Addressing Unmet Medical Needs in Type 1 Diabetes: A Review of Drugs Under Development.

The incidence of type 1 diabetes (T1D) is increasing worldwide and there is a very large need for effective therapies. Essentially no therapies other than insulin are currently approved for the treatment of T1D. Drugs already in use for type 2 diabetes and many new drugs are under clinical development for T1D, including compounds with both established and new mechanisms of action.

Successful Management of Type 2 Diabetes with Lifestyle Intervention: A Case Report.

Background: The prevalence of diabetes is growing worldwide. The primary symptom of diabetes mellitus is elevated blood sugar. This is usually treated with lifestyle intervention and drugs according to an algorithm based on glycated hemoglobin (HbA1c) levels.

Addressing unmet medical needs in type 2 diabetes: a narrative review of drugs under development.

The global burden of type 2 diabetes is increasing worldwide, and successful treatment of this disease needs constant provision of new drugs. Twelve classes of antidiabetic drugs are currently available, and many new drugs are under clinical development. These include compounds with known mechanisms of action but unique properties, such as once-weekly DPP4 inhibitors or oral insulin.

A transient improvement in renal function occurs after ischemic stroke.

Background: Neurohumoral effects have been suggested to affect kidney function. Stroke is a condition where regulation of the renin-angiotensin system and sympathetic nerve activity are altered.

Methods: Renal function as estimated by serum creatinine was analyzed over 1 week in 220 patients after acute ischemic stroke.

Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism.

Aim: Recently, a novel susceptibility locus for coronary artery disease (CAD) has been identified on chromosome 9p21.3, linked to the single-nucleotide polymorphism (SNP) rs1333049 G>C. However, the physiological mechanism through which this locus confers an increased CAD-risk is still unknown.

Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2 diabetes mellitus.

Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes mellitus (T2DM). It has been shown that alpha-lipoic acid (ALA) improves endothelial function and oxidative stress in these patients. The present study investigated if ALA reduces ADMA in patients with T2DM.

High-molecular-weight adiponectin does not predict cardiovascular events in patients with type 2 diabetes.

Low circulating high-molecular-weight (HMW) adiponectin might be associated with increased cardiovascular risk. This study aimed to investigate the relationship between HMW adiponectin and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) with an adverse cardiovascular risk profile. The investigation took place in a specialized outpatient clinic for metabolic diseases and included 147 patients with T2DM following a cross-sectional and a prospective study protocol.

ADMA, cardiovascular disease and diabetes.

The endogenous competitive nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk marker for future cardiovascular events. Elevated ADMA concentrations have been described in patients with an adverse cardiovascular risk profile. Recently, various studies investigated the independent role of ADMA as a cardiovascular risk predictor in several patient cohorts.

Plasma asymmetric dimethylarginine and cardiovascular events in patients with acute decompensated heart failure.

This prospective study investigated whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to cardiovascular events in patients with acute heart failure. It has been reported that increased plasma ADMA concentrations are associated with adverse cardiovascular outcome in chronic heart failure. In 118 patients with acute decompensated heart failure and impaired left ventricular function, ADMA and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by high-performance liquid chromatography and by an enzyme-linked immunosorbent assay, respectively.

Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment.

Context: Insulin resistance plays a significant role in the pathogenesis of the polycystic ovary syndrome (PCOS) and represents a link to the unfavorable cardiovascular risk profile frequently found in affected patients. The endogenous nitric oxide synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality.

Objective: We investigated ADMA levels among other cardiovascular, metabolic, and hormonal parameters in women with PCOS and the effects of metformin treatment on these parameters.

Asymmetric dimethylarginine is increased in chronic thromboembolic pulmonary hypertension.

Rationale: Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide synthase (NOS) inhibitor, is increased in idiopathic pulmonary arterial hypertension and associated with unfavorable outcome.

Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH), although principally amenable to surgical removal of major pulmonary arterial obstructions by pulmonary endarterectomy, may show a small-vessel pulmonary arteriopathy similar to idiopathic pulmonary arterial hypertension. We hypothesized that ADMA plasma levels are increased in patients with CTEPH.

Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes.

Background: Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function.

Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion.

Objective: Ischemia-reperfusion (IR) injury causes tissue injury and endothelial dysfunction. There is evidence that oxidative stress plays an important role.

Methods: We tested if IR-induced endothelial dysfunction could be prevented by administration of the antioxidant vitamin C.

Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure.

Objective: The purpose of this study was to investigate whether elevated asymmetrical dimethylorginine (ADMA) concentrations are associated with increased cardiovascular risk in chronic heart failure (HF) patients.

Methods And Results: 253 patients with symptomatic chronic HF and impaired left ventricular function (median age 70 years, 202 males) were followed for a median of 14.2 months (interquartile range 6.

Effects of N-acetylcysteine against systemic and renal hemodynamic effects of endotoxin in healthy humans.

Objective: Systemic inflammation causes vasodilation and impairs the vascular response to catecholamines. There is evidence that altered vasoreactivity is associated with increased production of free radicals. We studied the influence of systemic doses of the antioxidant N-acetylcysteine on inflammatory cytokines and renal plasma flow and on the systemic pressor response to norepinephrine during experimental endotoxemia.

Rosiglitazone prevents free fatty acid-induced vascular endothelial dysfunction.

Context: Free fatty acids (FFAs) cause insulin resistance and vascular endothelial dysfunction. The peroxisome proliferator-activated receptor gamma agonist rosiglitazone acts as insulin sensitizer and could exert vasoprotective properties by preservation of endothelium-dependent vasodilation.

Objective: We tested the effect of rosiglitazone on FFA-induced endothelial dysfunction of the forearm resistance vessels, insulin sensitivity, asymmetric dimethylarginine (ADMA), and high-sensitivity C-reactive protein concentrations in humans.

Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes.

Objective: Circulating concentrations of an endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are elevated in patients with increased cardiovascular risk. We hypothesized that ADMA predicts cardiovascular events and enhances risk prediction independent of established risk markers in patients with type 2 diabetes.

Research Design And Methods: This prospective cohort study included 125 patients with type 2 diabetes.

Increase in visfatin after weight loss induced by gastroplastic surgery.

Objective: The recently described adipokine visfatin is produced in visceral fat and has been suggested to influence insulin resistance. To investigate whether visfatin concentrations are related to changes in body weight, this adipokine was measured in insulin-resistant severely obese patients before and after gastroplastic surgery.

Research Methods And Procedures: Visfatin, interleukin-6, high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), and other clinical parameters were assessed in 36 severely obese subjects (28 female; mean age, 43 years) with a median BMI of 44.

Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease.

Objective: Circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, are elevated in conditions associated with increased cardiovascular risk. We investigated whether elevated ADMA concentrations predict major adverse cardiovascular events (MACE) in patients with advanced peripheral artery disease (PAD).

Methods And Results: We prospectively enrolled 496 of 533 consecutive patients with PAD (median age 70 years, 279 males).

The cardiovascular risk marker asymmetrical dimethylarginine is not affected by venous thromboembolism.

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, causes vasoconstriction, impairs cardiac function, and may predict cardiovascular risk. The prognostic value of plasma ADMA concentrations in acute vascular situations may be confounded by concomitant factors such as clot formation. In an effort to address the effect of hemostatic system activation, the authors have measured plasma concentrations of ADMA, its stereoisomer symmetrical dimethylarginine (SDMA), and L-arginine in 74 patients with suspected deep vein thrombosis (DVT).

Free fatty acids normalize a rosiglitazone-induced visfatin release.

The detrimental effect of elevated free fatty acids (FFAs) on insulin sensitivity can be improved by thiazolidinediones (TZDs) in patients with type 2 diabetes mellitus. It is unknown whether this salutary action of TZD is associated with altered release of the insulin-mimetic adipocytokine visfatin. In this study, we investigated whether visfatin concentrations are altered by FFA and TZD treatment.

Increased visfatin concentrations in women with gestational diabetes mellitus.

The recently discovered adipocytokine visfatin has insulin-like properties. It lowers blood glucose and improves insulin sensitivity; however, clinical data on visfatin are limited. To evaluate the role of visfatin in GDM (gestational diabetes mellitus), we determined visfatin levels in women with GDM and in healthy pregnant controls.