Role of endogenous secretory RAGE (esRAGE) in defending against plaque formation induced by oxidative stress in type 2 diabetic patients.

Objectives: This study was conducted to examine the relationship between endogenous secretory receptors for advanced glycation end products (esRAGE) and oxidative stress in type 2 diabetic patients (T2DM) with/without advanced macro-angiopathy.

Methods: Sixty-one T2DM were assessed for glycemic control, lipid profile, AGEs, carboxymethyl-lysine (CML), soluble receptor for advanced glycation end products (sRAGE), esRAGE and vitamin E levels, and underwent echo-color-Doppler of the abdominal aorta and aorto-iliac tree, carotid and lower limb arteries to check for evidence of plaques.

Results: AGEs and CML levels were significantly higher in T2DM with plaques than in those without (P = 0.

The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM).

Glucose variability has recently been investigated in diabetic patients in several studies, but most of them considered only a few variability indicators and did not systematically correlate them with patients' HbA1c levels and other important characteristics. In thus study, the correlations between HbA1c levels and metabolic control (average glucose, AG), glucose variability (SD, CONGA, MAGE, MODD, BG ROC), hyperglycemia (HBGI), hypoglycemia (LBGI) and postprandial (AUC PP) indices were investigated in patients with type 1 and type 2 diabetes. The study involved 68 patients divided into 3 groups as follows: 35 patients had type 1 diabetes (group 1); 17 had type 2 diabetes and were taking multiple daily injections (MDI) of insulin (group 2); and 16 patients had type 2 diabetes treated with OHA and/or basal insulin (group 3).

Subclinical diastolic dysfunction in type 2 diabetic patients with and without carotid atherosclerosis: relationship with glyco-oxidation, lipid-oxidation and antioxidant status.

Objectives: The aim of this study was to evaluate subclinical diastolic dysfunction in type 2 diabetic patients and its relationship with glyco-oxidation, lipo-oxidation and antioxidant capacity in the presence or absence of carotid plaques.

Background: Subclinical diastolic dysfunction is the early stage of diabetic cardiomyopathy, the pathogenic mechanisms of which are still little known. In particular, few data are available on the role of glyco-oxidation, lipo-oxidation and antioxidant status, factors known to be involved in the atherosclerotic process.

Pregnancy outcome in immigrant women with gestational diabetes mellitus.

Recent studies show adverse outcomes of pregnancy among immigrant women from countries with high diabetes rates. We compared maternal and fetal outcomes in immigrant and Italian women with gestational diabetes mellitus (GDM) followed up at our center. Maternal characteristics considered were age, pre-pregnancy body mass index (BMI), HbA1c, frequency of insulin treatment, timing and mode of delivery, and hypertensive disorders; and, for fetal outcome, infants large or small for gestational age, and fetal complications.

Pregnancy outcome in morbidly obese women before and after laparoscopic gastric banding.

Background: Increasing numbers of pregnancies are seen in obese women treated surgically with laparoscopic adjustable gastric banding (LAGB). We compared their maternal and fetal outcomes with obese women without LAGB and normal-weight controls.

Methods: Sixty-nine obese women with LAGB (83 pregnancies) were compared with 120 obese women without LAGB and 858 controls.

Pregnancy complicated by diabetes: what is the best level of HbA1c for conception?

To reduce the congenital malformations that occur in pregnancies complicated by diabetes, it is essential to achieve and maintain a good metabolic control before conception. In this context, measuring HbA1c is considered as the gold standard for monitoring metabolic control in diabetes and various different HbA1c levels have been recommended as optimal in the preconception period for diabetic women planning a pregnancy. An analysis of key studies published on this issue until now clearly shows that HbA1c levels correlate closely with the occurrence of congenital malformations and other neonatal complications characteristic of pregnant diabetic women.

Management of gestational diabetes mellitus.

The incidence of gestational diabetes mellitus (GDM) is on the increase and, if not diagnosed, managed and treated adequately, can have unfavorable maternal and fetal outcomes. Several studies have shown that glycemic values considered as adequate in the past when monitoring GDM failed to contain these adverse outcomes and randomized trials are needed to ascertain whether these targets should be lowered. Dietary restrictions remain the mainstay of GDM management and suitable physical exercise can help too.

Pregnancy complicated by type 2 diabetes: an emerging problem.

The prevalence of type 2 diabetes in pregnancy has increased everywhere in recent years. A number of studies have suggested that adverse maternal and fetal outcomes in these women have approached the figures for type 1 diabetic pregnancies. A low rate of planned pregnancies, suboptimal metabolic control and obesity have emerged as significant factors contributing towards poor outcome in these women, so efforts should be made to monitor these patients more carefully in order to improve this situation.

NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction.

Introduction: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are characterized by insulin resistance and often associated with male hypogonadism.

Aim: To discriminate the specific contribution of T2DM and MetS to male hypogonadism.

Methods: A consecutive series of 1,134 (mean age 52.

Multivariate analysis of matrix-assisted laser desorption/ionization mass spectrometric data related to glycoxidation products of human globins in nephropathic patients.

To clarify the possible pathogenetic role of oxidation products originated from the glycation of proteins, human globins from nephropathic patients have been studied by matrix-assisted laser desorption/ionization mass spectrometry (MALDI), revealing not only unglycated and monoglycated globins, but also a series of different species. For the last ones, structural assignments were tentatively done on the basis of observed masses and expectations for the Maillard reaction pattern. Consequently, they must be considered only propositive, and the discussion which will follow must be considered in this view.

Off-line liquid chromatography-MALDI by with various matrices and tandem mass spectrometry for analysis of glycated human serum albumin tryptic peptides.

Advanced glycation end-product (AGE)/peptides, arising from in vivo digestion of glycated proteins, are biologically important compounds, due to their reactivity against circulating and tissue proteins. For information on their possible structure, in vitro glycation of HSA and its further enzymatic digestion were performed. The resulting digestion product mixture was analysed directly by MALDI MS with various matrices [2,5-dihydroxy benzoic acid (DHB) and alpha-cyano-4-hydroxy cinnamic acid (CHCA)].

Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease.

Objective: Advanced glycation end products (AGEs), pentosidine and malondialdehyde (MDA), are elevated in type 2 diabetic subjects with coronary and carotid angiopathy. We investigated the relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD).

Research Design And Methods: AGEs, pentosidine, MDA, TRAP, vitamin E, and ankle-brachial index (ABI) were measured in 99 consecutive type 2 diabetic subjects and 20 control subjects.

The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey.

Objective: We aimed at assessing the degree of association and the predictive power of the metabolic syndrome with regard to clinically detectable complications in patients with diabetes.

Research Design And Methods: Metascreen is a cross-sectional survey of metabolic syndrome and clinically detected diabetes complications performed in 8,497 patients (7,859 with type 2 diabetes and 638 with type 1 diabetes) randomly chosen in 176 diabetes outpatient clinics throughout Italy. The metabolic syndrome was defined according to either the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) or the International Diabetes Federation (IDF) diagnostic criteria.

Polymorphisms of insulin receptor substrate 1 and beta3-adrenergic receptor genes in gestational diabetes and normal pregnancy.

Gestational diabetes mellitus (GDM) is considered an important risk factor for the development of type 2 diabetes mellitus. We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and beta3-adrenergic receptor (ADRB3 Trp64Arg, beta3-AR) gene mutations, considered potential modifying factors in the etiology of type 2 diabetes mellitus. We evaluated the 2 gene mutations in late gestation in 627 pregnant women, all studied using the glucose challenge test, followed (in positive tests) by the oral glucose tolerance test (100 g, Carpenter and Coustan [J Obstet Gynecol.

Comprehensive analysis of glycated human serum albumin tryptic peptides by off-line liquid chromatography followed by MALDI analysis on a time-of-flight/curved field reflectron tandem mass spectrometer.

Glycated peptides arising from in vivo digestion of glycated proteins, usually called advanced glycation end (AGE) product peptides, are biologically relevant compounds due to their reactivity towards circulating and tissue proteins. To investigate their structures, in vitro glycation of human serum albumin (HSA) has been performed and followed by enzymatic digestion. Using different MALDI based approaches the digestion products obtained have been compared with those arising from enzymatic digestion of the protein.

The role of mass spectrometry in the study of non-enzymatic protein glycation in diabetes: an update.

Recent studies on non-enzymatic protein glycation are reviewed, and results are critically discussed. Advanced glycation end products (AGE) levels in the body reflect a balance between their formation and catabolism. AGE proteolysis leads to the formation of low-molecular-weight AGE (AGE peptides) that are normally excreted in urine.

Therapy Insight: sexual and bladder dysfunction associated with diabetes mellitus.

Diabetes mellitus affects 3-6% of the population. Patients with diabetes experience chronic vascular complications, which lead to a wide range of medical problems. Genitourinary problems are included among these complications, related to both neuropathy and vasculopathy.

Plasma fatty acids and lipoproteins in type 2 diabetic patients.

Background: The dyslipidemia of type 2 diabetic patients is characterized by high VLDL, abnormal LDL composition and low HDL cholesterol concentrations. The aim of this study was to establish whether the type of dietary fats affects LDL size and density and HDL cholesterol concentrations in these patients.

Methods: Plasma phospholipid fatty acid composition, which reflects the type of dietary fatty acids, was quantified by gas chromatography.

Glyco-oxidation in diabetes and related diseases.

Background: Recent evidence has shown that hyperglycemia is able to cause increased production of superoxide on the mitochondrial transport chain, and that this is the key event which activates some events such as increased AGE formation, increased hexosamine and polyol flux, and activation of PKC, all believed to be important for the development of the chronic complications of diabetes, aging and uremia. In this context, non-enzymatic protein glyco-oxidation leads to the formation of a series of products whose intra- and extra-cellular accumulation is of key importance in the pathogenesis of these chronic diseases.

Methods: Various spectrometric approaches, such as matrix-assisted laser desorption ionisation (MALDI), and liquid chromatography-electrospray ionisation (ESI) were used.

Autoantibodies against oxidized LDLs and atherosclerosis in type 2 diabetes.

Objective: The aim of our study was to examine, in type 2 diabetic patients, the relationship between autoantibodies against oxidatively modified LDL (oxLDL Ab) and two indexes of atherosclerosis, intimal-medial thickness of the common carotid artery (CCA-IMT), which reflects early atherosclerosis, and the ankle-brachial index (ABI), which reflects advanced atherosclerosis.

Research Design And Methods: Thirty newly diagnosed type 2 diabetic patients, 30 type 2 diabetic patients with long duration of disease, and 56 control subjects were studied. To detect oxLDL Ab, the ImmunoLisa Anti-oxLDL Antibody ELISA was used.

Importance of measuring products of non-enzymatic glycation of proteins.

Non-enzymatic glycation products are a complex and heterogeneous group of compounds which accumulate in plasma and tissues in diabetes and renal failure. There is emerging evidence that these compounds may play a role in the pathogenesis of chronic complications associated with diabetes and renal failure. So measurement of the products of non-enzymatic glycation has a twofold meaning: on one hand, measurement of early glycation products can estimate the extent of exposure to glucose and the subject's previous metabolic control; on the other hand, measurement of intermediate and late products of the glycation reaction is a precious instrument in verifying the relationship between glycation products and tissue modifications.

Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

Background: Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal.

Methods: In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD).

Results: A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD.

Enzymatic digestion and mass spectrometry in the study of advanced glycation end products/peptides.

An extensive study was carried out on HSA and non-enzymatically glycated HSA by enzymatic digestion with trypsin and endoproteinase Lys-C, with the aim of identifying specific glycated peptides deriving from enzymatic digestion of glycated HSA. They may be considered, in pectore, as advanced glycation end products/peptides. These compounds, important at a systemic level in diabetic and nephropathic subjects, are produced by enzymatic digestion of in vivo glycated proteins: They are related to the pathological state of patients and have been invoked as responsible for tissue modifications.

Biological variability of albumin excretion rate and albumin-to-creatinine ratio in hypertensive type 2 diabetic patients.

The importance of measuring microalbuminuria is well established. However, only scanty data are available concerning the biological variability of albumin excretion in type 2 diabetic subjects. We report our experience from a large clinical trial of a new antihypertensive drug (Lercanidipine) designed to reduce albumin excretion and blood pressure in type 2 diabetic patients with hypertension and microalbuminuria.

Glyoxal and methylglyoxal levels in diabetic patients: quantitative determination by a new GC/MS method.

Determination of glyoxal and methylglyoxal levels in plasma is of great interest, since it allows us to evaluate oxidation processes occurring in glycated proteins. A method based on a simple derivatization procedure followed by gas chromatography/mass spectrometry (GC/MS) analysis has been developed. Ten diabetic patients were evaluated before and after improvement of glycemic control.