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

Abstract Objective A correlation between myopia and insulin-resistance has been suggested. We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood. Design Population-based, retrospective, cohort study. Methods 1,329,705 adolescents (579,543 women, 43.6%) aged 16-19 years, medically examined before mandatory military service during 1993-2012; and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up. Results There was an interaction between myopia and sex with T2D (P<0.001). For women, T2D incidence rates (per 100,000 person-years) were 16.6, 19.2, and 25.1 for those without myopia, and with mild-to-moderate and high myopia, respectively. These corresponded to HRs of 1.29 (95%CI 1.14-1.45) and 1.63 (1.21-2.18) for women with mild-to-moderate and high myopia, respectively, compared to those without myopia, after adjustment for age at study entry, birth year, adolescent BMI, cognitive performance, socioeconomic status, and immigration status. Results persisted in extensive sensitivity and subgroup analyses. When managed as a continuous variable, every 1 diopter lower spherical equivalent yielded a 6.5% higher adjusted HR for T2D incidence (P= 0.003). There was no significant association among men. Conclusions For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis.

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Snoring frequency and risk of type 2 diabetes mellitus: a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2020-042469 ◽

2021 ◽

Vol 11 (5) ◽

pp. e042469

Author(s):

Ningbin Dai ◽

Qianwen Shi ◽

Yujie Hua ◽

Yu Guo ◽

Zheng Bian ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cohort Study ◽

Interaction Effect ◽

Chinese Population ◽

Cox Regression ◽

Baseline Survey ◽

Increased Risk

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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Quantitative Measurement of Full-Length and C-Terminal Proteolyzed RBP4 in Serum of Normal and Insulin-Resistant Humans using a Novel Mass Spectrometry Immunoassay

Endocrinology ◽

10.1210/en.2011-1750 ◽

2012 ◽

Vol 153 (3) ◽

pp. 1519-1527 ◽

Cited By ~ 19

Author(s):

Qin Yang ◽

Iratxe Eskurza ◽

Urban A. Kiernan ◽

David A. Phillips ◽

Matthias Blüher ◽

...

Keyword(s):

Mass Spectrometry ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Full Length ◽

Clinical Severity ◽

Glucose Disposal ◽

Insulin Resistant ◽

Glucose Disposal Rate

Serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant humans and correlate with severity of insulin resistance in metabolic syndrome. Quantitative Western blotting (qWestern) has been the most accurate method for serum RBP4 measurements, but qWestern is technically complex and labor intensive. The lack of a reliable, high-throughput method for RBP4 measurements has resulted in variability in findings in insulin-resistant humans. Many commonly used ELISAs have limited dynamic range. Neither the current ELISAs nor qWestern distinguish among full-length and carboxyl terminus proteolyzed forms of circulating RBP4 that are altered in different medical conditions. Here, we report the development of a novel quantitative mass spectrometry immunoaffinity assay (qMSIA) to measure full-length and proteolyzed forms of RBP4. qMSIA and qWestern of RBP4 were performed in identical serum aliquots from insulin-sensitive/normoglycemic or insulin-resistant humans with impaired glucose tolerance or type 2 diabetes. Total RBP4 qMSIA measurements were highly similar to qWestern and correlated equally well with clinical severity of insulin resistance (assessed by clamp glucose disposal rate, r = −0.74), hemoglobin A1c (r = 0.63), triglyceride/high-density lipoprotein (r = 0.55), waist/hip (r = 0.61), and systolic blood pressure (r = 0.53, all P < 0.001). Proteolyzed forms of RBP4 accounted for up to 50% of total RBP4 in insulin-resistant subjects, and des(Leu)-RBP4 (cleavage of last leucine) correlated highly with insulin resistance (assessed by glucose disposal rate, r = −0.69). In multiple regression analysis, insulin resistance but not glomerular filtration rate was the strongest, independent predictor of serum RBP4 levels. Thus, qMSIA provides a novel tool for accurately measuring serum RBP4 levels as a biomarker for severity of insulin resistance and risk for type 2 diabetes and metabolic syndrome.

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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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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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Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001481 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001481

Author(s):

Giuseppe Penno ◽

Emanuela Orsi ◽

Anna Solini ◽

Enzo Bonora ◽

Cecilia Fondelli ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cohort Study ◽

Prospective Cohort ◽

Age And Gender ◽

Death Rates ◽

Risk Of Death ◽

Renal Hyperfiltration ◽

Increased Risk ◽

And Gender

IntroductionIn addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent predictor of death in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian multicenter study.Research design and methodsThis observational, prospective cohort study enrolled 15 773 patients with type 2 diabetes consecutively attending 19 Italian diabetes clinics in 2006–2008. Serum creatinine, albuminuria, cardiovascular risk factors, and complications/comorbidities were assessed at baseline. Vital status on 31 October 2015 was retrieved for 15 656 patients (99.26%). Patients were stratified (A) by absolute estimated glomerular filtration rate (eGFR) values in eGFR deciles or Kidney Disease: Improving Global Outcomes (KDIGO) categories and (B) based on age-corrected thresholds or age and gender-specific 95th and 5th percentiles in hyperfiltration, hypofiltration, and normofiltration groups.ResultsThe highest eGFR decile/category and the hyperfiltration group included (partly) different individuals with similar clinical features. Age and gender-adjusted death rates were significantly higher in deciles 1, 9, and 10 (≥103.9, 50.9–62.7, and <50.9 mL/min/1.73 m2, respectively) versus the reference decile 3 (92.9–97.5 mL/min/1.73 m2). Mortality risk, adjusted for multiple confounders, was also increased in deciles 1 (HR 1.461 (95% CI 1.175 to 1.818), p=0.001), 9 (1.312 (95% CI 1.107 to 1.555), p=0.002), and 10 (1.976 (95% CI 1.673 to 2.333), p<0.0001) versus decile 3. Similar results were obtained by stratifying patients by KDIGO categories. Death rates and adjusted mortality risks were significantly higher in hyperfiltering and particularly hypofiltering versus normofiltering individuals.ConclusionsIn type 2 diabetes, both high-normal eGFR and hyperfiltration are associated with an increased risk of death from any cause, independent of confounders that may directly impact on mortality and/or affect GFR estimation. Further studies are required to clarify the nature of this relationship.Trial registration numberNCT00715481.

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Type 2 diabetes and COVID-19 related mortality in the critical care setting: A national cohort study in England, March-July 2020

10.2337/figshare.13034210 ◽

2020 ◽

Author(s):

John M. Dennis ◽

Bilal A Mateen ◽

Raphael Sonabend ◽

Nicholas J Thomas ◽

Kashyap A Patel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Critical Care ◽

Cohort Study ◽

Care Setting ◽

Critical Care Setting ◽

Risk Of Death ◽

Risk Increase ◽

Increased Risk ◽

All Cause Mortality

Objective: To describe the relationship between type 2 diabetes and all-cause mortality amongst adults with COVID-19 in the critical care setting. Research Design and Methods: Nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between March 1, 2020 and July 27, 2020. Cox proportional hazards models were used to estimate 30 day in-hospital all-cause mortality associated with type 2 diabetes, adjusted for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease). Results: 19,256 COVID-19 related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70), and 5,447 ICU admissions (mean age 58). 3,524 (18.3%) had type 2 diabetes. 5,077 people (26.4%) died during the study period. People with type 2 diabetes were at increased risk of death (adjusted hazard ratio (aHR) 1.23 [95%CI 1.14;1.32]), results were consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with increasing age (age 18-49 aHR 1.50 [95%CI 1.05;2.15]; age 50-64 1.29 [1.10;1.51]; age 65 or greater 1.18 [1.09;1.29], p-value for age:type 2 diabetes interaction 0.002). Conclusions: Type 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.

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

10.2337/figshare.16775743.v1 ◽

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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Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting

Heart and Vessels ◽

10.1007/s00380-016-0875-1 ◽

2016 ◽

Vol 32 (3) ◽

pp. 269-278 ◽

Cited By ~ 1

Author(s):

Thomas Nyström ◽

Martin J. Holzmann ◽

Björn Eliasson ◽

Ann-Marie Svensson ◽

Jeanette Kuhl ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery ◽

Artery Bypass ◽

Glucose Disposal ◽

Bypass Grafting ◽

Term Survival ◽

Estimated Glucose Disposal Rate ◽

Glucose Disposal Rate

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Type 2 diabetes and COVID-19 related mortality in the critical care setting: A national cohort study in England, March-July 2020

10.2337/figshare.13034210.v1 ◽

2020 ◽

Author(s):

John M. Dennis ◽

Bilal A Mateen ◽

Raphael Sonabend ◽

Nicholas J Thomas ◽

Kashyap A Patel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Critical Care ◽

Cohort Study ◽

Care Setting ◽

Critical Care Setting ◽

Risk Of Death ◽

Risk Increase ◽

Increased Risk ◽

All Cause Mortality

Objective: To describe the relationship between type 2 diabetes and all-cause mortality amongst adults with COVID-19 in the critical care setting. Research Design and Methods: Nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between March 1, 2020 and July 27, 2020. Cox proportional hazards models were used to estimate 30 day in-hospital all-cause mortality associated with type 2 diabetes, adjusted for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease). Results: 19,256 COVID-19 related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70), and 5,447 ICU admissions (mean age 58). 3,524 (18.3%) had type 2 diabetes. 5,077 people (26.4%) died during the study period. People with type 2 diabetes were at increased risk of death (adjusted hazard ratio (aHR) 1.23 [95%CI 1.14;1.32]), results were consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with increasing age (age 18-49 aHR 1.50 [95%CI 1.05;2.15]; age 50-64 1.29 [1.10;1.51]; age 65 or greater 1.18 [1.09;1.29], p-value for age:type 2 diabetes interaction 0.002). Conclusions: Type 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.

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