An atypical hyperosmolar hyperglycemic state and diabetic ketoacidosis induced by sodium-glucose cotransporter-2 inhibitors: A case report.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become the best choice of second-line oral antidiabetic drugs for patients with heart or chronic kidney disease. However, it is not clear how safe this treatment is for elderly patients, especially Asians, who are known to be more insulin deficient than Caucasian individuals with a similar insulin resistance. Here, we report a case concerning an elderly patient with type 2 diabetes mellitus without insulin dependence, whose antidiabetic medication had recently been changed to include an SGLT-2 inhibitor. The patient presented with an atypical hyperosmolar hyperglycemic state and diabetic ketoacidosis but recovered after insulin pump treatment and fluid supplementation. The patient was discharged with a prescription of a mixed-type insulin injection instead of oral antidiabetic medications for diabetes control. Our case demonstrates that if SGLT-2 inhibitors are administered to elderly Asian patients, their benefits and adverse effects should be carefully monitored.

The influence of disease-modifying anti-rheumatic drugs and corticosteroids on the association between rheumatoid arthritis and skin cancer: a nationwide retrospective case-control study in Taiwan.

OBJECTIVES: To investigate the influence of corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs, including conventional synthetic and biologic DMARDs) treatment on the association between rheumatoid arthritis (RA) and non-melanoma skin cancer (NMSC). METHODS: This nationwide retrospective case-control study retrieved data from Taiwan National Health Insurance Research Database during 1995-2013. Cases with newly-diagnosed NMSC (n=19,603) were matched with control without NMSC in a 1:1 ratio according to age, sex, and reference date. The aforementioned association was analysed using conditional logistic regression and adjustments for age, sex, residential regions, occupations, and co-morbidities. Causality cannot be inferred by case-control study. RESULTS: Compared to patients without RA, the patients with RA had a significantly higher association with NMSC (adjusted odds ratio (AOR)=2.23, 95% confidence interval (CI) 1.6-3.1, p<0.001), especially those using cyclosporine (AOR=5.7, 95%CI 2.2-14.86; ≥65 years: AOR=7.28, 95%CI 2.16-24.56), etanercept (AOR=5.27, 95%CI 1.15-24.27; ≥65 years: AOR=8.95, 95%CI 1.12-71.85), and d-penicillamine (AOR=4.79, 95%CI 1.63-14.12; ≥65 years: AOR=3.81, 95%CI 1.26-11.52); those using higher cumulative doses of corticosteroids and methotrexate (corticosteroids: >10g: AOR=2.96, 95%CI 1.67-5.22; >10g and ≥65years: AOR=3.5, 95%CI 1.77-6.92; methotrexate: 1-3g: AOR=2.57, 95%CI 1.13-5.82; >3g: AOR=4.64, 95%CI 1.74-12.4; >3g and ≥65 years: AOR=10.17, 95%CI 2.34-44.26); and those using more kinds of DMARDs (any 3: AOR=3.72, 95%CI 1.67-8.26; any 5: AOR=2.81, 95%CI 1.13-7.04; any 6: AOR=5.23, 95%CI 1.14-24.14; 7-8: AOR=4.06, 95%CI 1.14-14.49). CONCLUSIONS: The patients with RA had significantly increased associations with NMSC, especially those receiving cyclosporine, etanercept, and d-penicillamine; higher cumulative doses of corticosteroids and methotrexate; or more kinds of DMARDs in combination or in sequence. The aforementioned associations were much stronger in the elderly.

A survey of dermatological diseases among older male adults of a Veterans Home in Southern Taiwan.

BACKGROUNDS: The dermatologic diseases of the dependent elderly require special attention. METHODS: This screening and treatment service of dermatological diseases was conducted in a Veterans Home in Southern Taiwan. RESULTS: A total of 337 male residents were screened with mean age 83 years (range 46-99). 271 (80.4 %) residents were in dependent status. Their skin diseases were recorded and the distribution pattern was compared with those in the other studies. Comparing by Chi-square test, scabies, bacterial infection, chronic ulcers, pruritus, and brown spots on the legs were present significantly in certain major systemic diseases, respectively. Higher prevalence of certain skin diseases was related to the severity of disability or major systemic diseases of the residents. Actinic keratosis and non-melanoma skin cancers were early detected and managed. CONCLUSIONS: The distribution patterns of skin diseases in a Veterans Home were unique. It provides the evidences on appropriate management and key nursing points for dependent elderly.

A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

High HbA1c level was the most important factor associated with prevalence of diabetic retinopathy in Taiwanese type II diabetic patients with a fixed duration.

BACKGROUND: To identify the prevalence and related risk factors for diabetic retinopathy (DR) in non-insulin dependent diabetes in Taiwan. METHODS: A retrospective review of type II diabetic patients in the Diabetes Shared Care System database of our Hospital enrolled from 2002 to 2009. A retinopathy severity score was assigned according to fundus examination by indirect ophthalmoscopy or binocular biomicroscopy. RESULTS: Data was collected on 901 subjects, 497 males and 404 females. Of these, 230 (25.53 %) had DR at enrolment. Compared with patients without DR, those with DR were more likely to be female (p = 0.03) or have higher HbA1c (p < 0.001), longer duration of diabetes (p < 0.001), hypertension (p < 0.001), higher systolic blood pressure (p < 0.001), higher diastolic blood pressure (p = 0.05), as well as impaired renal function (p = 0.001). In subgroup analysis stratified by diabetes duration, HbA1c was the most consistent independent risk factor associated to the prevalence of DR. Higher systolic blood pressure and female sex were significantly independent risk factors only in patients with a duration of diabetes < 4 years. On the contrary, old onset age showed a protective effect against DR only in those with a disease duration > 8 years. CONCLUSIONS: High HbA1c level was the most important factor associated with prevalence of DR in Taiwanese type II DM patients with a fixed duration.

Elevated serum retinol-binding protein 4 concentrations are associated with chronic kidney disease but not with the higher carotid intima-media thickness in type 2 diabetic subjects.

To examine the association of serum retinol-binding protein 4 (RBP4) concentrations with carotid intima-media thickness (CIMT) in type 2 diabetic subjects with chronic kidney disease (CKD). A total of 239 type 2 diabetic patients (64 ± 13 years, 154 males) were divided into two groups: one with CKD, defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m(2) (n = 86), and one without (n = 153). We recorded clinical and biochemical data as well as CIMT. The patients with CKD were older, had had diabetes mellitus longer, and had higher incidence of hypertension, dyslipidemia and microalbuminuria than those without. They also had higher serum concentrations of RBP4 (44.8 ± 6.4 vs 39.5 ± 4.9 µg/mL, p < 0.001), higher mean CIMT (0.75 ± 0.16 vs 0.69 ± 0.14 mm, p = 0.0070), and higher incidence of carotid plaques (27.9 vs 11.8 %, p = 0.002). The RBP4 were negatively correlated with eGFR (r = -0.514, p < 0.001). However, the RBP4 were not correlated with mean CIMT (r = 0.065, p = 0.318). Moreover, when dividing the patients into two groups by the mean CIMT, those with mean CIMT above 0.71 mm did not have different RBP4 concentrations compared with those below (41.5 ± 5.7 vs 41.3 ± 6.3 µg/mL, p = 0.856). In conclusion, we observed an elevation of serum RBP4 concentrations and CIMT levels in type 2 diabetic subjects with CKD. However, the elevated RBP4 were not associated with the higher CIMT among these patients.

Patterns and their correlates of seeking treatment for erectile dysfunction in type 2 diabetic patients.

INTRODUCTION: Diabetic patients are at high risk of having erectile dysfunction (ED), but their doctors rarely pay attention to this association. AIM: To evaluate the treatment-seeking patterns and their correlates for ED in type 2 diabetic patients. METHODS: A questionnaire containing Sexual Health Inventory for Men and questions inquiring treatment-seeking patterns was mailed or given to 4,040 subjects who had visited our endocrinology outpatient department for diabetes during January 2004 to May 2006. MAIN OUTCOME MEASURES: The prevalence of being bothered and having interest in treatment, and the percentage having sought treatment in regard to ED and their correlates with age and ED severity. RESULTS: Of the subjects with questionnaire completed, 83.9% (708/844) had ED. Among the subjects with different severity of ED, the moderate group had the highest percentages regarding prevalence of being bothered (89.4%), having interest in treatment (78.5%), and having sought treatment (46.2%). Of all the subjects, only 14.2% had ever visited Western physicians, whereas embarrassment and misinformation about ED treatment were the leading reasons for never doing so. Over half (56.6%) of those with ED wished to discuss ED problem with their doctors, and of them 90.4% wished the doctors to initiate to broach this issue. CONCLUSIONS: The prevalence of ED and the concerns about it were high in these diabetic patients. ED severity was the major determinant of their treatment-seeking decision, whereas only few of them had ever sought professional help. Routine screening of ED in diabetic patients is recommended.

Association of glycemic control with risk of erectile dysfunction in men with type 2 diabetes.

INTRODUCTION: Improvement in glycemic control is likely to reduce the risk of diabetic complication, while its effect on erectile dysfunction (ED) remains unclear. AIM: The aim of this study was to evaluate the association of glycemic control with risk of ED in type 2 diabetics. METHODS: A self-administered questionnaire containing Sexual Health Inventory for Men was obtained from 792 subjects with type 2 diabetes at our institution. Clinical data were obtained through chart review. MAIN OUTCOME MEASURES: The contribution of glycemic control assessed by glycated hemoglobin (HbA(1c)) level as well as age, duration of diabetes, hypertension (HT), dyslipidemia, and cigarette smoking to risk of ED was evaluated. RESULTS: Of 792 subjects, 83.6% reported having ED and 43.2% had severe ED. HbA(1c) level (%) adjusted for age and duration of diabetes was significantly associated with ED (OR 1.12, 95% CI: 1.01-1.25). None of HT, dyslipidemia, and cigarette smoking was a significant risk factor for ED after adjusted for age and duration of diabetes. HbA(1c) level, age, and duration of diabetes were significant independent risk factors for ED among the younger group (age < or = 60 years), and only age and duration of diabetes were independent risk factors among the older group (age > 60 years). For the risk of severe ED, compared with no and mild to moderate ED, HbA(1c) level, duration of diabetes, and HT were independent risk factors among the younger group, and only age was an independent factor among the older group. CONCLUSIONS: Better glycemic control probably would reduce the prevalence of ED and its severity among the younger men with type 2 diabetes. For the older group, aging was the major determinant for ED risk among this population with type 2 diabetes.

Common hemoglobin variants in southern Taiwan and their effect on the determination of HbA1c by ion-exchange high-performance liquid chromatography.

BACKGROUND: Patients with hemoglobin (Hb) variants may produce false HbA1c measurement. This study aimed to detect the common Hb variants in southern Taiwan and to evaluate their effect on the determination of HbA1c. METHODS: A total of 1,434 samples collected for HbA1c measurement at Kaohsiung Veterans General Hospital in southern Taiwan in March 2008 were submitted for Hb variant analysis by Primus CLC-385. HbA1c measurements were obtained using ion-exchange high-performance liquid chromatography (HPLC) (Tosoh HLC-723 G7) for routine analysis. Patients identified with Hb variants were recalled for boronate-affinity HPLC analysis. The values of estimated average glucose (eAG) were converted from HbA1c. Values of eAG-FPG, calculated by eAG minus fasting plasma glucose (FPG), were compared to estimate the accuracy of HbA1c measurement in patients with Hb variants. RESULTS: Among the 1,434 patients, the mean standard deviation of FPG was 162.8 +/- 60.5 mg/dL, HbA1c was 8.28 +/- 1.97%, and eAG was 190.9 +/- 56.6 mg/dL. Five Hb variants were detected in 11 patients, the incidence being 0.76%. Hb J was identified in 4 patients, Hb G in 2 patients, Hb E in 1 patient, Hb owari in 3 patients, and high fetal hemoglobin (HbF) in 1 patient. Abnormal HPLC chromatograms were seen among the patients with Hb J, E, G and HbF, but not in the patients with Hb owari. In patients with Hb variants, FPG was 149.5 +/- 39.9 mg/dL, HbA1c was 7.29 +/- 2.01%, and eAG was 162.5 +/- 57.7 mg/dL. Lower values of eAG-FPG may have occurred in the patients with Hb J and E, and in those with high HbF. On scattergrams of the relationship between HbA1c and FPG, the plots of Hb J, E and high HbF lay below the regression line of non-Hb variants. Inconsistent Hb values between both methods were only observed among some samples of patients with Hb variants. CONCLUSION: The existence of Hb variants may result in false HbA1c measurement. The possible presence of spuriously low HbA1c levels or abnormal HPLC chromatograms by using ion-exchange methods should be kept in mind.

Correlates of depression in type 2 diabetic elderly patients: a correlational study.

OBJECTIVES: This aim of this study was to investigate depression and related factors in elderly patients (65 years) with type 2 diabetics. METHODS: The study utilized a descriptive-correlational design. Convenience sampling was applied to enroll 156 subjects, aged >or= 65 years from diabetic outpatient clinics at three hospitals in Kaohsiung. This study applied the Personal Resource Questionnaire 2000 (PRQ 2000), Taiwan Geriatric Depression Scale (TGDS), and a form for demographic data. RESULTS: (1) The mean index score for depression level was 26, indicating that study subjects had a low level of depression. The social support index score was 76. (2) Significant differences in TGDS scores existed for diabetes duration, diabetes complications, and treatment type. (3) Social support and regular exercise were significantly and negatively correlated with depression. (4) Social support and diabetes complications were significant correlates of depression and accounted for 25.9% of variance in depression. CONCLUSION: Analytical results may assist nurses in understanding depression and related factors for diabetic patients aged >or= 65. Therefore, this study could form a basis for caring older people with diabetes, and provide a reference for further research.

Ten-eleven translocation 1 dysfunction reduces 5-hydroxymethylcytosine expression levels in gastric cancer cells.

A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry. The results revealed that 5hmC expression levels were markedly lower in gastric cancer tissues compared with corresponding adjacent normal tissues. Furthermore, a decrease in 5hmC expression levels was associated with a decrease in TET1 protein expression levels in gastric cancer tissues. The ectopic expression level of TET1 may increase the 5hmC expression level in gastric cancer cells. In addition, the results revealed that TET1 protein expression was markedly different in regards to subcellular localization, and mislocalization was significantly associated with the depletion of 5hmC expression levels in gastric cancer. Together, the results of the present study indicated that TET1 dysfunction reduces 5hmC expression levels, and this phenomenon may serve a crucial role in gastric cancer progression.

Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan.

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.

Elevated serum anti-endothelial cell autoantibodies titer is associated with lupus nephritis in patients with systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease associated with endothelial dysfunction and the existence of multiple species of autoantibodies. However, the association between endothelial dysfunction and renal manifestations remains unclear in Taiwanese SLE patients. METHODS: Serum samples were collected from SLE patients with biopsy-proven lupus nephritis (n = 32), stable SLE patients (n = 32) and healthy controls (n = 32). The SLE Disease Activity Index (SLEDAI) of SLE patients was scored, and levels of anti-endothelial cell antibodies (AECA) and anti-endothelial activities in serum samples were measured by cell-enzyme-linked immunosorbent assay and crystal violet assay, respectively, using cultured human endothelial EA.hy926 cells. RESULTS: Significantly higher AECA (p<0.001) and anti-endothelial activities (p<0.001) were found in sera from patients with lupus nephritis compared with that from stable SLE patients or controls. Moreover, AECA titers (p<0.001) and anti-endothelial activities (p<0.001) were strongly correlated with SLEDAI scores in these patients. CONCLUSION: The strong correlations of AECA and anti-endothelial activity with lupus nephritis activity support an endothelial origin for renal complications in Taiwanese SLE patients.

Modulation of angiogenic processes in cultured endothelial cells by low density lipoproteins subfractions from patients with familial hypercholesterolemia.

OBJECTIVE: Electronegative low density lipoprotein (LDL) subfractions are cytotoxic to endothelial cells. To continue our study of homozygotic familial hypercholesterolemic (FH)-LDL, we report the effects of FH-LDL subfractions (FH-L1 to FH-L5) on the angiogenic processes in cultured endothelial cells. METHODS AND RESULTS: Subconfluent bovine aortic endothelial cells (BAEC) were treated with LDL subfractions (20 microg/ml), and the effects on angiogenic functions, including cell proliferation, migration, apoptosis, tube formation, secretion of matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) were determined. The electronegative FH-L4 and FH-L5 inhibited cell proliferation while the other FH-LDL subfractions and LDL from normocholesterolemic subjects (N-LDL) had negligible effects. Like Cu2+ ox-LDL, FH-L5 strongly inhibited endothelial cell viability and FH-L4 had a milder effects. Similarly, FH-L4 and FH-L5 but not the other subfractions retarded cell migration, induced cell apoptosis, and perturbed tube formation by BAEC in matrigel. FH-L5 inhibited secretion of MMP-2 and MMP-9 by BAEC without affecting their endogenous levels. In contrast, FH-L5 increased the VEGF expression in endothelial cells. CONCLUSIONS: Our results show for the first time that FH-L5, a circulating LDL subfraction from hypercholesterolemic patients, modulates various angiogenic processes, thereby dysregulating endothelial function in a way that may be atherogenic.

Blockade of endothelin-1 release contributes to the anti-angiogenic effect by pro-opiomelanocortin overexpression in endothelial cells.

Pro-opiomelanocortin (POMC) is the precursor of several neuropeptides, such as corticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and the endogenous opioid, beta-endorphin (EP). ACTH-dependent Cushing's syndrome is characterized by ACTH overproduction and is associated with an increased risk of cardiovascular disease. Endothelial dysfunction has been recognized as an early marker of cardiovascular disease. However, the mechanism underlying endothelial dysfunction by ACTH overexpression in Cushing's patients remains elusive. Endothelial cells, the primary cells producing endothelin (ET)-1, are both the source and target of POMC-derived peptides. In the present study, we generated adenovirus vectors (Ad) encoding POMC (Ad-POMC) and green fluorescent protein (GFP; Ad-GFP) to investigate whether POMC gene transfer altered the ET-1 homeostasis and angiogenic functions in human EA.hy926 endothelial cells. Via adenovirus gene delivery, the POMC-transduced EA.hy926 cells released significantly elevated ACTH and beta-EP levels (P < 0.001). In addition, POMC gene delivery significantly decreased the ET-1 release (P < 0.001) without affecting the ET-1 messenger RNA (mRNA) level. Despite no effect on the secretion of matrix metalloproteinases (MMPs) and cell proliferation, POMC gene delivery significantly inhibited the migration (P < 0.01) and tube-forming capability (P < 0.01) of endothelial cells. Moreover, the POMC-induced inhibition of tube formation could be partially reversed by adding exogenous ET-1 (P < 0.05). In summary, the attenuated ET-1 release and angiogenic processes by POMC overexpression may contribute to endothelial dysfunction, thereby providing a link between Cushing's syndrome and cardiovascular diseases.

Hyperthyroidism is associated with higher plasma endothelin-1 concentrations.

The objective of this study was to determine the change of plasma endothelin (ET)-1 concentrations and insulin resistance index after therapy for hyperthyroidism. We studied 20 patients with hyperthyroidism (15 women and 5 men; age, 34.0 +/- 2.8 years), and 31 patients with euthyroid goiters as controls (27 women, 4 men; age, 37.0 +/- 2.4 years). All hyperthyroid patients were treated with antithyroid drugs. The patients received evaluations before and after normalization of thyroid function. The evaluations included body mass index (BMI), body fat, and measurement of circulating concentrations of thyroid hormones, glucose, insulin, and ET-1. Hyperthyroid subjects had higher plasma ET-1 concentrations than the control group (P < 0.001). No significant differences in serum glucose and insulin concentrations or insulin resistance index estimated by the R value of the homeostasis model assessment (HOMA-R) were noted between the groups. Plasma ET-1 concentrations decreased after correction of hyperthyroidism compared with pretreatment (P = 0.006). Serum glucose concentrations decreased after correction of hyperthyroidism (P = 0.005). Moreover, both body weight-adjusted insulin concentrations and the HOMA-R index were also decreased after correction of hyperthyroidism compared with pretreatment (P = 0.026 and P = 0.019, respectively). Pearson's correlation revealed that plasma ET-1 levels positively correlated with serum triiodothyronine (T3) and free thyroxine (FT4) levels. Serum insulin levels and the HOMA-R index positively correlated with BMI and body fat. The HOMA-R index also positively correlated with serum T3 and FT4 levels. Neither insulin levels nor the HOMA-R index correlated with ET-1 levels. Hyperthyroidism is associated with higher plasma ET-1 concentrations. In addition, correction of hyperthyroidism is also associated with a decrease of plasma ET-1 levels as well as the insulin resistance index calculated by HOMA-R.

The effects of different doses of atorvastatin on plasma endothelin-1 levels in type 2 diabetic patients with dyslipidemia.

We investigated the effects of three different daily doses (10 mg, 20 mg, and 40 mg) of atorvastatin, a relatively new and potent statin, on plasma endothelin (ET)-1 and highly sensitive C-reactive protein (CRP) levels in type 2 diabetic subjects. Twenty-nine type 2 diabetic patients with dyslipidemia were enrolled and randomly assigned to receive atorvastatin orally at 10 mg (A10; n = 10), 20 mg (A20; n = 10), or 40 mg (A40; n = 9) daily for 12 weeks. Levels of plasma total cholesterol and low-density lipoprotein (LDL)-cholesterol (C) in all three studied groups were significantly decreased after treatment with atorvastatin for 12 weeks (all groups, P < 0.001). However, the greatest LDL-C lowering effect and the highest percentage of subjects achieving the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) LDL-C goal were observed in the A20 group. All diabetic subjects had a higher plasma ET-1 concentration (A10, 1.02 +/- 0.37 pg/ml, mean +/- SD; A20, 1.17 +/- 0.55 pg/ml; and A40, 0.87 +/- 0.45 pg/ml) than that of age- and sex-matched normal control subjects (0.64 +/- 0.15 pg/ml; all groups, P < 0.001). Plasma ET-1 levels showed a borderline significant decrease at the end of study, by 22% in diabetic subjects treated with 10 mg atorvastatin (P = 0.05 compared with baseline), and by 30% in subjects treated with 20 mg atorvastatin (P = 0.06, compared with baseline). Paradoxically, the 40-mg dose of atorvastatin provided an increase of 2% in plasma ET-1 levels at the end of study, which is significantly different (P < 0.05) and marginally significant (P = 0.057) from the levels of the 10- and 20-mg doses, respectively. Similarly, although insignificantly, plasma concentrations of CRP also tended to decrease by 12% and 48%, and paradoxically increased by 18% in diabetic patients treated with 10 mg, 20 mg, and 40 mg atorvastatin, respectively. The clinical significance of these biphasic lipid-independent statin effects is unknown and the present study suggests that 20 mg atorvastatin may have the best benefits in treating diabetic patients with dyslipidemia.

Risk of skin cancer in patients with diabetes mellitus: A nationwide retrospective cohort study in Taiwan.

Increasing evidence suggests that certain types of cancers are more common in people with diabetes mellitus (DM). This study aimed to investigate the risk of skin cancer in patients with DM in Taiwan. In this retrospective cohort study using data from the Taiwan Longitudinal Health Insurance Research Database, the risk of developing overall skin cancer, including nonmelanoma skin cancer (NMSC) and melanoma, was compared by Poisson regression analysis and Cox regression analysis between the DM and non-DM cohorts. The DM cohort with newly diagnosed DM (n = 41,898) and a non-DM cohort were one-to-one matched by age, sex, index date, and comorbidities (coronary artery disease, hyperlipidemia, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and obesity). Compared with non-DM cohort statistically, for the people with DM aged ≥60 years, the incidence rates of overall skin cancer and NMSC were significantly higher (overall: DM/non-DM: number [n] = 99/76, incidence rate ratio [IRR] = 1.44, P = 0.02; NMSC: DM/non-DM: n = 94/66, IRR = 1.57, P = 0.005). By Cox regression analysis, the risk of developing overall skin cancer or NMSC was significantly higher after adjusting for sex, comorbidities, and overall diseases with immunosuppression status (overall: adjusted hazard ratio [AHR] = 1.46, P = 0.01; NMSC: AHR = 1.6, P = 0.003). Other significant risk factors were older males for skin cancer (overall: AHR = 1.68, P = 0.001; NMSC: AHR = 1.59, P = 0.004; melanoma: AHR = 3.25, P = 0.04), chronic obstructive pulmonary disease for NMSC (AHR = 1.44, P = 0.04), and coronary artery disease for melanoma (AHR = 4.22, P = 0.01). The risk of developing melanoma was lower in the DM cohort than in the non-DM cohort, but without significance (AHR = 0.56, P = 0.28; DM/non-DM: n = 5/10). The incidence rate and risk of developing overall skin cancer, including NMSC, was significantly higher in older adults with DM. Other significant risk factors for older adults with DM were males for NMSC and melanoma, chronic obstructive pulmonary disease for NMSC, and coronary artery disease for melanoma.

Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells.

The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression.

Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer.

MicroRNAs (miRNAs) are short noncoding RNAs derived from the 3' and 5' ends of the same precursor. However, the biological function and mechanism of miRNA arm expression preference remain unclear in breast cancer. We found significant decreases in the expression levels of miR-193a-5p but no significant differences in those of miR-193a-3p in breast cancer. MiR-193a-3p suppressed breast cancer cell growth and migration and invasion abilities, whereas miR-193a-5p suppressed cell growth but did not influence cell motility. Furthermore, NLN and CCND1, PLAU, and SEPN1 were directly targeted by miR-193a-5p and miR-193a-3p, respectively, in breast cancer cells. The endogenous levels of miR-193a-5p and miR-193a-3p were significantly increased by transfecting breast cancer cells with the 3'UTR of their direct targets. Comprehensive analysis of The Cancer Genome Atlas database revealed significant differences in the arm expression preferences of several miRNAs between breast cancer and adjacent normal tissues. Our results collectively indicate that the arm expression preference phenomenon may be attributable to the target gene amount during breast cancer progression. The miRNA arm expression preference may be a means of modulating miRNA function, further complicating the mRNA regulatory network. Our findings provide a new insight into miRNA regulation and an application for breast cancer therapy.