OBJECTIVEHypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown.RESEARCH DESIGN AND METHODSThe study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.RESULTSThere were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]).CONCLUSIONSSymptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.

To evaluate the impact of gene polymorphisms of Cytochrome P450 2C9 (CYP2C9), Vitamin K epoxide reductase complex subunit 1 (VKORC1) and Cytochrome P450 4F2 (CYP4F2) and clinical factors on warfarin maintenance dose in Han-Chinese patients from main land. DNA was extracted from 115 patients taking warfarin for more than 3 months with a stable international normalized ratio (INR) and genotyped for CYP2C9*3, VKORC1-1639 and CYP4F2 (rs2108622) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Univariate analysis and multiple regression analysis were undertaken to assess the effect of genetic and clinical factors on the warfarin maintenance dose. Our study demonstrated that patients carrying CYP4F2 CT or TT allele needed a significantly higher warfarin dose compared to those carrying CC ((3.36 ± 0.14 mg/d vs. 2.77 ± 0.14 mg/d), P = 0.004). We also confirmed CYP2C9 *3 variant was related to lower warfarin dose (2.01 ± 0.23 mg/d) requirement compared to wild type (3.21 ± 0.11 mg/d) (P = 0.001). VKORC1-1639 AG genotype was associated with a higher maintenance dose compared to those with the AA genotype (4.06 ± 0.21 mg/d vs. 2.95 ± 0.11 mg/d, P < 0.001). The multiple linear regression model including VKORC1-1639G>A, CYP2C9, CYP4F2 and clinical factors (body surface area (BSA) and age) could explain 42 % of the variance in the warfarin maintenance dose. We developed a dose algorithm based on genetic polymorphism and clinical variables for Han-Chinese patients and evaluated its performance. CYP4F2 rs2108622 has a small but significant association with warfarin stable dose in Han-Chinese population.

AimsInflammation contributes to increased cardiovascular morbidity and mortality associated with activation of the reninangiotensin -aldosterone system. The aim of this study was to investigate whether eplerenone, a selective aldosterone receptor antagonist, has anti-inflammatory effects on viral myocarditis. Methods and resultsFour-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the encephalomyocarditis (EMC) virus. Mice were fed with standard chow (control) or with chow containing 2.5 mg/kg of eplerenone, starting either on day 0 (inoculation) or day 7. Survival at 28 days was significantly higher in the mice which started eplerenone treatment on day 0 (35 vs. 15% in controls, each n ¼ 40, P , 0.05). The area of myocardial fibrosis on day 28 was significantly smaller in the eplerenone-treated mice than in controls (19.8 + 2.6%, n ¼ 14, vs. 33.4 + 5.4%, n ¼ 6, mean+SEM, P , 0.05). Gene expression of mouse mast cell proteases-4 and -5, matrix metalloproteinase-9, and type I procollagen on day 6 after EMC virus inoculation was significantly decreased in the hearts of eplerenone-treated mice. ConclusionThese results suggest that eplerenone has anti-inflammatory effects, and exerts its beneficial effects on viral myocarditis by suppression of genes related to mast cells and cardiac remodelling in the hearts of mice.--

Elderly individuals with abdominal obesity and low skeletal muscle mass have higher all-cause and cardiovascular mortality risk.