Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers for end-stage renal disease/mortality in type 2 diabetes

Aims

To compare angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for end-stage renal disease (ESRD) development and all-cause mortality in veterans with macroalbuminuria and with newly documented type 2 diabetes.

Methods

A retrospective cohort study utilizing data from the national Department of Veterans Affairs (VA) databases. The study followed 5166 subjects without a history of use of ACEIs or ARBs. To control for differences in baseline characteristics between groups, comparisons of subjects ACEIs and ARBs were made by incorporating propensity scores analysis into multivariate logistic regression. This resulted in adjusted odds ratios and 95% confidence intervals for ESRD development and all-cause mortality.

Results

The sample was followed up to five years with a mean follow-up of three years. Subjects taking ACEIs has lower odds of ESRD development (OR, 0.33 [95% CI, 0.13–0.82]) and all-cause mortality (OR, 0.10 [95% CI, 0.04–0.21]) than ARBs.

Conclusions

This study shows that ACEIs are associated with lower ESRD development and all-cause mortality than ARBs. This may have implications for guidelines which currently suggest that these two therapeutic classes provide similar benefits in people with newly diagnosed type 2 diabetes and macroalbuminuria.     

Oral contraceptive use and abnormal glucose regulation in Swedish middle aged women

Aim

To investigate the association between oral contraceptive (OC) use and abnormal glucose regulation in Swedish middle aged women.

Methods

A prospective population-based study including 4794 women, aged 36-56 at baseline. None had previously diagnosed diabetes. At both baseline and follow-up 8 years later, the women were examined by oral glucose tolerance test. Information regarding lifestyle factors and anthropometric measurements were collected.

Results

At baseline, current use of OCs was associated with pre (Odds ratio, OR 4.1, 95%CI 2.2-7.8) but not with type 2 diabetes. The association to prediabetes was entirely linked to IGT (OR 7.1, 3.3-15.8) in current users of OCs and in former users (OR 2.1, 1.1-3.9). Women who used OC at baseline had a better cardiovascular disease risk profile; lower body mass index (BMI), more physically active and less smoking. At follow-up, the increased risk did not persist.

Conclusion

Current use of OC was associated with a four times increased risk of having prediabetes and seven times of having impaired glucose tolerance. No increased risk persisted at the follow-up, suggesting that the risk due to prior use of OC is decreasing with time. The healthier lifestyle in women who used OCs may have contributed to reduced long-term risk of prediabetes.     

Increased insulinogenic index is an independent determinant of nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance

Background

Although insulin resistance is involved in nonalcoholic fatty liver disease, role of abnormalities in early phase of insulin secretion has not been examined.

Aims

We examined which anthropometric and metabolic parameters, including insulinogenic index during oral glucose tolerant test, were independently associated with the disease activity of nonalcoholic fatty liver disease.

Methods

A total of 114 consecutive biopsy-proven nonalcoholic fatty liver disease patients without type 2 diabetes were enrolled.

Results

Age, aspartate aminotransferase, free fatty acid, ferritin type IV collagen, hyaluronic acid, procollagen N-terminal peptide, fasting plasma glucose and 2-h insulin after glucose loading were significantly higher in patients with impaired glucose tolerance than those with normal glucose tolerance. Multiple stepwise regression analysis revealed that glycated haemoglobin, decreased density ratio of liver to spleen in computed tomography and increased insulinogenic index were independently associated with nonalcoholic fatty liver disease activity score in normal glucose tolerance patients, whereas aspartate aminotransferase and 2-h insulin in impaired glucose tolerance subjects. However, there were no significant independent correlations between insulinogenic index and steatosis grade/fibrosis stage in normal glucose tolerance patients.

Conclusion

The present study suggests that increased early phase of insulin secretion may contribute to nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance.     

Relative contribution of obesity and serum adiponectin to the development of hypertension

Aims

The aim of this study was to investigate the association between serum adiponectin level and new-onset hypertension, and the relative contribution of obesity and low serum adiponectin levels to the development of hypertension in normotensive men and women.

Methods

We analyzed 1553 adults (584 men and 969 women) without hypertension, aged 40–70 years, who had participated in a cohort study in both time periods from 2005 to 2008 for baseline and 2008 to 2011 for follow-up. We divided participants into sex-specific tertiles according to serum adiponectin levels. We defined the highest tertile of serum adiponectin as ‘high adiponectin’. Participants were then stratified into four groups: the non-obese with high adiponectin; the non-obese with low adiponectin; the obese with high adiponectin; and the obese with low adiponectin.

Results

During an average of 2.6 years of follow-up, 79 men (13.5%) and 99 women (10.2%) developed hypertension. Low serum adiponectin level was an independent predictor of new-onset hypertension in men (Odds Ratio[OR]: 1.99; 95% CI: 1.03–3.86). The Obese men with low adiponectin had an increased risk of new-onset hypertension compared with the control group (OR: 2.80; 95% CI: 1.35–5.81). In postmenopausal women, the obese subjects with low adiponectin had an increased risk of new-onset hypertension compared with the control group (OR: 2.41; 95% CI 1.16–5.04).

Conclusion

Low serum adiponectin levels were associated with an increased risk of new-onset hypertension in men and postmenopausal women.     

Use of antidepressants and statins and short-term risk of new-onset diabetes among high risk adults

Aims

We evaluated the association of combined use of antidepressants and statins and the risk of new-onset diabetes among high-risk adults.

Methods

We used a retrospective, observational, longitudinal design among adults (age ≥22 years) who were diabetes free at baseline and had reported hypertension or hyperlipidemia or heart disease. We used data were from 2004 to 2009 Medical Expenditure Panel Survey and identified from self-reported diabetes or insulin use. We categorized antidepressants and statins use into four groups: antidepressants only, statins only, combined use of antidepressants and statins (antidepressants–statins), and neither antidepressant nor statins. We conducted chi-square and multivariable logistic regressions to examine the association between use of antidepressants–statins and new-onset diabetes after controlling for demographic and economic characteristics, health-status, access to care, presence of depression, and lifestyle risk factors.

Results

In our study sample, 9.3% used antidepressants only, 10.7% used statins only and 2.4% adults reported use of antidepressants–statins. Nearly 2% of the study sample reported new-onset diabetes. In unadjusted analyses, significantly higher proportion of adults using antidepressants–statins (3.2%) reported new-onset diabetes compared to those using neither antidepressants nor statins (1.1%). However, after controlling for all other variables in multivariable regression we did not observe a statistically significant association between use of antidepressants–statins and new-onset diabetes.

Conclusions

Our study results do not suggest that use of antidepressants–statins may increase the risk of new-onset diabetes. Future research needs to examine this relationship with specific combinations of these drug classes and using longer follow up periods.     

Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients

Background

The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy and safety profile of polymer-free vs. durable polymer DES by a comprehensive meta-analysis of RCTs.

Methods

MEDLINE, Google Scholar, EMBASE and Cochrane databases were searched for RCTs comparing polymer-free to durable polymer DES. Safety endpoints at short-term (≤1 year) and long-term follow-up (>1-year) were: death, myocardial infarction (MI) and stent thrombosis (ST); main efficacy endpoints were: target lesion revascularization (TLR) and target vessel revascularization (TVR).

Results

Eight RCTs including 6178 patients were included. No significant differences in mortality were observed between polymer-free and durable polymer DESs at both short- and long-follow up (OR [95% CI] = 0.79 [0.58–1.08], p = 0.14; and 0.80 [0.58–1.10], p = 0.17 respectively); polymer free and durable polymer DESs provided comparable short and long-term MI rates; at short-term: OR [95% CI] = 1.13 [0.83–1.54], p = 0.44 and at long-term: OR [95% CI] = 1.27 [0.87–1.85], p = 0.22. Similarly, these two different devices proved equally effective in regards to ST, TLR and TVR over the short and long follow-up period.

Conclusions

Polymer-free DESs are as safe and effective as durable polymer DES; however, there is no evidence of any additional benefits provided by this new technology.     

Likelihood of obstructive coronary disease in metabolic syndrome patients with abnormal stress echocardiography

Background

Metabolic syndrome (MetSx) encompasses several risk factors for macrovascular coronary artery disease. An association between MetSx and coronary syndrome X has also been reported, suggesting that patients with MetSx are more likely to have endothelial dysfunction in the setting of angiographically normal coronary arteries. It remains unknown whether MetSx patients with abnormal stress echocardiography (SE) are more likely to have obstructive coronary disease (CAD) compared to patients without MetSx.

Methods

We identified symptomatic patients without known CAD and abnormal SE who underwent coronary angiography within 4 weeks after the SE. Patients were grouped according to their MetSx and impaired fasting glucose (IFG) status. We compared the proportion of patients with obstructive CAD in each subgroup using the x² test. Multivariate regression analysis was used to adjust for the pre-test probability of underlying coronary artery disease.

Results

Among 583 consecutive symptomatic patients who had an abnormal SE and were referred for angiography, 158 (36%) met the NCEP definition of MetSx. MetSx patients had a trend towards having more obstructive CAD than those without MetSx (OR 1.44, p = 0.07). After adjusting for pre-test probability of coronary disease, smoking and LDL-C, MetSx/IFG combination was an independent predictor of obstructive CAD (OR 2.06 [1.24-3.44], p < 0.001) but MetSx with normal fasting blood glucose was not (OR 0.91 [0.47-1.70], p 0.09).

Conclusion

Symptomatic patients with MetSx and IFG are more likely to have angiographically significant CAD after abnormal SE than patients without MetSx or those with normal fasting blood glucose.     

Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting stents in diabetics with multi-vessel disease: An updated systematic review and meta-analysis

Background

Currently, the appropriateness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is uncertain due to limited evidence from few randomised controlled trials (RCTs). We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD patients using an evidence-based approach.

Methods

A systematic review and meta-analyses were conducted to compare the risk of all-cause mortality, myocardial infarction (MI), repeat revascularisation, cerebrovascular events (CVE), and major adverse cardiac or cerebrovascular events (MACCE).

Results

A total of 1,837 and 3,052 DM-MVD patients were pooled from four RCTs (FREEDOM, SYNTAX, VA CARDS, and CARDia) and five non-randomised studies. At mean follow-up of 3 years, CABG compared with PCI-DES was associated with a lower risk of all-cause mortality and MI in RCTs. By contrast, no significant differences were observed in the mean 3.5-year risk of all-cause mortality and MI in non-randomised trials. However, the risk of repeat revascularisations following PCI-DES compared with CABG was 2.3 (95% CI = 1.8–2.8) and 3.0 (2.3–4.2)-folds higher in RCTs and non-randomised trials, respectively. Accordingly, the risk of MACCE at 3 years following CABG compared with PCI-DES was lower in both RCTs and non-randomised trials [0.65 (: 0.55–0.77); and 0.77 (0.60–0.98), respectively].

Conclusions

Based on our pooled results, we recommend CABG compared with PCI-DES for patients with DM-MVD. Although non-randomised trials suggest no additional survival-, MI-, and CVE- benefit from CABG over PCI-DES, these results should be interpreted with care.     

Traditional Cardiovascular Risk Factors and the Presence of Obstructive Coronary Artery Disease in Men and Women

Background

Extensive research has demonstrated the importance of traditional cardiovascular risk factors in predicting acute coronary events. Our main objective was to evaluate the relationship between traditional risk factors and the presence of obstructive coronary artery disease (CAD), and to explore potential differences in men vs women.

Methods

An observational study was conducted in a population-based cohort of stable patients who underwent cardiac catheterization in Ontario, Canada. We examined the relationship of diabetes, hypertension, hyperlipidemia, and smoking with the presence of obstructive CAD in men and women using multivariable logistic regression models.

Results

Of the 46,490 patients who were included in our study, 61.2% were men and 38.8% were women. We found that 97% of patients with obstructive CAD had at least 1 conventional cardiovascular risk factor. The adjusted odds ratios (ORs) for obstructive CAD in women with diabetes (OR, 1.51), hypertension (OR, 1.38), and smoking (OR, 1.39) were statistically significantly greater than in men (OR, 1.20 for diabetes; OR, 1.08 for hypertension; OR, 1.14 for smoking; P < 0.001). The sex difference was even greater for patients with multiple risk factors. For example, the association with obstructive CAD in women with 4 cardiac risk factors (OR, 4.30; 95% confidence interval, 3.49-5.28) was almost doubled compared with men (OR, 2.26; 95%confidence interval, 1.99-2.57; P < 0.001).

Conclusions

Almost all patients with stable CAD undergoing cardiac catheterization had at least 1 traditional cardiac risk factor. Importantly, the association between multiple cardiac risk factors and the presence of obstructive CAD is substantially stronger in women than men.     

Absence of Oral Anticoagulation and Subsequent Outcomes Among Outpatients with Atrial Fibrillation

Background

Prior studies have shown a treatment gap in oral anticoagulation (OAC) use among patients with atrial fibrillation yet have incompletely characterized factors associated with failure to treat and subsequent outcomes in contemporary practice.

Influence of obesity and malnutrition on acute heart failure

Introduction and objectives

Obesity is an independent risk factor for the development of heart failure. Several recent studies have found better outcomes of heart failure for obese patients, an observation termed as the “obesity paradox.” On the other hand, the negative effect of malnutrition on the evolution of heart failure has also been clearly established.

Methods

Data from the Minimum Basic Data Set were analyzed for all patients discharged from all the departments of internal medicine in hospitals of the Spanish National Health System between the years 2006 and 2008. The information was limited to those patients with a primary or secondary diagnosis of heart failure. Patients with a diagnosis of obesity or malnutrition were identified. The mortality and readmission indexes of obese and malnourished patients were compared against the subpopulation without these diagnoses.

Results

A total of 370 983 heart failure admittances were analyzed, with 41 127 (11.1%) diagnosed with obesity and 4105 (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients. Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83 95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR: 1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors.

Conclusions

Obesity in patients admitted for HF substantially reduces in-hospital mortality risk and the possibility of early readmission, whereas malnutrition is associated with important increases in in-hospital mortality and risk of readmission in the 30 days following discharge.Full English text available from:www.revespcardiol.org     

The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation

Aims

To evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT).

Methods

We performed a retrospective study of 145 patients without diabetes who received kidney transplantations at our hospital. The 5-time point OGTT was performed before transplantation. The area under a receiver-operating characteristic curve (aROC) was used for evaluating the predictive power of 5-time point OGTT values.

Results

Seventeen patients developed NODAT within 1 year after transplantation. All postload plasma glucose (PPG) levels were higher in patients who developed NODAT than in those who did not; fasting plasma glucose levels were not different. The aROC for the area under the glucose concentration-time curve was significantly greater than that for fasting plasma glucose. Univariate and multivariate analyses showed that each PPG level was an independent risk factor for NODAT. Furthermore, patients with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) could be stratified with a 1-h plasma glucose (1h-PG) cut-off point of 8.4 mmol/L. The incidences of NODAT were 23.5%, 16.7%, 9.1%, and 0% for patients with IGT + 1h-PG ≥8.4 mmol/L,IGT + 1h-PG <8.4 mmol/L, NGT + 1h-PG ≥ 8.4 mmol/L, and NGT + 1h-PG < 8.4 mmol/L, respectively.

Conclusions

The area under the glucose concentration-time curve and each PPG concentration during the 5-time point OGTT are strong predictors of NODAT. A 1h-PG cut-off point of 8.4 mmol/L plus NGT/IGT can be used to identify patients at intermediate and high risk of developing NODAT.     

Retinal microvascular calibre and risk of incident diabetes: the multi-ethnic study of atherosclerosis

Aim

To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.

Methods

The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.

Results

After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.

Conclusion

Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.     

Dosage of statin,cardiovascular comorbidities,and risk of atrial fibrillation: A nationwide population-based cohort study

Background

Statin has potential protective effects against atrial fibrillation. Clinically, there is a need to predict the atrial fibrillation protective effects in statin-treated patients. The purpose of this study was to investigate if cardiovascular co-morbidities or cumulative defined daily doses (cDDDs) of statin use could predict statin efficacy in atrial fibrillation prevention.

Methods

Patients aged ≥ 50 years were identified from the Taiwan National Health Insurance Research Database. Medical records of 171,885 patients were used in this study, and 40,001 (23.3%) of the patients received statin therapy (≥ 28 cDDDs). Risk of new-onset atrial fibrillation in statin users and non-users (< 28 cDDDs) was estimated.

Results

During the 9-year follow-up period, 6049 patients experienced new-onset atrial fibrillation. Overall, statin therapy reduced the risk of atrial fibrillation by 28% (adjusted hazard ratio [HR] 0.72; 95% CI 0.68 to 0.77). There was a dose–response relationship between statin use and the risk of atrial fibrillation. The adjusted HRs for atrial fibrillation were 1.04, 0.85, and 0.50 when cDDDs ranged from 28 to 90, 91 to 365, and more than 365, respectively. Subgroup analysis showed that statin use was more beneficial in patients with higher CHADS₂ and CHA₂DS₂VASc scores than those with a score of 0 (P value for interaction < 0.001). The therapy provided no obvious beneficial effect in those with a CHADS₂ score of 0, a CHA₂DS₂VASc score of 0, or cDDDs less than 91.

Conclusions

Statin therapy reduces the risk of new-onset atrial fibrillation in a dose-dependent manner, and is beneficial in patients with cardiovascular co-morbidities.     

Rheumatoid factor as predictor of response to abatacept,rituximab and tocilizumab in rheumatoid arthritis: Systematic review and meta-analysis

Objective

To identify if rheumatoid factor (RF) is predictor of response to rituximab (RTX), abatacept (ABT), and tocilizumab (TCZ) in rheumatoid arthritis (RA).

Methods

Systematic review and meta-analysis of clinical trials and observational studies based on a sensitive search. Meta-regression was used to explore causes of heterogeneity. Unpublished data of clinical trials provided by the authors were also included.

Results

The electronic search captured 3221 references and 422 meeting abstracts. By hand search, four additional articles were also identified. A total of 23 studies meet the purpose of the study and were included in the review. RF positivity at starting predicts better ACR20 [OR, 1.95 (1.24, 3.08)], ACR50 [OR, 5.38 (2.50, 11.60)] and EULAR response [OR, 3.52 (1.66, 7.45)] in 14 studies with RTX, and better ACR20 [OR, 1.51 (1.21, 1.90)] in 6 studies with TCZ. In 3 studies with ABT, no association was found between response and RF [OR 1.36 (0.97, 1.90)]. No asymmetries in the funnel plots or significant variables were found in the meta-regression.

Conclusion

In RA, RF positivity predicts better response to RTX and TCZ but not to ABT.     

Glucose metabolism in patients with essential hypertension

Purpose

Arterial hypertension is an insulin-resistant condition that has been associated with an increased incidence of diabetes. We assessed the prevalence of glucose abnormalities in a population of patients with essential hypertension.

Methods

In this cross-sectional study, 420 consecutively referred essential hypertensive patients were studied at 16 hypertension clinics in university and community hospitals of Spain. Fasting and 2-hour plasma glucose and insulin levels were determined in nondiabetic patients.

Results

An abnormal glucose metabolism was diagnosed in 68.5% (95% confidence interval [CI], 63.7%-72.9%) of the patients. Isolated insulin resistance, defined by a homeostasis model assessment-estimated insulin resistance (HOMA-IR) equal to or above 3.8, was shown in 9.3% (95% CI, 6.7%-12.5%); impaired fasting glucose in 11.2% (95% CI, 8.6%-14.7%); impaired glucose tolerance in 22.5% (95% CI, 18.5%-26.9%); silent undiagnosed type 2 diabetes in 11.5% (95% CI, 8.6%-14.5%); and known diabetes mellitus in 13.9% (95% CI, 10.4%-17.2%) of the patients. According to the European Group for the Study of Insulin Resistance and the Adult Treatment Program III criteria, the metabolic syndrome was diagnosed in 41.5% (95% CI, 35.9%-47.3%) and 47.9% (95% CI, 43.1%-52.8%) of the patients, respectively. The prevalence of left ventricular hypertrophy (defined by a left ventricular mass index [LVMI] >125 g/m²) was 44.2%. The relation between HOMA-IR and LVMI was statistically nonsignificant, and the LVMI values in the HOMA-IR quartiles were similar. Only 27 patients (6.4%) showed good control of cardiovascular risk factors. In most patients (273, 65%; 95% CI, 60.3%-69.4%) 2 or more cardiovascular risk factors were identified as not being under control.

Conclusions

Two thirds of the patients attending hypertension clinics with essential hypertension show an abnormal glucose metabolism. The metabolic syndrome can be identified in a substantial number of these patients, and 2 or more cardiovascular risk factors are not controlled in the majority of patients.     

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials

Aims/hypothesis

The association between sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes.

Methods

We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs.

Results

In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]).

Conclusions/interpretation

Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.

     

Diabetes complications and adverse health outcomes after coronary revascularization

Aims

To examine effects of diabetes complications on health outcomes following coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), comparing outcomes for patients with diabetes complications to those without diabetes complications.

Methods

Retrospective analysis of discharge data for 61,566 patients with diabetes age 45 or older who had CABG or PCI in 2007 in United States community hospitals, using data from the Nationwide Inpatient Sample. Analysis included propensity score-adjusted logistic regression.

Results

Of all patients, 21.2% of the weighted sample had diabetes complications. Older patients, Blacks and Hispanics, and those with greater illness severity were more likely to have diabetes complications. Unadjusted rates of in-hospital mortality, postoperative stroke, and renal failure were higher for patients with diabetes complications (rate ratios 2.2, 1.8, and 9.8, respectively; all p < 0.0001). In adjusted results, having diabetes complications was associated with higher odds of in-hospital mortality (odds ratio, OR 1.62, 95% confidence interval, CI 1.37–1.91) and renal failure (OR 3.03, CI 1.71–5.39). Compared to CABG, PCI was associated with extra risk of postoperative renal failure for those with diabetes complications.

Conclusion

Among patients with diabetes having revascularization, those with diabetes complications have higher risks of in-hospital death and renal failure irrespective of having CABG or PCI.     

Fibroblast growth factor 23, the ankle-brachial index,and incident peripheral artery disease in the Cardiovascular Health Study

Background

Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.

Methods

Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.

Results

The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1–1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76–1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75–1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28–3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79–2.70).

Conclusions

In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.     

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults

Background

Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied.

Objective

To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults.

Research Design

This was a retrospective cohort study.

Participants

Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers.

Intervention

We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers.

Main Measures

Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity.

Key Results

A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67–2.01), diabetes with complications (OR 2.50; 95 % CI 1.88–3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04–1.25). Secondary and sensitivity analyses demonstrated similar findings.

Conclusions

Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.KEY WORDS: Overweight/obesity, Diabetes, Diabetic complications, Adverse events, Observational study, Satins, Primary prevention