OBJECTIVE -Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS-A randomized, placebo-controlled, doubleblind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years.RESULTS -Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P Ͻ 0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P ϭ 0.006).CONCLUSIONS -There was no effect of 2 years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group. Diabetes Care 27:2887-2892, 2004C ardiovascular disease (CVD), including cerebrovascular disease, coronary artery disease (CAD), and peripheral vascular disease, is the most important cause of mortality in patients with type 2 diabetes (1). The severity and progression of atherosclerosis can be assessed noninvasively by ultrasonographic measurements of the intima-media thickness (IMT) in the carotid and femoral arteries. Ultrasonographic IMT measurements of the far wall relate to histological IMT measurements (2). Carotid IMT correlates with prevalent CVD (3), angiographically proven coronary atherosclerosis (4), and risk factors for CVD, including LDL cholesterol (5,6). In prospective studies, carotid IMT has proven to be predictive of CVD (7-9), and as a consequence, IMT is increasingly used as an intermediate end point in clinical trials. Mean common carotid IMT in middle-aged subjects without CAD is reported to range from 0.71 to 0.91 mm in diabetic patients vs. 0.66 to 0.74 mm in control subjects (10,11). In diabetes, IMT is less consistently correlated to classical risk factors such as LDL cholesterol. Importantly, at the time our study was designed, data on the progression and predictive value of IMT in type 2 diabetes were lacking.During the last 10 years, large clinical trials have demonstrated that HMG-CoA (hydroxy-methylglutaryl coenzyme A) reductase inhibitors (statins) reduce the risk of cardiovascular events in the setting of secondary and primary preventio...

OBJECTIVE -Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD. RESEARCH DESIGN AND METHODS-A randomized, placebo-controlled, doubleblind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years.RESULTS -Determinants of baseline FMD were diabetes duration, common carotid intimamedia thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years.CONCLUSIONS -The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability. Diabetes Care 28:1668 -1674, 2005C ardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes (1). Endothelial dysfunction precedes the development of atherosclerotic plaques and is believed to be reversible (2). Nitric oxide (NO) is a key molecule in this process. It modulates blood flow and vascular permeability, limits inflammation and coagulation, and diminishes vascular smooth muscle cell proliferation and migration. Type 2 diabetes is associated with endothelial dysfunction; the underlying mechanisms are complex and related to hyperglycemia (sorbitol, hexosamine, protein kinase C, and advanced glycation end product pathways) and insulin resistance, resulting in mitochondrial superoxide overproduction and thus decreased NO availability (3). Regarding insulin, its vasodilatory capacity is at least in part NO dependent (4,5), thus explaining how insulin resistance might be related to endothelial dysfunction.Flow-mediated dilation (FMD) of the brachial artery is a noninvasive technique for measuring endothelial function. FMD of the brachial artery has been shown to be the result of endothelium-derived NO release (6) and is related to coronary vasoreactivity (7). FMD has proven to be predictive for the presence of coronary artery disease (8,9), for future cardiovascular events (10 -12), and for postoperative cardiovascular events (13) in high-risk populations. Improvement in FMD predicts a favorable cardiovascular outcome in postmenopausal hypertensive women (2). However, in patients at lower risk, FMD was not independently associated with outcome (14). FMD is impaired in patients with type 2 diabetes with reported FMD values of 4.47-12.3% in control subjects vs. 2.96 -6.1...

The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission.

No abstract

Valproic acid induced coma is presented in an adult patient without a history of metabolic disease. Liver biopsy revealed a reduction in activity of carbamyl phosphate synthetase-I, an enzyme obligated for transformation of ammonia to urea in the urea cycle. After recovery CT scan follow-up showed marked cerebral atrophy which did not exist prior to the state of coma. Risk factors are discussed.