Although hyperhomocysteinemia, an independent cardiovascular risk factor, is common in type 2 diabetes with nephropathy, the mechanism(s) of this alteration is not known. In healthy humans, hyperinsulinemia increases methionine transmethylation, homocysteine transsulfuration, and clearance. No such data exist in type 2 diabetes either in the fasting state or in response to hyperinsulinemia. To this purpose, seven male type 2 diabetic patients with albuminuria (1.2 ؎ 0.4 g/day, three with mild to moderate renal insufficiency) and seven matched control subjects were infused for 6 h with L-[methyl-2 H 3 , 1-13 C]methionine. Methionine flux, transmethylation, and disposal into proteins as well as homocysteine remethylation, transsulfuration, and clearance were determined before and after euglycemic hyperinsulinemia (ϳ1,000 pmol/l). In type 2 diabetic subjects, homocysteine concentration was twofold greater (P < 0.01) and methionine transmethylation and homocysteine clearance lower (from ϳ15 to >50% and from ϳ40 to >100%, respectively; P < 0.05) than in control subjects. The insulin-induced increments of methionine transmethylation, homocysteine transsulfuration, and clearance were markedly reduced in type 2 diabetic subjects (by more than threefold, P < 0.05 or less vs. control subjects). In contrast, methionine methyl and carbon flux were not increased in the patients. In conclusion, pathways of homocysteine disposal are impaired in type 2 diabetes with nephropathy, both in postabsorptive and insulin-stimulated states, possibly accounting for the hyperhomocysteinemia of this condition. Diabetes

In type 2 diabetes, the ingestion of a fast-absorbable protein results in a greater post-prandial aminoacidemia and a higher beta-cell secretion than the ingestion of a 'slow' protein. Whether these changes can be maintained chronically in combination with hypoglycemic therapy, possibly also resulting in better glycemic control, remains to be established.

-Methionine is a sulfur-containing amino acid that is reversibly converted into homocysteine. Homocysteine is an independent cardiovascular risk factor frequently associated with the insulin resistance syndrome. The effects of insulin on methionine and homocysteine kinetics in vivo are not known. Six middle-aged male volunteers were infused with L-[methyl-2 H3, 1-13 C]methionine before (for 3 h) and after (for 3 additional hours) an euglycemic hyperinsulinemic (150 mU/l) clamp. Steady-state methionine and homocysteine kinetics were determined using either plasma (i.e., those of methionine) or intracellular (i.e., those of plasma homocysteine) enrichments. By use of plasma enrichments, insulin decreased methionine rate of appearance (R a; both methyl-and carbon Ra) by 25% (P Ͻ 0.003 vs. basal) and methionine disposal into proteins by 50% (P Ͻ 0.0005), whereas it increased homocysteine clearance by ϳ70% (P Ͻ 0.025). With intracellular enrichments, insulin increased all kinetic rates, mainly because homocysteine enrichment decreased by ϳ40% (P Ͻ 0.001). In particular, transmethylation increased sixfold (P Ͻ 0.02), transsulfuration fourfold (P ϭ 0.01), remethylation eightfold (P Ͻ 0.025), and clearance eightfold (P Ͻ 0.004). In summary, 1) physiological hyperinsulinemia stimulated homocysteine metabolic clearance irrespective of the model used; and 2) divergent changes in plasma methionine and homocysteine enrichments were observed after hyperinsulinemia, resulting in different changes in methionine and homocysteine kinetics. In conclusion, insulin increases homocysteine clearance in vivo and may thus prevent homocysteine accumulation in body fluids. Use of plasma homocysteine as a surrogate of intracellular methionine enrichment, after acute perturbations such as insulin infusion, needs to be critically reassessed.clearance; transsulfuration; transmethylation; euglycemic clamp METHIONINE, A SULFUR-CONTAINING AMINO ACID that is abundant in meat and other animal proteins, is converted intracellularly to homocysteine through transmethylation with a methyl acceptor (4). Homocysteine, i.e., the demethylated form of methionine, is not normally present in the amino acid sequences of proteins, but it can accumulate in blood as well as in intracellular fluids in a number of conditions, such as arteriosclerosis (21), renal failure (33), Alzheimer's disease (2), neural tube defects (17), and others.Although not yet included in the cluster of factors associated with the insulin resistance syndromes (30, 36), homocysteine is usually increased in many of these conditions, such as type 2 diabetes, in particular with kidney insufficiency and/or proteinuria (35), obesity (13), and hypertension, particularly associated with diabetes (19). Thus a disturbance in the regulation by insulin of methionine/homocysteine metabolism can be suspected.Physiological hyperinsulinemia inhibited whole body leucine and phenylalanine appearance from endogenous body proteins in a dose-response fashion (7,27). Insulin also either decreased or did not a...

Fibrin glue injection is a safe procedure and seems to reduce type II endoleak rates. Patients who received this procedure had fewer CT examinations, with reduced health-care costs.

Anastomotic connections between the developing internal carotid and basilar arterial system exist in early fetal life. Rarely, these carotid-basilar anastomoses will persist into adult life unilaterally or, rarely, bilaterally. 1 A 78-year-old woman was admitted to the Vascular Surgery Division of Padua University (VSDPU). For 30 days, she had experienced focal (transischemic attacks with right-sided paresis-5 episodes) and nonfocal (syncope and multiple attacks of vertigo) cerebral symptoms. Digital subtraction angiography (DSA) confirmed a duplex scanning result showing a 85% stenosis of left carotid bifurcation and revealed a persistent proatlantal intersegmental artery (PIA), arising 2 cm from the origin of left internal carotid artery (ICA). The plaque was ulcerated and extended into the external carotid artery, ICA, and the PIA origin. The first and second tracts (V 1, V 2 ) of the left vertebral artery were not visualized. The left ICA had a 60% intracranial stenosis (A [Cover]).There was a 40% right carotid bifurcation stenosis with a 50% intracranial tandem stenotic lesion. The right vertebral artery was hypoplasic without intracranial connection with the basilar artery. Most of the cerebral posterior territory was supplied by the left PIA. Very poor connections were visualized between carotid and posterior territory circulation.The patient underwent left carotid endarterectomy according to a previously described VSDPU technique 2 (general anesthesia, continuous electroencephalogram monitoring, heparinization, routine delayed shunting, and polytetrafluoroethylene patching). Surgery planning took into account not only intraoperative routine shunt perfusion of the ICA but also the necessity of perfusion of the PIA due to the demonstration of incomplete circle of Willis. After left laterocervical incision and exposure of the common carotid artery, external carotid artery, ICA, and PIA with the no-touch technique, vessel clamping was followed by longitudinal arteriotomy. Two intraluminal balloon shunts (Pruitt-Inahara model 2000-49; LeMaitre Vascular, Inc, Burlington, Mass) were used after plaque removal. The first shunt was inserted distally into the ICA, and proximally into the common carotid artery. The second shunt was inserted distally into the PIA, and proximally into the common carotid artery. Proximal ends of both shunts were placed in contiguity inside the common carotid artery; balloons were partially inflated with a vessel loop encircling the artery to help with hemostasis (B). Ischemia time was 4 minutes for the carotid territory and 5 minutes for the posterior territory. Electroencephalogram frequency and amplitude decreased significantly after clamping and returned to normal after insertion of the shunts.Cerebrovascular symptoms disappeared after surgery and the patient had no problems during 12 months of follow-up. Patency of the ICA and PIA was assessed by duplex scanning and documented by DSA (C).This report differs from an unpublished case, also successfully operated in 1982 by the senior a...