Shih-Yuan Hung

Antiplatelet therapy is recommended for secondary prevention in patients with diabetes and peripheral arterial disease (PAD), particularly after a diabetic foot event. Nevertheless, the relative effectiveness of aspirin, clopidogrel, and cilostazol for long-term outcomes remains uncertain. Using the Taiwan Health and Welfare Data Center database, we identified 2,597 adults with type 2 diabetes who experienced their first diabetic foot disease (DFD) event with concurrent PAD between 2016 and 2019 and subsequently received a single antiplatelet agent for secondary prevention after stabilization. Outcomes included major lower extremity amputation (LEA), major adverse limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards and Fine-Gray competing risk models were used to estimate hazard ratios (HRs) and subdistribution HRs (sHRs) with 95% confidence intervals (CIs). Baseline characteristics indicated higher comorbidity burdens in the clopidogrel and cilostazol groups. After adjustment, the risks of LEA and MACE did not differ significantly among treatment groups. Compared with aspirin, cilostazol was associated with a higher risk of MALE (sHR 1.45 [95% CI 1.15-1.84]), whereas clopidogrel showed a nonsignificant trend (sHR 1.31 [95% CI 0.99-1.72]). Both cilostazol (HR 1.21 [95% CI 1.06-1.39]) and clopidogrel (HR 1.25 [95% CI 1.07-1.46]) were associated with higher all-cause mortality. Exploratory subgroup analyses showed no significant mortality differences among dialysis patients, and sensitivity analyses yielded consistent results. Among diabetic patients with PAD and a history of a foot event, aspirin was associated with comparable limb and cardiovascular outcomes, and potentially favorable survival, compared with clopidogrel or cilostazol. These observational findings suggest aspirin is a practical antiplatelet option for secondary prevention in this high-risk population, though further precise trials are needed to verify.

Purpose: Glucose metabolism is associated with several endocrine disorders. Anti-diabetes drugs are crucial in controlling diabetes and its complications; nevertheless, few studies have been carried out involving endocrine function. This study aimed to investigate the association between anti-diabetes drugs and endocrine parameters. Patients and Methods: We performed a study of 180 consecutive patients with type 2 diabetes who attended a medical center. Laboratory measurements of metabolic values and endocrine parameters were assessed after a stable treatment regimen of more than 12 weeks. The differences in various endocrine parameters were compared between subjects with or without certain anti-diabetes drugs, with the administrated anti-diabetes drugs being analyzed to find independent risks associated with elevated endocrine parameters. Results: After maintaining stable treatment, acceptable glycemic control was noted with an average HbA1c of 7.55% in females and 7.43% in males. Participants taking sulfonylurea (55.8 vs 26.34 ng/L, P=0.043), dipeptidyl peptidase-4 inhibitor (DPP4i) (47.14 vs 32.26 ng/L, P=0.096), or sodium-glucose co-transporter 2 inhibitor (SGLT2i) (64.58 vs 28.11 ng/L, P=0.117) had higher plasma renin concentrations compared to those without this drug but the aldosterone levels did not differ, as well as for other adrenal tests and thyroid function. Under linear regression modeling, SGLT2i was found to be independently associated with a risk of high renin level (beta coefficient: 30.186, 95% confidence interval: 1.71─58.662, P=0.038), whereas sulfonylurea only had borderline associations (B: 21.143, 95% CI: − 2.729─45.014, P=0.082). Additionally, renin-angiotensin-aldosterone system (RAAS) blockade (B: 36.728, 95% CI: 12.16─61.295, P=0.004) or diuretics (B: 47.847, 95% CI: 2.039─93.655, P=0.041) was also independently associated with increased renin levels. Conclusion: SGLT2i was the only class of anti-diabetes drugs independently associated with elevated renin levels, with results similar to RAAS blockade and diuretics. Although SGLT2i appears to protect reno- and cardio-function, the clinical impact of increased renin warrants further precise study for verification.

Objective: The use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) may be associated with ketoacidosis. Therefore, the associated risk factors should be identified. In particular, information regarding the effects of the co-administration of anti-diabetic drugs is lacking. Methods: We performed a retrospective study of 68 consecutive patients with diabetes who were taking an SGLT2i and attending a single medical center. After a period of treatment (median 78 days), their circulating ketone concentrations were measured. The concomitant use of other anti-diabetic drugs was analyzed to identify independent risk factors associated with ketosis. Results: Twenty-five participants were taking empagliflozin, 23 were taking dapagliflozin, and 20 were taking canagliflozin. During the treatment period, no ketoacidotic events were recorded and their mean circulating ketone concentrations at the end of the study period were similar (0.3 mmol/L in the empagliflozin group, 0.26 mmol/L in the dapagliflozin group, and 0.25 mmol/L in the canagliflozin group). After adjustment for the use of anti-diabetic drugs, pioglitazone was found to be independently associated with a risk of high circulating ketone concentration (B value: 0.361, 95% confidence interval: 0.181–0.541). Conclusion: SGLT2i-associated ketoacidosis was found to be infrequent, but the concomitant use of pioglitazone was associated with a higher risk of ketosis.

Aims/Introduction: To investigate the association between specific bacterial pathogens and treatment outcome in patients with limb‐threatening diabetic foot infection (LT‐DFI).Materials and Methods: Consecutive patients treated for LT‐DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 and 2017. Patients with positive wound culture results at first aid were enrolled. Clinical factors, laboratory data, and wound culture results were compared. Lower‐extremity amputations and in‐hospital mortality were defined as a poor outcome.Results: Among the 558 patients, 272 (48.7%) patients had lower extremity amputation and 22 (3.9%) patients had in‐hospital mortality. Gram‐negative bacterial (GNB) infection was the independent factor following factors adjustment. When all the 31 microorganisms were analyzed, onlyE. coli(adjusted odds ratio [aOR], 3.01; 95% CI, 1.60–5.65),Proteusspp. (aOR, 2.99; 95% CI, 1.69–5.29), andPseudomonas aeruginosa(aOR, 2.00; 95% CI 1.20–3.32) were associated with poor outcome. The analysis of specific GNB species in association with major‐ or minor‐ amputation have been reported. No specific pathogen was associated with cause of death in patients with mortality within 30 days. The antimicrobial‐resistant strains were not associated with a poor treatment outcome.Conclusions: The presence of GNB was associated with limb amputations. This study provides insight into more timely and appropriate management of the diabetic foot infection.

Objective: Balanced nutrition is important for patients with diabetes, and nutrition might well influence diabetes-related complications, although there is limited evidence for this supposition at present. Consequently, we investigate the association between dietary behaviors and renal function decline among patients with diabetes.Research design and methods: From 2011 to 2013, a total of 2797 patients with type 2 diabetes participated in the Diabetes Shared Care Program at Chang Gung Memorial Hospital. All received nutritional consulting by dieticians and an eight-item list of unhealthy dietary behaviors, which included the excessive intake of carbohydrates, fats, protein, fruit, pickled foods, dessert and alcohol, as well as inadequate dietary vegetable. Estimated glomerular filtration rate (eGFR) decline ≥40% was defined as a surrogate end point for kidney damage. Independent dietary risk factors predicting poor renal outcomes were assessed.Results: Stable mean glycated hemoglobin (A_1c) (7.78% to 7.75%, p=0.151), improved cholesterol (174.04 to 170.13 mg/dL, p2, p<0.001). A total of 125 subjects had eGFR decline ≥40% and 2672 had stable renal progression.In regression analysis, 625 stable renal patients (selected via propensity score matching) and 125 subjects with eGFR decline ≥40% demonstrated excessive pickled foods to be predictive of poor renal outcomes (OR 1.861, 95% CI 1.230 to 2.814, p=0.003).Conclusions: Our study suggests that excessive pickled foods deteriorate renal function more than other unhealthy dietary behaviors in patients with diabetes.

Objective To study the prevalence and trends of lower extremity complications of diabetes over an 8-year period in a single nation. Research design and methods Nationwide data for people with type 2 diabetes (T2D) and diabetic foot complications (DFCs) were analyzed over an 8-year period (2007–2014) from National Health Insurance Research Database using the International Classification of Diseases, Ninth Revision disease coding. The DFCs were defined as ulcers, infections, gangrene, and hospitalization for peripheral arterial disease (PAD). Trends of patient characteristics, foot presentation, and the execution of major procedures were studied, including lower-extremity amputations (LEAs). Results Along with the T2D population increasing over time, the absolute number of people with DFCs increased by 33.4%, but retained a prevalence of around 2% per year. The annual incident of LEAs decreased from 2.85 to 2.06 per 1000 T2D population (p=0.001) with the major LEA proportion decreasing from 56.2% to 47.4% (pConclusions DFCs remain a sustained major medical problem. These nationwide long-term data suggest trends toward older people with greater comorbidities such as PAD and renal disease. Nevertheless, promising trends of reducing gangrene on presentation paired with increases in vascular interventions support continued vigilance and rapid, coordinated interdisciplinary diabetic foot care.

Diabetic foot infection (DFI) is a major complication of diabetic foot that lead to nontraumatic lower-extremity amputation (LEA). Such distal infection of the body having systemic inflammatory response syndrome (SIRS) is rarely reported. Consecutive patients treated for limb-threatening DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 to 2017. Clinical factors, laboratory data, perfusion, extent, depth, infection and sensation (PEDIS) wound score in 519 subjects with grade 3 DFI and 203 presenting SIRS (28.1%) were compared. Major LEA and in-hospital mortality were defined as poor prognosis. Patients presenting SIRS had poor prognosis compared with those with grade 3 DFI (14.3% versus 6.6% for major LEA and 6.4% versus 3.5% for in-hospital mortality). Age, wound size, and HbA1c were independent risk factors favoring SIRS presentation. Perfusion grade 3 (odds ratio 3.37, p = 0.044) and history of major adverse cardiac events (OR 2.41, p = 0.036) were the independent factors for poor prognosis in treating patients with DFI presenting SIRS. SIRS when presented in patients with DFI is not only limb- but life-threatening as well. Clinicians should be aware of the clinical factors that are prone to develop and those affecting the prognosis in treating patients with limb-threatening foot infections.

Background: Infectious gangrene of the foot is a serious complication of diabetes that usually leads to a certain level of lower‐extremity amputation (LEA). Nevertheless, the long‐term survival and factors associated with mortality in such patients have yet to be elucidated.Methods: A total of 157 patients with type 2 diabetes who received treatment for infectious foot gangrene at a major diabetic foot center in Taiwan from 2002 to 2009 were enrolled, of whom 90 had major LEAs (above the ankle) and 67 had minor LEAs (below the ankle). Clinical data during treatment were used for the analysis of survival and LEA, and survival was tracked after treatment until December 2012.Results: Of the 157 patients, 109 died, with a median survival time of 3.12 years and 5‐year survival rate of 40%. Age [hazard ratio 1.04 (95% confidence interval 1.01–1.06)], and major LEA [1.80 (1.05–3.09)] were independent factors associated with mortality. Patients with minor LEAs had a better median survival than those with major LEAs (5.5 and 1.9 years, respectively, P < 0.01). An abnormal ankle‐brachial index was an independent risk factor [odds ratio 3.12 (95% CI 1.18–8.24)] for a poor outcome (major LEA) after adjusting for age, smoking status, hypertension, major adverse cardiac events, and renal function.Conclusions: Efforts to limit amputations below the ankle resulted in better survival of patients with infectious foot gangrene. An abnormal ankle‐brachial index may guide physicians to make appropriate decisions with regards to the amputation level.