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The Effects of Intensive Glycemic Control on Clinical Outcomes Among Patients With Type 2 Diabetes With Different Levels of Cardiovascular Risk and Hemoglobin A1c in the ADVANCE Trial

OBJECTIVE

To study whether the effects of intensive glycemic control on major vascular outcomes (a composite of major macrovascular and major microvascular events), all-cause mortality, and severe hypoglycemia events differ among participants with different levels of 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and hemoglobin A1c (HbA1c) at baseline.

RESEARCH DESIGN AND METHODS

We studied the effects of more intensive glycemic control in 11,071 patients with type 2 diabetes (T2D), without missing values, in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, using Cox models.

RESULTS

During 5 years’ follow-up, intensive glycemic control reduced major vascular events (hazard ratio [HR] 0.90 [95% CI 0.83–0.98]), with the major driver being a reduction in the development of macroalbuminuria. There was no evidence of differences in the effect, regardless of baseline ASCVD risk or HbA1c level (P for interaction = 0.29 and 0.94, respectively). Similarly, the beneficial effects of intensive glycemic control on all-cause mortality were not significantly different across baseline ASCVD risk (P = 0.15) or HbA1c levels (P = 0.87). The risks of severe hypoglycemic events were higher in the intensive glycemic control group compared with the standard glycemic control group (HR 1.85 [1.41–2.42]), with no significant heterogeneity across subgroups defined by ASCVD risk or HbA1c at baseline (P = 0.09 and 0.18, respectively).

CONCLUSIONS

The major benefits for patients with T2D in ADVANCE did not substantially differ across levels of baseline ASCVD risk and HbA1c.




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Sleep Duration Patterns in Early to Middle Adulthood and Subsequent Risk of Type 2 Diabetes in Women

OBJECTIVE

To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes.

RESEARCH DESIGN AND METHODS

Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20–25, 26–35, 36–45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses’ Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009–2017) using multivariable Cox proportional hazards models.

RESULTS

We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50]).

CONCLUSIONS

Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for.




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Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users

OBJECTIVE

The vast number of antihyperglycemic medications and growing amount of evidence make clinical decision making difficult. The aim of this study was to investigate the safety of antihyperglycemic dual and triple therapies for type 2 diabetes management with respect to major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality in a real-life clinical setting.

RESEARCH DESIGN AND METHODS

Cox regression models were constructed to analyze 20 years of data from the Danish National Patient Registry with respect to effect of the antihyperglycemic therapies on the three end points.

RESULTS

A total of 66,807 people with type 2 diabetes were treated with metformin (MET) including a combination of second- and third-line therapies. People on MET plus sulfonylurea (SU) had the highest risk of all end points, except for severe hypoglycemia, for which people on MET plus basal insulin (BASAL) had a higher risk. The lowest risk of major adverse cardiovascular events was seen for people on a regimen including a glucagon-like peptide 1 (GLP-1) receptor agonist. People treated with MET, GLP-1, and BASAL had a lower risk of all three end points than people treated with MET and BASAL, especially for severe hypoglycemia. The lowest risk of all three end points was, in general, seen for people treated with MET, sodium–glucose cotransporter 2 inhibitor, and GLP-1.

CONCLUSIONS

Findings from this study do not support SU as the second-line treatment choice for patients with type 2 diabetes. Moreover, the results indicate that adding a GLP-1 for people treated with MET and BASAL could be considered, especially if those people suffer from severe hypoglycemia.




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Erratum. Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach. Diabetes Care 2020;43:852-859




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Blood Pressure Variability and Risk of Heart Failure in ACCORD and the VADT

OBJECTIVE

Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure (HF) is less clear. We examined the relationship between blood pressure variability and risk of HF in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management.

RESEARCH DESIGN AND METHODS

Data were drawn from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Veterans Affairs Diabetes Trial (VADT). Coefficient of variation (CV) and average real variability (ARV) were calculated for systolic (SBP) and diastolic blood pressure (DBP) along with maximum and cumulative mean SBP and DBP during both trials.

RESULTS

In ACCORD, CV and ARV of SBP and DBP were associated with increased risk of HF, even after adjusting for other risk factors and mean blood pressure (e.g., CV-SBP: hazard ratio [HR] 1.15, P = 0.01; CV-DBP: HR 1.18, P = 0.003). In the VADT, DBP variability was associated with increased risk of HF (ARV-DBP: HR 1.16, P = 0.001; CV-DBP: HR 1.09, P = 0.04). Further, in ACCORD, those with progressively lower baseline blood pressure demonstrated a stepwise increase in risk of HF with higher CV-SBP, ARV-SBP, and CV-DBP. Effects of blood pressure variability were related to dips, not elevations, in blood pressure.

CONCLUSIONS

Blood pressure variability is associated with HF risk in individuals with type 2 diabetes, possibly a consequence of periods of ischemia during diastole. These results may have implications for optimizing blood pressure treatment strategies in those with type 2 diabetes.




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Use of Glucagon-Like Peptide 1 Receptor Agonists and Risk of Serious Renal Events: Scandinavian Cohort Study

OBJECTIVE

To assess the association between use of glucagon-like peptide 1 (GLP-1) receptor agonists and risk of serious renal events in routine clinical practice.

RESEARCH DESIGN AND METHODS

This was a cohort study using an active-comparator, new-user design and nationwide register data from Sweden, Denmark, and Norway during 2010–2016. The cohort included 38,731 new users of GLP-1 receptor agonists (liraglutide 92.5%, exenatide 6.2%, lixisenatide 0.7%, and dulaglutide 0.6%), matched 1:1 on age, sex, and propensity score to a new user of the active comparator, dipeptidyl peptidase 4 (DPP-4) inhibitors. The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospitalization for renal events. Secondary outcomes were the individual components of the main outcome. Hazard ratios (HRs) were estimated using Cox models and an intention-to-treat exposure definition. Mean (SD) follow-up time was 3.0 (1.7) years.

RESULTS

Mean (SD) age of the study population was 59 (10) years, and 18% had cardiovascular disease. A serious renal event occurred in 570 users of GLP-1 receptor agonists (incidence rate 4.8 events per 1,000 person-years) and in 722 users of DPP-4 inhibitors (6.3 events per 1,000 person-years, HR 0.76 [95% CI 0.68–0.85], absolute difference –1.5 events per 1,000 person-years [–2.1 to –0.9]). Use of GLP-1 receptor agonists was associated with a significantly lower risk of renal replacement therapy (HR 0.73 [0.62–0.87]) and hospitalization for renal events (HR 0.73 [0.65–0.83]) but not death from renal causes (HR 0.72 [0.48–1.10]). When we used an as treated exposure definition in which patients were censored at treatment cessation or switch to the other study drug, the HR for the primary outcome was 0.60 (0.49–0.74).

CONCLUSIONS

In this large cohort of patients seen in routine clinical practice in three countries, use of GLP-1 receptor agonists, as compared with DPP-4 inhibitors, was associated with a reduced risk of serious renal events.




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Microbiota-Related Metabolites and the Risk of Type 2 Diabetes

OBJECTIVE

Recent studies have highlighted the significance of the microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes.

RESEARCH DESIGN AND METHODS

5,181 participants from the cross-sectional Metabolic Syndrome in Men (METSIM) study that included Finnish men (age 57 ± 7 years, BMI 26.5 ± 3.5 kg/m2) having metabolomics data available were included in our study. Metabolomics analysis was performed based on fasting plasma samples. On the basis of an oral glucose tolerance test, Matsuda ISI and Disposition Index values were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit, and 522 participants developed type 2 diabetes.

RESULTS

Creatine, 1-palmitoleoylglycerol (16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol (18:1), 1-myristoylglycerol (14:0), dimethylglycine, and 2-hydroxyhippurate (salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoylglycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.

CONCLUSIONS

Several novel and previously reported microbial metabolites related to the gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes.




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Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study

OBJECTIVE

To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA.

RESEARCH DESIGN AND METHODS

This age-, sex-, BMI-, and diabetes duration–matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.

RESULTS

A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3–5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.

CONCLUSIONS

Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.




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Using the BRAVO Risk Engine to Predict Cardiovascular Outcomes in Clinical Trials With Sodium-Glucose Transporter 2 Inhibitors

OBJECTIVE

This study evaluated the ability of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine to accurately project cardiovascular outcomes in three major clinical trials—BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS), and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction (DECLARE-TIMI 58) trial—on sodium–glucose cotransporter 2 inhibitors (SGLT2is) to treat patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Baseline data from the publications of the three trials were obtained and entered into the BRAVO model to predict cardiovascular outcomes. Projected benefits of reducing risk factors of interest (A1C, systolic blood pressure [SBP], LDL, or BMI) on cardiovascular events were evaluated, and simulated outcomes were compared with those observed in each trial.

RESULTS

BRAVO achieved the best prediction accuracy when simulating outcomes of the CANVAS and DECLARE-TIMI 58 trials. For the EMPA-REG OUTCOME trial, a mild bias was observed (~20%) in the prediction of mortality and angina. The effect of risk reduction on outcomes in treatment versus placebo groups predicted by the BRAVO model strongly correlated with the observed effect of risk reduction on the trial outcomes as published. Finally, the BRAVO engine revealed that most of the clinical benefits associated with SGLT2i treatment are through A1C control, although reductions in SBP and BMI explain a proportion of the observed decline in cardiovascular events.

CONCLUSIONS

The BRAVO risk engine was effective in predicting the benefits of SGLT2is on cardiovascular health through improvements in commonly measured risk factors, including A1C, SBP, and BMI. Since these benefits are individually small, the use of the complex, dynamic BRAVO model is ideal to explain the cardiovascular outcome trial results.




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Predicting the Risk of Inpatient Hypoglycemia With Machine Learning Using Electronic Health Records

OBJECTIVE

We analyzed data from inpatients with diabetes admitted to a large university hospital to predict the risk of hypoglycemia through the use of machine learning algorithms.

RESEARCH DESIGN AND METHODS

Four years of data were extracted from a hospital electronic health record system. This included laboratory and point-of-care blood glucose (BG) values to identify biochemical and clinically significant hypoglycemic episodes (BG ≤3.9 and ≤2.9 mmol/L, respectively). We used patient demographics, administered medications, vital signs, laboratory results, and procedures performed during the hospital stays to inform the model. Two iterations of the data set included the doses of insulin administered and the past history of inpatient hypoglycemia. Eighteen different prediction models were compared using the area under the receiver operating characteristic curve (AUROC) through a 10-fold cross validation.

RESULTS

We analyzed data obtained from 17,658 inpatients with diabetes who underwent 32,758 admissions between July 2014 and August 2018. The predictive factors from the logistic regression model included people undergoing procedures, weight, type of diabetes, oxygen saturation level, use of medications (insulin, sulfonylurea, and metformin), and albumin levels. The machine learning model with the best performance was the XGBoost model (AUROC 0.96). This outperformed the logistic regression model, which had an AUROC of 0.75 for the estimation of the risk of clinically significant hypoglycemia.

CONCLUSIONS

Advanced machine learning models are superior to logistic regression models in predicting the risk of hypoglycemia in inpatients with diabetes. Trials of such models should be conducted in real time to evaluate their utility to reduce inpatient hypoglycemia.




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Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial

OBJECTIVE

The LEADER trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for the CV benefit observed with liraglutide in the LEADER trial.

RESEARCH DESIGN AND METHODS

We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors.

RESULTS

Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates.

CONCLUSIONS

These analyses identify HbA1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation.




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Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease

OBJECTIVE

Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA.

RESEARCH DESIGN AND METHODS

Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea Cardiovascular End Points (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A1c (HbA1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded.

RESULTS

Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or in new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable.

CONCLUSIONS

Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.





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Longevity Gene May Protect against a Notorious Alzheimer's Risk Gene

Some nominally high-risk individuals may have a lower chance of developing dementia than once thought

-- Read more on ScientificAmerican.com




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The Coronavirus Pandemic Puts Children at Risk of Online Sexual Exploitation

One conversation could keep your kids safe

-- Read more on ScientificAmerican.com



  • Mind
  • Behavior & Society

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In Judging Risk, Our Fears Are Often Misplaced

Shortly after the Sept. 11, 2001, attacks, psychologist Jennifer Lerner conducted a national field experiment: She asked a random sampling of Americans how likely it was that they would be the victim of a terrorist attack in the next 12 months.




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Taking More Risks Because You Feel Safe

The housing market is in free fall: Quick -- let's protect homeowners against foreclosure.




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Packing Protection or Packing Suicide Risk?

Seventeen years ago, a couple of criminologists at the University of Maryland published an interesting paper about the 1976 District ban on handguns -- a ban that was recently overturned by the Supreme Court on the grounds it was inimical to the constitutional right of Americans to bear arms to p...




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Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study

OBJECTIVE

Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke).

RESEARCH DESIGN AND METHODS

Based on the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort (n = 27,548), we constructed case-cohorts including a random subsample of 2,500 participants and all physician-verified incident cases of type 2 diabetes (n = 820; median follow-up time 6.5 years) and CVD (n = 508; median follow-up time 8.2 years). Information on the relative abundance of 39 N-glycan groups in baseline plasma samples was generated by chromatographic profiling. We selected predictive N-glycans for type 2 diabetes and CVD separately, based on cross-validated machine learning, nonlinear model building, and construction of weighted prediction scores. This workflow for CVD was applied separately in men and women.

RESULTS

The N-glycan–based type 2 diabetes score was strongly predictive for diabetes risk in an internal validation cohort (weighted C-index 0.83, 95% CI 0.78–0.88), and this finding was externally validated in the Finland Cardiovascular Risk Study (FINRISK) cohort. N-glycans were moderately predictive for CVD incidence (weighted C-indices 0.66, 95% CI 0.60–0.72, for men; 0.64, 95% CI 0.55–0.73, for women). Information on the selected N-glycans improved the accuracy of established and clinically applied risk prediction scores for type 2 diabetes and CVD.

CONCLUSIONS

Selected N-glycans improve type 2 diabetes and CVD prediction beyond established risk markers. Plasma protein N-glycan profiling may thus be useful for risk stratification in the context of precisely targeted primary prevention of cardiometabolic diseases.




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Association Between the Use of Antidepressants and the Risk of Type 2 Diabetes: A Large, Population-Based Cohort Study in Japan

OBJECTIVE

This study aimed to reveal the associations between the risk of new-onset type 2 diabetes and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes.

RESEARCH DESIGN AND METHODS

In this large-scale retrospective cohort study in Japan, new users of antidepressants (exposure group) and nonusers (nonexposure group), aged 20–79 years, were included between 1 April 2006 and 31 May 2015. Patients with a history of diabetes or receipt of antidiabetes treatment were excluded. Covariates were adjusted by using propensity score matching; the associations were analyzed between risk of new-onset type 2 diabetes and the duration of antidepressant use/dose of antidepressant in the exposure and nonexposure groups by using Cox proportional hazards models. Changes in glycated hemoglobin (HbA1c) level were examined in groups with continuous use, discontinuation, or a reduction in the dose of antidepressants.

RESULTS

Of 90,530 subjects, 45,265 were in both the exposure and the nonexposure group after propensity score matching; 5,225 patients (5.8%) developed diabetes. Antidepressant use was associated with the risk of diabetes onset in a time- and dose-dependent manner. The adjusted hazard ratio was 1.27 (95% CI 1.16–1.39) for short-term low-dose and 3.95 (95% CI 3.31–4.72) for long-term high-dose antidepressant use. HbA1c levels were lower in patients who discontinued or reduced the dose of antidepressants (F[2,49] = 8.17; P < 0.001).

CONCLUSIONS

Long-term antidepressant use increased the risk of type 2 diabetes onset in a time- and dose-dependent manner. Glucose tolerance improved when antidepressants were discontinued or the dose was reduced after diabetes onset.




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Risk Factors for First and Subsequent CVD Events in Type 1 Diabetes: The DCCT/EDIC Study

OBJECTIVE

The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events.

RESEARCH DESIGN AND METHODS

CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes.

RESULTS

Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA1c was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA1c; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]).

CONCLUSIONS

Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained.




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Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach

OBJECTIVE

To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.

RESEARCH DESIGN AND METHODS

A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m2 and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.

RESULTS

The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient’s data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.

CONCLUSIONS

The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.




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Mental Health Risks and Resilience among Somali and Bhutanese Refugee Parents

Somali and Bhutanese refugees are two of the largest groups recently resettled in the United States and Canada. This report examines factors that might promote or undermine the mental health and overall well-being of children of these refugees, with regard to factors such as past exposure to trauma, parental mental health, educational attainment, social support, and discrimination.




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Gestational Diabetes in High-Risk Populations

Wilfred Fujimoto
Apr 1, 2013; 31:90-94
Diabetes Advocacy




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Fact Check: Does Pubic Hair Grooming Increase the Risk of Getting an STI?

Sexually transmitted infections (STIs) are on the rise, and many people are curious about the reasons why. While the cause is obviously multifactorial, some have suggested that at least part of the rise in STIs may be due to increasing rates of pubic hair grooming in men and women alike. Given that it’s not uncommon for people to experience cuts and skin irritation from genital grooming practices, it at least sounds plausible in theory that pubic hair shaving could potentially increase infection risk. But what does the research actually say?




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Foundations of Utility and Risk (FUR) Conference, Sydney, July 1-4, 2020

ABSTRACT SUBMISSION DEADLINE JANUARY 15, 2020 The Foundations of Utility and Risk (FUR) Conference will, for the first time, take place in the Asia Pacific area in 2020. We invite all Economists and other Social Scientists interested in the study of Decision-making to submit papers to the conference. Since 1982, FUR gathers every two years […]

The post Foundations of Utility and Risk (FUR) Conference, Sydney, July 1-4, 2020 appeared first on Decision Science News.




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Federal Watchdog Finds Risk of Head Start Fraud, Ranking Republican Seeks Hearing

Officials have not done enough to prevent fraud in Head Start programs, the GAO said. The findings prompted Rep. Virginia Foxx, R-N.C., the ranking member of the House education and labor committee, to call for a hearing on the federally funded preschool program for low-income children.




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Teachers at Higher Risk of COVID-19 Wonder: Should I Even Go Back?

As the national conversation on reopening schools accelerates, experts say the best way to protect vulnerable teachers might be to not have them in school buildings at all.




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Did a Misunderstanding Put One State's Aid for Disadvantaged Students At Risk?

U.S. Secretary of Education Betsy DeVos is not famous for pressuring states into desired outcomes, but did put at least two states' Title I funding on "high-risk" status last year.




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Teachers at Higher Risk of COVID-19 Wonder: Should I Even Go Back?

As the national conversation on reopening schools accelerates, experts say the best way to protect vulnerable teachers might be to not have them in school buildings at all.




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Emerging Risk Issues for Practice Managers.




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Water quality risk assessment of carp biocontrol for Australian waterways / edited by Justin D. Brookes & Matthew R. Hipsey.




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Option pricing with bivariate risk-neutral density via copula and heteroscedastic model: A Bayesian approach

Lucas Pereira Lopes, Vicente Garibay Cancho, Francisco Louzada.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 801--825.

Abstract:
Multivariate options are adequate tools for multi-asset risk management. The pricing models derived from the pioneer Black and Scholes method under the multivariate case consider that the asset-object prices follow a Brownian geometric motion. However, the construction of such methods imposes some unrealistic constraints on the process of fair option calculation, such as constant volatility over the maturity time and linear correlation between the assets. Therefore, this paper aims to price and analyze the fair price behavior of the call-on-max (bivariate) option considering marginal heteroscedastic models with dependence structure modeled via copulas. Concerning inference, we adopt a Bayesian perspective and computationally intensive methods based on Monte Carlo simulations via Markov Chain (MCMC). A simulation study examines the bias, and the root mean squared errors of the posterior means for the parameters. Real stocks prices of Brazilian banks illustrate the approach. For the proposed method is verified the effects of strike and dependence structure on the fair price of the option. The results show that the prices obtained by our heteroscedastic model approach and copulas differ substantially from the prices obtained by the model derived from Black and Scholes. Empirical results are presented to argue the advantages of our strategy.




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Risk-Aware Energy Scheduling for Edge Computing with Microgrid: A Multi-Agent Deep Reinforcement Learning Approach. (arXiv:2003.02157v2 [physics.soc-ph] UPDATED)

In recent years, multi-access edge computing (MEC) is a key enabler for handling the massive expansion of Internet of Things (IoT) applications and services. However, energy consumption of a MEC network depends on volatile tasks that induces risk for energy demand estimations. As an energy supplier, a microgrid can facilitate seamless energy supply. However, the risk associated with energy supply is also increased due to unpredictable energy generation from renewable and non-renewable sources. Especially, the risk of energy shortfall is involved with uncertainties in both energy consumption and generation. In this paper, we study a risk-aware energy scheduling problem for a microgrid-powered MEC network. First, we formulate an optimization problem considering the conditional value-at-risk (CVaR) measurement for both energy consumption and generation, where the objective is to minimize the loss of energy shortfall of the MEC networks and we show this problem is an NP-hard problem. Second, we analyze our formulated problem using a multi-agent stochastic game that ensures the joint policy Nash equilibrium, and show the convergence of the proposed model. Third, we derive the solution by applying a multi-agent deep reinforcement learning (MADRL)-based asynchronous advantage actor-critic (A3C) algorithm with shared neural networks. This method mitigates the curse of dimensionality of the state space and chooses the best policy among the agents for the proposed problem. Finally, the experimental results establish a significant performance gain by considering CVaR for high accuracy energy scheduling of the proposed model than both the single and random agent models.




risk

COVID-19 transmission risk factors. (arXiv:2005.03651v1 [q-bio.QM])

We analyze risk factors correlated with the initial transmission growth rate of the COVID-19 pandemic. The number of cases follows an early exponential expansion; we chose as a starting point in each country the first day with 30 cases and used 12 days. We looked for linear correlations of the exponents with other variables, using 126 countries. We find a positive correlation with high C.L. with the following variables, with respective $p$-value: low Temperature ($4cdot10^{-7}$), high ratio of old vs.~working-age people ($3cdot10^{-6}$), life expectancy ($8cdot10^{-6}$), number of international tourists ($1cdot10^{-5}$), earlier epidemic starting date ($2cdot10^{-5}$), high level of contact in greeting habits ($6 cdot 10^{-5}$), lung cancer ($6 cdot 10^{-5}$), obesity in males ($1 cdot 10^{-4}$), urbanization ($2cdot10^{-4}$), cancer prevalence ($3 cdot 10^{-4}$), alcohol consumption ($0.0019$), daily smoking prevalence ($0.0036$), UV index ($0.004$, smaller sample, 73 countries), low Vitamin D levels ($p$-value $0.002-0.006$, smaller sample, $sim 50$ countries). There is highly significant correlation also with blood type: positive correlation with RH- ($2cdot10^{-5}$) and A+ ($2cdot10^{-3}$), negative correlation with B+ ($2cdot10^{-4}$). We also find positive correlation with moderate C.L. ($p$-value of $0.02sim0.03$) with: CO$_2$ emissions, type-1 diabetes, low vaccination coverage for Tuberculosis (BCG). Several such variables are correlated with each other and so they likely have common interpretations. We also analyzed the possible existence of a bias: countries with low GDP-per capita, typically located in warm regions, might have less intense testing and we discuss correlation with the above variables.




risk

Risk Factors for Peri-implant Diseases  

9783030391850 978-3-030-39185-0




risk

Adaptive risk bounds in univariate total variation denoising and trend filtering

Adityanand Guntuboyina, Donovan Lieu, Sabyasachi Chatterjee, Bodhisattva Sen.

Source: The Annals of Statistics, Volume 48, Number 1, 205--229.

Abstract:
We study trend filtering, a relatively recent method for univariate nonparametric regression. For a given integer $rgeq1$, the $r$th order trend filtering estimator is defined as the minimizer of the sum of squared errors when we constrain (or penalize) the sum of the absolute $r$th order discrete derivatives of the fitted function at the design points. For $r=1$, the estimator reduces to total variation regularization which has received much attention in the statistics and image processing literature. In this paper, we study the performance of the trend filtering estimator for every $rgeq1$, both in the constrained and penalized forms. Our main results show that in the strong sparsity setting when the underlying function is a (discrete) spline with few “knots,” the risk (under the global squared error loss) of the trend filtering estimator (with an appropriate choice of the tuning parameter) achieves the parametric $n^{-1}$-rate, up to a logarithmic (multiplicative) factor. Our results therefore provide support for the use of trend filtering, for every $rgeq1$, in the strong sparsity setting.




risk

Integrative survival analysis with uncertain event times in application to a suicide risk study

Wenjie Wang, Robert Aseltine, Kun Chen, Jun Yan.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 51--73.

Abstract:
The concept of integrating data from disparate sources to accelerate scientific discovery has generated tremendous excitement in many fields. The potential benefits from data integration, however, may be compromised by the uncertainty due to incomplete/imperfect record linkage. Motivated by a suicide risk study, we propose an approach for analyzing survival data with uncertain event times arising from data integration. Specifically, in our problem deaths identified from the hospital discharge records together with reported suicidal deaths determined by the Office of Medical Examiner may still not include all the death events of patients, and the missing deaths can be recovered from a complete database of death records. Since the hospital discharge data can only be linked to the death record data by matching basic patient characteristics, a patient with a censored death time from the first dataset could be linked to multiple potential event records in the second dataset. We develop an integrative Cox proportional hazards regression in which the uncertainty in the matched event times is modeled probabilistically. The estimation procedure combines the ideas of profile likelihood and the expectation conditional maximization algorithm (ECM). Simulation studies demonstrate that under realistic settings of imperfect data linkage the proposed method outperforms several competing approaches including multiple imputation. A marginal screening analysis using the proposed integrative Cox model is performed to identify risk factors associated with death following suicide-related hospitalization in Connecticut. The identified diagnostics codes are consistent with existing literature and provide several new insights on suicide risk, prediction and prevention.




risk

BART with targeted smoothing: An analysis of patient-specific stillbirth risk

Jennifer E. Starling, Jared S. Murray, Carlos M. Carvalho, Radek K. Bukowski, James G. Scott.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 28--50.

Abstract:
This article introduces BART with Targeted Smoothing, or tsBART, a new Bayesian tree-based model for nonparametric regression. The goal of tsBART is to introduce smoothness over a single target covariate $t$ while not necessarily requiring smoothness over other covariates $x$. tsBART is based on the Bayesian Additive Regression Trees (BART) model, an ensemble of regression trees. tsBART extends BART by parameterizing each tree’s terminal nodes with smooth functions of $t$ rather than independent scalars. Like BART, tsBART captures complex nonlinear relationships and interactions among the predictors. But unlike BART, tsBART guarantees that the response surface will be smooth in the target covariate. This improves interpretability and helps to regularize the estimate. After introducing and benchmarking the tsBART model, we apply it to our motivating example—pregnancy outcomes data from the National Center for Health Statistics. Our aim is to provide patient-specific estimates of stillbirth risk across gestational age $(t)$ and based on maternal and fetal risk factors $(x)$. Obstetricians expect stillbirth risk to vary smoothly over gestational age but not necessarily over other covariates, and tsBART has been designed precisely to reflect this structural knowledge. The results of our analysis show the clear superiority of the tsBART model for quantifying stillbirth risk, thereby providing patients and doctors with better information for managing the risk of fetal mortality. All methods described here are implemented in the R package tsbart .




risk

Tail expectile process and risk assessment

Abdelaati Daouia, Stéphane Girard, Gilles Stupfler.

Source: Bernoulli, Volume 26, Number 1, 531--556.

Abstract:
Expectiles define a least squares analogue of quantiles. They are determined by tail expectations rather than tail probabilities. For this reason and many other theoretical and practical merits, expectiles have recently received a lot of attention, especially in actuarial and financial risk management. Their estimation, however, typically requires to consider non-explicit asymmetric least squares estimates rather than the traditional order statistics used for quantile estimation. This makes the study of the tail expectile process a lot harder than that of the standard tail quantile process. Under the challenging model of heavy-tailed distributions, we derive joint weighted Gaussian approximations of the tail empirical expectile and quantile processes. We then use this powerful result to introduce and study new estimators of extreme expectiles and the standard quantile-based expected shortfall, as well as a novel expectile-based form of expected shortfall. Our estimators are built on general weighted combinations of both top order statistics and asymmetric least squares estimates. Some numerical simulations and applications to actuarial and financial data are provided.




risk

Risk Models for Breast Cancer and Their Validation

Adam R. Brentnall, Jack Cuzick.

Source: Statistical Science, Volume 35, Number 1, 14--30.

Abstract:
Strategies to prevent cancer and diagnose it early when it is most treatable are needed to reduce the public health burden from rising disease incidence. Risk assessment is playing an increasingly important role in targeting individuals in need of such interventions. For breast cancer many individual risk factors have been well understood for a long time, but the development of a fully comprehensive risk model has not been straightforward, in part because there have been limited data where joint effects of an extensive set of risk factors may be estimated with precision. In this article we first review the approach taken to develop the IBIS (Tyrer–Cuzick) model, and describe recent updates. We then review and develop methods to assess calibration of models such as this one, where the risk of disease allowing for competing mortality over a long follow-up time or lifetime is estimated. The breast cancer risk model model and calibration assessment methods are demonstrated using a cohort of 132,139 women attending mammography screening in the State of Washington, USA.




risk

This French Woman Risked Her Life to Document Nazi Theft

During the Nazi occupation of France, many valuable works of art were stolen from the Jeu de Paume museum and relocated to Germany. One brave French woman kept detailed notes of the thefts




risk

A Leopard Risks Her Life to Steal Food

A female leopard is risking life and limb by trying to steal food from another male leopard. One wrong move and the male, a third bigger than she is, could make her pay.




risk

Identifying regions at risk with Google Trends: the impact of Covid-19 on US labour markets

BIS Bulletin No 8, April 2020. Information on local labour markets and Google searches can be used to construct a measure of the vulnerability of employment in different regions of the United States to the Covid-19 shock. Regional exposure to Covid-19 varies significantly, ranging from a low of 2% to a high of 98% of total local employment. We test for the usefulness of the Covid-19 exposure measure by showing that areas with higher exposure report more Google search queries related to the pandemic and unemployment benefits.




risk

Basel Committee publishes consultation paper on revisions to the credit valuation adjustment risk framework

Press release about the Basel Committee publishing consultation paper on revisions to the credit valuation adjustment risk framework, 28 November 2019.




risk

Basel Committee meets to review vulnerabilities and emerging risks, advance supervisory initiatives and promote Basel III implementation

Basel Committee Press release "Basel Committee meets to review vulnerabilities and emerging risks, advance supervisory initiatives and promote Basel III implementationl", 27 February 2020.




risk

Basel Committee issues progress report on banks' implementation of the "Principles for effective risk data aggregation and reporting"

BCBS Press release "Basel Committee issues progress report on banks' implementation of the 'Principles for effective risk data aggregation and reporting'", 29 April 2020




risk

As Quebec revises reopening dates, government risks adding uncertainty to uncertain times

Quebecers, like the rest of the world, are growing accustomed to the uncertainty that's accompanied the pandemic. But they may not appreciate their government adding to that already hefty burden.



  • News/Canada/Montreal

risk

Afraid to return to work? CERB eligibility at risk if you don't

Some Prince Edward Islanders are raising concerns about returning to work under the province's plan to ease back COVID-19 restrictions, but if they choose to stay home they could lose financial support from the federal government.



  • News/Canada/PEI

risk

Michigan Orders Flint Hospital To Reduce Legionnaires' Risks

Michigan officials are ordering a Flint hospital to take steps to reduce the risk of exposure to Legionella bacteria and Legionnaires' disease at the facility.