This consensus statement is an update of the 2010 American College of Sports Medicine position stand on exercise and type 2 diabetes. Since then, a substantial amount of research on select topics in ...exercise in individuals of various ages with type 2 diabetes has been published while diabetes prevalence has continued to expand worldwide. This consensus statement provides a brief summary of the current evidence and extends and updates the prior recommendations. The document has been expanded to include physical activity, a broader, more comprehensive definition of human movement than planned exercise, and reducing sedentary time. Various types of physical activity enhance health and glycemic management in people with type 2 diabetes, including flexibility and balance exercise, and the importance of each recommended type or mode are discussed. In general, the 2018 Physical Activity Guidelines for Americans apply to all individuals with type 2 diabetes, with a few exceptions and modifications. People with type 2 diabetes should engage in physical activity regularly and be encouraged to reduce sedentary time and break up sitting time with frequent activity breaks. Any activities undertaken with acute and chronic health complications related to diabetes may require accommodations to ensure safe and effective participation. Other topics addressed are exercise timing to maximize its glucose-lowering effects and barriers to and inequities in physical activity adoption and maintenance.
The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at ...lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.
BACKGROUND:In the EMPA-REG OUTCOME trial (BI 10773 Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) in patients with type 2 diabetes mellitus and atherosclerotic ...cardiovascular disease, in comparison with placebo, empagliflozin reduced the risks of 3-point major adverse cardiovascular events (3-point MACE), cardiovascular and all-cause death, and hospitalization for heart failure. We investigated whether these effects varied across the spectrum of baseline cardiovascular risk.
METHODS:Cardiovascular death, all-cause mortality, 3-point MACE, and hospitalization for heart failure in the pooled empagliflozin and placebo groups were analyzed in subgroups by prior myocardial infarction and stroke at baseline, and by estimated baseline cardiovascular risk based on the 10-point TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention.
RESULTS:Of 7020 patients who received the study drug, 65% had a prior myocardial infarction or stroke, and 12%, 40%, 30%, and 18% were at low, intermediate, high, and highest estimated cardiovascular risk according to TIMI Risk Score for Secondary Prevention (≤2, 3, 4, and ≥5 points, respectively). In the placebo group, 3-point MACE occurred during the trial in 7.3%, 9.4%, 12.6%, and 20.6% of patients at low, intermediate, high, and highest estimated baseline risk, respectively. Relative reductions in risk of cardiovascular death, all-cause mortality, 3-point MACE and hospitalization for heart failure with empagliflozin versus placebo were consistent in patients with and without prior myocardial infarction and/or stroke and across subgroups by TIMI Risk Score for Secondary Prevention at baseline (P>0.05 for randomized group-by-subgroup interactions).
CONCLUSIONS:Despite all patients having atherosclerotic cardiovascular disease, patients in EMPA-REG OUTCOME demonstrated a broad risk spectrum for cardiovascular events. Reductions in key cardiovascular outcomes and mortality with empagliflozin versus placebo were consistent across the range of cardiovascular risk.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT01131676.
Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with ...hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.
L’hypertension et le diabète de type 2 sont des affections concomitantes fréquentes. L’hypertension est deux fois plus fréquente chez les patients atteints de diabète que chez ceux qui n’en sont pas atteints. De plus, les patients atteints d’hypertension sont souvent résistants à l’insuline et sont plus susceptibles de souffrir de diabète que les personnes normotendues. Chez les diabétiques, la principale cause de morbidité et de mortalité est la maladie cardiovasculaire, qui est exacerbée par l’hypertension. En conséquence, le diabète et l’hypertension sont étroitement interreliés en raison de facteurs de risques similaires, comme la dysfonction endothéliale, l’inflammation vasculaire, le remodelage artériel, l’athérosclérose, la dyslipidémie et l’obésité. On observe un chevauchement important entre les complications cardiovasculaires du diabète et celles de l’hypertension liées principalement à des maladies microvasculaires et macrovasculaires. Des mécanismes communs, comme une stimulation du système rénine-angiotensine-aldostérone, un stress oxydatif, une inflammation et une activation du système immunitaire, sont susceptibles de contribuer à la relation étroite entre le diabète et l’hypertension. Dans cet article, nous abordons le diabète et l’hypertension comme des affections concomitantes et nous parlons des caractéristiques physiopathologiques des complications vasculaires associées à ces affections. Nous soulignons également certains mécanismes vasculaires qui prédisposent à ces deux affections, en mettant l’accent sur les produits finaux de glycation avancée, le stress oxydatif, l’inflammation, le système immunitaire et les micro-ARN. Finalement, nous présentons certaines connaissances sur les traitements actuels ciblant le diabète et les complications cardiovasculaires et nous présentons de nouveaux agents qui pourraient avoir un pouvoir vasoprotecteur chez les patients diabétiques.
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To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 ...diabetes.
We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite.
We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 1.24-1.48; I(2) = 9.5%), 36% for leucine (1.36 1.17-1.58; I(2) = 37.4%), 35% for valine (1.35 1.19-1.53; I(2) = 45.8%), 36% for tyrosine (1.36 1.19-1.55; I(2) = 51.6%), and 26% for phenylalanine (1.26 1.10-1.44; I(2) = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 0.81-0.96 and 0.85 0.82-0.89, respectively; both I(2) = 0.0%).
In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated ...with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.
Obesity is associated with the accumulation of pro‐inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes ...mellitus type 2 (DM2). Although the role of pro‐inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL‐4, IL‐5, and IL‐13, which keep adipose tissue macrophages (ATMs) in an anti‐inflammatory, M2‐like state. Diet‐induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in VAT, characterized by IFN‐γ. A key event is a shift of ATMs toward an M1 phenotype. Recent studies show that obesity‐induced adipocyte hypertrophy results in upregulated surface expression of stress markers. Adipose stress is detected by local sentinels, such as NK cells and CD8+ T cells, which produce IFN‐γ, driving M1 ATM polarization. A rapid accumulation of pro‐inflammatory cells in VAT follows, leading to inflammation. In this review, we provide an overview of events leading to adipose tissue inflammation, with a special focus on adipose homeostasis and the obesity‐induced loss of homeostasis which marks the initiation of VAT inflammation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial hyperglycemia and its detrimental ...physiological complications, especially in type 2 diabetes. The carbohydrate hydrolysing enzyme, α-glucosidase, is generally competitively inhibited by the α-glucosidase inhibitors and results in the delayed glucose absorption in small intestine, ultimately controlling the postprandial hyperglycemia. Here we have reviewed the most recent updates in the bioactive α-glucosidase inhibitors category. This review provides an overview of the α-glucosidase inhibitory potentials and efficiency of controlling postprandial hyperglycemia of various bioactive compounds such as flavonoids, phenolic compound, polysaccharide, betulinic acid, tannins, anthocyanins, steroids, polyol, polyphenols, galangin, procyanidins, hydroxyl-α-sanshool, hydroxyl-β-sanshool, erythritol, ganomycin, caffeoylquinic acid, resin glycosides, saponins, avicularin, oleanolic acids, urasolic acid, ethanolic extracts etc., from various dietary and non-dietary naturally occurring sources.
•α-glucosidase inhibitors delay glucose absorption in small intestine.•Various α-glucosidase inhibitors from dietary and non-dietary sources have been reported.•α-glucosidase inhibitors control postprandial hyperglycemia.•4. AGIs delay polysaccharide digestion to activate GLP1 which stimulates insulin secretion.•AGIs exhibit competitive inhibition and diminish carbohydrate hydrolysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices.
To evaluate the comparative effectiveness and ...safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 DPP-4 inhibitors, sodium-glucose cotransporter 2 SGLT-2 inhibitors, and glucagon-like peptide-1 GLP-1 receptor agonists) and selected metformin-based combinations in adults with type 2 diabetes.
English-language studies from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, indexed from inception through March 2015 (MEDLINE search updated through December 2015).
Paired reviewers independently identified 179 trials and 25 observational studies of head-to-head monotherapy or metformin-based combinations.
Two reviewers independently assessed study quality and serially extracted data and graded the strength of evidence.
Cardiovascular mortality was lower for metformin versus sulfonylureas; the evidence on all-cause mortality, cardiovascular morbidity, and microvascular complications was insufficient or of low strength. Reductions in hemoglobin A1c values were similar across monotherapies and metformin-based combinations, except that DPP-4 inhibitors had smaller effects. Body weight was reduced or maintained with metformin, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors and increased with sulfonylureas, thiazolidinediones, and insulin (between-group differences up to 5 kg). Hypoglycemia was more frequent with sulfonylureas. Gastrointestinal adverse events were highest with metformin and GLP-1 receptor agonists. Genital mycotic infections were increased with SGLT-2 inhibitors.
Most studies were short, with limited ability to assess rare safety and long-term clinical outcomes.
The evidence supports metformin as first-line therapy for type 2 diabetes, given its relative safety and beneficial effects on hemoglobin A1c, weight, and cardiovascular mortality (compared with sulfonylureas). On the basis of less evidence, results for add-on therapies to metformin were similar to those for monotherapies.
Agency for Healthcare Research and Quality.
We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and ...other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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