Wei-Hao Hsu

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.

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.

Abnormally Low or High Ankle-Brachial Index Is Associated With the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus

Although some studies have reported an association between peripheral artery disease (PAD) and diabetic retinopathy (DR) in patients with diabetes, whether or not a causal relationship exists is unknown. The aim of this study was to investigate whether PAD, as indicated by an abnormally low or high ankle-brachial index (ABI), is associated with the development of DR in patients with type 2 diabetes mellitus (DM) without DR. We enrolled 414 (221 men and 193 women) patients with type 2 DM who underwent ABI measurements at our outpatient clinic. PAD was defined as an abnormally low (<0.9) or high (≥1.3) ABI in either leg, and DR was defined as being non-proliferative or proliferative. Of the enrolled patients, 69 (16.7%) had an ABI <0.9 or ≥1.3. The median follow-up period was 23 (15–40) months, during which 74 (17.9%) patients developed DR. In multivariate analysis, an ABI <0.9 or ≥1.3 was independently associated with the development of DR (vs. ABI ≥0.9 to <1.3; hazard ratio, 2.186; 95% confidence interval, 1.261 to 3.789; p = 0.005). An abnormal ABI was associated with the development of DR in our patients with type 2 DM without DR.

Effect of metformin on kidney function in patients with type 2 diabetes mellitus and moderate chronic kidney disease

Background Impaired renal function can lead to the accumulation of metformin, and elevated concentrations of metformin have been associated with lactic acidosis. The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30–0 ml/min/1.73 m2) on renal function. Methods A total of the 616 patients were enrolled from the research database of Kaohsiung Medical University Hospital from January 1 to 2009 and December 31, 2013. The patients were divided into two groups: those who continued metformin treatment (continuation group; n = 484), and those who discontinued metformin treatment for at least 100 days (interruption group; n = 132). Results The slope of eGFR in the metformin interruption group was statistically lower than that in the metformin continuation group (0.75 ± 0.76 vs. –1.32 ± 0.24 mL/min/1.73 m2/year, p = 0.0007). After adjusting for baseline covariates in the multivariate linear regression analysis, the continuation of metformin (unstandardized coefficient β, –2.072; 95% confidence interval, –3.268– –0.876) was a risk factor for the patients with DM and moderate CKD. Conclusions Metformin may have an adverse effect on renal function in patients with type 2 DM and moderate CKD.

ASSOCIATIONS BETWEEN TRIGLYCERIDE/HIGH-DENSITY LIPOPROTEIN CHOLESTEROL RATIO AND MICRO- AND MACROANGIOPATHIES IN TYPE 2 DIABETES MELLITUS

OBJECTIVE The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been reported to be a marker of insulin resistance. The aim of this study was to investigate associations between the TG/HDL-C ratio and micro- and macroangiopathies in patients with type 2 diabetes mellitus (DM). METHODS A total of 1,981 (851 male and 1,130 female) patients with type 2 DM were enrolled from our outpatient clinic. These patients were stratified into 4 groups according to TG/HDL-C ratio quartiles. RESULTS There were significant trends for stepwise increases in albuminuria ≥30 mg/g ( P<.001), coronary artery disease (CAD, P = .040), cerebrovascular disease (CVA, P = .002) and ankle-brachial index (ABI) <0.9 ( P = .001) corresponding to TG/HDL-C ratio quartiles, but not diabetic retinopathy ( P = .105). Furthermore, quartile 4 of the TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and ABI <0.9 after multivariate analysis compared to quartile 1. CONCLUSION A high TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and peripheral artery occlusive disease (PAOD) in patients with DM, which translated into an increased risk of cardiovascular disease. ABBREVIATIONS ABI = ankle-brachial index; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; CVA = cerebrovascular disease; DM = diabetes mellitus, DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; OR = odds ratio; PAOD = peripheral artery occlusive disease; TGs = triglycerides.

Association Between Metabolic Syndrome and Microvascular and Macrovascular Disease in Type 2 Diabetic Mellitus

Background: The prevalence of metabolic syndrome (MetS) in patients with type 2 diabetes mellitus is high. The aim of this study was to investigate the association between MetS and micro‐ and macrovascular disease in patients with diabetes and the associated risk factors. Methods: The study enrolled 1,986 (854 men and 1,132 women) patients with type 2 diabetes mellitus from outpatient clinics. MetS was defined according to the Adult Treatment Panel III for Asians. Results: Of the enrolled patients, 1,363 had MetS and 623 did not. The patients with MetS had significantly higher rates of albuminuria (40.8% vs. 21.8%, P < 0.001), retinopathy (37.9% vs. 28.6%, P < 0.001), coronary artery disease (19.4% vs. 11.6%, P < 0.001), cerebrovascular disease (5.8% vs. 3.2%, P = 0.014), and an ankle‐brachial index < 0.9 or ≥ 1.3 (6.1% vs. 3.0%, P = 0.015). Moreover, there were significant trends for stepwise increases in albuminuria, retinopathy, coronary artery disease, cerebrovascular disease and peripheral artery disease corresponding to the number of MetS components (all P for trend < 0.05). Risk factors including MetS, old age, sex, wide pulse pressure, increased hemoglobin A1c, dyslipidemia and decline renal function were associated with micro‐ and macrovascular disease. Conclusions: MetS and the number of its components were significantly associated with micro‐ and macrovascular disease in the study patients with diabetes and this resulted in a higher risk of cardiovascular disease. Screening programs to allow for early detection and interventions should be established to lower the risk of cardiovascular disease.

Fatal outcome of persistent/recurrent Cushing's disease after pituitary surgery

Cushing’s disease (CD), resulting from adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, is rare, with an annual incidence of 2e3 million people. Transsphenoidal surgery (TSS) is the first-line treatment. However, the remission rate for initial TSS varies widely with a substantial risk of persistent/recurrent disease. The diagnosis and management of persistent/recurrent CD still remains a challenge for clinicians [1]. We present a case of CD with rapid relapse within 2 months after effective TSS, progressing to fatal recurrent intracranial hemorrhage. A 43-year-old man, manifesting with typical Cushing’s appearance, sought help for his rapid body weight loss of 13 kg within 2 months. His biochemistry revealed hyperglycemia (HbA1C, 13.4%; plasma glucose, 697 mg/dL), hypokalemia (K, 2.6 mEq/L), metabolic alkalosis (pH 7.489; HCO 3 , 33.9 mM), elevated serum cortisol 33.97 (normal, 5e25 mg/dL) and plasma ACTH 346.06 (normal, 10e50 pg/ mL). Cushing’s disease was confirmed by a high dose dexamethasone test (HDT) and pituitary magnetic resonance imaging showing a pituitary macroadenoma (Fig. 1A and B). Trans-sphenoidal adenomectomy was executed to achieve declining plasma ACTH 42 pg/mL and serum cortisol 20.73 mg/dL and marked clinical improvement (HbA1c, 5.9%; K, 4.2 mEq/L) postoperatively. However, his condition deteriorated again with raised plasma ACTH (156 pg/mL) and serum cortisol 39.91 (mg/dL) 2 months later. HDT and pituitary magnetic resonance imaging confirmed recurrent Cushing’s disease. Re-operation, radiotherapy, or bilateral adrenalectomy was strongly suggested but the patient refused and disappeared thereafter. When he came back, his plasma ACTH and serum cortisol were extremely elevated to 433.2 pg/mL and 77.4 mg/dL, respectively, combined with multiple spine fractures.