Triple therapy combinations for the treatment of type 2 diabetes - A network meta-analysis

Aim: To estimate and compare the results from all randomised trials of triple combinations of anti-diabetes therapies that reported the reduction of glycated haemoglobin (HbA1c) and associated effects on body weight and hypoglycaemia. Methods: PubMed and the Cochrane Library were searched for trials with at least one study arm on triple therapy and which reported the differences in mean change in HbA1c between two study arms. These were included in a network meta-analysis. Results: Altogether, 15,182 participants from 40 trials with treatment duration of 6-12 months were included. Compared with none/placebo added to dual therapy, the addition of a drug therapy from six of eight drug classes to existing dual therapy resulted in significant additional mean reductions in HbA1c from -0.56% (-6.2 mmol/mol; dipeptidyl peptidase 4 inhibitors) to -0.94% (-10.3 mmol/mol; thiazolidinediones). Of the six drug classes, three were associated with less favourable weight change and two were associated with more favourable weight change when compared with none/placebo added to dual therapy. Furthermore, five drug classes were associated with greater odds of hypoglycaemia. Similar results were observed in analyses of studies with a 6 month treatment duration and after excluding study arms that contained insulin. Conclusions: Overall triple therapy combinations were similar in improving diabetes control although there were some differences in adverse effects. By balancing the risks and benefits of each therapy, the estimates of pairwise comparisons of triple therapies for HbA1c, body weight and hypoglycaemia provided in this study may further inform evidence based practice

Presentations of major peripheral arterial disease and risk of major outcomes in patients with type 2 diabetes: results from the ADVANCE-ON study.

BACKGROUND: Peripheral arterial disease (PAD) is known to be associated with high cardiovascular risk, but the individual impact of PAD presentations on risk of macrovascular and microvascular events has not been reliably compared in patients with type 2 diabetes. We aimed to evaluate the impact of major PAD, and its different presentations, on the 10-year risk of death, major macrovascular events, and major clinical microvascular events in these patients. METHODS: Participants in the action in diabetes and vascular disease: PreterAx and DiamicroN modified-release controlled evaluation (ADVANCE) trial and the ADVANCE-ON post-trial study were followed for a median of 5.0 (in-trial), 5.4 (post-trial), and 9.9 (overall) years. Major PAD at baseline was subdivided into lower-extremity chronic ulceration or amputation secondary to vascular disease and history of peripheral revascularization by angioplasty or surgery. RESULTS: Among 11,140 participants, 516 (4.6 %) had major PAD at baseline: 300 (2.7 %) had lower-extremity ulceration or amputation alone, 190 (1.7 %) had peripheral revascularization alone, and 26 (0.2 %) had both presentations. All-cause mortality, major macrovascular events, and major clinical microvascular events occurred in 2265 (20.3 %), 2166 (19.4 %), and 807 (7.2 %) participants, respectively. Compared to those without PAD, patients with major PAD had increased rates of all-cause mortality (HR 1.35, 95 % CI 1.15-1.60, p = 0.0004), and major macrovascular events (1.47 [1.23-1.75], p < 0.0001), after multiple adjustments for region of origin, cardiovascular risk factors and treatments, peripheral neuropathy markers, and randomized treatments. We have also observed a trend toward an association of baseline PAD with risk of major clinical microvascular events [1.31 (0.96-1.78), p = 0.09]. These associations were comparable for patients with a lower-extremity ulceration or amputation and for those with a history of peripheral revascularization. Furthermore, the risk of retinal photocoagulation or blindness, but not renal events, increased in patients with lower-extremity ulceration or amputation [1.53 (1.01-2.30), p = 0.04]. CONCLUSIONS: Lower-extremity ulceration or amputation, and peripheral revascularization both increased the risks of death and cardiovascular events, but only lower-extremity ulceration or amputation increased the risk of severe retinopathy in patients with type 2 diabetes. Screening for major PAD and its management remain crucial for cardiovascular prevention in patients with type 2 diabetes (ClinicalTrials.gov number, NCT00949286)

Fifteen Minutes of Chair-Based Yoga Postures or Guided Meditation Performed in the Office Can Elicit a Relaxation Response

This study compared acute (15 min) yoga posture and guided meditation practice, performed seated in a typical office workspace, on physiological and psychological markers of stress. Twenty participants completed three conditions: yoga, meditation, and control (i.e., usual work) separated by ≥24 hrs. Yoga and meditation significantly reduced perceived stress versus control, and this effect was maintained postintervention. Yoga increased heart rate while meditation reduced heart rate versus control (P\u3c0.05). Respiration rate was reduced during yoga and meditation versus control (P\u3c0.05). Domains of heart rate variability (e.g., SDNN and Total Power) were significantly reduced during control versus yoga and meditation. Systolic and diastolic blood pressure were reduced secondary to meditation versus control only (P\u3c0.05). Physiological adaptations generally regressed toward baseline postintervention. In conclusion, yoga postures or meditation performed in the office can acutely improve several physiological and psychological markers of stress. These effects may be at least partially mediated by reduced respiration rate

The Sydney Diabetes Prevention Program: A community-based translational study

Background. Type 2 diabetes is a major public health problem in Australia with prevalence increasing in parallel with increasing obesity. Prevention is an essential component of strategies to reduce the diabetes burden. There is strong and consistent evidence from randomised controlled trials that type 2 diabetes can be prevented or delayed through lifestyle modification which improves diet, increases physical activity and achieves weight loss in at risk people. The current challenge is to translate this evidence into routine community settings, determine feasible and effective ways of delivering the intervention and providing on-going support to sustain successful behavioural changes. Methods/Design. The Sydney Diabetes Prevention Program (SDPP) is a translational study which will be conducted in 1,550 participants aged 50-65 years (including 100 indigenous people aged 18 years and older) at high risk of future development of diabetes. Participants will be identified through a screening and recruitment program delivered through primary care and will be offered a community-based lifestyle modification intervention. The intervention comprises an initial individual session and three group sessions based on behaviour change principles and focuses on five goals: 5% weight loss, 210 min/week physical activity (aerobic and strength training exercise), limit dietary fat and saturated fat to less than 30% and 10% of energy intake respectively, and at least 15 g/1000 kcal dietary fibre. This is followed by 3-monthly contact with participants to review progress and offer ongoing lifestyle advice for 12 months. The effectiveness and costs of the program on diabetes-related risk factors will be evaluated. Main outcomes include changes in weight, physical activity, and dietary changes (fat, saturated fat and fibre intake). Secondary outcomes include changes in waist circumference, fasting plasma glucose, blood pressure, lipids, quality of life, psychological well being, medication use and health service utilization. Discussion. This translational study will ascertain the reach, feasibility, effectiveness and cost-effectiveness of a lifestyle modification program delivered in a community setting through primary health care. If demonstrated to be effective, it will result in recommendations for policy change and practical methods for a wider community program for preventing or delaying the onset of type 2 diabetes in high risk people. © 2010 Colagiuri et al; licensee BioMed Central Ltd

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

BACKGROUND In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. METHODS We invited surviving participants, who had previously been assigned to perindopril–indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure–lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure–lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure–lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events

Bimodal Distribution of Glucose Is Not Universally Useful for Diagnosing Diabetes

OBJECTIVE—Bimodality in the distribution of glucose has been used to define the cut point for the diagnosis of diabetes. Previous studies on bimodality have primarily been in populations with a high prevalence of type 2 diabetes, including one study in a white Caucasian population. All studies included participants with known diabetes. The aim of this study was to assess whether a bimodal structure is a general phenomenon in fasting plasma glucose (FPG) and 2-h plasma glucose that is useful for deriving a common cut point for diabetes in populations of different origin, both including and excluding known diabetes

Recommendations of the 2007 Healthy Lifestyle Forum to Help Combat Childhood Obesity

Senator Guy Barnett has held eight Healthy Lifestyle Forums to Help Combat Childhood Obesity since entering the Senate in 2002. The most recent forum, held on 20 June 2007 at Australian Parliament House Canberra, brought together approximately 60 concerned members of health care, academia, industry and public health to develop useful interventions and ideas for fighting childhood obesity. This report details the recommendations of the groups convened. They were asked to consider actions in the key areas of: clinical/health care system monitoring/benchmarking infant and early childhood schools and the wider community, and industry and private sector solutions

Study protocol of an investigation of attention and prediction error as mechanisms of action for latent inhibition of dental fear in humans

Background Evidence suggests that dental anxiety and phobia are frequently the result of direct associative fear conditioning but that pre-exposure to dental stimuli prior to conditioning results in latent inhibition of fear learning. The mechanisms underlying the pre-exposure effect in humans, however, are poorly understood. Moreover, pain sensitivity has been linked to dental fear conditioning in correlational investigations and theory suggests it may moderate the latent inhibition effect, but this hypothesis has not been directly tested. These gaps in our understanding are a barrier to the development of evidence-based dental phobia prevention efforts. Methods Healthy volunteers between the ages of 6 and 35 years will be enrolled across two sites. Participants will complete a conditioning task in a novel virtual reality environment, allowing for control over pre-exposure and the examination of behaviour. A dental startle (a brief, pressurized puff of air to a tooth) will serve as the unconditioned stimulus. Using a within-subjects experimental design, participants will experience a pre-exposed to-be conditioned stimulus, a non-pre-exposed to-be conditioned stimulus, and a neutral control stimulus. Two hypothesized mechanisms, changes in prediction errors and attention, are expected to mediate the association between stimulus condition and fear acquisition, recall, and retention. To ascertain the involvement of pain sensitivity, this construct will be measured through self-report and the cold pressor task. Discussion Dental phobia negatively affects the dental health and overall health of individuals. This study aims to determine the mechanisms through which pre-exposure retards conditioned dental fear acquisition, recall, and retention. A randomized control trial will be used to identify these mechanisms so that they can be precisely targeted and maximally engaged in preventative efforts

Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial

AIMS/HYPOTHESIS: Previous studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. METHODS: We studied participants in the ADVANCE trial with data available for baseline HbA1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA1c and HbA1c predicted from a simple linear regression of HbA1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA1c. RESULTS: Intensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14-17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA1c was a stronger predictor of these outcomes than HGI. CONCLUSIONS/INTERPRETATION: HGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA1c, clinical use of HGI in type 2 diabetes cannot currently be recommended

Chronic diseases and multi-morbidity - a conceptual modification to the WHO ICCC model for countries in health transition

Background: The burden of non-communicable diseases is rising, particularly in low and middle-income countries undergoing rapid epidemiological transition. In sub-Saharan Africa, this is occurring against a background of infectious chronic disease epidemics, particularly HIV and tuberculosis. Consequently, multi-morbidity, the co-existence of more than one chronic condition in one person, is increasing; in particular multimorbidity due to comorbid non-communicable and infectious chronic diseases (CNCICD). Such complex multimorbidity is a major challenge to existing models of healthcare delivery and there is a need to ensure integrated care across disease pathways and across primary and secondary care. Discussion: The Innovative Care for Chronic Conditions (ICCC) Framework developed by the World Health Organization provides a health systems roadmap to meet the increasing needs of chronic disease care. This framework incorporates community, patient, healthcare and policy environment perspectives, and forms the cornerstone of South Africa’s primary health care re-engineering and strategic plan for chronic disease management integration. However, it does not significantly incorporate complexity associated with multimorbidity and CNCICD. Using South Africa as a case study for a country in transition, we identify gaps in the ICCC framework at the micro-, meso-, and macro-levels. We apply the lens of CNCICD and propose modification of the ICCC and the South African Integrated Chronic Disease Management plan. Our framework incorporates the increased complexity of treating CNCICD patients, and highlights the importance of biomedicine (biological interaction). We highlight the patient perspective using a patient experience model that proposes that treatment adherence, healthcare utilization, and health outcomes are influenced by the relationship between the workload that is delegated to patients by healthcare providers, and patients’ capacity to meet the demands of this workload. We link these issues to provider perspectives that interact with healthcare delivery and utilization. Summary: Our proposed modification to the ICCC Framework makes clear that healthcare systems must work to make sense of the complex collision between biological phenomena, clinical interpretation, beliefs and behaviours that follow from these. We emphasize the integration of these issues with the socio-economic environment to address issues of complexity, access and equity in the integrated management of chronic diseases previously considered in isolation