scholarly journals Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population

2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Serum Creatinine ◽  
Cox Regression ◽  
Tertiary Care ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
New Onset

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.

scholarly journals Awaking Blood Pressure Surge and Progression to Microalbuminuria in Type 2 Normotensive Diabetic Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michelangela Barbieri ◽  
Maria Rosaria Rizzo ◽  
Ilaria Fava ◽  
Celestino Sardu ◽  
Nicola Angelico ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cox Regression ◽  
Blood Pressure Monitoring ◽  
Adult Patients ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Pressure Surge

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.

scholarly journals Association between uric acid level and incidence of macroalbuminuria in people with type 2 diabetes mellitus: A 4.5-year cohort study

2019 ◽  
Author(s):  
Yun-Ju Lai ◽  
Yu-Yen Chen ◽  
Li-Jung Chen ◽  
Po-Wen Ku ◽  
Kuo-Chuan Hung ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Cox Regression Analysis ◽  
Increased Risk

Abstract Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from a community hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve. Results: We included 247 qualified subjects (mean age: 64.78 years old [standard deviation=11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident macroalbuminuria (adjusted hazard ratio=2.39; 95% confidence interval: 1.53-3.75; p<0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident macroalbuminuria. Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes.

scholarly journals Serum creatinine levels and risk of incident type 2 diabetes mellitus or dysglycemia in middle-aged Japanese men: a retrospective cohort study

2018 ◽  
Vol 6 (1) ◽  
pp. e000492 ◽  
Author(s):  
Mamoru Takeuchi ◽  
Hironori Imano ◽  
Isao Muraki ◽  
Yuji Shimizu ◽  
Mina Hayama-Terada ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Creatinine ◽  
Incident Type ◽  
Increased Risk ◽  
Incident Type 2 Diabetes ◽  
Fasting Plasma Glucose Concentration

ObjectiveTo assess the association between low serum creatinine levels and an increased risk of type 2 diabetes mellitus and dysglycemia.Research design and methodsWe conducted a retrospective cohort study of 3313 Japanese male workers aged 30–55 years, who underwent annual health check-ups during 2001–2008 and showed no type 2 diabetes mellitus, and underwent follow-up examinations until March 2013. Dysglycemia was defined as a fasting plasma glucose concentration of ≥110 mg/dL (6.1 mmol/L), or a non-fasting plasma glucose concentration of ≥140 mg/dL (7.8 mmol/L). A Cox proportional model was used to calculate HRs and 95% CIs for developing type 2 diabetes mellitus or dysglycemia.ResultsDuring the median 6.7-year follow-up, there were 207 cases of incident type 2 diabetes mellitus and 596 cases of incident dysglycemia, including 115 cases of type 2 diabetes mellitus among the subjects with normal glucose concentrations at baseline. After adjustment for age, body mass index and known diabetes risk factors, the multivariable HR of type 2 diabetes mellitus for the lowest category of serum creatinine (<0.7 mg/dL) vs the highest category (0.9–1.1 mg/dL) was 1.9 (95% CI 1.2 to 2.9; P for trend 0.03). The multivariable HRs of dysglycemia for the lowest category of serum creatinine versus the highest category was 1.5 (95% CI 1.1 to 1.9; P for trend 0.01).ConclusionsLow serum creatinine levels were associated with an increased risk of type 2 diabetes mellitus and dysglycemia.

scholarly journals Relationship between diabetic retinopathy stages and risk of major lower-extremity arterial disease in patients with type 2 diabetes

2020 ◽  
Author(s):  
Ninon Foussard ◽  
Pierre-Jean Saulnier ◽  
Louis Potier ◽  
Stéphanie Ragot ◽  
Fabrice Schneider ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Lower Extremity ◽  
Incidence Rate ◽  
Cox Regression ◽  
Arterial Disease ◽  
Lower Extremity Arterial Disease ◽  
C Statistic

<b>Objective. </b>We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors in this relationship in a prospective cohort of patients with type 2 diabetes. <p><b>Research design and methods</b><b>. </b>Diabetic retinopathy was staged at baseline as absent, non-proliferative or proliferative. Cox regression model was fitted to compute HR (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. Retinopathy-LEAD association was assessed in subgroups by age, gender, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy to stratify LEAD risk was assessed using c-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).<b></b></p> <p><b>Results. </b>Among 1320 participants without a baseline history of LEAD, 94 (7.1%) patients developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6, 95%CI [7.8–11.7] per 1000 person-years). The LEAD incidence rate increased by worsening retinopathy: absent 5.5 (3.9–7.8), non-proliferative 14.6 (11.1–19.3), proliferative 20.1 (11.1–36.3) per 1000 person-years. Compared with absent retinopathy, non-proliferative (multi-adjusted HR 2.31, 95%CI [1.43–3.81], p=0.0006) and proliferative retinopathy (3.14 [1.40–6.15], p=0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced c-statistic (+0.023 [0.003–0.044], p=0.02), IDI (0.209 [0.130 – 0.321], p<0.001) and NRI (0.562 [0.382– 0.799], p<0.001) for LEAD risk, beyond traditional risk factors.</p> <p><b>Conclusions. </b>An independent dose-response relationship was observed between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for LEAD risk stratification, suggesting its usefulness as LEAD predictor.<b></b></p>

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

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

<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>

Abstract P025: Perceived Stress and Incidence of Type 2 Diabetes: a 35-Year Follow-up Study of Middle Aged Swedish Men

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Masuma Novak
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Prior History ◽  
Diabetes Incidence ◽  
Middle Aged ◽  
Cox Regression Analysis

OBJECTIVE_ To explore the incidence cases of diabetes over 35 years of follow-up in middle-aged Swedish men in relation to their severity of stress at baseline. RESEARCH DESIGHN AND METHODS_ This was a population-based random sample of 7 495 men derived from the Primary Prevention cohort study (Gothenburg) aged 47-55 years and without prior history of diabetes at baseline (1970-1973). Self-perceived psychological stress during the previous years was assessed with a single-item in the questionnaire. Incident diabetes from hospital discharge and death registries was collected during the 35 years follow-up. Cox proportional hazards regression was used to evaluate association of stress with incidence of diabetes. RESULTS_ During the follow up of 35 years, 884 men developed diabetes. The crude incidence rate was 46.32 per 1000 persons-years. At baseline, 15.5% men reported to experience permanent stress. The age-adjusted cumulative incidence of type diabetes in men who had permanent stress was 16%, compared with 12% for those with no or periodic stress. In age-adjusted Cox regression analysis, men with permanent stress had a higher risk of diabetes incident (hazard ratio 1.52 [95% CI 1.26-1.82]) compared with men with periodic or no stress (referent). The excess risk of diabetes incident associated with permanent stress remained significant after adjusting for age, socioeconomic status (SES), smoking, physical inactivity, alcohol abuse, height, BMI, serum-cholesterol, hypertension, systolic and diastolic blood pressure. CONCLUSIONS_ Perceived permanent stress in middle aged Swedish men was an important long-term predictor of diabetes incidence. The association of stress was independent of SES, lifestyle and other conventional type 2 diabetes risk factors. The significant impact of stress on diabetes, as demonstrated in this study, emphasizes need for prevention strategies including intervention programmes for people with permanent stress.

scholarly journals Dipstick proteinuria and risk of type 2 diabetes mellitus: a nationwide population-based cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jimin Jeon ◽  
Jinkwon Kim
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cohort Study ◽  
Significant Risk ◽  
Health Screening ◽  
Increased Risk ◽  
New Onset

Abstract Background Proteinuria has been recognized as a marker of systemic inflammation and endothelial dysfunction associated with insulin resistance and β-cell impairment, which can contribute to the development of type 2 diabetes mellitus (T2DM). However, it is unknown whether the dipstick proteinuria test has a predictive value for new-onset T2DM. Methods This retrospective cohort study analyzed 239,287 non-diabetic participants who participated in the Korean nationwide health screening program in 2009–2010. Proteinuria was determined by the urine dipstick test at the baseline health screening. We performed multivariate Cox proportional regression analyses for the development of new-onset T2DM. Follow-up was performed until December 2015. Results During the mean follow-up period of 5.73 years, 22,215 participants were diagnosed with new-onset T2DM. The presence of proteinuria was significantly associated with an increased risk of T2DM (adjusted hazard ratio: 1.19, 95% confidence interval: 1.10, 1.29). There was a positive dose–response relationship between the degree of dipstick proteinuria and T2DM risk. This significant association between proteinuria and T2DM risk was consistent regardless of the fasting glucose level at baseline. Conclusions Dipstick proteinuria is a significant risk factor for new-onset T2DM. Therefore, proteinuria might be a useful biomarker to identify those at a high risk for developing T2DM.

scholarly journals Increased Arterial Stiffness as a Predictor for Onset and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yaxin An ◽  
Yuxian Yang ◽  
Bin Cao ◽  
Huan Dong ◽  
Aihua Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Logistic Regression ◽  
Diabetic Retinopathy ◽  
Regression Analysis ◽  
Arterial Stiffness ◽  
New Onset

Introduction. Brachial–ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis. Methods. The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted. Results. Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR = 1.62 (1.22, 2.15), p < 0.001 , and T3: OR = 2.58 (1.86, 3.58), p < 0.001 ) and STDR group (T3: OR = 3.87 (1.87, 8.02), p < 0.001 ). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR ( HR = 2.24 , 95% CI (1.24, 4.03), p = 0.007 , for T2 baPWV and HR = 2.90 , 95% CI (1.49, 5.64), p = 0.002 , for T3 baPWV) after adjustments for multiple factors. Conclusions. Our results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.

scholarly journals Relationship between diabetic retinopathy stages and risk of major lower-extremity arterial disease in patients with type 2 diabetes

2020 ◽  
Author(s):  
Ninon Foussard ◽  
Pierre-Jean Saulnier ◽  
Louis Potier ◽  
Stéphanie Ragot ◽  
Fabrice Schneider ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Lower Extremity ◽  
Incidence Rate ◽  
Cox Regression ◽  
Arterial Disease ◽  
Lower Extremity Arterial Disease ◽  
C Statistic

<b>Objective. </b>We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors in this relationship in a prospective cohort of patients with type 2 diabetes. <p><b>Research design and methods</b><b>. </b>Diabetic retinopathy was staged at baseline as absent, non-proliferative or proliferative. Cox regression model was fitted to compute HR (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. Retinopathy-LEAD association was assessed in subgroups by age, gender, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy to stratify LEAD risk was assessed using c-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).<b></b></p> <p><b>Results. </b>Among 1320 participants without a baseline history of LEAD, 94 (7.1%) patients developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6, 95%CI [7.8–11.7] per 1000 person-years). The LEAD incidence rate increased by worsening retinopathy: absent 5.5 (3.9–7.8), non-proliferative 14.6 (11.1–19.3), proliferative 20.1 (11.1–36.3) per 1000 person-years. Compared with absent retinopathy, non-proliferative (multi-adjusted HR 2.31, 95%CI [1.43–3.81], p=0.0006) and proliferative retinopathy (3.14 [1.40–6.15], p=0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced c-statistic (+0.023 [0.003–0.044], p=0.02), IDI (0.209 [0.130 – 0.321], p<0.001) and NRI (0.562 [0.382– 0.799], p<0.001) for LEAD risk, beyond traditional risk factors.</p> <p><b>Conclusions. </b>An independent dose-response relationship was observed between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for LEAD risk stratification, suggesting its usefulness as LEAD predictor.<b></b></p>

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

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

<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>

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