Lifestyle intervention to prevent diabetes: intensive and cost effective

PURPOSE OF REVIEW: Type 2 diabetes is a major cause of morbidity and mortality, and despite treatment advances appears to be increasing in incidence. Since individuals at risk for the disease are usually identifiable in the prediabetic phase of impaired glucose tolerance, early intervention might prevent diabetes and hence its complications from developing. Obesity and sedentary living are powerful determinants of diabetes, and thus lifestyle change is a logical approach to prevention of this disease. Recent clinical trials have now tested the effectiveness of this intervention and form the basis for this review. RECENT FINDINGS: Three clinical trials have demonstrated that, compared with usual care, lifestyle intervention significantly reduced progression rates to diabetes in prediabetic individuals. Each trial incorporated individualization and repeated long-term contacts with facilitators, in which dietary and physical activity goal setting and behavior modification were central themes. Progression to diabetes was reduced in the Da Qing study by approximately 40%, in the Finnish Diabetes Prevention Study by 58% and in the Diabetes Prevention Program by 58%. The Diabetes Prevention Program included a cost-benefit unit that estimated the per capita costs of the lifestyle intervention to exceed that of the usual care group by Dollars 3540, which translated to a cost of Dollars 15,700 per case of diabetes prevented. Lifetime cost-utility analysis demonstrated an overall cost of Dollars 1100 per quality-adjusted life year. SUMMARY: These findings make the case for translation of research findings to healthcare systems. Although there is more to be learned about effective strategies in clinical practice, it seems clear that the intervention needs to incorporate individualization and long-term interaction with trained facilitators.     

Engagement,Retention, and Progression to Type 2 Diabetes: A Retrospective Analysis of the Cluster-Randomised "Let's Prevent Diabetes" Trial

BackgroundPrevention of type 2 diabetes mellitus (T2DM) is a global priority. Let’s Prevent Diabetes is a group-based diabetes prevention programme; it was evaluated in a cluster-randomised trial, in which the primary analysis showed a reduction in T2DM (hazard ratio [HR] 0.74, 95% CI 0.48–1.14, p = 0.18). We examined the association of engagement and retention with the Let’s Prevent Diabetes prevention programme and T2DM incidence.ConclusionsThis study suggests that being retained/engaged in a relatively low-resource, pragmatic diabetes prevention programme for those at high risk is associated with reductions in the progression to T2DM in comparison to those who receive standard care. Nonengagers and nonretainers share similar high-risk traits. Service providers of programmes should focus on reaching these hard-to-reach groups.

Trial Registration

ClinicalTrials.gov ISRCTN80605705     

Leukocyte telomere length in the Finnish Diabetes Prevention Study

Leukocyte telomere length (TL) is considered a biomarker for biological aging. Shortened TL has been observed in many complex diseases, including type 2 diabetes (T2DM). Lifestyle intervention studies, e.g. the Diabetes Prevention Study (DPS), have shown a decrease in the incidence of T2DM by promoting healthy lifestyles in individuals with impaired glucose tolerance (IGT). Our aim was to study in the DPS the influence of the lifestyle intervention on TL. TL was measured by quantitative PCR-based method at two time points (N = 334 and 343) on average 4.5 years apart during the active intervention and post-intervention follow-up. TL inversely correlated with age. Our main finding was that TL increased in about two thirds of the individuals both in the intervention and in the control groups during follow-up; TL increased most in individuals with the shortest TL at the first measurement. TL was not associated with development of T2DM, nor did lifestyle intervention have an effect on TL. No association between insulin secretion or insulin resistance indices and TL was observed. We did not detect an association between TL and development of T2DM in the DPS participants. It could be due to all participants being overweight and having IGT at baseline, both of which have been found to be independently associated with shorter leukocyte TL in some earlier studies. TL had no substantial role in worsening of glucose tolerance in people with IGT. Our study confirms that leukocyte TL can increase with time even in obese people with impaired glucose metabolism.     

Prevention and treatment of type 2 diabetes in youth

Parallel to the increase in obesity worldwide, there has been a rise in the prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents. The etiology of T2DM in youth, similar to adults, is multifactorial including genetic and environmental factors, among them obesity, sedentary lifestyle, family history of the disease, high-risk ethnicity and insulin resistance phenotype playing major roles. Treatment of T2DM should not have a glucocentric approach; it should rather target improving glycemia, dyslipidemia, hypertension, weight management and the prevention of short- and long-term complications. Prevention strategies, especially in high-risk groups, should focus on environmental change involving participation of families, schools, the food and entertainment industries and governmental agencies. Presently, limited pharmacotherapeutic options need to be expanded both for childhood T2DM and obesity. The coming decades will prove very challenging for healthcare providers battling socioeconomic waves conducive to obesity and T2DM. Evidence-based research and clinical experience in pediatrics, possibly modeled after adult trials, need to be developed if this public health threat is to be contained.     

Diabetes prevention--from physiology to implementation.

One of the major challenges today is the development of prevention programs for the clinical practice. Our aim was to develop a concept for a primary diabetes prevention program to be implemented in general health care. Lifestyle intervention addressing diet and exercise has reduced the diabetes risk by up to 58%. Early preventive pharmacological strategies have yielded a diabetes risk reduction of 25-30%. These findings offer a compelling evidence base, but delivery of intervention and care is essential. The challenge therefore is the management of prevention and intervention programs considering scientific aspects and practical requirements during implementation. The Diabetes Prevention Workgroup at the German Diabetes Association has developed a concept for a decentralized prevention program. Based on the results of the prevention studies, the intervention concept consists of a three-step program including identification of the individuals at high risk to develop type 2 diabetes (1), followed by general intervention based on individual choice (2) and maintained continuous intervention for motivation maintenance (3). Structured prevention programs will enable nationwide prevention of diabetes mellitus without consuming large resources. This process will be challenging and time consuming, requiring many partners but resulting in a profitable "health" investment.     

在实验动物水平通过恢复和改善胰岛β细胞功能的糖尿病治疗新进展

糖尿病是一个世界性问题,在中国就有超过1.3亿人患有糖尿病.糖尿病主要分为1型糖尿病和2型糖尿病.遗憾的是,糖尿病至今尚未达成有效的预防和治愈手段.但是,近年来的一系列突破性的研究成果,让我们看到了治愈糖尿病的希望.在这里我们回顾了目前关于1型糖尿病和2型糖尿病可能的治愈途径的研究进展.这些途径包括胰岛移植和1型糖尿病...     

The diabetic vasculature: Physiological mechanisms of dysfunction and influence of aerobic exercise training in animal models

Diabetes mellitus (DM) is associated with a number of complications of which chronic vascular complications are undoubtedly the most complex and significant consequence. With a significant impact on health care, 50–80% of people with diabetes die of cardiovascular disease (including coronary artery disease, stroke, peripheral vascular disease and other vascular disease), making it the major cause of morbidity and mortality in diabetic patients. A healthy lifestyle is essential in the management of DM, especially the inclusion of aerobic exercise, which has been shown effective in reducing the deleterious effects in vasculature. Interest in exercise studies has increased significantly with promising results that demonstrate a future for investigation. Considering the importance of this emerging field, the aim of this mini-review is to summarize and integrate animal studies investigating physiological mechanisms of vascular dysfunction and remodeling in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and how these are influenced by chronic aerobic exercise training.     

Diabetes as a risk factor for Alzheimer’s disease in the Middle East and its shared pathological mediators

The incidence of Alzheimer’s disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Despite nationwide efforts to increase awareness, the prevalence of Diabetes Mellitus (DM) has risen significantly in the Middle East and North African (MENA) region which might be due to rapid urbanization, lifestyle changes, lack of physical activity and rise in obesity. Growing body of evidence indicates that DM and AD are linked because both conditions involve impaired glucose homeostasis and altered brain function. Current theories and hypothesis clearly implicate that defective insulin signaling in the brain contributes to synaptic dysfunction and cognitive deficits in AD. In the periphery, low-grade chronic inflammation leads to insulin resistance followed by tissue deterioration. Thus insulin resistance acts as a bridge between DM and AD. There is pressing need to understand on how DM increases the risk of AD as well as the underlying mechanisms, due to the projected increase in age related disorders. Here we aim to review the incidence of AD and DM in the Middle East and the possible link between insulin signaling and ApoE carrier status on Aβ aggregation, tau hyperphosphorylation, inflammation, oxidative stress and mitochondrial dysfunction in AD. We also critically reviewed mutation studies in Arab population which might influence DM induced AD. In addition, recent clinical trials and animal studies conducted to evaluate the efficiency of anti-diabetic drugs have been reviewed.     

Effectiveness of Community-Wide and Individual High-Risk Strategies to Prevent Diabetes: A Modelling Study

Background

Diabetes has been described as one of the most important threats to the health of developed countries. Effective population strategies to prevent diabetes have not been determined but two broad strategies have been proposed: “high-risk” and “community-wide” strategies.

Methods

We modelled the potential effectiveness of two strategies to prevent 10% of new cases of diabetes in Ontario, Canada over a 5-year period. The 5-year risk of developing physician-diagnosed diabetes was estimated for respondents to the Canadian Community Health Survey 2003 (CCHS 2.1, N = 26 232) using a validated and calibrated diabetes risk tool (Diabetes Population Risk Tool [DPoRT]). We estimated how many cases of diabetes could be prevented using two different strategies: a) a community-wide strategy that would uniformly reduce body mass index (BMI) in the entire population; and b) a high baseline risk strategy using either pharmacotherapy or lifestyle counselling to treat people who have an increased risk of developing diabetes.

Results

In 2003, the 5-year risk of developing diabetes was 4.7% (383 600 new diagnosed cases of diabetes in 8 189 000 Ontarians aged 20+) and risk was moderately diffused (0.5%, 3.1% and 17.9% risk in the 1^st, 5^th (median) and 10^th deciles of risk). A 10% reduction in new cases of diabetes would have been achieved under any of the following scenarios: if BMI was 3.5% lower in the entire population; if lifestyle counselling covered 32.2% of high-risk people (371 900 of 1 155 000 people with 5 year diabetes risk greater than 10%); or, if pharmacotherapy covered 65.2% of high-risk people.

Conclusions

Prevention using pharmacotherapy alone requires unrealistically high coverage levels to achieve modest population reduction in new diabetes cases. On the other hand, in recent years few jurisdictions have been able to achieve a reduction in BMI at the population level, let alone a reduction of BMI of 3.5%.     

Diabetes mellitus and the β cell: the last ten years

Diabetes is a major global problem. During the past decade, the genetic basis of various monogenic forms of the disease, and their underlying molecular mechanisms, have been elucidated. Many genes that increase type 2 diabetes (T2DM) risk have also been identified, but how they do so remains enigmatic. Nevertheless, defective insulin secretion emerges as the main culprit in both monogenic and polygenic diabetes, with environmental and lifestyle factors, via obesity, accounting for the current dramatic increase in T2DM. There also have been significant advances in therapy, particularly for some monogenic disorders. We review here what ails the β cell and how its function may be restored.     

The Impact of Diabetes Education on Improving Patient Outcomes

Background: Diabetes education provided by certified diabetes educators (CDEs) can help improve the lives of patients with diabetes mellitus (DM). With morbidity, mortality, and medical costs of increasing concern, diabetes educators must provide patients and primary caregivers with the tools to improve their DM and the motivation and understanding to help them meet their goals.Objective: The goal of this article was to determine the effectiveness of education provided by CDEs in an American Diabetes Association-recognized outpatient program for adults.Methods: Review of the literature from 2003 to 2006 was undertaken using the search terms diabetes education, efficacy of lifestyle education, AIC reduction, and certified diabetes educators. Landmark studies such as the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Diabetes Prevention Program were also cited. The staff at Saint Joseph's Hospital, Center for Diabetes Care, developed a questionnaire to ascertain how patients were managing key indicators related to DM. Data were gathered on patients who had both an initial visit (IV) during 2003 and 2004 and a follow-up visit (FUV) that typically took place 4.5 months later. During their IV, patients were assessed, provided with basic information, and set goals. They then participated in 2 subsequent classes within the next few months on DM self-management and returned for the FUV The questionnaire was completed at both the IV and FUV The answers were blinded. Data were examined to determine if diabetes education provided by CDEs changed patient behaviors and decreased glycosylated hemoglobin (A1C) values.Results: A total of 501 patients had an IV and an FUV Between visits, mean AlC level decreased significantly from 7.9% to 6.7%; mean weight decreased significantly from 198.6 to 196.0 lb; systolic blood pressure decreased from 132.8 to 131.5 mm Hg and diastolic blood pressure decreased from 79.4 to 77.1 mm Hg; medication adherence increased from 5% to 21% for 4 classes of medication; exercise increased from 58% (284) to 80% (403) of patients; and self-monitoring of blood glucose levels increased from 53% (260) to 98% (476) of patients. More than half of the 89% (446) of patients who set goals at the W met their goals.Conclusion: The diabetes education provided by CDEs helped patients adopt the healthier lifestyle behaviors needed to control their DM and to reduce their AlC levels.     

Tau underlies synaptic and cognitive deficits for type 1, but not type 2 diabetes mouse models

Diabetes mellitus (DM) is one of the most devastating diseases that currently affects the aging population. Recent evidence indicates that DM is a risk factor for many brain disorders, due to its direct effects on cognition. New findings have shown that the microtubule‐associated protein tau is pathologically processed in DM; however, it remains unknown whether pathological tau modifications play a central role in the cognitive deficits associated with DM. To address this question, we used a gain‐of‐function and loss‐of‐function approach to modulate tau levels in type 1 diabetes (T1DM) and type 2 diabetes (T2DM) mouse models. Our study demonstrates that tau differentially contributes to cognitive and synaptic deficits induced by DM. On one hand, overexpressing wild‐type human tau further exacerbates cognitive and synaptic impairments induced by T1DM, as human tau mice treated under T1DM conditions show robust deficits in learning and memory processes. On the other hand, neither a reduction nor increase in tau levels affects cognition in T2DM mice. Together, these results shine new light onto the different molecular mechanisms that underlie the cognitive and synaptic impairments associated with T1DM and T2DM.     

Circulating RNAs as predictive markers for the progression of type 2 diabetes

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.     

Appropriate,timely, and rational treatment of type 2 diabetes mellitus: Meeting the challenges of primary care

Diabetes now affects >24 million people in the United States. As the prevalence of diabetes continues to increase, long-term complications of diabetes have emerged as major health care issues. Although much focus has been placed on diabetes, it is important to note that prediabetes, the intermediate state of type 2 diabetes mellitus (DM), is not benign. The progression to type 2 DM for patients with impaired glucose tolerance (IGT) is 6% to 10% per year; for persons with both impaired fasting glucose and IGT, the cumulative incidence of diabetes in 6 years may be as high as 60%. Given the significant clinical and financial impact of both conditions, it is vital that clinicians initiate treatment of diabetes and prediabetes early and aggressively. Despite advances in diabetes treatment, many health care providers do not initiate or intensify therapy appropriately during patient visits, which contributes to poor diabetes control. Although management of blood pressure and lipid levels can be complex, glycemic control is often problematic for patients and their clinicians. Thus, clinicians must learn to use the various pharmacologic and nonpharmacologic strategies effectively to achieve glucose targets in their patients with type 2 DM. Patients with prediabetes should be managed with a combination of lifestyle intervention and appropriately timed pharmacotherapy. Pancreatic β-cell preservation should be a primary metabolic target.     

Glucocentricity or adipocentricity: a critical view of consensus and clinical guidelines for the treatment of type 2 diabetes mellitus

Eighty percent of patients with type 2 diabetes mellitus (T2DM) are overweight or obese, which in turn is associated with other cardiovascular risk factors and an increased risk of cancer. Large intervention studies focused on intensive glycemic control have failed to show a reduction of cardiovascular events in T2DM patients. The two major concerns in these studies were weight gain and severe hypoglycemia in the arms of intensive intervention, which could have mitigated the potential beneficial effect of glycemic control. On the contrary, weight loss in diabetic patients through changes in lifestyle, drugs and/or surgery simultaneously improves all cardiovascular risk factors including hyperglycemia. Bariatric surgery has shown an early resolution of T2DM in a large percentage of patients and a decrease of diabetes-specific mortality. Despite this, all consensus and recommendations for the treatment of T2DM focus their decisions on the glycated hemoglobin value. This article aims to open a debate on the need to replace the glucose-centered therapeutic strategy for a weight-centered strategy.     

The Impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives

The incidence of obesity and type 2 diabetes (T2DM) in the Western world has increased dramatically during the recent decades. According to the American Cancer Society, pancreatic cancer (PC) is the fourth leading cause of cancer‐related death in the United States. The relationship among obesity, T2DM and PC is complex. Due to increase in obesity, diabetes, alcohol consumption and sedentary lifestyle, the mortality due to PC is expected to rise significantly by year 2040. The underlying mechanisms by which diabetes and obesity contribute to pancreatic tumorigenesis are not well understood. Furthermore, metabolism and microenvironment within the pancreas can also modulate pancreatic carcinogenesis. The risk of PC on a population level may be reduced by modifiable lifestyle risk factors. In this review, the interactions of diabetes and obesity to PC development were summarized, and novel strategies for the prevention and treatment of diabetes and PC were discussed.     

Islet Autoimmunity Identifies a Unique Pattern of Impaired Pancreatic Beta-Cell Function,Markedly Reduced Pancreatic Beta Cell Mass and Insulin Resistance in Clinically Diagnosed Type 2 Diabetes

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage.     

Multi-centre cluster randomised trial comparing a community group exercise programme with home based exercise with usual care for people aged 65 and over in primary care: protocol of the ProAct 65+ trial

Background

Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in Type 2 Diabetes Mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester).

Design

A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care.

Methods

ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-Oral Glucose Tolerance Tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments.

Discussion

ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians.

Trial registration

Clinicaltrial.gov (NCT00318032).     

The contribution of gastrointestinal microbiota in the existence of type 2 diabetes in Saudi Arabia: Current information and perspectives

Diabetes mellitus (DM) is a genuine international health issue, with Saudi Arabia ranking among the top nations with the largest diabetes prevalence. Following the International Diabetes Federation (IDF), 3.8 million Saudi Arabian people had diabetes in 2014. The occurrence of diabetes in Saudi Arabia is likely to elevate due to the current trend in the general rise of socio-economic status, which positively correlates with diabetes prevalence. The incidence of Type 2 diabetes (T2D) is highest within the age group ≥ 45 years, especially in Riyadh and Jeddah, the metro cities of Saudi Arabia. Previous studies have shown that the incidence of T2D is larger in urban regions (25.5%) than in rural regions (19.5%). Both Riyadh and Jeddah are urban areas with different food habits and locations in Saudi Arabia. Recent studies have indicated the correlation between altered alimentary tract microbiota with type 2 diabetes. Gut microbiota plays a critical role in degrading undigested dietary compounds and releasing a vast array of metabolites that directly and indirectly affects host health. In the current review, we shed light on the state of information on the realization of the types and functions of the alimentary tract microbiome and how it plays a causative agent in the up growth of T2D.