Oxidative stress and autonomic nerve function in early type 1 diabetes.

Introduction: The biochemical mechanisms by which hyperglycemia causes microvascular disease and neuropathy are poorly understood. Experimental studies have established that oxidative stress is present in diabetic rodents with neuropathy, and that antioxidant therapy is protective. Oxidative stress is also present in human diabetes, but its clinical importance is uncertain.

Lipid peroxidation in early type 1 diabetes mellitus is unassociated with oxidative damage to DNA.

Oxidative stress damages DNA in experimental diabetes, and in vitro studies have suggested that it is linked to lipid peroxidation. The objective of the study was to determine whether lipid peroxidation, as assessed with malondialdehyde excretion in recent-onset type 1 diabetes mellitus, is associated with oxidative damage to DNA, as assessed from 8-hydroxydeoxyguanosine excretion. A 3-year longitudinal study of recent-onset type 1 diabetes mellitus was performed.

Effect of octreotide on postmenopausal hot flushes.

We have previously documented that octreotide therapy suppresses sweating and palpitations in patients with the postural tachycardia syndrome. We now report that octreotide also suppresses these and related symptoms in patients with postmenopausal hot flushes.

Luminescence experiments involved in the mechanism of streptozotocin diabetes and cataract formation.

Streptozotocin (STZ)-induced diabetes is linked to excessive nitric oxide (NO), and possibly peroxynitrite (OONO(-)) and/or other nitrogen oxides, e.g. nitrogen trioxide (N(2)O(3)), which damages DNA of pancreatic beta cells, causing death and loss of insulin.

Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with octreotide LAR.

The purpose of this study was to determine whether autonomic neuropathy and the postural tachycardia syndrome can be treated with octreotide LAR (Long Acting Release). This was an open-label pilot project. Protocol 1 Patients with autonomic neuropathy (n = 4) were given increasing doses of octreotide LAR once a month for three months.

Antibodies to GAD65 and peripheral nerve function in the DCCT.

Antibodies to the smaller isoform of glutamic acid decarboxylase (GAD65Ab) have been linked to the presence of neuropathy in Type 1 diabetes in several small studies. We attempted to confirm this association by measuring GAD65Ab, GAD65Ab epitopes and IA-2Ab in 511 patients who participated in the Diabetes Control and Complications Trial (DCCT). We also tested for correlations between these autoantibodies and C-peptide and glycemic control.

Sympathetic sudomotor disturbance in early type 1 diabetes mellitus is linked to lipid peroxidation.

The present study was performed to determine whether increased lipid peroxidation, as assessed from malondialdehyde (MDA) excretion, is associated with deterioration in peripheral nerve function in early type 1 diabetes mellitus. These parameters were measured annually for 3 years in 36 patients who entered the study less than 2 years after the diagnosis of diabetes. Malondialdehyde excretion was 1.

Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine.

We assessed the potency of octreotide and midodrine, and their combination, in the treatment of the postural tachycardia syndrome (POTS) and orthostatic intolerance (OI). Nine patients with POTS and six patients with OI stood for up to 1 hour while their HR and BP were monitored. Patients received on separate days, midodrine 10 mg 1 hour before testing, octreotide 0.

Nitrosative stress in early Type 1 diabetes. David H. P. Streeten Memorial Lecture.

Although hyperglycemia has been shown to cause peripheral nerve dysfunction in patients with diabetes, the biochemical mechanisms for this effect are poorly understood. The excessive production of reactive oxygen species and reactive nitrogen species has been proven to be detrimental in experimental diabetes, but there is little evidence that these metabolic events take place clinically and are physiologically important in man. To assess this we measured nitrite and nitrate (indices of nitric oxide production), nitrotyrosine (an index of peroxynitrite), 8-isoprostaglandin F-2 alpha, an isoprostane reflective of oxidative stress and lipid peroxidation, and uric acid, an index of antioxidant defense in patients with recently diagnosed Type 1 diabetes and aged-matched controls.

Peroxynitrite versus nitric oxide in early diabetes.

Background: Peroxynitrite is a toxic compound formed during the inactivation of nitric oxide (NO) by the superoxide anion. The physiologic significance of this pathway of NO metabolism has never been documented in vivo. Because peroxynitrite provides a pathway for the inactivation of NO we postulated that peroxynitrite's correlation with physiologic parameters would be the opposite of those associated with NO, which is a vasodilator and suppresses sudomotor function.

Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes.

The purpose of this study was to analyze biochemical measures of oxidative stress and assess their relationship to insulin requirements early in type 1 diabetes. Thirty-seven patients enrolled in a 3-yr longitudinal study of the effects of oxidative stress on the early natural history of this disorder. We measured plasma nitrite and nitrate (collectively NOx), nitrotyrosine, and 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)).

Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes.

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.