Mei-Yueh Lee

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Studies have shown an association between diabetes and cancer in Western countries; but this, as well as the influence of associated metabolic factors, must be confirmed by a prospective study in other population groups. This study aimed to investigate whether the strong association of cancer and diabetes is independent from the influence of hypertension, dyslipidemia, and gout in the Taiwanese population. A total of 985,815 study subjects were identified from the National Health Insurance in 1997 and followed up from 1998 to 2009. The demographic characteristics between patients with diabetes and cancer, including age, sex, hypertension, dyslipidemia, and gout, were analyzed using the χ(2) test. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risks of cancer. A total of 104,343 diabetic patients were followed up from 1998 to 2009. After adjusting for sex, age, hypertension, dyslipidemia, and gout, the incidences of cancer at any site and in the liver, colon, lungs, and prostate in diabetic patients were independently higher, with risk ratios of 1.56 (95% confidence interval [CI], 1.43-1.71), 1.67 (95% CI, 1.39-2.01), 1.75 (95% CI, 1.49-2.06), 1.54 (95% CI, 1.26-1.88), and 1.56 (95% CI, 1.19-2.04), respectively. Only breast cancer did not show any clinical significance. There was an increased incidence of cancer at any site in the diabetic patients compared with nondiabetic subjects. The most common cancers were liver, colon, lung, breast, and prostate cancer; and except for breast cancer, their incidences increased independently of hypertension, dyslipidemia, and gout in patients with diabetes.

The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

Objective Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. Materials and Methods In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. Results Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4%) and 72 (0.2%), and for newly developed chronic kidney disease 245 (8.1%) and 663 (2.3%), respectively. Ever use of pioglitazone [1.59(1.32–1.91)], cumulative dose of pioglitazone <10,500 mg [1.69 (1.37–2.01)] and >10,500 mg [1.34 (1.04–1.73)], and duration of therapy <12 months [1.68 (1.36–2.08)] and >12 months [1.39 (1.09–1.76)] were associated with the development of chronic kidney disease. Conclusions There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001), 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002), 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI) −27.587, −0.374), −26.847 (95% CI −37.562, −16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004), 2.801 (p = 0.005), and −3.568 (p ≤ 0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Conclusions: Dengue patients with diabetes tended to have more severe thrombocytopenia and were more likely to have DHF/DSS. Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98), 0.72 (95% CI, 0.58–0.91) and 0.76 (95% CI, 0.60–0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.

Link between Peripheral Artery Disease and Heart Rate Variability in Hemodialysis Patients

Peripheral artery disease (PAD) and low heart rate variability (HRV) are highly prevalent in hemodialysis patients, and both are associated with increased cardiovascular morbidity and mortality. This study aims to examine the suggested relationship between PAD and HRV, and the relationship of parameters before and after hemodialysis. This study enrolled 161 maintenance hemodialysis patients. PAD was defined as ABI < 0.9 in either leg. HRV was performed to assess changes before and after hemodialysis. The change in HRV (△HRV) was defined as post-hemodialysis HRV minus pre-hemodialysis HRV. Patients’ clinical parameters were collected from the dialysis records. All HRV parameters except high frequency (HF) % were lower in patients with PAD than patients without PAD, though not achieving significant level. In patients without PAD, HF (P = 0.013), low frequency (LF) % (P = 0.028) and LF/HF (P = 0.034) were significantly elevated after hemodialysis, whereas no significant HRV parameters change was noted in patients with PAD. Serum intact parathyroid hormone was independently associated with △HF (β = -0.970, P = 0.032) and △LF% (β = -12.609, P = 0.049). Uric acid level (β = -0.154, P = 0.027) was negatively associated with △LF/HF in patients without PAD. Our results demonstrated that some of the HRV parameters were significantly increased after hemodialysis in patients without PAD, but not in patients with PAD, reflecting a state of impaired sympatho-vagal equilibrium. Severity of secondary hyperparathyroidism and hyperuricemia contributed to lesser HRV parameters increase after hemodialysis in patients without PAD.

Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10‐month withdrawal of pioglitazone in patients with Type 2 diabetes

To investigate the recovery of thiazolidinedione‐induced body weight gain and haematopoietic changes after stopping pioglitazone treatment in patients with Type 2 diabetes.

Abnormally Low or High Ankle-Brachial Index Is Associated with Proliferative Diabetic Retinopathy in Type 2 Diabetic Mellitus Patients.

Although some studies have reported that low ankle-brachial index (ABI) is associated with diabetic retinopathy (DR) in diabetic patients, it remains controversial as to which stage of DR. The aim of this study is to assess whether peripheral artery disease (PAD), indicated by abnormally low or high ABI, is associated with different stages of DR in patients with type 2 diabetes mellitus (DM), and further evaluate the risk factors. A total of 2001 (858 men and 1143 women) patients with type 2 DM who underwent ABI measurement in an outpatient clinic were enrolled. PAD was defined as ABI < 0.9 or ≧ 1.3 in either leg. DR was classified as non-DR, nonproliferative DR and proliferative DR stages. The clinical data were analyzed and the risk factors for abnormal ABI were determined by multivariate logistic regression analysis. The prevalence of ABI < 0.9 or ≧ 1.3 was 3.0%. Multivariate forward logistic regression analysis identified proliferative DR (vs. non-DR) was associated with abnormal ABI (odds ratio, 1.718; 95% confidence interval, 1.152 to 2.562; p = 0.008), but nonproliferative DR was not. Furthermore, the presence of coronary artery disease, cerebrovascular disease, declining renal function and patients without diuretics use were associated with abnormal ABI in patients with proliferative DR. Our study in patients of type 2 DM demonstrated that PAD was associated with proliferative DR. We emphasize the recommendation of performing the ABI test in this population at risk.

Greater HbA1c variability is associated with increased cardiovascular events in type 2 diabetes patients with preserved renal function, but not in moderate to advanced chronic kidney disease

Emerging evidence suggests that glycemic variability may be a more reliable measure of glycemic control than mean HbA1c in type 2 diabetes mellitus. This study aimed to determine if HbA1c variability is associated with cardiovascular events in type 2 diabetic patients and if different renal functions affect such association. This longitudinal study enrolled 8259 diabetic patients from the Kaohsiung Medical University Research Database in 2009 and were followed-up until 2015. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1c and cardiovascular events were defined as hospitalization for coronary artery disease, unstable angina, myocardial infarction, stroke, peripheral artery disease, and cardiovascular death. The patients were grouped into two based on their estimated glomerular filtration rate (eGFR) ≥ 60 or < 60 min/ml/1.73m2. In a mean follow-up period of 6.3 years, cardiovascular events were recorded in 8.9% of the patients. In an adjusted Cox model, high HbA1c SD (hazard ratio, 1.290; 95% confidence interval, 1.008–1.650; p = 0.043), but not mean HbA1c, was associated with significantly increased risk of cardiovascular events in patients with eGFR ≥ 60 min/ml/1.73m2. This association was not seen in patients with eGFR < 60 min/ml/1.73m2. In this study, greater HbA1c variability is associated with increased risk of cardiovascular among patients with preserved renal function, but not in those with moderate to advanced chronic kidney disease.

Association of Brachial-Ankle Pulse Wave Velocity and Cardiomegaly With Aortic Arch Calcification in Patients on Hemodialysis

AbstractAortic arch calcification (AoAC) is associated with cardiovascular and all-cause mortality in end-stage renal disease population. AoAC can be simply estimated with an AoAC score using plain chest radiography. The objective of this study is to evaluate the association of AoAC with brachial-ankle pulse wave velocity (baPWV) and cardiomegaly in patients who have undergoing hemodialysis (HD).We retrospectively determined AoAC and cardiothoracic ratio (CTR) by chest x-ray in 220 HD patients who underwent the measurement of baPWV. The values of baPWV were measured by an ankle-brachial index-form device. Multiple stepwise logistic regression analysis was used to identify the factors associated with AoAC score >4.Compared patients with AoAC score ≦4, patients with AoAC score >4 had older age, higher prevalence of diabetes and cerebrovascular disease, lower diastolic blood pressure, higher baPWV, higher CTR, higher prevalence of CTR ≧50%, lower total cholesterol, and lower creatinine level. After the multivariate stepwise logistic analysis, old age, cerebrovascular disease, high baPWV (per 100 cm/s, odds ratio [OR] 1.065, 95% confidence interval [CI] 1.003–1.129, P = 0.038), CTR (per 1%, OR 1.116, 95% CI 1.046–1.191, P = 0.001), and low total cholesterol level were independently associated with AoAC score >4.Our study demonstrated AoAC severity was associated with high baPWV and high CTR in patients with HD. Therefore, we suggest that evaluating AoAC on plain chest radiography may be a simple and inexpensive method for detecting arterial stiffness in HD patients.