scholarly journals Skin autofluorescence predicts cancer in subjects with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e001312
Author(s):  
Ninon Foussard ◽  
Alice Larroumet ◽  
Marine Rigo ◽  
Kamel Mohammedi ◽  
Laurence Baillet-Blanco ◽  
...  

IntroductionSubjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methodsFrom 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.ResultsThe participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).ConclusionsSkin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kamel Mohammedi ◽  
Stephen Harrap ◽  
Giuseppe Mancia ◽  
Michel Marre ◽  
Neil Poulter ◽  
...  

Abstract Background Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes. Methods We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models. Results Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers. Conclusions PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.


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.


2020 ◽  
Vol 9 (9) ◽  
pp. 3009
Author(s):  
José Antonio Rubio ◽  
Sara Jiménez ◽  
José Luis Lázaro-Martínez

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.


2019 ◽  
Author(s):  
Yun-Ju Lai ◽  
Yu-Yen Chen ◽  
Li-Jung Chen ◽  
Po-Wen Ku ◽  
Kuo-Chuan Hung ◽  
...  

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.


2021 ◽  
Author(s):  
Yongfu Yu ◽  
Melissa Soohoo ◽  
Henrik Toft Sørensen ◽  
Jiong Li ◽  
Onyebuchi A. Arah

<b>OBJECTIVE</b> <p>To evaluate associations between gestational diabetes mellitus (GDM) and various incident cardiovascular disease (CVD) endpoints, considering the effects of mediating role of type 2 diabetes and shared environmental/familial factors.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>This population-based cohort study included 1002486 parous women in Denmark during 1978-2016. We used Cox regression to (i) examine the associations of GDM with overall and type-specific CVDs using full-cohort and sibling-matched analysis; (ii) quantify the impact of type 2 diabetes after GDM using mediation analysis; and (iii) assess whether these associations were modified by pre-pregnancy obesity or maternal history of CVD.</p> <p><b>RESULTS</b></p> <p>Women with a history of GDM had a 40% increased overall CVD risk (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 1.35-1.45). Sibling-matched analyses yielded similar results(HR, 1.44; 95%CI, 1.28-1.62). Proportion of association between GDM and overall CVD explained by subsequent type 2 diabetes was 23.3%(15.4%-32.8%). We observed increased risks of specific CVDs, including 65% increased stroke risk and more than two-fold risks for myocardial infarction, heart failure, and peripheral artery disease. The elevated overall risks were more pronounced among women with GDM and pre-pregnancy obesity or maternal history of CVD. </p> <p><b>CONCLUSIONS</b></p> <p>A history of GDM was associated with increased risks of overall and specific CVDs. Increased risks were partly explained by subsequent type 2 diabetes and the need to identify other pathways remains important. Continuous monitoring of women with a history of GDM, especially those with pre-pregnancy obesity or maternal history of CVD, may provide better opportunities to reduce their cardiovascular risk.</p>


2018 ◽  
Vol 104 (4) ◽  
pp. 1313-1324 ◽  
Author(s):  
Sarah C W Marott ◽  
Børge G Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Marianne Benn

Abstract Context Obesity, glucose, insulin resistance [homeostatic model assessment, version 2, for insulin resistance (HOMA2-IR)], and insulin secretion (HOMA2-β) have been associated with type 2 diabetes (T2D) observationally. However, the causal, genetic contribution of each parameter to this risk is largely unknown and important to study because observational data are prone to confounding but genetic, causal data are free of confounding and reverse causation. Objective We examined the causal, genetic contribution of body mass index (BMI), glucose level, C-peptide level, HOMA2-IR, and HOMA2-β to the risk of T2D in 95,540 individuals from the Copenhagen General Population Study and estimated the absolute 10-year risks. Methods Cox regression analysis, instrumental variable analysis, and Poisson regression analysis were performed to estimate the observational hazard ratios, causal, genetic ORs, and absolute 10-year risks of T2D. Results For 1-SD greater level, BMI was associated with an observational 66% (95% CI, 62% to 72%) and causal, genetic 121% (95% CI, 25% to 291%) greater risk of T2D; glucose with an observational 44% (95% CI, 41% to 46%) and causal, genetic 183% (95% CI, 56% to 416%) greater risk of T2D; and HOMA2-IR with an observational 30% (95% CI, 18% to 44%) and causal, genetic 12% (95% CI, 2% to 22%) greater risk of T2D. In contrast, for 1-SD greater level, HOMA2-β was associated with an observational 14% (95% CI, 11% to 16%) and causal, genetic 21% (95% CI, 8% to 32%) lower risk of T2D. The upper tertiles of HOMA2-IR were associated with absolute 10-year diabetes risks of 31% and 37% in obese women and men, age &gt;60 years, and a glucose level of 6.1 to 11.0 mmol/L. Conclusions BMI, glucose level, HOMA2-IR, and HOMA2-β are causally associated with T2D.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D McGuire ◽  
B Zinman ◽  
S E Inzucchi ◽  
S D Anker ◽  
C Wanner ◽  
...  

Abstract Background and aims The EMPA-REG OUTCOME trial included patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular (CV) disease. Empagliflozin reduced the risk of 3-point major adverse CV events (MACE; composite of CV death, myocardial infarction [MI], or stroke) by 14%, CV death by 38% and hospitalisation for heart failure (HF) by 35% vs placebo in analyses of time to first event. We assessed the effect of empagliflozin on all-cause hospitalisation in post-hoc analyses of all (first and recurrent) events. Materials and methods Patients were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care. We assessed the effects of empagliflozin pooled vs placebo on first event of all-cause hospitalisation using Cox regression and all (first and recurrent) events of all-cause hospitalisation using a negative binomial model. Results A total of 7020 patients were treated (4687 empagliflozin; 2333 placebo, mean [SD] age 63 [9] years, 71% male, 47% with history of MI, 23% with history of stroke, 10% with HF). In this analysis, 1725/4687 (36.8%) empagliflozin patients and 925/2333 (39.6%) placebo patients experienced an event leading to hospitalisation. The adjusted hazard ratio (HR; 95% CI) vs placebo for first all-cause hospitalisation using the Cox regression model was 0.89 (0.82, 0.96; p=0.0033; Figure); In analyses of all (first and recurrent) hospitalisation events, there were 3168 events in the empagliflozin group and 1863 in the placebo group. The adjusted event rate ratio (95% CI) vs placebo was 0.83 (0.76, 0.91; p<0.0001; Figure). Conclusion In the EMPA-REG OUTCOME trial, risk reductions with empagliflozin were seen in both first and all hospitalisation events and were numerically more favourable in analyses of all events vs analyses of first events. These analyses expand on the favourable CV effects of empagliflozin by also showing a reduction in the total burden of hospitalisation events in patients with T2D and established CV disease. Acknowledgement/Funding Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance


2016 ◽  
Vol 69 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Meilin Zhang ◽  
Li Zheng ◽  
Ping Li ◽  
Yufeng Zhu ◽  
Hong Chang ◽  
...  

Background/Aims: Our aim was to evaluate whether visceral adiposity index (VAI) could predict the risk of type 2 diabetes (T2D) in different genders and to compare the predictive ability between VAI and other fatness indices. Methods: Four thousand seventy-eight participants including 1,817 men and 2,261 women, aged 18 and older and free of T2D at baseline were enrolled in 2010 and followed up for 4 years. New cases of T2D were identified via the annual medical examination. Cox regression analysis was used to assess the association between VAI and incidence of T2D. Receiver operating characteristic curve and area under the curves (AUC) were applied to compare the prediction ability of T2D between VAI and other fatness indices. Results: During the 4-year follow-up, 153 (8.42%) of 1,817 men and 88 (3.89%) of 2,261 women developed T2D. The multivariable-adjusted hazards ratios for developing T2D in the highest tertile of VAI scores were 2.854 (95% CI 1.815-4.487) in men and 3.551 (95% CI 1.586-7.955) in women. The AUC of VAI was not higher than that of other fatness indices. Conclusions: VAI could predict the risk of T2D among Chinese adults, especially in women. However, the prediction ability of T2D risk for VAI was not higher than that of the other fatness indices.


2010 ◽  
Vol 14 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Asnawi Abdullah ◽  
Johannes Stoelwinder ◽  
Susan Shortreed ◽  
Rory Wolfe ◽  
Christopher Stevenson ◽  
...  

AbstractObjectiveThe evidence for the association between obesity and the risk of type 2 diabetes has been derived mainly from the analysis of the degree of obesity. The role of the duration of obesity as an independent risk has not been fully explored. The objective of the present study was to investigate the association between the duration of obesity and the risk of type 2 diabetes.DesignProspective cohort study.SettingThe Framingham Heart Study (FHS), follow-up from 1948 to 1998.SubjectsA total of 1256 FHS participants who were free from type 2 diabetes at baseline, but were obese on at least two consecutive of the study’s twenty-four biennial examinations, were included. Type 2 diabetes status was collected throughout the 48 years of follow-up of the study. The relationship between duration of obesity and type 2 diabetes was analysed using time-dependent Cox models, adjusting for a number of covariates.ResultsThe unadjusted hazard ratio (HR) for the risk of type 2 diabetes for men was 1·13 (95 % CI 1·09, 1·17) and for women was 1·12 (95 % CI 1·08, 1·16) per additional 2-year increase in the duration of obesity. Adjustment for sociodemographic variables, family history of diabetes, health behaviour and physical activity made little difference to these HR. For women the evidence of a dose–response relationship was less clear than for men, particularly for women with an older age at obesity onset.ConclusionsThe duration of obesity is a relevant risk factor for type 2 diabetes, independent of the degree of BMI.


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