A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).

OBJECTIVE: It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established. RESEARCH DESIGN AND METHODS: A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months. RESULTS: Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe. CONCLUSION: Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.

Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment.

OBJECTIVE: Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in beta-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease. RESEARCH DESIGN AND METHODS: Thirteen newly diagnosed diet-unresponsive type 2 diabetic patients were treated with continuous subcutaneous insulin infusion (CSII) for 2 weeks and followed longitudinally while being treated with diet alone. RESULTS: Four patients were considered therapeutic failures since CSII failed to induce euglycemia (n = 1) or glucose control deteriorated within 6 months after CSII (n = 3). The remaining nine patients were maintained on diet alone with adequate control from 9 to > 50 months (median +/- SE, 26 +/- 4.8 months). In five patients, glycemic control deteriorated after 9-36 months, but a repeat 2-week CSII treatment reestablished control in four patients. One of these patients underwent a third CSII treatment 13 months later. At the time this article was written, six patients of the initial group were still controlled without medication 16-59 months (median +/- SE, 45.5 +/- 6.6 months) after the initiation of treatment. Body weight remained unchanged in all patients. CONCLUSIONS: These findings suggest that in a significant proportion of type 2 diabetic patients who fail to respond to dietary measures, short-term intensive insulin treatment can effectively establish responsiveness, allowing long-term glycemic control without medication. Further studies are required to establish whether simpler treatment regimens could be equally effective. If the hypothesis offered here finds support, present approaches to the management of newly diagnosed type 2 diabetes may need to be revised.

Benign cystic mesothelioma: a rare cause of ascites in a case with familial Mediterranean fever.

Benign cystic mesothelioma (BCM) is a rare neoplasm of the peritoneum, consisting of solitary or multiple cysts arising from mesothelial cells. Here we report a patient with a previous diagnosis of familial Mediterranean fever (FMF) presenting with abdominal distension and ascites which were found to be due to BCM. The co-existence of these two entities has not been reported previously. Ascites as the presenting feature of BMC is also a rare observation.

Are individuals with glutathione S-transferase GSTT1 null genotype more susceptible to in vitro oxidative damage?

Recent epidemiological studies proposed that glutathione S-transferase (GST) T1 null genotype was correlated with an increased susceptibility to diseases associated with oxidative stress, including cancer. A comparative study using erythrocytes from individuals with GSTT1 null genotype was carried out to determine how resistance to oxidative stress is affected by lack of this gene, and whether the GST status of a person is an important factor in risk toward oxidant chemicals. Malondialdehyde and carbonyl levels and fluorescence and chemiluminescence formation were used as biomarkers of oxidative stress in erythrocytes exposed in vitro to cumene hydroperoxide (CumOOH), an oxidizing agent. When peroxidation-dependent changes in these parameters were compared between GSTT1 null genotype and controls, who are both GSTM1 and GSTT1 positive, no significant differences were found between the two genotypes, although the erythrocytes of the GSTT1 null group had lower GSTT1 activity toward CumOOH. Our results indicate that erythrocytes from individuals with GSTT1 null genotype are not abnormally susceptible to CumOOH-induced oxidant challenge.

The effect of feto-maternal blood type incompatibility on development of gestational diabetes mellitus.

OBJECTIVE: To assess the relation between fetal and maternal blood type (ABO, Rh) incompatibility and development of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 500 pregnant women underwent diagnostic test for GDM by a 100-g oral glucose tolerance test (OGTT) after an 8 to 12-h overnight fast participated in this study. OGTT was performed between the 24-28 weeks of gestation, but participants who were at high risk for GDM were tested after the first prenatal visit. In the postpartum period, maternal and infant blood types were determined. Presence of GDM was evaluated in terms of matched and unmatched fetal and maternal ABO and Rh blood types separately. RESULTS: GDM was detected in 235 participants. Unmatched ABO blood types between the mother-infant pairs were present in 44.7% (n=105) of GDM (+) and 35.8 % (n=95) of GDM (-) patients. Incompatible feto-maternal ABO blood type was positively correlated with development of GDM which was marginally significant. (p=0.045; R=1.2;95% CL; 1.004-1.48). However, Rh feto-maternal blood type incompatibility was not related with development of GDM. CONCLUSIONS: Feto-maternal ABO blood type incompatibility may be a weak risk factor for the development of GDM.

Evaluation of the left ventricular systolic and diastolic functions by echocardiography in patients with acute leukemia.

Eighteen patients with acute leukemia were studied to evaluate their left ventricular systolic and diastolic function by M mode, two-dimensional and Doppler echocardiographic techniques. The study group was compared with another group of 18 patients of similar age with iron deficiency anemia. The latter group had a comparable heart rate and levels of Hb. There were no differences in systolic function, whereas the diastolic function was lower in patients with acute leukemia (E/A ratio = 1.1 +/- 0.3 vs. 1.42 +/- 0.5, p < 0.05). It is concluded that left ventricular diastolic dysfunction is more common in patients with acute leukemia and may be an indicator of restrictive cardiomyopathy.

The antihypertensive effects of doxazosin on the arterial system: changes in peripheral vascular resistance and wall tension.

Background: Hypertension is characterized by structural and functional abnormalities that affect the entire cardiovascular system, including the large arteries. The antihypertensive efficacy of doxazosin, a selective alpha(1) antagonist, and its effects on the arterial system were investigated. Method: In our double-blind, randomized, placebo-controlled study including 30 hypertensive patients (doxazosin group: nine males, 11 females; mean age 45+/-12 years; placebo group: four males, six females; mean age 47+/-9 years), the systolic, diastolic and mean blood pressure (BP), heart rate, diameter and area of the brachial artery, peak systolic velocity, end-diastolic velocity, pulsatility index (PI), resistance index (RI), S/D (systolic velocity/diastolic velocity), flow volume, local resistance, and wall tension were recorded before and 4 h after the administration of 2 mg doxazosin or placebo. The two groups were statistically compared. Results: In the doxazosin group, systolic, diastolic and mean pressures decreased significantly (P<0.001), while heart rate remained unchanged. Local resistance (P<0.001), RI (P<0.05), PI (P<0.05), and wall tension (P<0.001) all decreased significantly, while flow volume increased significantly (P<0.05). However, no significant changes were observed in arterial diameter, surface area, peak systolic velocity, end-diastolic velocity or S/D ratio. The placebo group did not show a significant difference in any of the parameters listed above. Conclusion: The antihypertensive effect of doxazosin is accompanied by a reduction in brachial arterial wall tension that occurs without any change in arterial diameter. The lack of change in the diameter of the artery leads us to suggest different effects on other vasomotor determinants.