FREE THYROID HORMONES AND MORTALITY IN CAUCASIANS UNDERGOING ANGIOGRAPHY: THE LUDWIGSHAFEN RISK AND CARDIOVASCULAR HEALTH (LURIC) STUDY.

OBJECTIVE: Alterations in thyroid hormone functions are associated with mortality and morbidity. Data on euthyroid individuals are very limited and controversial. We therefore investigated the relationship between circulating thyroid hormones and all-cause and cardiovascular (CV) mortality in participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and their association with morbidity. METHODS: LURIC, a prospective, observational study of a hospital-based cohort of Caucasians, was recruited between June 1997 and May 2001 at the Ludwigshafen General Hospital, Ludwigshafen, Germany. Mortality was recorded for a follow-up period of 10 years. The current investigation includes 2,507 patients without overt thyroid disease who all underwent coronary angiography. Blood was drawn before angiography. We evaluated the association between thyroid hormone concentrations and mortality. RESULTS: Low free triiodothyronine (FT3) (hazard ratio [HR], 1.00 versus 0.54; lowest versus highest quartile) and high free thyroxine (FT4) (HR, 1.52 versus 1.00; highest versus lowest quartile) were significant predictors of all-cause and CV mortality, independent of age and sex. Thyroid-stimulating hormone showed no consistent correlation with mortality. CONCLUSION: High FT4 and low FT3 concentrations are significantly related to all-cause and CV mortality. These findings suggest that free thyroid hormones should be measured and considered in patients at intermediate to high risk of coronary heart disease. ABBREVIATIONS: BMI = body mass index CAD = coronary artery disease CCI = Charlson Comorbidity Index CI = confidence interval CV = cardiovascular eGFR = estimated glomerular filtration rate FT3 = free triiodothyronine FT4 = free thyroxine HR = hazard ratio T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia.

OBJECTIVE: Dyslipidemia in patients with type 2 diabetes is characterized by elevated triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and a predominance of small dense low-density lipoprotein (LDL) particles. Also, patients suffer from ß-cell dysfunction, chronic systemic inflammation, increased hormonal visceral adipose tissue activity, and an increased risk of cardiovascular events. The aim of our study was to investigate the effect of a fixed pioglitazone + metformin (PM) combination (vs. glimepiride + metformin [GM]) on diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: A total of 288 type 2 diabetes patients completed this double-blind parallel study (187 men, 101 women; age [mean ± SD], 59 ± 10 years; body mass index, 32.6 ± 5.1 kg/m(2); hemoglobin A1c [HbA1c], 7.3 ± 0.8%). They were randomized to PM or GM for 6 months. Observation parameters at baseline and end point included HDL, LDL, triglycerides, fasting insulin, fasting glucose, total adiponectin, intact proinsulin, and high-sensitivity C-reactive peptide (hsCRP). RESULTS: HDL increased in the PM group by 0.08 ± 0.25 mmol/L (GM, -0.01 ± 0.2.8 mmol/L; P < 0.001 vs. PM), whereas LDL increased in both groups (GM, 0.25 ± 0.90 mmol/L; PM, 0.29 ± 0.66 mmol/L; difference not significant between groups). Improvements were seen for triglycerides (PM, -0.47 ± 1.30; GM, -0.19 ± 1.39 mmol/L), HbA1c (PM, -0.8 ± 0.9%; GM, -1.0 ± 0.9%), and glucose (PM, -1.2 ± 2.1; GM, -1.2 ± 2.2 mmol/L). Decreases in fasting insulin (PM, -5.2 ± 11.9; GM, -0.1 ± 9.8 µU/mL; P < 0.001 between groups), hsCRP (PM, -0.9 ± 1.9; GM, 0.0 ± 1.8 mg/L; P < 0.001), and fasting intact proinsulin (PM, -5.5 ± 11.1; GM, -0.1 ± 10.0 pmol/L; P < 0.001) and an increase in adiponectin (PM, +6.8 ± 6.4 mg/L; GM, +0.7 ± 2.7 mg/L; P < 0.001) were seen in the PM arm, only. CONCLUSIONS: With comparable glycemic control, the fixed PM combination was more efficacious on HDL cholesterol improvement than the GM combination. Additional positive effects were observed for biomarkers of lipid metabolism, ß-cell function, activity of the visceral adipose tissue, and chronic systemic inflammation.