Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement.

OBJECTIVE: Intrinsic imperfections of thyroid hormone replacement therapy may affect long-term general well-being. In patients with Hashimoto thyroiditis (HT), cognitive functioning may be affected via altered thyroid hormones action as well as by the autoimmune process. The aim of this study was to evaluate cognitive function and quality of life (QoL) in patients on long-term levothyroxine replacement for HT in relation to thyroid function tests and TPO (thyroid-peroxidase) antibody (TPOAb) status. DESIGN: Retrospective cross-sectional study. PATIENTS AND MEASUREMENTS: One-hundred-and thirty patients with HT on long-term levothyroxine replacement and 111 euthyroid control subjects. Both groups were divided into two age subgroups, 20-49 years (N = 59 vs N = 79) and > 50 years (N = 71 vs N = 32). Evaluation included biochemical and neuropsychological tests, evaluating attention, global cognitive status, verbal and working memory, executive function, depression and anxiety, and quality of life. We used ANOVA and partial correlations to test for significant associations. RESULTS: FT4 (free-thyroxine), FT3 (free-triiodothyronine) levels and FT3/FT4 ratio were not different between patients and controls. Mean TSH (thyroid-stimulating hormone) was normal in all subjects but significantly higher in the patients (20-49 yrs:3.64 ± 2.74 vs 1.93 ± 1.10, >50 yrs:3.93 ± 2.84 vs 1.91 ± 0.90). Antibodies (TgAb,TPOAb) were higher in patients. Global cognitive function (MMSE-Mini mental state examination), conceptual tracking (TMT-Trail Making Test:A/B), verbal divergent thinking (like Phonemic fluency test), and anxiety and depression scores were significantly worse in patients vs controls. QoL was impaired in patients. there was a significant negative correlation between antibodies (TPOAb, TgAb) and quality in life (total SF36 score). CONCLUSION: Patients on long-term levothyroxine replacement show persistent impairments in both cognitive functioning and general well-being.

Oxidized Low Density Lipoprotein and High Sensitive C-Reactive Protein in Non-Diabetic, Pre-Diabetic and Diabetic Patients in the Acute Phase of the First Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

BACKGROUND: Oxidized low density lipoprotein (ox-LDL) and high-sensitive C-reactive protein (hs-CRP) are elevated in diabetes mellitus (DM) and associated with accelerated atherosclerosis. Little is known about their dynamics in the acute phase of ST segment elevation myocardial infarction (STEMI), especially in relation to the presence of DM and pre-diabetes (pre-DM). This study aimed to analyze time-dependent changes in ox-LDL and hs-CRP regarding the presence of pre-DM and DM in STEMI patients treated by primary percutaneous coronary intervention (pPCI). METHODS: In 103 consecutive patients with the first anterior STEMI ox-LDL and hs-CRP were measured before pPCI, on day 2 and day 7 after pPCI. RESULTS: Patients were classified into: non-diabetics, pre-diabetics and diabetics. In each group the maximal ox-LDL concentration was found on admission, decreased on day 2 and reached the lowest values on day 7 (p<0.001). Diabetics had the highest ox-LDL concentrations compared to pre-diabetics and non-diabetics (on admission: p=0.028, on day 2: p=0.056, on day 7: p=0.004). hs-CRP concentration rose from admission, reached its peak on day 2 and decreased on day 7, in each group (p<0.001). Significant differences in hs-CRP concentrations were found between non-diabetics and pre-diabetics on admission (p=0.018) and day 2 (p=0.026). In a multivariate analysis DM was an independent determinant of high ox-LDL concentrations. Both ox-LDL and hs-CRP significantly correlated with Killip class, left ventricular ejection fraction, NT-proBNP and peak troponin I. CONCLUSIONS: In patients with the first STEMI treated by pPCI there were significant differences in ox-LDL and hs-CRP concentrations between non-diabetics, pre-diabetics and diabetics. Ox-LDL and hs-CRP concentrations were related to heart failure parameters.

Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function.

BACKGROUND: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). METHODS: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. RESULTS: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). CONCLUSION: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

[Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly].

BACKGROUND/AIM: It has been proved that a highly sensitive C-reactive protein (hsCRP) can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt) would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. METHODS: The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, non-HDL-C, hemoglobin Alc (HbA1c) were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women) were divided into three groups according to their hsCRP levels: a low (< 1 mg/L, n=70), average (1 to 3 mg/L, n=69), and high (3-10 mg/L, n=69) hsCRP group. Associations of all-cause Mt with different risk factors were examined using logistic regression analysis. RESULTS: The hsCRP level showed a significant positive correlation with waist (r = 0.199, p = 0.004) and hip (r = 0.187, p = 0.007) circumferences, body mass index (r = 0.143, p = 0.040) and serum triglyceride level (r = 0.139, p = 0.045) and significant negative correlation with HDL-C (r = -0.164, p = 0.018). Ratios TC/HDL-C and TG/HDL-C were significantly smaller in the low hsCRP group compared to the average hsCRP group (p = 0.019,p = 0.045, respectively) and without significant differences compared with the high hsCRP group. Two years after the baseline examination 22.1% participants died from all-cause Mt. After adjustment for other risk factors, a TC was significantly associated with all-cause Mt only in high hsCRP group: Odds ratio (OR) = 3.71 (95% confidence interval-CI: 1.09-12.63). CONCLUSIONS: In this study a high hsCRP was an important factor to identify functionally dependent elderly at high risk who may have more benefit from agressive lipid lowering treatment.

[Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance].

Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA beta index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA beta) and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA beta index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

[Oxidized LDL and lipids as risk factors for ischemic heart disease in type 2 diabetes].

BACKGROUND: [corrected] Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). Factors that contribute to endothelial cell dysfunction associated with the initiation of atherosclerosis include oxidative stress. The aim of this study was to investigate the relationship between lipid profile and oxidative stress in type 2 diabetics with and without ischemic heart disease (IHD). METHODS: We studied 80 patients with T2D, 40 with IHD (group A1) and 40 without IHD (group A2). We also studied 51 non-diabetics, 31 with IHD (group B1), and 20 without IHD (group B2 control group). Lipid profile was estimated by the total cholesterol, HDL cholesterol, LDL cholesterol, the level of triglyceride (Tg), lipoproteina a (Lp a), Apo A I, A II, B 100 and E. To evaluate the oxidative status we measured circulating oxidized LDL (ox LDL), erythrocyte antioxidative enzyme activity: superoxide dismutase (E-SOD), glutathione peroxidase (E-GPX), as well as the total antioxidative serum activity (TAS). Inflammatory reaction was estimated by C-reactive protein (CRP) and fibrinogen. RESULTS: No significant difference was found in the lipid profile in groups A1, A2 and B1, but the group B2 had the lowest one. Lp a level was significantly higher in group B1 comparing to other groups (p < 0.05). There was no significant difference in the level of ox LDL between the groups. In diabetics, ox LDL positively correlated with the total cholesterol, LDL cholesterol, non HDL cholesterol, Apo B 100 and the relations between LDL/HDL and Tg/HDL (p < 0.001), as well as with Tg and fibrinogen (p < 0.05). In group B1, ox LDL positively correlated with total cholesterol, Tg (p < 0.01), LDL, and non HDL cholesterol (p < 0.05) and significantly with Apo B 100 (p < 0.001). There was no significant difference in the antioxidant enzyme activities between the groups of diabetics (A1 and A2), but fibrinogen was higher in the group with IHD (group A1, p < 0.05). Group B1 had lower E-SOD activity than the groups A1 and A2 (p < 0.05), but CRP was higher (p < 0.05). There were no significant correlations between oxLDL and CRP in groups A1 and A2, but it was statistically significant in the group B1 (p < 0.05). CONCLUSION: In this study we demonstrated the increased oxidative stress in diabetics compared to non-diabetics regardless of the presence of IHD. Fibrinogen, but not CRP, was higher in diabetics with IHD, compared to diabetics without IHD. The increased oxidative stress, the reduced antioxidative activity E-SOD, and the higher level of CRP were found in non-diabetics with IHD compared to non-diabetics without IHD.

[Relationship between low glomerular filtration rate, hypertension, and microalbuminuria in type 1 diabetes mellitus].

AIM: To investigate the influence of low glomerular filtration rate, as well as of systolic and diastolic hypertension, on microalbuminuria in patients with type 1 diabetes mellitus. METHODS: Twenty seven patients with type 1 diabetes mellitus (18 males, 9 females) were studied. All of the patients were below 50 years of age. In 93% of the cases, the duration of diabetes was less than 15 years. GFR was determined, after intravenous injection in the lying position, by using a 99m-Tc-DTPA, while microalbuminuria was calculated for the 24-hour urine using the nephelometric immunoassay (30-300 mg/24 h). The patients were divided into 3 groups according to the value of GFR. The values ranged from 90 to 125 ml/min/1.73 m2 were considered normal (in 63% of the patients in group 1), those above that range were considered as hyperfiltration (in 22.2% of the patients in group 2), while those below that range were considered as hypofiltration (in 13.8% of the patient in group 3). RESULTS: Data analyzed with the one-way ANOVA, indicated a significant statistical difference between the 3 groups in the duration of diabetes (p < 0.05), micro-albuminuria (p < 0.01), systolic BP (p < 0.01), diastolic BP (p < 0.05), fructosamine (p = 0.50), urea (p < 0.05), creatinine (p = 0.05), and uric acid (p < 0.05). Microalbuminuria correlated with the age of patients (p <0.05) (Spearman's rho), diabetes mellitus duration (p < 0.01), systolic BP (p < 0.05), diastolic BP (p < 0.05), LDL-cholesterol (p < 0.05). There was no statistically significant correlation between GFR and the other parameters. Hypertension, microalbuminuria, and the duration of diabetes correlated positively with the reduction of GFR, revealing the most frequent reduction of GFR in the patients with more than 15-year duration of diabetes. CONCLUSIONS: Hypertension and low GFR were associated with microalbuminuria in type 1 diabetes, while the duration of diabetes was shown to be the independent risk factor for the development of microalbuminuria.

[Effect of glycemic control on microalbuminuria and arterial blood pressure in patients with type 1 diabetes].

INTRODUCTION: Diabetic nephropathy is the leading cause of hypertension in type 1 diabetes. Microalbuminuria is usually the first manifestation of renal disease and antedate hypertension. The aim of this study was to investigate relationships between glycemic control, hypertension and microalbuminuria in type 1 diabetics. MATERIAL AND METHODS: We studied 27 type 1 diabetics, 18 male and 9 female, aged 18-50 years, with a duration of diabetes <20 years. Glycemic control was assessed using glycosylated hemoglobin (HbA1c) measurements, fructosamine and lipid analysis. 24-h urinary albumin excretion rate was evaluated by radioimmunoassay. Patients with persistent urinary albumin excretion rate 30-300 mg/24 h were defined as microalbuminuric (Group A--41% patients) and lower than that, as normoalbuminuric (Group B--59%). We examined them twice: first in poor glycemic control and then in good glycemic control. RESULTS: We found significant differences (Student's t-test) between groups in regard to microalbuminuria (p <0.01), diabetes duration (p=0.05), systolic blood pressure (BP) and diastolic BP (p<0.05). Systolic BP (p<0.01), diastolic BP (p<0.01) and microalbuminuria (p=0.05) positively correlated (Spearman's rho) with poor glycemic control in Group A. In both groups there was a significant improvement in glycemic control and regression in systolic and diastolic BP (p<0.01), but only Group B showed significant reduction in urinary albumnin excretion rate (p<0.01). DISCUSSION AND CONCLUSION: In this study, type 1 diabetics showed regression in systolic and diastolic hypertension with improvements of glycemic control regardless of presence of microalbuminuria, but only normoalbuminuric showed significant reduction in urinary albumin excretion rate.

[The prevalence of hypertension and microalbuminuria in diabetes mellitus type 1 and type 2].

INTRODUCTION: The prevalence of hypertension is two times higher in diabetics than in non-diabetics. In type 1 diabetes mellitus (T1DM), the incidence of hypertension is similar to the incidence of nephropathy. In obese patients with type 2 DM (T2DM) there can be associated complications of hyperinsulinaemia, dyslipidaemia, and hypertension, which can lead to coronary artery disease and stroke. These associated complications are the result of a genetic defect that produces insulin resistance--Syndrome X. Increased microalbuminuria correlates with increased levels of blood pressure (BP) and increased LDL cholesterol, and this is why microalbuminuria is associated with an increase in cardiovascular deaths in diabetics, even in the absence of renal failure. AIM: The aim of this study was to research the influence of a patient's age, diabetes duration, and obesity on the frequency of hypertension and its association with microalbuminuria in T1 DM and T2DM. METHOD: 168 hospitalised patients with DM (79 T1DM, 89 T2DM) were analysed. The main outcome measures were: 24-hour urinary albumin excretion rate by radioimmunoassay (MA = 30-300 mg/24h), arterial hypertension (systolic BP > or = 140 mm Hg and/or diastolic BP > or = 90 mm Hg), and body mass index (BMI). RESULTS: Microalbuminuria was detected in 42% of patients with T1DM and 47% of patients with T2DM. 34% of T1DM patients and 78% of T2DM patients were hypertensive. Patients were divided into four groups, according to the presence of hypertension and microalbuminuria: Group I--patients with hypertension and MA, Group II--patients with hypertension but without MA, Group III--patients without hypertension and MA, Group IV--patients without hypertension but with MA. 44% of T1DM patients were without hypertension and microalbuminuria, while the most frequent T2DM patients were those with hypertension (37% with and 41% without microalbuminuria). A significant correlation between BMI and diastolic BP in both types of DM (p < 0.01 for T1DM, and p < 0.05 for T2DM) was discovered. T2DM hypertensive patients were obese and there was a significant correlation between a patient's systolic BP and his or her age (p < 0.05). CONCLUSION: These results suggest that hypertension can be prevented in patients with T2DM with weight reduction. There was a significant association between hypertension and microalbuminuria, especially in T1DM patients. Tight control of blood pressure is essential for the reduction of microalbuminuria as well as further micro- and macro-vascular diabetic complications.