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

2011 ◽  
Vol 29 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Melinda L. Irwin ◽  
Catherine Duggan ◽  
Ching-Yun Wang ◽  
Ashley Wilder Smith ◽  
Anne McTiernan ◽  
...  

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.

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Alexander Zabala ◽  
Vladimer Darsalia ◽  
Marcus Lind ◽  
Ann-Marie Svensson ◽  
Stefan Franzén ◽  
...  

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.


2021 ◽  
Author(s):  
Anca Balintescu ◽  
Marcus Lind ◽  
Mikael Andersson Franko ◽  
Anders Oldner ◽  
Maria Cronhjort ◽  
...  

<b>Objective</b> <p>To investigate the nature of<b> </b>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.<b></b></p> <p><b>Research design and methods</b></p> <p>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.</p> <p><b>Result</b></p> <p>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).</p> <p><b>Conclusions</b></p> <p>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. </p>


2021 ◽  
Author(s):  
Anca Balintescu ◽  
Marcus Lind ◽  
Mikael Andersson Franko ◽  
Anders Oldner ◽  
Maria Cronhjort ◽  
...  

<b>Objective</b> <p>To investigate the nature of<b> </b>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.<b></b></p> <p><b>Research design and methods</b></p> <p>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.</p> <p><b>Result</b></p> <p>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).</p> <p><b>Conclusions</b></p> <p>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. </p>


Author(s):  
L. Fernández-Arce ◽  
N. Robles-Rodríguez ◽  
A. Fernández-Feito ◽  
A. Llaneza-Folgueras ◽  
A. I. Encinas-Muñiz ◽  
...  

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.


2020 ◽  
Vol 9 (9) ◽  
pp. 3001
Author(s):  
Sara Sokooti ◽  
Lyanne M. Kieneker ◽  
Martin H. de Borst ◽  
Anneke Muller Kobold ◽  
Jenny E. Kootstra-Ros ◽  
...  

C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal and Vascular End-Stage Disease study without type 2 diabetes at baseline. C-peptide was measured in plasma with an electrochemiluminescent immunoassay. Cox proportional hazards regression was used to evaluate the association between C-peptide level and type 2 diabetes development. Median C-peptide was 722 (566–935) pmol/L. During a median follow-up of 7.2 (6.0–7.7) years, 289 individuals developed type 2 diabetes. In multivariable-adjusted Cox regression models, we observed a significant positive association of C-peptide with the risk of type 2 diabetes independent of glucose and insulin levels (hazard ratio (HR): 2.35; 95% confidence interval (CI): 1.49–3.70). Moreover, we found significant effect modification by hypertension and albuminuria (p < 0.001 and p = 0.001 for interaction, respectively), with a stronger association in normotensive and normo-albuminuric subjects and absence of an association in subjects with hypertension or albuminuria. In this population-based cohort, elevated C-peptide levels are associated with an increased risk of type 2 diabetes independent of glucose, insulin levels, and clinical risk factors. Elevated C-peptide level was not independently associated with an increased risk of type 2 diabetes in individuals with hypertension or albuminuria.


2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.


2019 ◽  
Vol 105 (1) ◽  
pp. 152-162 ◽  
Author(s):  
Alexandra K Lee ◽  
Mark Woodward ◽  
Dan Wang ◽  
Toshiaki Ohkuma ◽  
Bethany Warren ◽  
...  

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: &gt;10% loss, 4% to 10% loss, stable (±&lt;4%), 4% to 10% gain, and &gt;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 &gt;10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had &gt;10% weight gain. Over the following 3 years of the trial, &gt;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.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michelangela Barbieri ◽  
Maria Rosaria Rizzo ◽  
Ilaria Fava ◽  
Celestino Sardu ◽  
Nicola Angelico ◽  
...  

Background. We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes.Methods. Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP.Results. After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (−0.67±1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86±6.92 mmHg) during follow-up were 17.41 (95% CI 6.26–48.42);pfor trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6[1.4]to 36.8[7.1],p<0.001.Conclusion. An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.


BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e042469
Author(s):  
Ningbin Dai ◽  
Qianwen Shi ◽  
Yujie Hua ◽  
Yu Guo ◽  
Zheng Bian ◽  
...  

ObjectiveTo evaluate the association between snoring frequency and type 2 diabetes mellitus (T2DM) according to age and gender in Chinese population.DesignA cohort study was performed in Suzhou site of the China Kadoorie Biobank. Residents who didn’t suffer from T2DM at baseline survey (2004–2008) and in half a year after baseline were enrolled in this study and followed cause-specific morbidity until 31 December 2013. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Cox regression models were used to estimate HRs and 95% CIs for the snoring and T2DM association.SettingWuzhong district, Suzhou, China.ParticipantsA total of 49 453 participants (men: 41.8%; mean age: 51.14±10.28 years) were enrolled in this study.Outcome measuresT2DM cases were defined as International Classification of Diseases 10th Revision code of E11 and were identified through disease registries and health insurance databases.ResultsDuring a media of 7.18 years follow-up, 1120 T2DM cases were identified. Higher T2DM incidence was observed in participants with frequent and occasional snoring compared with those without (4.80 and 2.87 vs 2.39 per 1000 person-years). The multivariable-adjusted model found snoring was independently associated with T2DM (HR 1.28, 95% CI 1.20 to 1.38), both in men (HR 1.25, 95% CI 1.10 to 1.41) and women (HR 1.28, 95% CI 1.17 to 1.39). Moreover, a significant multiplicative interaction effect between snoring and age was detected on T2DM risk (p=0.015).ConclusionsSnoring was independently associated with an increased risk of T2DM in Chinese population, both in men and women. Meanwhile, there was an interaction effect between snoring and age on T2DM risk.


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