scholarly journals Visit-to-visit variability of glycated albumin was associated with incidence or progression of lower extremity atherosclerotic disease

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yun Shen ◽  
Dongjun Dai ◽  
Jingyi Lu ◽  
Yufei Wang ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lower Extremity ◽  
Glycated Albumin ◽  
Atherosclerotic Disease ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Unit Increase ◽  
Cox Proportional Hazard Regression

Abstract Background The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of lower extremity atherosclerotic disease (LEAD). Method We performed a prospective cohort study of 436 patients with type 2 diabetes (258 men and 178 women) with at least 3 measurements of HbA1c and GA prior to baseline investigation from the Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital. Different HbA1c and GA variability markers were calculated. Multivariable Cox proportional hazard regression models were used to demonstrate the association between visit-to-visit HbA1c and GA variability and the risk of incident or progressive LEAD. Results During a mean follow-up period of 3.77 years, 112 participants developed LEAD. Multivariate-adjusted hazard ratios (HRs) of LEAD across tertiles of GA-CV values were 1.00, 1.06 (95% confidence interval [CI] 0.65–1.75), and 1.71 (95% CI 1.07–2.73) (P for trend = 0.042), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of LEAD primary were found. Multivariate-adjusted HRs of LEAD for each 1 unit increase in GA-CV, GA-VIM and GA-ARV were 1.03 (95% CI 1.01–1.06), 1.32 (95% CI 1.03–1.69), and 1.07 (95%CI 1.01–1.15), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of LEAD. Conclusions Visit-to-visit variability of GA may be an optimal biomarker in relation to LEAD risk among patients with type 2 diabetes.

scholarly journals Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

2021 ◽  
Author(s):  
Shanjie Wang ◽  
Ye Wang ◽  
Xin Wan ◽  
Junchen Guo ◽  
Yiying Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mortality Risk ◽  
Cobalamin Deficiency ◽  
Diabetic Patients ◽  
Cardiac Mortality ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
Cox Proportional Hazard Regression

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12<sub>low/high</sub> and MMA<sub>low/high</sub> (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA<sub>high</sub>B12<sub>high</sub>) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA<sub>low</sub>B12<sub>low</sub>, MMA<sub>low</sub>B12<sub>high</sub>, MMA<sub>high</sub>B12<sub>low</sub>, and MMA<sub>high</sub>B12<sub>high</sub> groups were<sub> </sub>1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

scholarly journals Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

2021 ◽  
Author(s):  
Shanjie Wang ◽  
Ye Wang ◽  
Xin Wan ◽  
Junchen Guo ◽  
Yiying Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mortality Risk ◽  
Cobalamin Deficiency ◽  
Diabetic Patients ◽  
Cardiac Mortality ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
Cox Proportional Hazard Regression

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12<sub>low/high</sub> and MMA<sub>low/high</sub> (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA<sub>high</sub>B12<sub>high</sub>) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA<sub>low</sub>B12<sub>low</sub>, MMA<sub>low</sub>B12<sub>high</sub>, MMA<sub>high</sub>B12<sub>low</sub>, and MMA<sub>high</sub>B12<sub>high</sub> groups were<sub> </sub>1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

Increased Serum WISP1 Levels are Associated with Lower Extremity Atherosclerotic Disease in Patients with type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Yangyang Cheng ◽  
Xiaohui Du ◽  
Bilin Zhang ◽  
Junxia Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lower Extremity ◽  
Interleukin 6 ◽  
Atherosclerotic Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Newly Diagnosed

Abstract Background Serum wnt1-induced signaling pathway protein 1 (WISP1) levels are increased with obesity, which is a common complication associated with lower extremity atherosclerotic disease (LEAD). However, to date, the relationship between elevated WISP1 levels and the incidence of lower extremity atherosclerotic disease (LEAD) in type 2 diabetes mellitus (T2DM) remains unclear. Methods 174 newly diagnosed type 2 diabetic patients were enrolled in our study. Patients were divided into two groups, LEAD group (n=100) and control group (n=74). Anthropometric parameters, blood pressure and some biochemical parameters were obtained. Body composition was detected by bioelectrical impedance analysis (BIA). Levels of serum insulin were determined by radioimmunoassay. Serum WISP1 and interleukin 6 (IL-6) levels were determined using an enzyme-linked immunosorbent assay. Results It was shown that serum WISP1 levels in diabetic patients with LEAD were higher than those without LEAD (P<0.001). Serum WISP1 levels were positively related with waist circumference (r=0.237, P=0.003), waist-hip ratio (r=0.22, P=0.006), visceral fat area (r=0.354, P<0.001), serum creatinine (r=0.192, P=0.012), interleukin 6 (r=0.182, P=0.032), c-reactive protein (r=0.681, P<0.001), triglycerides (r=0.119, P<0.001), fasting glucose (r=0.196, P=0.011), glycated hemoglobin (r=0.284, P<0.001), and HOMA-IR (r=0.285, P<0.026). Compared with the lowest tertile, the odds ratio of the middle tertile for LEAD incidence was 3.27 (95% CI, 1.24–8.64) and 4.46 (95% CI, 1.62–12.29) for the highest tertile after adjusting confounding factors. Conclusion The results suggest that increased serum WISP1 levels independently contribute to the incidence of LEAD in patients with newly diagnosed T2DM.

scholarly journals Association of Mean and Variability of HbA1c with Heart Failure in Patients with Type 2 Diabetes

2021 ◽  
Vol 10 (7) ◽  
pp. 1401
Author(s):  
You-Ting Lin ◽  
Wei-Lun Huang ◽  
Hung-Pin Wu ◽  
Man-Ping Chang ◽  
Ching-Chu Chen
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Hba1c Level ◽  
Care Program ◽  
Good Glycemic Control ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Hba1c Variability

Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that the HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of mean and variability of HbA1c with HF in patients with T2DM. Using Diabetes Share Care Program data, patients with T2DM who had mean HbA1c (HbA1c-Mean), and HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12–24 months during 2001–2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7–7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008–2018 were estimated using Cox proportional hazard models. A total of 3824 patients were included, of whom 315 patients developed HF during the observation period of 11.72 years. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean <7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. In conclusion, mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with good glycemic control was also important for the development of HF in patients with T2DM.

scholarly journals Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
You-Bin Lee ◽  
Kyungdo Han ◽  
Bongsung Kim ◽  
Seung-Eun Lee ◽  
Ji Eun Jun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Cox Regression ◽  
Early Mortality ◽  
Hazard Ratios ◽  
Epidemiological Characteristics

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.

scholarly journals Intake of whole grain foods and risk of type 2 diabetes: results from three prospective cohort studies

BMJ ◽  
2020 ◽  
pp. m2206 ◽  
Author(s):  
Yang Hu ◽  
Ming Ding ◽  
Laura Sampson ◽  
Walter C Willett ◽  
JoAnn E Manson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Brown Rice ◽  
Whole Grains ◽  
Health Study ◽  
Whole Grain ◽  
Breakfast Cereal ◽  
Hazard Ratios ◽  
Grain Foods

Abstract Objective To examine the associations between the intake of total and individual whole grain foods and the risk of type 2 diabetes. Design Prospective cohort studies. Setting Nurses’ Health Study (1984-2014), Nurses’ Health Study II (1991-2017), and Health Professionals Follow-Up Study (1986-2016), United States. Participants 158 259 women and 36 525 men who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline. Main outcome measures Self-reports of incident type 2 diabetes by participants identified through follow-up questionnaires and confirmed by a validated supplementary questionnaire. Results During 4 618 796 person years of follow-up, 18 629 participants with type 2 diabetes were identified. Total whole grain consumption was categorized into five equal groups of servings a day for the three cohorts. After adjusting for lifestyle and dietary risk factors for diabetes, participants in the highest category for total whole grain consumption had a 29% (95% confidence interval 26% to 33%) lower rate of type 2 diabetes compared with those in the lowest category. For individual whole grain foods, pooled hazard ratios (95% confidence intervals) for type 2 diabetes in participants consuming one or more servings a day compared with those consuming less than one serving a month were 0.81 (0.77 to 0.86) for whole grain cold breakfast cereal, 0.79 (0.75 to 0.83) for dark bread, and 1.08 (1.00 to 1.17) for popcorn. For other individual whole grains with lower average intake levels, comparing consumption of two or more servings a week with less than one serving a month, the pooled hazard ratios (95% confidence intervals) were 0.79 (0.75 to 0.83) for oatmeal, 0.88 (0.82 to 0.94) for brown rice, 0.85 (0.80 to 0.90) for added bran, and 0.88 (0.78 to 0.98) for wheat germ. Spline regression showed a non-linear dose-response association between total whole grain intake and the risk of type 2 diabetes where the rate reduction slightly plateaued at more than two servings a day (P<0.001 for curvature). For whole grain cold breakfast cereal and dark bread, the rate reduction plateaued at about 0.5 servings a day. For consumption of popcorn, a J shaped association was found where the rate of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day. The association between higher total whole grain intake and lower risk of type 2 diabetes was stronger in individuals who were lean than in those who were overweight or obese (P=0.003 for interaction), and the associations did not vary significantly across levels of physical activity, family history of diabetes, or smoking status. Conclusion Higher consumption of total whole grains and several commonly eaten whole grain foods, including whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, and wheat germ, was significantly associated with a lower risk of type 2 diabetes. These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes.

scholarly journals May the Mediterranean diet attenuate the risk of type 2 diabetes associated with obesity: the Seguimiento Universidad de Navarra (SUN) cohort

2017 ◽  
Vol 117 (10) ◽  
pp. 1478-1485 ◽  
Author(s):  
Sonia Eguaras ◽  
Maira Bes-Rastrollo ◽  
Miguel Ruiz-Canela ◽  
Silvia Carlos ◽  
Pedro de la Rosa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adverse Effects ◽  
Mediterranean Diet ◽  
Weight Changes ◽  
Product Term ◽  
Hazard Ratios ◽  
The Mediterranean ◽  
Incident Cases

AbstractIt is likely that the Mediterranean diet (MedDiet) may mitigate the adverse effects of obesity on the incidence of type 2 diabetes mellitus (T2DM). We assessed this hypothesis in a cohort of 18 225 participants initially free of diabetes (mean age: 38 years, 61 % women). A validated semi-quantitative 136-item FFQ was used to assess dietary intake and to build a 0–9 score of adherence to MedDiet. After a median of 9·5-year follow-up, 136 incident cases of T2DM were confirmed during 173 591 person-years follow-up. When MedDiet adherence was low (≤4 points), the multivariable-adjusted hazard ratios (HR) were 4·07 (95 % CI 1·58, 10·50) for participants with BMI 25–29·99 kg/m2 and 17·70 (95 % CI 6·29, 49·78) kg/m2 for participants with BMI≥30 kg/m2, (v.<25 kg/m2). In the group with better adherence to the MedDiet (>4 points), these multivariable-adjusted HR were 3·13 (95 % CI 1·63, 6·01) and 10·70 (95 % CI 4·98, 22·99) for BMI 25–30 and ≥30 kg/m2, respectively. The P value for the interaction was statistically significant (P=0·002). When we assessed both variables (BMI and MedDiet) as continuous, the P value for their interaction product-term was marginally significant (P=0·051) in fully adjusted models. This effect modification was not explained by weight changes during follow-up. Our results suggest that the MedDiet may attenuate the adverse effects of obesity on the risk of T2DM.

scholarly journals Sudomotor dysfunction independently predicts incident cardiovascular–renal events and all-cause death in type 2 diabetes: the Joint Asia Diabetes Evaluation register

2018 ◽  
Vol 34 (8) ◽  
pp. 1320-1328 ◽  
Author(s):  
Lee Ling Lim ◽  
Amy W C Fu ◽  
Eric S H Lau ◽  
Risa Ozaki ◽  
Kitty K T Cheung ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Screening Strategy ◽  
Composite Score ◽  
Risk Markers ◽  
Chinese Adults ◽  
Non Invasive ◽  
Hazard Ratios ◽  
Never Smokers

AbstractBackgroundEarly detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular–renal events in type 2 diabetes (T2D).MethodsSUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012–13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular–renal events until 2015.ResultsIn this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0–13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01–1.04], 1.04 (1.00–1.07) and 1.04 (1.00–1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09–2.23) for CKD and 3.11 (95% CI 1.27–7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.ConclusionsA low ESC composite score independently predicts incident cardiovascular–renal events and death in T2D, which may improve the screening strategy for early intervention.

scholarly journals Low-, medium- and high-glycaemic index carbohydrates and risk of type 2 diabetes in men

2010 ◽  
Vol 105 (8) ◽  
pp. 1258-1264 ◽  
Author(s):  
Minna E. Similä ◽  
Liisa M. Valsta ◽  
Jukka P. Kontto ◽  
Demetrius Albanes ◽  
Jarmo Virtamo
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Index ◽  
Diabetes Risk ◽  
Glycaemic Load ◽  
Nutrient Density ◽  
Cox Proportional Hazard ◽  
Diet History Questionnaire ◽  
Diet History

Findings on dietary glycaemic index (GI) and glycaemic load (GL) as risk factors for type 2 diabetes have been controversial. We examined the associations of dietary GI and GL and the associations of substitution of lower-GI carbohydrates for higher-GI carbohydrates with diabetes risk in a cohort of Finnish men. The cohort consisted of 25 943 male smokers aged 50–69 years. Diet was assessed, at baseline, using a validated diet history questionnaire. During a 12-year follow-up, 1098 incident diabetes cases were identified from a national register. Cox proportional hazard modelling was used to estimate the risk of diabetes, and multivariate nutrient density models were used to examine the effects of substitution of different carbohydrates. Dietary GI and GL were not associated with diabetes risk; multivariate relative risk (RR) for highest v. lowest quintile for GI was 0·87 (95 % CI 0·71, 1·07) and for GL 0·88 (95 % CI 0·65, 1·17). Substitution of medium-GI carbohydrates for high-GI carbohydrates was inversely associated with diabetes risk (multivariate RR for highest v. lowest quintile 0·75, 95 % CI 0·59, 0·96), but substitution of low-GI carbohydrates for medium- or high-GI carbohydrates was not associated with the risk. In conclusion, dietary GI and GL were not associated with diabetes risk, and substitutions of lower-GI carbohydrates for higher-GI carbohydrates were not consistently associated with a lower diabetes risk. The associations of dietary GI and GL with diabetes risk should be interpreted by considering nutritional correlates, as foods may have different properties that affect risk.

scholarly journals Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors

2021 ◽  
Author(s):  
Spela Zerovnik ◽  
Mitja Kos ◽  
Igor Locatelli
Keyword(s):  
Type 2 Diabetes ◽  
Lower Extremity ◽  
Study Cohort ◽  
Dipeptidyl Peptidase 4 ◽  
Intention To Treat ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
History Of

Abstract Aims To compare the influence of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of lower extremity amputations in patients with type 2 diabetes in Slovenia. Methods This retrospective cohort study included patients aged 40 years or more who were administered a newly introduced SGLT2i or DPP-4i between June 2014 and June 2018. Patients treated with insulin at baseline and patients with a history of amputation were excluded. Patients were matched in a 1:1 ratio using propensity score matching. Survival analysis was performed; hazard ratio (HR) and ratios of cumulative hazards at 1, 2, 3, and 4 years were estimated. On-treatment and intention-to-treat approaches were used. Results The study cohort (mean age: 64 years) consisted of 2,939 new users of SGLT2i (empagliflozin, 59%; dapagliflozin, 41%) matched to 2,939 new users of DPP-4i. In the on-treatment analysis (median follow-up of 2 years), the incidence of amputations was higher in SGLT2i than in DPP-4i users (4.2 vs. 2.7 per 1,000 patient years), resulting in a HR of 1.58 (95% CI 0.85–2.92; p = 0.145). An intention-to-treat analysis yielded to similar HR of 1.86 (95% CI: 1.10–3.14; p = 0.020). There was no difference in amputation rates in the first two years, but SGLT2i users had a 2.81-fold higher (95% CI: 1.63–4.84; p = 0.007) cumulative hazard of amputation at 4 years than did DPP-4i users. Conclusions Compared with DPP-4i use, SGLT2i use did not result in a statistically significant higher overall risk of lower extremity amputations. However, the results suggest that SGLT2i may increase the risk of amputation with long-term use.

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