Long-Term Sulfonylurea Use and Impaired Awareness of Hypoglycemia Among Patients With Type 2 Diabetes in Taiwan.

PURPOSE: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. METHODS: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. RESULTS: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. CONCLUSIONS: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Gender differences in cognitive function and its associated factors among older adults with type 2 diabetes.

Diabetes is widely prevalent among older people and can influence accelerated cognitive decline. Gender-based disparities may contribute to variations in cognitive decline. This study examined gender differences in cognitive function and associated factors among older adults with diabetes. A cross-sectional study was conducted involving 318 Taiwanese older adults with type 2 diabetes. Demographic, health, and diabetes-related data were collected, and cognitive neuropsychological tests were evaluated. Compared to men, women with diabetes showed significantly poorer performance in global cognitive function and executive function. Age, years of education, sleep quality, and HbA1c were correlated with domains of cognitive function in men, whereas age, years of education, depressive symptoms, HbA1c, and duration of diabetes were associated with domains of cognitive function among women. Nurses should recognize gender differences in factors associated with cognitive function in older adults with diabetes and should develop individualized interventions to improve patients' cognitive function.

Incidence of idiopathic cardiomyopathy in patients with type 2 diabetes in Taiwan: age, sex, and urbanization status-stratified analysis.

BACKGROUND: The epidemiology of diabetes and idiopathic cardiomyopathy have limited data. We investigated the overall and the age-, sex-, and urbanization-specific incidence and relative hazard of idiopathic cardiomyopathy in association with type 2 diabetes and various anti-diabetic medications used in Taiwan. METHODS: A total of 474,268 patients with type 2 diabetes were identified from ambulatory care and inpatient claims in 2007-2009 from Taiwan's National Health Insurance (NHI) database. We randomly selected 474,266 age-, sex-, and diagnosis date-matched controls from the registry of NHI beneficiaries. All study subjects were linked to ambulatory care and inpatient claims (up to the end of 2016) to identify the possible diagnosis of idiopathic cardiomyopathy. The person-year approach with Poisson assumption was used to estimate the incidence, and Cox proportional hazard regression model with Fine and Gray's method was used to estimate the relative hazards of idiopathic cardiomyopathy in relation to type 2 diabetes. RESULTS: The overall incidence of idiopathic cardiomyopathy for men and women patients, respectively, was 3.83 and 2.94 per 10,000 person-years, which were higher than the corresponding men and women controls (2.00 and 1.34 per 10,000 person-years). Compared with the control group, patients with type 2 diabetes were significantly associated with an increased hazard of idiopathic cardiomyopathy (adjusted hazard ratio [aHR]: 1.60, 95% confidence interval [CI]: 1.45-1.77] in all age and sex stratifications except in those men aged > 64 years. Patients with type 2 diabetes aged < 45 years confronted the greatest increase in the hazard of idiopathic cardiomyopathy, with an aHR of 3.35 (95% CI 2.21-5.06) and 3.48 (95% CI 1.60-7.56) for men and women, respectively. The usage of some anti-diabetic medications revealed lower risks of idiopathic cardiomyopathy. CONCLUSIONS: In Taiwan, diabetes increased the risk of idiopathic cardiomyopathy in both sexes and in all age groups, except in men aged > 64 years. Younger patients were vulnerable to have higher HRs of idiopathic cardiomyopathy. Some anti-diabetic medications may reduce the risks of cardiomyopathy.

Risk of heart failure in a population with type 2 diabetes versus a population without diabetes with and without coronary heart disease.

AIMS: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Perinatal and childhood risk factors for early-onset type 1 diabetes: a population-based case-control study in Taiwan.

BACKGROUND: Certain factors originating from the perinatal and childhood periods are suspected of contributing to the recent increasing trend of childhood type 1 diabetes (T1D) incidence. This study sought to investigate the relationships between various perinatal and childhood risk factors and T1D incidence in young children (<10 years). METHODS: We used a nested case-control design based on 1,478,573 live births born in 2000-05 in Taiwan. Cases were 632 incident cases of T1D between 2000 and 2008. Ten matched controls for each case were randomly selected. Information on various perinatal risk factors was also identified from claim data. Multiple conditional logistic regression was employed to estimate odds ratio (OR) and 95 confidence interval (CI) of T1D. RESULTS: Childhood infection was significantly associated with an increased risk of T1D (OR = 1.46, 95% CI = 1.23-1.73). Increased risk of T1D was also noted in children born to younger mothers (<25 years) (OR = 1.94, 95% CI = 1.34-2.81), older fathers (>30 years) (OR = 1.56 (95% CI = 1.16-2.10) to 1.57 (95% CI = 1.19-2.05), mothers with Caesarean section (CS) (OR = 2.35, 95% CI = 1.52-3.64), and mothers with gestational diabetes mellitus (OR = 4.36, 95% CI = 2.76-7.77). Fathers with T1D (OR = 7.36, 95% CI = 1.02-57.21) or type 2 diabetes (OR = 1.54, 95% CI = 1.04-2.26) were observed to substantially increase the risk of offspring T1D. CONCLUSIONS: Certain modifiable perinatal factors such as infection and CS may predispose incidence of T1D in young children.

A large scale population-based cohort study on the risk of ovarian neoplasm in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate whether the risk of developing ovarian cancer is elevated in women with diabetes mellitus. METHODS: The study is a population-based cohort study. Women with type 2 diabetes (n=319,310) and age-matched controls (n=319,308) were selected from the ambulatory care claims and beneficiary registry in 2000, respectively. Selected patients were linked to the in-patient claims (2000-2008) to identify admissions due to ovarian (ICD-9-CM: 183.xx) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of ovarian cancer in relation to diabetes were calculated using multivariate Cox proportional hazard regression model. RESULTS: The overall incidence density rate of ovarian cancer was estimated at 1.87 (95% confidence interval (CI) 1.70-2.05) per 10,000 patient-years for patients with diabetes. The corresponding figures for controls were slightly lower at 1.79 per 10,000 patient-years. The incidence density of ovarian cancer was increased with age in diabetes but not in controls. The covariate-adjusted HR for ovarian cancer was statistically compared with null (adjusted HR=1.06, 95% CI=0.92-1.22) in women with diabetes. Moderately elevated HR was noted in women with diabetes aged <50 (adjusted HR=1.17, 95% CI=0.82-1.65) and in women with diabetes aged >65 (adjusted HR=1.10, 95% CI=0.92-1.42). The null association between diabetes and ovarian cancer remains true regardless of the disease duration of diabetes. CONCLUSION: This large-scale cohort study provides little support on the putative association between type 2 diabetes and the risk of ovarian cancer.

Improving the one-year mortality of stroke patients: an 18-year observation in a teaching hospital.

Long-term follow-up and comparison of serial changes in the one-year mortality after stroke are important in assessing the quality of stroke management. This study determined the one-year survival rate and prognostic factors of hospitalized hemorrhagic and ischemic stroke patients from 1991 to 2008 in a teaching hospital in Taiwan. We also evaluated the improvements in the one-year mortality after stroke during an 18-year study period. Patients admitted for cerebral hemorrhage (n = 3,678) and cerebral infarction (n = 16,010), identified from an in-patient electronic database, were linked to the National Death Registry of Taiwan. Actuarial analysis was used to determine the one-year survival rates, and Cox proportional hazard regression model was used to investigate the predictors for the one-year mortality of stroke patients. For patients with cerebral hemorrhage and infarction and who were admitted from 1991 to 2008, the one-year survival rates were 71% and 84%, respectively. In addition, stroke patients who also suffered from myocardial infarction, chronic renal illness, and pneumonia and had high Charlson comorbidity index scores showed increased risks of mortality due to cerebral hemorrhage and infarction. Compared with the patients admitted from 1991 to 1996, those admitted from 1997 to 2002 and from 2003 to 2008 showed 15%-20% and 20%-25% reduction in one-year mortality risk in cerebral hemorrhage and infarction, respectively. This result demonstrates the continuous quality improvement of stroke management in the hospital from 1991 to 2008. Further reduction in one-year mortality can be achieved by early recognition and prompt treatment of certain comorbidities.

Comparison of all-cause mortality associated with non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in Taiwan MJ cohort.

OBJECTIVES: The global burden of non-alcoholic fatty liver disease (NAFLD) is rising. An alternative term, metabolic dysfunction-associated fatty liver disease (MAFLD), instead highlights the associated metabolic risks. This cohort study examined patient classifications under NAFLD and MAFLD criteria and their associations with all-cause mortality. METHODS: Participants who attended a paid health check-up (2012-2015) were included. Hepatic steatosis (HS) was diagnosed ultrasonographically. NAFLD was defined as HS without secondary causes, while MAFLD involved HS with overweight/obesity, type 2 diabetes mellitus, or ≥2 metabolic dysfunctions. Mortality was tracked via the Taiwan Death Registry until November 30, 2022. RESULTS: Of 118,915 participants, 36.9% had NAFLD, 40.2% had MAFLD, and 32.9% met both definitions. Participants with NAFLD alone had lower mortality, and those with MAFLD alone had higher mortality, than individuals with both conditions. After adjustment for potential confounders, the hazard ratios (HRs) for all-cause mortality were 1.08 (95% confidence interval [CI], 0.78 to 1.48) for NAFLD alone and 1.26 (95% CI, 1.09 to 1.47) for MAFLD alone, relative to both conditions. Advanced fibrosis conferred greater mortality risk, with HRs of 1.93 (95% CI, 1.44 to 2.58) and 2.08 (95% CI, 1.61 to 2.70) for advanced fibrotic NAFLD and MAFLD, respectively. Key mortality risk factors for NAFLD and MAFLD included older age, unmarried status, higher body mass index, smoking, diabetes mellitus, chronic kidney disease, and advanced fibrosis. CONCLUSIONS: All-cause mortality in NAFLD and/or MAFLD was linked to cardiometabolic covariates, with risk attenuated after multivariable adjustment. A high fibrosis-4 index score, indicating fibrosis, could identify fatty liver disease cases involving elevated mortality risk.

Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality.

AIM: In patients with type 2 diabetes (T2D), levels of hypoglycemia and their risk of mortality are not well understood. The aim of this study was to ascertain the correlation among disparate levels of hypoglycemia and patients with T2D's achieved mean glycated hemoglobin A1c (HbA1c) with all-cause and cardiovascular mortality. METHODS: 27,932 T2D patients taking hypoglycemic medications at outpatient visits for more than 6 months between 2008 and 2018 were linked to Taiwan's National Death Registry. We determined the respective mortality rates with Poisson assumption, and explored the relative risks of all-cause and cardiovascular mortality according to dissimilar levels of hypoglycemia with their achieved mean HbA1c by Cox proportional hazard regression model with adjustment of potential confounders. RESULTS: T2D patients with level 3 hypoglycemia had the highest rates of all-cause and cardiovascular mortality. Compared with those who never encountered hypoglycemia, study subjects with level 1 and level 2 hypoglycemia did not show excessive risks of either all-cause or cardiovascular mortality. Only those with level 3 hypoglycemia revealed marginal risk of all-cause (Hazard ratio [HR]: 1.18; 95% Confidence Interval [CI] 1.04-1.33) but not cardiovascular mortality (HR: 1.16; 95% CI 0.88-1.53). In T2D patients with hypoglycemia, only those with mean HbA1c ≥9.0% increased all-cause mortality in level 3 hypoglycemia, and cardiovascular mortality in level 1 hypoglycemia. CONCLUSIONS: Elevated risk of all-cause mortality was exclusively found in patients with level 3 hypoglycemia. In T2D patients with hypoglycemia, mean HbA1c ≥ 9% increased all-cause or cardiovascular mortality. Aggressive treatment of accompanying serious illness in severe hypoglycemia may help reduce mortality in patients with T2DM.

The relationship of low-density lipoprotein cholesterol and all-cause or cardiovascular mortality in patients with type 2 diabetes: a retrospective study.

Background: The optimal levels of low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes (T2D) are not currently clear. In this study, we determined the relationship between various mean LDL-C and all-cause or cardiovascular mortality risks in patients with T2D, stratifying by albumin level, age, sex, and antilipid medication use. We also evaluated the association of LDL-C standard deviation (LDL-C-SD) and all-cause and cardiovascular mortality by type of antilipid medication use. Methods: A total of 46,675 T2D patients with a prescription for antidiabetic agents >6 months from outpatient visits (2003-2018) were linked to Taiwan's National Death Registry to identify all-cause and cardiovascular mortality. The Poisson assumption was used to estimate mortality rates, and the Cox proportional hazard regression model was used to assess the relative hazards of respective mortality in relation to mean LDL-C in patient cohorts by albumin level, age, sex, and antilipid use adjusting for medications, comorbidities, and laboratory results. We also determined the overall, and anti-lipid-specific mortality rates and relative hazards of all-cause and cardiovascular mortality associated with LDL-C-SD using the Poisson assumption and Cox proportional hazard regression model, respectively. Results: All-cause and cardiovascular mortality rates were the lowest in T2D patients with a mean LDL-C > 90-103.59 mg/dL in the normal albumin group (≥ 3.5 g/dL). Compared to T2D patients with a mean LDL-C > 90-103.59 mg/dL, those with a mean LDL-C ≤ 77 mg/dL had an elevated risk of all-cause mortality in both the normal and lower albumin groups. T2D patients with a mean LDL-C ≤ 90 and > 103.59-119 mg/dL had relatively higher risk of cardiovascular mortality in the normal albumin group, but in the lower albumin group (<3.5 g/dL), any level of mean LDL-C ≤ 119 mg/dL was not significantly associated with cardiovascular mortality. Increased risks of all-cause and cardiovascular mortality were observed in patients with a mean LDL-C ≤ 77 mg/dL in both sexes and in all age groups except in those aged <50 years, a lower mean LDL-C was not associated with cardiovascular mortality. Similarly, patients with an LDL-C-SD <10th and > 90th percentiles were associated with significant risks of all-cause and cardiovascular mortality. In statin users, but not fibrate users, lower and higher levels of mean LDL-C and LDL-C-SD were both associated with elevated risks of all-cause and cardiovascular mortality. Conclusions: The optimal level of LDL-C was found to be >90-103.59 mg/dL in T2D patients. Lower and higher levels of mean LDL-C and LDL-C-SD were associated with all-cause and cardiovascular mortality, revealing U-shaped associations. Further studies are necessary to validate the relationship between optimal LDL-C levels and all-cause and cardiovascular mortality in patients with diabetes.

Age- and sex-specific risks of colorectal cancers in diabetic patients.

Diabetes has been reported to increase the risk of colorectal neoplasm in most but not all studies. However, the data on age- and sex-specific incidence rates and relative risks associated with diabetes are limited. We carried out this population-based cohort study to investigate the overall sex- and age-specific risks of colorectal cancer in association with diabetes. Diabetic patients (n = 615,532) and age- and sex-matched control individuals (n = 614,871), selected from the claim datasets, were followed up from 2000 to 2006. The rates of admission due to colon and rectum cancers were estimated using the person-years approach, and the age- and sex-specific hazard ratio (HR) for both the malignancies were determined using the Cox regression model. The overall incidence rate of colon cancer was 9.94 per 10,000 patient-years for the diabetic patients, as opposed to 7.84 per 10,000 patient-years for the control-group patients. The corresponding observation for rectal cancer was 7.16 and 6.28 per 10,000 patient-years. Diabetic patients aged ≥ 45 years had significantly high HRs for developing colon cancer (1.20-1.45-fold). We also noted a significantly high HR of rectal cancer in diabetic men (1.18-fold) aged ≥ 45 years, but not in diabetic women. In conclusion, diabetes may significantly increase the risk of colorectal cancer, especially in patients aged 45-64 years. Diabetologists should keep this relationship in mind while treating middle-aged diabetic men and should also advise these patients to undergo regular screening tests for colorectal cancer.

Parathyroid adenoma presenting as chronic pancreatitis: A case report and literature review.

BACKGROUND: Most patients with parathyroid adenomas are asymptomatic and rarely present with chronic pancreatitis (CP). Several studies have reported a positive association between primary hyperparathyroidism (PHPT) and pancreatitis. Parathyroidectomy is the definitive treatment for PHPT. IV bisphosphonates can be considered the drug of choice for bridge to surgery. METHODS: We reported a 57-year-old female patient was admitted to the emergency room with left upper quadrant abdominal pain and a diagnosis of recurrent pancreatitis. Magnetic Resonance Cholangiopancreatography confirmed the diagnosis of CP. The patient had no common etiology of pancreatitis. Persistent hypercalcemia was noted despite administering intravenous fluids, and Calcitonin. Intravenous Pamidronate, a Bisphosphonate derivative, was also administered. Although calcium levels initially decreased, they were later found to rebound to previous levels. RESULTS: A diagnosis of parathyroid adenoma and PHPT was made based on the elevated parathyroid hormone levels and cervical ultrasonography indicated right inferior parathyroid adenoma. Technetium-99m methoxy-isobutyl-isonitrile scintigraphy revealed a focal hot spot of tracer accumulation at the right lower thyroid bed. The patient underwent right lower parathyroidectomy smoothly and successfully. After right lower parathyroidectomy, she had normal serum calcium levels (9.2 mg/dL) and parathyroid hormone (16.1 pg/mL). There was no recurrent abdominal pain after the operation. CONCLUSION: CP is a rare manifestation of parathyroid adenoma. When patients with a history of recurrent pancreatitis, without common causes of pancreatitis, present persistent elevated serum calcium levels, PHPT could be suspected.

Age and sex-specific associations of visit-to-visit variability of glycated hemoglobin A1c with all-cause mortality in patients with diabetes.

BACKGROUND: Visit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV. METHODS: To investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003-2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan's National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c. RESULTS: The lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged <50 years while in those aged >69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50-69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c. CONCLUSION: HbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management.

Low mean HbA1c does not increase all-cause and cardiovascular mortality in patients with diabetes: Effect-modifications by anemia and chronic kidney disease stages.

BACKGROUND: Previous studies reported that low levels of glycated hemoglobin A1c (HbA1c) were associated with increased mortality. We investigated rates and risks of all-cause and cardiovascular mortality in association with mean HbA1c levels with stratification of anemia and chronic kidney disease (CKD) stages, major causes of low HbA1c. METHODS: 47,145 patients with prescription of antidiabetic agents >6 months in the outpatient visits (2003-2018) were linked to Taiwan's National Death Registry to identify all-cause and cardiovascular mortality. Poisson assumption was used to estimate the mortality rates, and the Cox proportional hazard regression model was used to evaluate the relative hazards of respective mortality in relation to mean HbA1c in different statuses of anemia and CKD stages. RESULTS: All-cause and cardiovascular mortality rates were the lowest in non-anemic stages 1-2 CKD patients, and the highest in anemic stages 3-5 CKD patients. In stages 1-2 CKD, excessive HRs observed in those with mean HbA1c <6.0% (Hazard Ratio [HR]) 1.58; 95% Confidence Interval [CI] 1.18-2.12) became inconsequential after adjustment of medications and laboratory results (HR: 1.26; 95% CI 0.89-1.79). The similar patterns were observed in anemic stages 1-2 CKD, anemic or non-anemic stages 3-5 CKD. Low HbA1c was not related to cardiovascular mortality in any anemia status or CKD staging. CONCLUSIONS: Higher risks associated with low mean HbA1c and all-cause mortality were attenuated by adjustment of medications and comorbidities. It is imperative for the diabetologists to consider confounding effects of underlying illness before concluding low HbA1c associated higher mortality.

Risk of malignant neoplasms of liver and biliary tract in diabetic patients with different age and sex stratifications.

UNLABELLED: We prospectively investigated 615,532 diabetic patients and 614,871 age-matched and sex-matched control subjects selected from National Health Insurance claims for malignant neoplasms of liver and biliary tract (International Statistical Classification of Diseases and Related Health Problems, 9th edition, codes 155 and 156, respectively) between 2000 and 2006. The person-year approach with Poisson assumption was used to estimate the hazard rates. We also evaluated the age-specific and sex-specific relative risks of these two malignancies in relation to diabetes with Cox proportional hazard regression model with adjustment for potential confounders. The overall hazard rate of malignant neoplasm of the liver was 32.76 and 17.41 per 10,000 patient-years, respectively, for diabetic men and women; the corresponding figures for biliary tract neoplasm were much lower at 1.42 and 1.60 per 10,000 patient-years. Compared with control subjects, diabetic patients had a two-fold increased risk of malignant neoplasm of the liver, but this risk was attenuated by adjusting for selected clinical risk factors (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.17-1.25). Additionally, diabetic patients were associated with increased risk of biliary neoplasms with an approximate magnitude of 20%-30%, but the HR was attenuated and became insignificant after adjustment for clinical risk factors (HR 1.07; 95% CI 0.95-1.21). Diabetic patients with cirrhosis had the highest relative risk of liver neoplasm (HR 85.25; 95% CI 76.84-94.58), whereas those with cholangitis had the highest risk of biliary tract neoplasm (HR 70.30; 95% CI 51.95-95.12) compared with control subjects without any clinical risk factors. CONCLUSION: This population-based study confirms the association of diabetes with liver neoplasm and suggests that diabetic patients with certain clinical risk factors should be educated for strict adherence of liver neoplasm screening.

Trends in hospitalization for diabetic ketoacidosis in diabetic patients in Taiwan: analysis of national claims data, 1997-2005.

BACKGROUND/PURPOSE: Diabetic ketoacidosis (DKA) is a fatal complication of diabetes, and is strongly related to the quality of diabetes care. This study aimed to establish recent secular trends of incidence density (ID) of DKA in patients with diabetes in Taiwan and to explore the effects of age and sex on the risk of a DKA emergency. METHODS: Using the National Health Insurance claims data, we identified annual diabetic cohorts (around 650,000 diabetic patients annually) from 1997 to 2005, and searched for possible admissions due to DKA emergencies. We performed log-linear regression analysis to assess the trend in ID of DKA and to assess the independent effects of age and sex on the risk of DKA. RESULTS: Although the annual ID of DKA showed a slight but significant declining trend over the study period, from 6/1000 to 5/1000 person-years, the age/sex-specific analysis indicated that female patients aged ≤ 34 years showed a significantly increasing trend. Multivariate analysis revealed that calendar year and sex had significant but small independent effects on risk of DKA admission. In contrast, age was strongly associated with risk of DKA emergency. Compared with patients aged > 65 years, notably high adjusted rate ratios (ARRs) of DKA were observed in patients aged <15 years (ARR = 48.84) and 15-34 years (ARR =15.21). CONCLUSION: Although the overall ID of DKA linearly decreased between 1997 and 2005, significant rising trends were still observed in female diabetic patients aged < 35 years. More aggressive diabetic care programs aimed at young female patients should be considered to reduce this emergency and possibly fatal diabetic complications.

Factors determining the 1-year survival after operated hip fracture: a hospital-based analysis.

BACKGROUND: Factors associated with 1-year survival of hip fracture in Chinese ethnicities has not been clearly elucidated. The purpose of this study was to determine the 1-year survival associated with operated hip fracture and its prognostic factors in a district teaching hospital from January 1, 1998 to 2006. METHODS: Hip fracture admissions (ICD-9: 820) identified from an inpatient electronic database over a 9-year period were linked to Taiwan's national death registry. Actuarial analysis was used to determine the 1-year survival rates after hip fracture, which were further compared according to different concurrent illnesses. We used the Cox proportional hazard regression model to explore the significant determinants of 1-year survival of the study patients. RESULTS: The overall 1-year survival rate of all patients was 86%. This was lower if the operation was accompanied by certain co-morbidities, including heart failure [hazard ratio (HR) 6.12; 95% confidence interval (CI) 1.54-24.36], chronic obstructive pulmonary disease (HR 2.40; 95% CI 1.14-5.05), and pneumonia (HR 4.26; 95% CI 1.95-9.31). In addition, elderly patients (>84 years of age) (HR 7.34; 95% CI 2.49-21.58), arthroplasty (HR 3.69; 95% CI 1.10-12.43), operative delay >48 h (HR 2.86; 95% CI 1.08-7.54), low preoperative hemoglobin level (<11 g/dl) (HR 2.58; 95% CI 1.33-5.01), and high creatinine level (>or=2 mg/dl) (HR 2.52; 95% CI 1.07-5.95) were all significantly associated with increased mortality. CONCLUSIONS: The 1-year survival for patients in this study hospital, 86%, was comparable to or higher than that of previous studies. Improved survival rates among hip fracture patients may be achieved by early recognition and prompt treatment of associated medical illnesses.

Incidence of ambulatory care visits among female nursing staff in Taiwan: a claim data-based retrospective cohort analysis.

AIMS: To investigate the incidence of ambulatory care visits among female nursing staff in Taiwan. BACKGROUND: Literature frequently indicates increased risks of needlestick injury and musculoskeletal disorders among practicing nurses. With increased workload in the healthcare system, nursing staff could also be vulnerable to other diseases. DESIGN: A retrospective cohort study design including 27,624 female nursing staff with a contract with Taiwan's National Health Insurance (NHI) programme between 2001-2004. METHODS: Information on ambulatory care visits was retrieved from the NHI claim data. Comparison groups included other female medical personnel and active non-medical working women. Incidence rates of ambulatory care visits were calculated using person-year approach. Rate ratio adjusted for potential confounders was estimated from the Poisson regression model. RESULTS: The nurse cohort developed a total of 781,352 ambulatory care visits, representing an incidence rate of 85,285/10(4) person-years. Compared with the other female medical personnel, female nurses had significantly elevated incidence of genitourinary [adjusted rate ratio (ARR) = 1.20], circulatory (ARR = 1.14), mental (ARR = 1.12), infectious/parasitic diseases (ARR = 1.11) and pregnancy/birth complications (ARR = 1.07). Significantly increased incidence sustained for both infectious/parasitic diseases and pregnancy/birth complications as the nurse cohort was compared with the active non-medical working women. The nurses, on the contrary, had significantly lower ARRs than the comparison groups of neoplasm, injury, metabolic, respiratory, digestive and musculoskeletal diseases. CONCLUSIONS: Female nurses had increased incidences of certain types of systemic illness when compared with other medical personnel and with women working outside of the health industry. Whether the findings found in this study were region specific or could be applicable to other nations, requires further investigations. RELEVANCE TO CLINICAL PRACTICE: Policy makers and hospital administrators must not overlook nurses' potentially unseen health problems. A mandatory periodical physical examination for nursing staff must be considered.