Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.

Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

Type 2 diabetes mellitus.

The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes.

Physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity. Exercise improves blood glucose control in type 2 diabetes, reduces cardiovascular risk factors, contributes to weight loss, and improves well-being (1,2). Regular exercise may prevent or delay type 2 diabetes development (3). Regular exercise also has considerable health benefits for people with type 1 diabetes (e.g., improved cardiovascular fitness, muscle strength, insulin sensitivity, etc.) (4). The challenges related to blood glucose management vary with diabetes type, activity type, and presence of diabetes-related complications (5,6). Physical activity and exercise recommendations, therefore, should be tailored to meet the specific needs of each individual.

Physical activity recommendations and precautions may vary by diabetes type. The primary types of diabetes are type 1 and type 2. Type 1 diabetes (5%–10% of cases) results from cellular-mediated autoimmune destruction of the pancreatic β-cells, producing insulin deficiency (7). Although it can occur at any age, β-cell destruction rates vary, typically occurring more rapidly in youth than in adults. Type 2 diabetes (90%–95% of cases) results from a progressive loss of insulin secretion, usually also with insulin resistance. Gestational diabetes mellitus occurs during pregnancy, with screening typically occurring at 24–28 weeks of gestation in pregnant women not previously known to have diabetes. Prediabetes is diagnosed when blood glucose levels are above the normal range but not high enough to be classified as …

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Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.

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Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

Placebo

BACKGROUND The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear. PURPOSE To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes. DATA SOURCES 5 electronic databases (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months' duration) that included exercise, diet, and at least 1 other component; the comparator was standard care. DATA EXTRACTION One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality. DATA SYNTHESIS Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up. LIMITATION Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes: A Systematic Review and Meta-analysis

Many reviews report the effectiveness of exercise and dietary interventions in preventing diabetes, but how multifaceted lifestyle interventions affect clinically oriented outcomes across metabolic...

/pdf/lifestyle-interventions-for-patients-with-and-at-risk-for-3ityn43rc8.pdf

Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes

An evaluation of instruments for scoring physiological and behavioral cues of pain, non-pain related distress, and adequacy of analgesia and sedation in pediatric mechanically ventilated patients: A systematic review.

Elizabeth Sumamo Schellenberg

Papers

Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes: A Systematic Review and Meta-analysis

Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes

An evaluation of instruments for scoring physiological and behavioral cues of pain, non-pain related distress, and adequacy of analgesia and sedation in pediatric mechanically ventilated patients: A systematic review.

Acute Migraine Treatment in Emergency Settings