Type 2 Diabetes and all-cause mortality among Spanish women with breast cancer

Abstract Purpose To explore the effect of type 2 diabetes mellitus (T2DM) on the risk of death among women with breast cancer (BC). Methods A survival analysis was conducted among a cohort of women diagnosed with BC between 2006 and 2012 in Spain (n = 4,493). Biopsy or surgery confirmed BC cases were identified through the state population-based cancer registry with information on patients’ characteristics and vital status. Physician-diagnosed T2DM was confirmed based on primary health care clinical history. Cox regression analyses were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for all-cause death. Analyses were adjusted for age, hospital size, several clinical characteristics (including BC stage and histology, among others) and treatment modalities. Results Among the 4,493 BC women, 388 (8.6%) had coexisting T2DM. Overall, 1,299 (28.9%) BC women died during the completion of the follow-up and 785 (17.5%) did so during the first five years after BC diagnosis, resulting in a five-year survival rate of 82.5%. The death rate was higher in women with T2DM (43.8% died during whole period and 26.0% during the first five years) when compared with women without T2DM (27.5% and 16.7%, respectively). Accordingly, all-cause mortality was higher in women with T2DM (aHR: 1.22; 95% CI 1.03–1.44), especially if T2DM was diagnosed before BC (aHR:1.24; 95% CI 1.03–1.50) and in women with BC diagnosed before 50 years (aHR: 2.38; 95% CI 1.04–5.48). Conclusions T2DM was associated with higher all-cause mortality among Spanish women with BC, particularly when the T2DM diagnosis was prior to the BC.

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Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.4752 ◽

2011 ◽

Vol 29 (1) ◽

pp. 47-53 ◽

Cited By ~ 88

Author(s):

Melinda L. Irwin ◽

Catherine Duggan ◽

Ching-Yun Wang ◽

Ashley Wilder Smith ◽

Anne McTiernan ◽

...

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Cox Regression ◽

Treatment Strategies ◽

Breast Cancer Diagnosis ◽

C Peptide ◽

Risk Of Death ◽

Increased Risk ◽

Health Eating

Purpose To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. Patients and Methods This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Results Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Conclusion Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.

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Mannose-binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

10.2337/figshare.12240836 ◽

2020 ◽

Author(s):

Anne Gedebjerg ◽

Mette Bjerre ◽

Alisa Devedzic Kjaergaard ◽

Rudi Steffensen ◽

Jens Steen Nielsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Cox Regression ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

All Cause Mortality ◽

Binding Lectin

Objective: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. Research Design and Methods: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. Results: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. Conclusions: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.

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Mannose-binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

10.2337/figshare.12240836.v1 ◽

2020 ◽

Author(s):

Anne Gedebjerg ◽

Mette Bjerre ◽

Alisa Devedzic Kjaergaard ◽

Rudi Steffensen ◽

Jens Steen Nielsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Cox Regression ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

All Cause Mortality ◽

Binding Lectin

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The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz045 ◽

2019 ◽

Vol 105 (1) ◽

pp. 152-162 ◽

Cited By ~ 1

Author(s):

Alexandra K Lee ◽

Mark Woodward ◽

Dan Wang ◽

Toshiaki Ohkuma ◽

Bethany Warren ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Weight Change ◽

Cox Regression ◽

Lifestyle Changes ◽

Baseline Body Mass Index ◽

Diabetes Medication ◽

Increased Risk ◽

All Cause Mortality

Abstract Context Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. Objective To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. Design and Setting The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. Results Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. Conclusions In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.

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Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01394-4 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Alexander Zabala ◽

Vladimer Darsalia ◽

Marcus Lind ◽

Ann-Marie Svensson ◽

Stefan Franzén ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cohort Study ◽

Cox Regression ◽

Glucose Disposal ◽

Risk Of Death ◽

Increased Risk ◽

Estimated Glucose Disposal Rate ◽

Glucose Disposal Rate

Abstract Background and aims Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D. Materials and methods Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4–6, 6–8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R2 (± SE) values calculating the explainable log-likelihoods in the Cox regression. Results A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4–6, 6–8 and > 8 were: 0.77 (0.69–0.87), 0.68 (0.58–0.80) and 0.60 (0.48–0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70–0.94), 0.75 (0.64–0.88) and 0.68 (0.53–0.89). The attributed relative risk R2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively. Conclusion A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.

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Abstract P274: Kidney Filtration Markers and the Risk of Clinical Outcomes in Individuals With Type 2 Diabetes in the Advance Trial

Circulation ◽

10.1161/circ.141.suppl_1.p274 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Hyunju Kim ◽

Dan Wang ◽

John Chalmers ◽

Mark Woodward ◽

Elizabeth Selvin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Outcomes ◽

Regression Models ◽

Cox Regression ◽

All Cause Mortality ◽

Baseline Levels ◽

Controlled Evaluation ◽

Egfr Decline

Introduction: Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be particularly useful in adults with diabetes, but few studies examined the risk of clinical outcomes associated with filtration markers in adults with type 2 diabetes. Objective: We evaluated whether baseline levels and change in eGFR based on creatinine (Cr), cystatin C (Cys), and B 2 -microglobulin (B2M) were associated with the risk of clinical outcomes among individuals with type 2 diabetes. Methods: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, Cr, Cys, and B2M were measured in 7,217 participants at baseline and a random sample of 640 participants at the 1 year visit. We categorized baseline eGFR Cr , eGFR Cys , eGFR B2M , and the average across the 3 eGFR estimates (eGFR avg ) into quarters, and examined associations with major macrovascular and microvascular events together, and separately, and all-cause mortality using Cox regression models, adjusting for established risk factors. We also examined associations with continuous eGFR decline and increase (per 30%). Results: Over a median follow-up of 5 years, 1,313 combined major macrovascular (n=748) and microvascular events (n=637), and 743 deaths occurred. Lower levels of eGFR based on all three filtration markers individually and combined were associated with 1.5 to 2.2 times higher risk of combined major macrovascular and microvascular events, with similar patterns for other outcomes ( Table ). Per 30% decline in eGFR Cys and eGFR avg were associated with a >2-fold higher risk of all clinical outcomes, after additional adjustment of baseline eGFR. Conclusions: In adults with type 2 diabetes, baseline levels of eGFR based on alternative filtration markers and per 30% decline in eGFR Cys and eGFR avg were consistently associated with all clinical outcomes.

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Depressive symptoms and all-cause mortality in people with type 2 diabetes: A focus on potential mechanisms

The British Journal of Psychiatry ◽

10.1192/bjp.bp.114.154781 ◽

2016 ◽

Vol 209 (2) ◽

pp. 142-149 ◽

Cited By ~ 13

Author(s):

Giesje Nefs ◽

Victor J. M. Pop ◽

Johan Denollet ◽

François Pouwer

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Survival Time ◽

Edinburgh Postnatal Depression Scale ◽

Cox Regression ◽

Depression Scale ◽

All Cause Mortality ◽

Mediating Mechanisms

BackgroundDepression has been associated with increased all-cause mortality in people with type 2 diabetes.AimsTo test whether anhedonia, dysphoria and anxiety are differentially associated with all-cause mortality and examine symptom-specific behavioural or pathophysiological mechanisms.MethodA total of 1465 people completed the Edinburgh Postnatal Depression Scale in 2005 and were followed until death or 31 December 2010. Cox regression analyses compared survival time for people with a low v. high baseline dysphoria/anhedonia/anxiety score and identified mediating mechanisms.ResultsAfter a mean follow-up of 1878 days (s.d. = 306), 139 participants had died. At all time points, people with anhedonia had an almost twofold increased mortality risk compared with those without anhedonia. Physical activity met criteria for mediation. Symptoms of dysphoria and anxiety were not associated with survival time.ConclusionsSymptoms of anhedonia predicted shorter survival time, whereas dysphoria/anxiety did not. Mechanistic pathways, in particular physical activity, should be explored further.

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Aggregation and combination of cardiovascular risk factors and their association with 10-year all-cause mortality: the PERU MIGRANT Study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02405-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Janina Bazalar-Palacios ◽

J. Jaime Miranda ◽

Rodrigo M. Carrillo-Larco ◽

Robert H. Gilman ◽

Liam Smeeth ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cox Regression ◽

Secondary Data ◽

National Registry ◽

Increased Risk ◽

All Cause Mortality

Abstract Objective To estimate the association between the aggregation and pair-wise combination of selected cardiovascular risk factors (CVRF) and 10-year all-cause mortality. Methods Secondary data analysis of the PERU MIGRANT study, a prospective population-based cohort. Ten-year all-cause mortality was determined for participants originally enrolled in the PERU MIGRANT Study (baseline in 2007) through the National Registry of Identification and Civil Status. The CVRF included hypertension, type 2 diabetes mellitus, hypercholesterolemia, and overweight/obesity. Exposures were composed of both the aggregation of the selected CVRF (one, two, and three or more CVRF) and pair-wise combinations of CVRF. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Findings Of the 989 participants evaluated at baseline, 976 (98.8%) had information about vital status at 10 years of follow-up (9992.63 person-years), and 63 deaths were recorded. In the multivariable model, adjusting for sociodemographic and lifestyle variables, participants with two CVRF (HR: 2.48, 95% CI: 1.03–5.99), and those with three or more CVRF (HR: 3.93, 95% CI: 1.21–12.74) had higher all-cause mortality risk, compared to those without any CVRF. The pair-wise combinations associated with the highest risk of all-cause mortality, compared to those without such comorbidities, were hypertension with type 2 diabetes (HR: 11.67, 95% CI: 3.67–37.10), and hypertension with overweight/obesity (HR: 2.76, 95% CI: 1.18–6.71). Conclusions The aggregation of two or more CVRF and the combination of hypertension with type 2 diabetes or overweight/obesity were associated with an increased risk of 10-year all-cause mortality. These risk profiles will inform primary and secondary prevention strategies to delay mortality from cardiovascular risk factors.

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Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study

10.2337/figshare.14173313 ◽

2021 ◽

Author(s):

Maoxiang Zhao ◽

Lulu Song ◽

Lan Sun ◽

Miao Wang ◽

Chi Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cox Regression ◽

Age Groups ◽

Onset Age ◽

Onset Type ◽

Diabetes Onset ◽

All Cause Mortality

Objective We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in Chinese population. Research design and methods This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan study. All participants were followed biennially until December 31, 2017. A total of 11,384 participants were diagnosed as type 2 diabetes during follow-up. For each case, one control was randomly selected matched for age (±1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% confidence intervals (CIs) of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus controls across age groups. Results During a median follow-up of 5.57 years, 1794 incident events (907 CVD events, of which were 725 strokes, and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age < 45 years had the highest risks of CVD and all-cause mortality relative to the matched controls, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. Conclusions The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age groups, and the associations were more evident in younger-onset type 2 diabetes.

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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes

10.2337/figshare.16775743 ◽

2021 ◽

Author(s):

Anca Balintescu ◽

Marcus Lind ◽

Mikael Andersson Franko ◽

Anders Oldner ◽

Maria Cronhjort ◽

...

Keyword(s):

Type 2 Diabetes ◽

Regression Analysis ◽

Cox Regression ◽

Cubic Spline ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk

Objective To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients. Research design and methods We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. Result Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). Conclusions In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis.

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