Hamiyet Yilmaz

Aspirin Resistance Is Associated with Glycemic Control, the Dose of Aspirin, and Obesity in Type 2 Diabetes Mellitus

OBJECTIVEnAspirin resistance (AR) is increased in diabetic patients. It is not known whether glycemic control has effect on AR.nnnDESIGNnTo test the hypothesis that glycemic control might have influence on aspirin resistance, we measured aspirin resistance and glycated hemoglobin (HbA1c) in diabetic patients. We also measured aspirin resistance in nondiabetic subjects and compared the results with the diabetic group.nnnMETHODSnWe examined AR in 108 diabetic patients and 67 nondiabetic subjects with impedance platelet aggregometry. Glycemic control was evaluated according to both fasting blood glucose (FBG) and HbA1c levels.nnnRESULTSnAccording to the analyses, diabetic patients had significantly higher AR (P < 0.01), alanine aminotransferase (P < 0.005), and body mass index (P < 0.05) and significantly lower high-density lipoprotein cholesterol (P < 0.005) levels compared with nondiabetic controls. A correlation analysis revealed that AR was positively correlated with body mass index (r = 0.190, P < 0.01), fasting blood glucose (r = 0.224, P < 0.001), and HbA1c levels (r = 0.297, P < .0001). Using low-dose aspirin (100 mg/d) was a risk factor for aspirin-resistant status in both diabetic patients (odds ratio 1.26, 95% confidence interval 1.01-1.58, P < 0.05) and overall study group (odds ratio 1.3, 95% confidence interval 1.08-1.56, P < 0.01).nnnCONCLUSIONSnThese data suggest that glycemic control, obesity, and the dose of aspirin have influence on AR in diabetic subjects. Further studies with larger groups are needed to clarify the role of glycemic control on AR.

Mean platelet volume in patients with subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) is frequently encountered in the general population. Since it is generally asymptomatic, these patients are mostly identified through routine screening or evaluation of non-specific symptoms. It has been suggested as a risk factor for cardiovascular disease. On the other hand, mean platelet volume (MPV), which is a determinant of platelet function, is an independent risk factor for cardiovascular disease. The aim of this study was to evaluate MPV values in subclinical hypothyroidic patients when they were subclinical hypothyroidic and became euthyroidic after 12 weeks of levothyroxine replacement therapy. Sixty patients with subclinical hypothyroidism and 78 euthyroid healthy subjects matched for age, gender and body mass index were enrolled in the study. None of the study subject had diabetes, hypertension or dyslipidemia. All the study subjects were evaluated by biochemical and platelet parameters. Subclinical hypothyroidic patients were then reevaluated with the same parameters when they became euthyroid after 12 weeks of levothyroxine treatment. Platelet counts and metabolic parameters, except serum triglyceride and high density lipoprotein cholesterol (HDLC) levels, were similar between the two groups. Serum triglyceride and MPV values were significantly higher (pTGu2009=u20090.007 and pMPVu2009<u20090.001) while HDLC levels were lower (pHDLCu2009=u20090.008) in the subclinical hypothyroidic group. MPV was found to be correlated with only antithyroid peroxidase (anti-TPO) antibody levels (Pu2009<u20090.001). MPV values were decreased after subclinical hypothyroidic patients became eythyroid. However, post-treatment MPV values were still higher (pu2009=u20090.035) in the patient group than in control group. These results suggest that subjects with SCH are susceptible to increased platelet activation and increased MPV values which contribute to increased risk of cardiovascular complications.

Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6xa0months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7xa0units/day in insulin alone group, decreased to 4.7xa0units/day in insulin plus rosiglitazone group, to 4.2xa0units/day in insulin plus metformin group, and to 2.7xa0units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4xa0kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6xa0kg). No significant change in lipid levels—except serum triglycerides—was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.

Two-year follow-up of thirty-two non-functional benign adrenal incidentalomas.

Objective: To evaluate the risk of developing endocrine hyperactivity and carcinoma during a period of up to 5 yr in patients with apparently benign and non-functioning adrenal incidentalomas. Patients and methods: Thirty-two patients (mean age: 57.0±8.3 yr) were investigated in a prospective follow-up study for a median time of 24 months. Twentyeight patients had unilateral and 4 had bilateral masses. Initial avarage mass diameter was 17.47±6.60 mm. All patients were followed up yearly by physical examination, metabolic parameters, hormonal evaluation [morning cortisol after 3-mg dexamethasone suppression, urinary metanephrines, and upright aldosterone/plasma renin activity (PRA)]. Results: Among the clinical characteristics, 48% of patients were obese, 20% were hypertensive, 13 had Type 2 diabetes and impaired glucose tolerance. During follow-up period no significant change in the functional status was observed and no malignant transformation occured. Only 1 patient developed subclinical Cushing’s syndrome at the end of the 1st year and referred to surgery. Change in mass size was correlated with homeostasis model assessment of insulin resistance (p=0.002), upright aldosterone/PRA (p=0.041), cortisol after dexamethasone suppression (p=0.048) and 24-h urinary normetanephrine (p=0.005) levels. Gender, body mass index, glucose metabolism, and blood pressure were not found to be correlated with change in mass size and functional status. Conclusions: Due to the extremely low risk of developing malignancy during up to 5 yr of follow-up, conservative approach for the management of adrenal incidentalomas is thought to be appropriate. However, possibility of evolution to hormonal hypersecretion makes long-term follow-up of 2-to-5 yr seems to be obligatory.

Mean platelet volume in patients with polycystic ovary disease

Polycystic ovary syndrome (PCOS) is a frequently encountered clinical condition characterized by chronic anovulation and hyperandrogenism. There are many reports pointing to the causal links between PCOS and cardiovascular disease (CVD). Although the level of risk for CVD remains uncertain in PCOS, there is substantial evidence that insulin resistance, obesity, dyslipidemia, hypertension, hypercoagulable state, and markers of abnormal vascular function possibly contribute to increased CVD risk [1, 2]. Platelets play a crucial role in the pathogenesis of thrombotic diseases. Circulating platelets are heterogeneous in size, density, and reactivity. The mean platelet volume (MPV), the accurate measure of platelet size, is considered a marker and determinant of platelet function since larger platelets are hemostatically more reactive than platelets of normal size, increasing the propensity to thrombosis [3]. Elevated MPV levels have been shown to be an independent risk factor for CVD [4, 5]. We investigated MPV in patients with PCOS alongside a comparable group of healthy control subjects. Eighty-five newly diagnosed PCOS patients who have no propensity to thrombotic or bleeding disorder and 81 ageand BMI (body mass index)matched regularly menstruating healthy non-hirsute women as the controls participated in this study. Demographic details of subjects are presented in Table I. All MPV measurements were performed on automated blood counter Cell-Dyn 4000 (Abbott Diagnostics, Santa Clara, CA, USA). The other parameters measured in fasting blood sample were glucose, insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, free testosterone and total testosterone, and estrogen. Glucose values obtained at 0, 30, 60, 90, and 120 minutes after a 75 g oral glucose tolerance test was also measured. Each subject’s level of insulin resistance was estimated based on the homeostasis model assessment insulin resistance (HOMA-IR) index. Clinical and laboratory features of patients with PCOS and control subjects are depicted in Table I. The MPV was significantly higher in patients with PCOS (8.5 1.4 fl) than control subjects (7.8 0.9 fl) (p1⁄4 0.002). There was no statistically significant difference regarding platelet absolute count in patients with PCOS (264 51 10/L) and control subjects (257 48 10/L). HOMA-IR index was significantly higher in patients with PCOS than control subjects (3.0 3.1 vs. 2.0 0.8, p1⁄4 0.02). We did not observe any significant correlation between MPV and age, BMI, HOMAIR, lipid parameters, and levels of estrogen, free and total testosterone in patients with PCOS. There was also no correlation between MPV and glucose values obtained at 0, 30, 60, 90, and 120 minutes after a 75 g oral glucose tolerance test. Although direct evidence for increased thrombotic risk is still lacking in patients with PCOS, increased propensity to thrombosis is suggested

A possible case of gynecomastia with fluoxetine.

ocardial band, troponin-T, viral markers, and serologic screening were normal. The patient was treated with an infusion of NaCl 0.9%. Colchicine and fluvastatin were stopped. Intraarticular steroid was administered for acute gouty arthritis. As the patient’s urine output increased, serum creatinine and CK decreased steadily. He was discharged 19 days after admission, feeling well, with CK 70 U/L and creatinine 1.4 mg/dL. Fluvastatin was reinitiated after the CK level was normalized. Renal function of the patient was normal 2 months later. Discussion. Two different mechanisms may be responsible for the pathogenesis in our patient. Drug interactions that potentiate adverse effects may occur when colchicine is coadministered with a statin since both drugs are metabolized by cytochrome P450 isoenzymes and myotoxic effects are well known.2,3 Colchicine and fluvastatin, however, are cleared through 2 different CYP450 isoenzymes. The second possible mechanism is synergistic myotoxicity.4 Statin therapy is associated with myonecrosis, membranous myeloid bodies, and vacuolization. Finally, statins can disrupt cytoskeletal integrity. In addition to this, colchicine induces myopathy via disruption of tubular function with subsequent vacuolization. Concerning the potential cytoskeletal toxicity of colchicine and statins, it would appear that their combined use produced a synergistic drug-induced myopathy via both pharmacokinetic and related pharmacodynamic mechanisms. According to the Naranjo probability scale, our case suggests that rhabdomyolysis was probably related to colchicine.5 Patients on colchicine therapy should be informed about the possible muscular and gastrointestinal adverse effects and advised to stop this drug immediately if any symptoms occur. In addition, if colchicine is used together with fluvastatin in renally impaired patients, one should be cautious about myotoxicity.

Insulin resistance is increased in alopecia areata patients

Increased insulin resistance (IR) has been found in androgenetic alopecia in several studies. However, IR has not been investigated in alopecia areata (AA). We aimed to investigate IR in AA patients and the controls. Anthropometric and demographic data were obtained from 51 AA patients and 36 controls. We measured insulin, c-peptide and blood glucose and HOMA-IR. Demographic characteristics of the two groups were similar. AA group had higher insulin [12.5u2009±u20097.01 vs. 8.3u2009±u20093.9 µIU/mL, p = 0.001], c-peptide [2.7u2009±u20091.07 vs. 2.1u2009±u20090.6u2009ng/mL, p = 0.007] and HOMA-IR levels [2.8u2009±u20091.6 vs. 1.9u2009±u20090.9, p = .004] than the controls. Patient and control groups were also similar regarding lipid profiles. In this study, we found increased IR in AA patients for the first time in literature. Increased inflammatory cytokines and hypothalamic–pituitary–adrenal axis activation may be responsible for this finding. Further studies with larger sample sizes may give additional information for IR in AA.

Fetuin-A levels in hyperthyroidism

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1. Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels.

Elevation of QT dispersion after obesity drug sibutramine.

Background QT dispersion (QTd) is an arrhythmia parameter that can be used to assess homogeneity of cardiac repolarization. An antiobesity drug sibutramine is linked with several cardiovascular adverse events, including arrhythmias. Previous studies showed that sibutramine may prolong the QT interval and may be associated with cardiac arrest. Objectives The aim of this study was to evaluate the effect of sibutramine on QTd. Methods The study group consisted of 65 consecutive patients with obesity. All patients were to receive 15 mg of sibutramine once a day in addition to standard care for lifestyle change. Twelve-lead ECG was performed before the onset of the medication and after 16 weeks of treatment. QTd was calculated. Results Three individuals were withdrawn from the study because of the adverse effects of sibutramine. Sixty-two patients with obesity were recruited into the study. All patients were women (62, 100%). Body weight (106.3 ± 15.0 kg vs. 101.6 ± 16.9 kg, P < 0.001) and low-density lipoprotein cholesterol (128.4 ± 29.7 mg/dl vs. 111.6 ± 24.6 mg/dl, P < 0.001) levels were significantly decreased whereas QTd (46.1 ± 22.6 ms vs. 53.7 ± 16.7 ms, P = 0.026) was significantly increased after 16 weeks of sibutramine treatment. The increase in QTd was not correlated with the decrease in body weight. There was no correlation between QTd and any conditions such as diabetes or hypertension. Conclusion This study has shown an elevation in QTd, which may lead to cardiac arrhythmias, after sibutramine treatment. Molecular mechanisms may play role in increasing QTd. Further randomized studies are needed to clarify cardiac adverse events of the sibutramine.

Polycystic Ovary Syndrome and Cardiovascular Disease

Young women have an inferior risk of cardiac events, but this benefit fades after menopause, leaving them at risk to develop a cardiovascular disease (CVD) (StrambaBadiale, Fox et al. 2006). Endocrine and gynecologic diseases may have impact on this pattern. Ever since the classical notice of Stein and Leventhal in 1935 (Stein and Leventhal. 1935), interest in polycystic ovaries (PCO) and its accompanying syndrome (PCOS) has grown from a ‘‘gynecological curiosity to a multisystem endocrinopathy’’ (Homburg 1996). Actually, polycystic ovary syndrome (PCOS), is the most common female endocrinopathy in up to 10% in reproductive age and appears to be related with an increased cardiovascular risk (Talbott, Guzick et al. 1995; Cibula, Cifkova et al. 2000). The syndrome is characterized by chronic anovulation and hyperandrogenism (Franks 1995; Scarpitta and Sinagra 2000). Cardiovascular disease and type 2 diabetes are two potential major long-term sequelae of this condition that is worth of examination.