scholarly journals Statin therapy and risk of polyneuropathy in type 2 diabetes: A Danish cohort study

2020 ◽  
Author(s):  
Frederik P. Kristensen ◽  
Diana H. Christensen ◽  
Brian C. Callaghan ◽  
Johnny Kahlert ◽  
Søren T. Knudsen ◽  
...  

OBJECTIVE <p>Statins may reduce the risk of diabetic polyneuropathy (DPN) due to lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy impacts the risk of DPN.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We identified all Danish incident type 2 diabetes patients during 2002-2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. </p> <p>RESULTS </p> <p>The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) non-users; median follow-up time was 6.2 years (interquartile range 3.4-9.6). The incidence rate of DPN events per 1000 person-years was similar in new users (4.0 [95% CI 3.8-4.2]), prevalent users (3.8 [3.6-3.9]) and non-users (3.8 [3.7-4.0]). The aHR for DPN was 1.05 (0.98-1.11) in new users, and 0.97 (0.91-1.04) in prevalent users, compared with statin non-users. New users had a slightly increased DPN risk during the first year (aHR 1.31 [1.12-1.53]) which vanished after more than 2 years of follow-up. Findings were similar in on-treatment and propensity score-matched analyses, and with additional adjustment for pre-treatment blood lipid levels.</p> <p>CONCLUSION </p> <p>Statin therapy is unlikely to increase or mitigate DPN risk in type 2 diabetes patients, although a small acute risk of harm cannot be excluded.</p>

2020 ◽  
Author(s):  
Frederik P. Kristensen ◽  
Diana H. Christensen ◽  
Brian C. Callaghan ◽  
Johnny Kahlert ◽  
Søren T. Knudsen ◽  
...  

OBJECTIVE <p>Statins may reduce the risk of diabetic polyneuropathy (DPN) due to lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy impacts the risk of DPN.</p> <p>RESEARCH DESIGN AND METHODS</p> <p>We identified all Danish incident type 2 diabetes patients during 2002-2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. </p> <p>RESULTS </p> <p>The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) non-users; median follow-up time was 6.2 years (interquartile range 3.4-9.6). The incidence rate of DPN events per 1000 person-years was similar in new users (4.0 [95% CI 3.8-4.2]), prevalent users (3.8 [3.6-3.9]) and non-users (3.8 [3.7-4.0]). The aHR for DPN was 1.05 (0.98-1.11) in new users, and 0.97 (0.91-1.04) in prevalent users, compared with statin non-users. New users had a slightly increased DPN risk during the first year (aHR 1.31 [1.12-1.53]) which vanished after more than 2 years of follow-up. Findings were similar in on-treatment and propensity score-matched analyses, and with additional adjustment for pre-treatment blood lipid levels.</p> <p>CONCLUSION </p> <p>Statin therapy is unlikely to increase or mitigate DPN risk in type 2 diabetes patients, although a small acute risk of harm cannot be excluded.</p>


Author(s):  
Khalid Mohamed ◽  
Rami Alharbi ◽  
Yazeed Aljoahni ◽  
Abdulmajeed Alamri ◽  
Mohammed Saeed ◽  
...  

2020 ◽  
Author(s):  
Kai-Cheng Chang ◽  
Shih-Chieh Shao ◽  
Shihchen Kuo ◽  
Chen-Yi Yang ◽  
Hui-Yu Chen ◽  
...  

Abstract Background Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. Methods We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016-2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every three months in the one-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. Results A total of 1,512 subjects receiving dulaglutide and 1,513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: -1.06%, p<0.001; liraglutide: -0.83%, p<0.001), with a significant between-group difference (-0.23%, 95% confidence interval: -0.38 to -0.08%, p<0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: -1.14 kg, -3.08 U/L and -2.08 ml/min/1.73 m2, p<0.01; liraglutide: -1.64 kg, -3.65 U/L and -2.33 ml/min/1.73 m2, p<0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (-2.47 mmHg, p<0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. Conclusions In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.


2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Elhadad ◽  
Christian Jonasson ◽  
Cornelia Huth ◽  
Rory Wilson ◽  
...  

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1000 plasma proteins in the KORA (Cooperative health research in the Region of Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the HUNT3 (Third wave of the Nord-Trøndelag Health Study) cohort (n=940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bi-directional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which eight are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding protein-2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations, and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.


2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Elhadad ◽  
Christian Jonasson ◽  
Cornelia Huth ◽  
Rory Wilson ◽  
...  

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1000 plasma proteins in the KORA (Cooperative health research in the Region of Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the HUNT3 (Third wave of the Nord-Trøndelag Health Study) cohort (n=940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bi-directional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which eight are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding protein-2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations, and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.


2021 ◽  
Author(s):  
Mei Jiao Li ◽  
Jing Ren ◽  
Wei Sen Zhang ◽  
Chao Qiang Jiang ◽  
Ya Li Jin ◽  
...  

Abstract Background To examine associations of baseline alcohol drinking with incident type 2 diabetes or impaired fasting glucose, and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B).Methods Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident type 2 diabetes was defined as fasting glucose ≥7.0 mmol/l or post-load glucose ≥11.1 mmol/l at follow-up examination (2008-2012), self-reported type 2 diabetes and/or initiation of hypoglycemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/l and <7 mmol/l. Results Of 15,716 participants without diabetes and 11,232 participants without diabetes and impaired fasting glucose at baseline, 1,624 (10.33%) developed incident type 2 diabetes, and 1,004 (8.94%) developed incident impaired fasting glucose during average 4 years of follow-up. After adjusting for sex, age, education, occupation, personal annual income, smoking, physical activity, body mass index, waist/hip ratio, health status, family history of diabetes, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident type 2 diabetes+impaired fasting glucose (odds ratio (OR) 1.08, 95% confidence interval (CI) 0.94-1.25, and 0.89 (0.68-1.16), respectively), but heavy alcohol drinking was associated with a higher risk of incident type 2 diabetes+impaired fasting glucose (1.83, 1.25-2.69). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B or ALDH2 genes with alcohol drinking on incident type 2 diabetes and/or impaired fasting glucose were found (p for interaction from 0.12 to 0.81). Conclusions Our results support a detrimental effect of heavy alcohol use on impaired fasting glucose and type 2 diabetes. No protective effect was found for those carrying lower risk alleles for ADH1B and ALDH2 genes.


2021 ◽  
Author(s):  
Chaterina Sujana ◽  
Veikko Salomaa ◽  
Frank Kee ◽  
Simona Costanzo ◽  
Stefan Söderberg ◽  
...  

<p><b>Objective: </b>Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVD) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and mid-regional pro-atrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD. </p> <p><b> </b></p> <p><b>Research Design and Methods:</b> Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-(BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models. </p> <p> </p> <p><b>Results: </b>Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95%CI] per 1-standard deviation increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without, but not in individuals with CVD (0.81 [0.76; 0.86] vs 1.04 [0.90; 1.19]; <i>P</i>-multiplicative interaction= 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs 0.81 [0.66; 0.99]; <i>P</i>-multiplicative interaction= 0.236). </p> <p> </p> <p><b>Conclusions:</b> NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.</p>


2018 ◽  
Vol 20 (6) ◽  
pp. 1479-1489 ◽  
Author(s):  
Kausik K. Ray ◽  
Lawrence A. Leiter ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duck-chul Lee ◽  
Carl J. Lavie ◽  
Timothy S. Church ◽  
Xuemei Sui ◽  
Steven N. Blair

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.


2020 ◽  
Vol 8 (1) ◽  
pp. e001187
Author(s):  
You-Bin Lee ◽  
Da Hye Kim ◽  
Eun Roh ◽  
So-Hyeon Hong ◽  
Jung A Kim ◽  
...  

ObjectiveVariability in estimated glomerular filtration rate (eGFR) has been associated with adverse outcomes in patients with diabetes or chronic kidney disease (CKD). However, no previous study has explored the relationship between eGFR variability and type 2 diabetes incidence.Research design and methodsIn this nationwide, longitudinal, cohort study, we investigated the association between eGFR variability and type 2 diabetes risk using the Korean National Health Insurance Service datasets from 2002 to 2017. eGFR variability was calculated using the variability independent of the mean (eGFR-VIM), coefficient of variation (eGFR-CV), standard deviation (eGFR-SD) and average real variability (eGFR-ARV).ResultsWithin 7 673 905.58 person-years of follow-up (mean follow-up: 3.19 years; n=2 402 668), 11 981 cases of incident type 2 diabetes were reported. The HRs and 95% CIs for incident type 2 diabetes increased according to advance in quartiles of eGFR-VIM (HR (95% CI): Q2, 1.068 (1.009 to 1.130); Q3, 1.077 (1.018 to 1.138); Q4, 1.203 (1.139 to 1.270)) even after adjusting for confounding factors including mean eGFR and mean fasting plasma glucose levels. The subgroup analyses according to risk factors as well as analyses using eGFR-CV, eGFR-SD and eGFR-ARV showed consistent results. The association between increased eGFR variability and type 2 diabetes risk was more prominent in men, individuals with dyslipidemia and those with CKD as shown in the subgroup analysis (p for interaction <0.001).ConclusionsIncreased eGFR variability may be an independent predictor of type 2 diabetes and might be useful for risk stratification of individuals without diabetes.


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