0000000000009579
AUTHOR
Andreas Pfützner
Endothelial Function and Arterial Stiffness in Uncomplicated Type 1 Diabetes and Healthy Controls and the Impact of Insulin on These Parameters during an Euglycemic Clamp
BACKGROUND In addition to its role in glucose metabolism, insulin has shown to exert numerous vascular effects, and an impaired vascular function of insulin is assumed to be a major contributor in the development of vascular complications. Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to investigate the effect of insulin on arterial stiffness and parameters of endothelial function in patients with type 1 diabetes and healthy control subjects. METHODS Fourteen patients with type 1 diabetes (six male, eight female) with a mean age of 36.6 +/- 11.8 …
Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT Study
We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance, plasma adiponectin, postprandial plasma glucose, insulin, and intact proinsulin levels in a nondiabetic population at cardiovascular risk. One hundred twenty-five nondiabetic patients at cardiovascular risk were randomized to pioglitazone (PIO), pioglitazone and simvastatin (PIO/SIM), or simvastatin (SIM) treatments. Blood samples were taken for the measurement of adiponectin and lipid levels. In addition, an oral glucose load with the measurements of glucose, insulin, and intact proinsulin levels was performed. Adiponectin levels increased from 14.0 ± 8.2 to 27.6 ± 14.5 …
Peripheral Leptin Levels in Narcoleptic Patients
Narcolepsy is a severe sleep disorder that in most patients is characterized by the deficiency of central orexin. Clinically, narcolepsy is associated with obesity. Currently, there is a literature controversy about the potential alteration of leptin levels in narcoleptic patients. Theoretically, diminished leptin levels could partially contribute to the observed overweight of patients. Two studies have reported decreased leptin levels, whereas a larger, recent study failed to detect differences between patients and controls.To help settle the controversy, we have measured peripheral leptin levels in 42 narcoleptic patients and in 31 body mass index-matched controls.No significant differenc…
Pilot study for the evaluation of morphological and functional changes in retinal blood flow in patients with insulin resistance and/or type 2 diabetes mellitus.
Background: The aim of this study was to investigate early morphological and functional pathology in the retinal micro-circulation in patients with insulin resistance and/or type 2 diabetes mellitus (T2DM). Methods: Fifty-four subjects, without features of retinopathy under ophthalmological investigation, were recruited for study participation and were classifed into three study groups according to their metabolic staging: (1) Group C comprised nondiabetic, insulin-sensitive subjects with a BMI <28kg/m2; (2) Group IR comprised nondiabetic, insulin-resistant, obese subjects with a BMI ≥28 kg/m2; and (3) Group DM comprised patients with manifested T2DM. Retinal microvascular blood flow was…
Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2.
The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2.A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months.HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p.0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p.0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p…
Elevated peripheral visfatin levels in narcoleptic patients.
OBJECTIVE: Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin) producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF). Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients. METHODS: For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females) with the diagnosis of narcolepsy according to DSM-IV and the Internatio…
Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain
What is already known about this subject • Despite encouraging effects of N-methyl-D-aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side-effects. • In a recent study in healthy volunteers, CNS 5161, a novel noncompetetive NMDA receptor antagonist, was well tolerated up to a dosage of 2000 µg without psychotropic side-effects. • This is the first study to evaluate the maximal tolerated dosage of CNS 5161 and to gain experience about the analgesic effect of CNS 5161 in patients with different pain syndromes. What this study adds • In patients with neuropathic pain CNS 5…
Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.
We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4±6.5 years; body mass index [BMI] 29.2±4.1 kg/m2; mean±SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator …
Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy
In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light. PNP was assessed using the neuropathy disability score (NDS) and by the evaluation of the vibration perception threshold (V…
Evaluation of CGMS® During Rapid Blood Glucose Changes in Patients with Type 1 Diabetes
CGMS (Medtronic Minimed, Duesseldorf, Germany) allows continuous glucose monitoring. Recent studies with invasive monitoring techniques revealed discrepancies in blood glucose measurements obtained from different anatomical sites compared with those from the fingertip. The aim of this study was to investigate the CGMS and a device for alternative site testing (AST) during dynamic blood glucose changes and to compare these results with fingertip measurements.Twelve patients with type 1 diabetes (seven women, five men; age, 33.3 +/- 8.7 years) received a 75-g oral glucose load. Insulin was applied intravenously (rapid glucose decline) or subcutaneously (moderate glucose decline) in a dosage b…
Investigation of insulin resistance in narcoleptic patients: dependent or independent of body mass index?
Alice Engel1,2, Jana Helfrich1, Nina Manderscheid1, Petra B Musholt3, Thomas Forst3, Andreas Pf&uuml;tzner3, Norbert Dahmen1,21Department of Psychiatry, University of Mainz, Germany; 2Fachklinik Katzenelnbogen, Katzenelnbogen, Germany; 3IKFE, Institute for Clinical Research and Development, Mainz, GermanyBackground: Narcolepsy is a severe sleep-wake cycle disorder resulting in most cases from a lack of orexin, the energy balance-regulating hormone. Narcoleptic patients have been reported to suffer from an excess morbidity of Type 2 diabetes, even after correction for their often elevated body mass index.Methods: To explore whether narcolepsy is specifically associated with a propensity …
Increased Arterial Augmentation and Augmentation Index as Surrogate Parameters for Arteriosclerosis in Subjects with Diabetes Mellitus and Nondiabetic Subjects with Cardiovascular Disease
Background: Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to compare these parameters in diabetic subjects and nondiabetic cardiovascular risk subjects with healthy control subjects. Methods: One hundred sixty-six nonsmoking subjects aged between 35 and 70 years were included in the study, which included 100 subjects with cardiovascular disease but not diabetes (mean age 62.73±8.75 years), 33 subjects with type 2 diabetes (66.58±2.69 years), and 33 healthy controls (51.89±8.91 years). In these subjects, arterial stiffness was measured by the diff…
Impact of insulin on microvascular blood flow and endothelial cell function in the postprandial state in patients with Type 1 diabetes.
The aim of the present study was to investigate postprandial microvascular blood flow following a standardized test meal in nondiabetic subjects and in patients with Type 1 diabetes after regular insulin or insulin lispro. In this open-label, randomised cross-over study, 20 nondiabetic participants and 20 patients with Type 1 diabetes were enrolled. To valuate the postprandial time course of skin microvascular blood flow, laser Doppler flux (LDF) readings were obtained at baseline and every 30 min following a standardized test meal. Furthermore, the microvascular response to acetylcholine (Ach) was measured, and blood was collected for the measurement of serum insulin and blood glucose leve…