AP：2020 Award

AP-1 RISK OF HEART FAILURE IN A POPULATION WITH TYPE 2 DIABETES VERSUS A POPULATION WITHOUT DIABETES WITH AND WITHOUT CORONARY HEART DISEASE

1,2H-F CHEN, 3C-A HO, 4,5C-Y LI,

1Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2School of Medicine, Fujen Catholic University, New Taipei City, Taiwan; 3Department of Surgery, Catholic Mercy Hospital, Hsinchu County, Taiwan; 4Department of Public Health, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Department of Public Health, College of Public Health, China Medical University, Taichung City, Taiwan

Purpose: To conduct a population-based study comparing age- and sex-specific risk estimates of heart failure (HF) between people with type 2 diabetes and people without diabetes, and to investigate the risks of HF in association with type 2 diabetes in people with various coronary heart diseases (CHDs).

Method: We used a nationally representative sample (one million people) selected from Taiwan’s National Health Insurance (NHI) system. A total of 34 291 patients with type 2 diabetes were identified from ambulatory care claims in 2000, and the same number of age- and sex-matched controls were randomly selected from the registry of NHI beneficiaries in the same year. All study subjects were linked to inpatient claims (2000-2013) to identify the possible admissions for HF. Using a Cox proportional hazard regression model, we compared the relative hazards of HF in relation to type 2 diabetes according to various age and sex stratifications. We also compared the relative hazard of HF between type 2 diabetes and controls, with and without histories of various CHDs and coronary revascularization procedures.

Result: Compared with absence of diabetes (control group), type 2 diabetes was significantly associated with an increased hazard of HF (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.40-1.54]. In both sexes, those with type 2 diabetes aged < 45 years had the highest increased hazard of HF, with an aHR of 2.54 (95% CI 1.62-3.98) and 4.12 (95% CI 2.35-7.23) for men and women, respectively. Compared with the control subjects without any CHD, people with type 2 diabetes without prior CHD had increased hazards of HF (aHR 1.54, 95% CI 1.41-1.68, in men and aHR 1.56, 95% CI 1.43-1.71, in women), which were similar to the aHRs for people without diabetes who had histories of heart diseases (aHR 1.60 and 1.55 for men and women, respectively).

Conclusion: Diabetes mellitus may increase the risk of HF in both men and women, as well as in all age groups, especially in young people. People with type 2 diabetes without CHD had a similarly increased risk of HF to that of control subjects with CHD. Certain coronary revascularization procedures and CHDs, including percutaneous transluminal coronary angiography, coronary artery bypass surgery and acute myocardial infarction, were found to greatly increase risk of HF in people with type 2 diabetes.

Conclusions: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.

AP-2 RACIAL DIFFERENCE IN BIOAVAILABILITY OF ORAL IBANDRONATE BETWEEN CAUCASIAN AND TAIWANESE POSTMENOPAUSAL WOMEN

1,2,3W-Y CHIU, 4C-J LIN, 1,2W-S YANG, 1,3K-S TSAI, 5J-Y REGINSTER

1Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan; 2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4School of Pharmacy, National Taiwan University, Taipei, Taiwan; 5Department of Public Health, Epidemiology and Health Economics, Liège State University, Liège, Belgium

Purpose: Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women.

Method: Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F).

Result: The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables. The suppressive effects of ibandronate on the bone turnover markers (sCTX and urinary CTX, NTX corrected by the urinary creatinine concentrations) were all higher in the Taiwanese group compared with the Caucasian cohort.

Conclusion: Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate, and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity.

AP-3 DIABETIC FOOT INFECTION PRESENTING SYSTEMIC INFLAMMATORY RESPONSE SYNDROME: A UNIQUE DISORDER OF SYSTEMIC REACTION FROM INFECTION OF THE MOST DISTAL BODY

1C-W LIN, 1S-Y HUNG, 1C-H HUANG, 2J-T YEH, 1,3Y-Y HUANG

1 Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital at Linkou, Taiwan; 2 Department of Plastic surgery, Chang Gung Memorial Hospital at Linkou, Taiwan; 3 Department of Medical Nutrition Therapy, Chang Gung Memorial Hospital, Taiwan

Purpose: 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. This study aimed to further understand the factors that are prone to development of SIRS in patients with DFI and factors affecting its prognosis.

Method: 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, 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.

Result: Patients presenting SIRS had poor prognosis compared with those with grade 3 DFI (14.3% vs. 6.6% for major LEA and 6.4% vs. 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.

Conclusion: 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.

AP-4 EARLY CARDIOVASCULAR RISK AND ALL-CAUSE MORTALITY FOLLOWING AN INCIDENT OF SEVERE HYPOGLYCEMIA: A POPULATION-BASED COHORT STUDY

1,2SC LO,

1,2YS YANG, 1,2EDY KORNELIUS, 2,3JY HUANG, 4YR LAI, 1,2CN HUANG, 5JY CHIOU.

1Department of Internal Medicine, Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital, Taichung, Taiwan; 2Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Pharmacy Division, Chung Shan Medical University Hospital, Taichung, Taiwan; 5Department of Health Policy and Management, Chung Shan Medical University, Taichung, Taiwan

Purpose: Severe hypoglycemia is associated with a high risk of cardiovascular events in patient with diabetes. The aim of this study was to clarify the temporal relationship between hypoglycemia and cardiovascular events

Method: This observational cohort study was conducted using Taiwan’s Longitudinal Cohort of Diabetes Patients Database, which included 360000 patients with newly diagnosed diabetes during the period 1999 to 2001. Patients with the first severe hypoglycemia after 2002 served as the study cohort. Each patient in the study cohort was matched with two control patients without severe hypoglycemia, based on a propensity score. A joinpoint regression model was used to determine trends in all-cause mortality and incidence of cardiovascular disease (CVD) events in both cohorts.

Result: A total of 10 157 patients with severe hypoglycemia and 20314 matched controls were recruited. Patients with severe hypoglycemia had a significantly higher risk of CVD (HR, 7.28; 95% CI, 5.19-10.20) and all-cause mortality (HR, 19.92; 95% CI, 13.42-29.56) during the first month compared with those without. In patients with severe hypoglycemia, the incidence of CVDs dropped by 17.29% monthly during the first 4months and slowly decreased (-0.67%) during subsequent months. All-cause mortality decreased by 16.55% and 3.24% monthly during months 0-6 and months 6-17, respectively.

Conclusion: Severe hypoglycemia is associated with a greater risk of cardiovascular events and death, especially during the first month following a hypoglycemic episode. Patients prone to severe hypoglycemia should be made aware of the elevated risk of subsequent cardiovascular events.