains low. The purpose of this article is to present a rationale for the investigation of targeted exercise prescriptions for the management and potential remission of T2DM in Polynesian people. The diabetes epidemic will be contextualized by contrasting historical observations of health and physical fitness with current trends and statistics related to significant T2DM risk factors (ie, obesity and inactivity). Longitudinal trials that have prescribed lifestyle-related and exercise interventions in this cohort will be critically reviewed, and novel research avenues will be proposed. Studies are currently required to investigate many critically important hypotheses in this cohort. The outcomes of such studies may facilitate the investigation of exercise prescriptions in other indigenous populations, including indigenous Australians, Americans and Africans, who also suffer a severe burden of T2DM.

Exercise training in high-risk ethnic populations with type 2 diabetes: a systematic review of clinical trials.

BACKGROUND: To review clinical trials that have prescribed exercise training in high-risk, ethnic populations with type 2 diabetes mellitus (T2DM) and delineate areas for future research. METHOD: A systematic review using computerized databases was performed. RESULTS: The systematic review located nine trials, including four uncontrolled trials, and five randomized controlled trials (RCTs) that included 521 participants. Cohorts studied included African, Indian, Polynesian, Hispanic, Arabian, and Chinese peoples and interventions included aerobic training, resistance training or a combination thereof. Several trials documented improvements in HbA1c, insulin action, body composition, blood lipids and systolic and diastolic blood pressure. In general, a longer duration and greater frequency of training resulted in greater adaptation. Studies demonstrating no effect were generally limited by an inadequate intervention. There was evidence of differential training responses between Caucasians and non-Caucasians in two studies drawing such comparisons. CONCLUSIONS: Robust RCTs prescribing appropriate, targeted interventions and investigating relevant outcomes may be required to stimulate greater advocacy for exercise as a therapeutic adjunct for diabetes management in these populations. Investigations should be extended to other high-risk populations, particularly indigenous peoples who suffer an extreme burden of T2DM. Translation of research into clinical application should remain the overall objective.

South Pacific Islanders resist type 2 diabetes: comparison of aerobic and resistance training.

The purpose of this study was to evaluate the effectiveness of two exercise modalities for improving glycosylated hemoglobin (HbA1c) and associated clinical outcomes in Polynesian adults diagnosed with type 2 diabetes and visceral obesity. Twenty-six adults were randomized to receive resistance training or aerobic training, 3×/week, for 16 weeks. Dependent variables collected before and after intervention included: diabetes markers including HbA1c, blood lipids, relevant cytokines (C-reactive protein, adiponectin), and anthropometric and hemodynamic indices. Eighteen participants (72% female; age: 49.3 ± 5.3 years; waist circumference: 128.7 ± 18.7 cm) completed the intervention and follow-up assessments. Body mass index in the whole cohort at baseline indicated Class III (morbid) obesity (43.8 ± 9.5 kg/m(2)). Compliance to training was 73 ± 19 and 67 ± 18% in the aerobic and resistance training groups, respectively. HbA1c remained elevated in both groups after training. Aerobic training reduced systolic and diastolic blood pressure and increased serum triglycerides (all P < 0.05). No other exercise-induced adaptations were noted within or between groups. Post hoc analysis using pooled data indicated that higher adherence to training (≥75% attendance, n = 8) significantly reduced waist circumference (P < 0.001) and tended to reduce body weight and fasting insulin (all P ≤ 0.11) versus lower adherence (<75% attendance, n = 10). In conclusion, this study did not demonstrate an improvement in HbA1c with exercise in morbidly obese Polynesian people. Future investigations involving exercise regimens that are more practicable and which involve greater frequency and duration of training may be required to induce significant and clinically meaningful adaptations in this unique diabetes population.