Abstract:
:Two years ago, data presented at the annual American Diabetes Association (ADA) meeting in New Orleans showed a marked decrease in deaths, especially those due to cardiovascular disease, with the use of empagliflozin. Two major questions have been asked: (i) was the result a fluke; and (ii) was it a class effect, or was it specific to the agent used? The hope that both questions would be answered by a second study has been answered: the conclusions of EMPA-REG were not an anomaly and it is a class effect, not one caused by a specific drug. Importantly, do these studies require us to alter our algorithms for the treatment of type 2 diabetes? The CANagliflozin cardioVascular Assessment Study (CANVAS) was designed similarly to EMPA-REG, enrolling individuals who either had known cardiac disease or were at high risk for cardiac disease. In fact, CANVAS involved two stages, CANVAS and CANVAS R, which can be analyzed together. There were 10 142 patients in the combined trial followed for a mean of 3.6 years. The average age was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had known cardiovascular disease. In EMPA-REG, 7020 patients were followed for 3.1 years, 28.5% were women, and all had established cardiovascular disease. The primary endpoint of both studies was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. In both studies, the components of the composite endpoint were studied along with other endpoints, including hospitalization for heart failure, all-cause mortality, and progression of renal disease. The primary endpoint was identically positive for superiority with hazard ratio of 0.86 for empagliflozin versus placebo and for canagliflozin versus placebo. Some differences were observed: both death from cardiovascular disease and all-cause mortality occurred significantly less frequently with empagliflozin in EMPA-REG, but the 13% lower total and cardiovascular mortality seen with canagliflozin in CANVAS was not statistically significant. Both studies showed a lower likelihood of hospitalization for heart failure with the intervention, even in patients without known heart failure at baseline, suggesting either that that diagnosis is often missed or that de novo heart failure may be prevented by these agents. Perhaps the strongest answer to the initial two questions comes from the CVD-REAL Study. Rather than being a randomized controlled clinical trial, that study analyzed medical claims, primary care or hospital records, and national registries from the US, Norway, Denmark, Sweden, Germany, and the UK, including 309 056 patients started on a sodium-glucose cotransporter 2 (SGLT2) inhibitor or on other glucose-lowering drugs using a propensity score matching algorithm. Canagliflozin was used by 53% of those receiving SGLT2 inhibitors, dapagliflozin was used by 42% and empagliflozin was used by 5%; those using these agents had hazard ratios for hospitalization for heart failure and for mortality of 0.61 and 0.49, respectively, with no differences either by country or by drug. The interesting hypothesis that this and the two controlled trials show the harm of alternative treatments of diabetes rather than the benefit of SGLT2 inhibitors has not been confirmed by subset analyses of drug use in the control groups. There are several potentially important differences between the studies. Strokes increased with empagliflozin in EMPA-REG (not statistically significant). There was a significantly increased likelihood of lower extremity amputation in CANVAS, although these events may not have been fully studied in EMPA-REG. Finally, the benefit of SGLT2 inhibitor therapy were seen within 3 months in EMPA-REG, while not appearing as rapidly in CANVAS. Furthermore, in neither study was there a reduction in non-fatal myocardial infarction. These considerations suggest that the benefit of SGLT2 inhibitors is not due to improvement in the underlying atherosclerotic process. It is likely that all SGLT2 inhibitors will receive an indication for secondary prevention of heart failure; whether the agents should be used in primary prevention is a much more difficult question, because it would require a very large study of patients without heart disease. The introduction of HbA1c measurements in the late 1970s radically and significantly improved our treatment of diabetes. However, our treatment of diabetes is ultimately not to lower HbA1c, but to prevent the complications of diabetes. Values of HbA1c are only a surrogate measure of diabetes. Currently, there is little agreement on the treatment algorithm for diabetes after metformin therapy. One may now argue that an SGLT2 inhibitor should be the preferred second-line therapy.
journal_name
J Diabetesjournal_title
Journal of diabetesauthors
Drexler Adoi
10.1111/1753-0407.12583subject
Has Abstractpub_date
2017-11-01 00:00:00pages
976-977issue
11eissn
1753-0393issn
1753-0407journal_volume
9pub_type
社论abstract:BACKGROUND:Diabetes is a risk factor for various cancers, but its prognostic role in renal cell carcinoma (RCC) is controversial and understudied. This study investigated the prognostic value of type 2 diabetes (T2D) in RCC patients. METHODS:The clinicopathological and follow-up data of 451 RCC patients undergoing rad...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12957
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Some reports suggest that concentrations of vitamin D are inversely, whereas concentrations of parathyroid hormone (PTH) are directly, associated with prevalent metabolic syndrome. Because of lingering uncertainty about these associations, we examined the cross-sectional associations between serum concentrat...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/j.1753-0407.2009.00046.x
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Adipocyte fatty acid-binding protein (A-FABP) has been recognized as an important player in macrophage cholesterol trafficking and inflammation, and may promote the development of atherosclerosis. To further elucidate the role of A-FABP in atherosclerosis in diabetes, we investigated the relationship between...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12549
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:The aims of the present study were to examine the association of cigarette smoking and alcohol consumption with impaired β-cell function in Chinese men, particularly the interaction of smoking and alcohol consumption on impaired insulin secretion. METHODS:A population-based cross-sectional study was perform...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12314
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:To evaluate the association between thyroid autoimmunity and psychiatric disorders (depression, anxiety, eating disorder, schizophrenia or attention-deficit/hyperactivity disorder) among adolescents and young adults with type 1 diabetes (11-25 years). METHODS:We compared 9368 type 1 diabetes patients with t...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.13145
更新日期:2020-12-16 00:00:00
abstract:BACKGROUND:Supervised treadmill exercise is the recommended therapy for peripheral arterial disease (PAD) patients with intermittent claudication (IC). However, most PAD patients do not exhibit typical symptoms of IC. The aim of the present study was to explore the efficacy and safety of intensive walking exercise in P...
journal_title:Journal of diabetes
pub_type: 杂志文章,meta分析,评审
doi:10.1111/1753-0407.12304
更新日期:2016-05-01 00:00:00
abstract::Skin autofluorescence is increased in diabetes, rises with age, and predicts diabetes-related complications. Exposure to secondhand smoke, because one or more family members are smokers, further increases skin autofluorescence in children and young adults with type 1 diabetes. Elimination of passive smoking should be ...
journal_title:Journal of diabetes
pub_type: 信件
doi:10.1111/1753-0407.12498
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Proprotein convertase subtilisin/kexin-type 9 (PCSK9) downregulates clearance of plasma cholesterol by liver. Its inactivation increases this clearance, reducing cardiovascular risk. However, a lack of PCSK9 could also lead to cholesterol accumulation in pancreatic islet beta cells, impairing insulin secreti...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12139
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Dipeptidyl peptidase-4 (DPP-4) is responsible for degradation of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), the endogenous incretins that stimulate glucose-dependent insulin secretion. The objective was to evaluate preclinical profile of a novel DPP-4 inhibitor ZYDPLA1. METHODS...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12233
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Limited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN). METHODS:An 11-week double-blind placebo-controlled trial was performed in Chinese pDPN patients randomized (1 : 1) to 300 mg/day pregabalin or placebo. The primary outcome ...
journal_title:Journal of diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/1753-0407.12585
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Although niacin often has beneficial effects on the lipoprotein profile, flushing is an untoward effect associated with its use. Aspirin can only reduce the flushing response by 30-40%. Thus, the aim of the present study was to investigate the mechanisms of niacin-induced flushing, with and without aspirin, ...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/j.1753-0407.2012.00216.x
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/j.1753-0407.2012.00227.x
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Atherosclerosis may be stimulated by the increased presence of insulin and tumor necrosis-factor-α (TNFα) with subsequent expression of vascular cell adhesion molecule-1 (VCAM-1). We hypothesized that extracellular signal-regulated kinase-5 (ERK5) plays an important role in insulin and TNFα-stimulated total ...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12132
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Metabolic syndrome (MetS) is highly prevalent worldwide, and its individual components obesity, diabetes, and hypertension have been identified as risk factors to develop severe coronavirus disease 2019 (COVID-19); however, data on MetS and clinical outcomes in COVID-19 are scarce. This study aims to determi...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.13157
更新日期:2021-01-16 00:00:00
abstract:BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the complications of type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM patients. Very few studies have found an association between the development and progression of DPN in T2DM and angiotensin-converting enzyme (ACE) gene insertion/d...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/j.1753-0407.2012.00205.x
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:Few studies have focused on postprandial incretin responses to different carbohydrate meals. Therefore, we designed a study to compare the different effects of two carbohydrates (75 g oral glucose, a monosaccharide and 100 g standard noodle, a polysaccharide, with 75 g carbohydrates equivalently) on postpran...
journal_title:Journal of diabetes
pub_type: 杂志文章,随机对照试验
doi:10.1111/1753-0407.12245
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:The effect of postload glucose spikes (PGS), the difference between 2 hour post-load plasma glucose (2hPLPG) and fasting plasma glucose (FPG), on post-myocardial infarction (post-MI) prognosis in nondiabetic patients is unexplored. METHODS:This is a retrospective cohort analysis of 847 nondiabetic post-MI s...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.13111
更新日期:2021-03-01 00:00:00
abstract::Highlights A large retrospective study indicates no association between GDM and most types of cancer; this is in contrast to a few smaller studies that have suggested an association with cancer. An increased risk of thyroid cancer in mothers with GDM was demonstrated. While this risk requires further investigation, it...
journal_title:Journal of diabetes
pub_type: 信件
doi:10.1111/1753-0407.12988
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Mitogen-inducible gene 6 (Mig-6) has an important role in the regulation of cholesterol homeostasis and bile acid synthesis. However, the physiological functions of Mig-6 in the liver remain poorly understood. METHODS:To investigate Mig-6 functioning in the liver, we used conditionally ablated Mig-6 using t...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12261
更新日期:2016-01-01 00:00:00
abstract::This article reviews the known pathophysiological mechanisms of comorbid gastroesophageal reflux disease (GERD) in the diabetic patient, discusses therapeutic options in care, and provides an approach to its evaluation and management. We searched for review articles published in the past 10 years through a PubMed sear...
journal_title:Journal of diabetes
pub_type: 杂志文章,评审
doi:10.1111/1753-0407.12279
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:To investigate the effect of hydroxypropyl methylcellulose (HPMC) on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model under a high-fat diet regimen. METHODS: Obese male C57BL/6J (B6) mice were fed either a high-fat (60% kcal), low-fat (10% kcal), or...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/j.1753-0407.2011.00118.x
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. METHODS:Diabetic mice were induced by streptozotocin (STZ) combined with a hi...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12938
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Asia is experiencing a type 2 diabetes epidemic, but prevalence differs by ethnicity and level of socioeconomic development. Singapore and Mauritius have implemented comprehensive campaigns to address this public health problem. We compared diabetes and obesity prevalence trends among Chinese and South Asian...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12497
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:The aim of the present study was to assess the quality of diabetes care and characteristics of the healthcare system in underdeveloped rural mountain areas of western China. METHODS:Questionnaires were used to collect data from 288 diabetic patients with a multistage cluster sampling method in Zhongjiang Co...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12433
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Primary care physicians frequently encounter people with type 2 diabetes mellitus (T2DM) with discordant values for fasting glucose and HbA1c. The aim of this study was to identify the prevalence and characteristics of people in whom blood glucose and HbA1c did not match. METHODS:Overall, 64 553 people with...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12823
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Genome-wide association studies (GWAS) have identified several genetic variants affecting gestational glucose metabolism. However, information regarding their known associations with gestational diabetes mellitus (GDM) risk remains scarce. METHODS:This study examined the associations of 12 gestational gluco...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12923
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:There is a wide variety of dressings currently available for the treatment of diabetic foot ulcers (DFUs). Because of a lack of evidence from head-to-head randomized controlled trials (RCTs), the relative effects of these dressings in DFU patients remain unclear. This study compared the efficacy of nine dres...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12871
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Elevated blood or urinary concentrations of endocrine-disrupting chemicals (EDCs) may be related to increased risk of type 2 diabetes (T2D). The aim of the present study was to assess the role of EDCs in affecting risk of T2D and related metabolic traits. METHODS:MEDLINE was searched for cross-sectional and...
journal_title:Journal of diabetes
pub_type: 杂志文章,meta分析,评审
doi:10.1111/1753-0407.12325
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:It is clear that aerobic training (AT) can delay pancreatic exhaustion and slow the progression from prediabetes to type 2 diabetes (T2D), but there is little information regarding the effects of resistance training (RT) in people with prediabetes. This study compared the effectiveness of RT and AT in improv...
journal_title:Journal of diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/1753-0407.12955
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indice...
journal_title:Journal of diabetes
pub_type: 杂志文章
doi:10.1111/1753-0407.12864
更新日期:2019-05-01 00:00:00