MicroRNA profiling in sera of patients with type 2 diabetes mellitus reveals an upregulation of miR-31 expression in subjects with microvascular complications

Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycaemia due to a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. Chronic hyperglycemia is associated with long-term micro- and macrovascular complications leading to dysfunction of several organs including kidney, heart, eye and nervous system. Early identification of chronic diabetic complications is necessary in order to prevent dysfunction and failure of these different organs. MicroRNAs (or miRNAs) are small endogenous RNAs, which negatively regulate gene expression. Recently, it has been demonstrated that miRNAs can be secreted by cells, thus being detectable in serum and in other biological fluids. Circulating microRNAs have been proposed as possible biomarkers of several diseases. Here, we performed a miRNAs expression profiling in the sera of T2D patients with or without vascular complications in order to find specific biomarkers to characterize T2D complications. We analyzed the expression of 384 microRNAs in serum pools from 3 groups of T2D patients: 12 T2D patients without any chronic complications, 12 T2D patients with macrovascular complications and 12 with microvascular complications. We found 223 miRNAs expressed in T2D,224 inT2D with microvascular and221 inT2D with macrovascular complications. Among expressed microRNAs, 45 resulted upregulated and 23 downregulated in microvascular patients sera, while 13 upregulated and 41 downregulated in macrovascular T2D patients compared to those without complications. We focused and validated microRNA miR-31 expression in single sera from each group, which resulted significantly upregulated in patients with microvascular complications and may be indeed related to the presence of microangiopathy. In conclusion, our study has identified miR-31 as a promising biomarker for diabetic microvascular complications; further prospective studies in the clinical setting are however required to establish the real utility of measuring serum circulating levels of this microRNA

HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: The renal insufficiency and cardiovascular events (RIACE) Italian Multicenter Study

OBJECTIVE: To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS: Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 \ub1 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS: Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS: In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications

Combination therapy with metformin plus vildagliptin in type 2 diabetes mellitus

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is pathophysiologically characterized by a combination of insulin resistance and beta-cell dysfunction. Consequently, a proper treatment of such a disease should target both of these defects. Dipeptidyl peptidase-4 (DPP-4) inhibitors are among the most recent additions to the therapeutic options for T2DM and are able to increase circulating levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thus stimulating glucose-dependent insulin secretion. AREAS COVERED: This paper provides an overview of the clinical results of combination therapy with metformin and the DPP-4 inhibitor vildagliptin in T2DM patients. EXPERT OPINION: Vildagliptin-metformin single-tablet combination is indicated for the treatment of T2DM patients not achieving a sufficient glycemic control at their maximally tolerated dose of metformin. Results from clinical trials provide evidence of vildagliptin efficacy administered in addition to metformin, as either first- or second-line treatment. The vildagliptin-metformin association seems to have favorable effects on beta-cell function and is characterized by good safety and tolerability profiles when compared with other antidiabetic agents. Of note, data available suggest that administration of fixed-dose combination products, together with the low incidence of adverse gastrointestinal events, may improve compliance and adherence of patients to therapy, resulting in an improved metabolic control

Fighting diabetic foot ulcers—The diabetologist: A king maker of the fight

Diabetic foot ulcer is a costly and serious complication of diabetes mellitus and is the major cause of non-traumatic limb amputations worldwide. Its development is primarily the result of diabetic neuropathy and/or peripheral arterial disease with accompanied bone abnormalities and is complicated by invasive infection. The management of this clinical condition focuses on identification of the "at-risk" foot, treatment of the ulcerated foot, and prevention of further complications. As diabetic foot ulcer represents the sum of multiple etiologies, its treatment requires a multidisciplinary team, which can result in a significant reduction in the incidence of ulcers, infections and amputations. The team should include a diabetologist, a podiatrist, an orthoptist, an educator and a plaster technician, in close collaboration with a vascular surgeon, an orthopedic/podiatric surgeon and a dermatologist. It is recommended that a diabetologist be the multidisciplinary team leader, as diabetic foot ulcer is a complication of diabetes and chronic hyperglycemia represents the main cause for its development. The appropriate composition of professionals involved in the team is institution-dependent and may vary worldwide, depending on the diabetic population. The concept of establishing a diabetic foot care team is recommended by all National and International Diabetes Scientific Societies and Associations

Effetto del naloxone e del naltrexone sulla spesa energetica post-prandiale e sulla risposta del pancreas endocrino ad un pasto misto nell'obesita essenziale. [Effect of naloxone and naltrexone on the postprandial energy expenditure and endocrine pancreas response to a mixed meal in essential obesity]

It has been recently shown that the opioid antagonists naloxone and naltrexone are able to reduce appetite and to raise energy expenditure in animal models. The results of studies in humans are inconclusive. In 10 female obese patients we have evaluated the effects of naloxone infusion (2 mg/2 h) on energy expenditure, measured by indirect calorimetry (Deltatrac) and on plasmatic levels of glucose, insulin, glucagon and somatostatin, fasting and after the assumption of a standard 567 kcal meal (C = 20%, P = 20%, L = 60%). We have repeated the tests after a dietary period of 1 month, associated with naltrexone assumption. Acute administration of naloxone caused similar effects at the beginning and at the end of the study; we have observed a raise of caloric expenditure, a decrease of hyperinsulinemia and a high response of somatostatin to metabolic stimulus. After therapy, even with a weight reduction of 6%, we haven't observed either variations of energy expenditure or hormonal level changes. We conclude that in obese women opioid hypertone plays a role in thermic effect of meals and in the impaired response to the nutrients of the gastroenteropancreatic axis. The absence of any effects of naltrexone on the variables that we have studied is perhaps due to the difference in the dose, way of administration and of the different action on the target receptor by the two opioid antagonists

Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) Study

BACKGROUND: Measurement of urinary albumin excretion (UAE) shows important intra-individual variability suggesting the need for multiple assessments. This study aimed at investigating the reproducibility of UAE in type 2 diabetes. METHODS: UAE was obtained from two to three samples collected in a 3- to 6-month period from 4062 of the 15 773 type 2 diabetic subjects participating in the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study in 2007-08. UAE was assessed as albumin excretion rate (AER) in 24-h urine collections from 833 subjects and albumin:creatinine ratio (A/C) in early-morning urine samples from 3229 patients. Albuminuria was measured by immunonephelometry or immunoturbidimetry. RESULTS: The median coefficient of variation (CV) was 32.5% (interquartile range: 14.3-58.9). Concordance rate between a single UAE and the geometric mean of multiple measurements was 94.6% for normoalbuminuria, 83.5% for microalbuminuria, 91.1% for macroalbuminuria and 90.6% for albuminuria (micro + macro). CV was significantly higher (P < 0.01) for AER measurement than for A/C and with immunoturbidimetry than with immunonephelometry, whereas concordance rates were similar between the two modalities of urine collection and the two assay methods. Receiver-operating characteristic (ROC) plots demonstrated a good performance of single UAE in predicting the geometric mean of multiple measures at the cut-off level of both microalbuminuria (ROC(AUC) 0.926; 95% confidence interval: 0.915-0.937) and macroalbuminuria (ROC(AUC) 0.950; 95% confidence interval: 0.927-0.973). CONCLUSIONS: Data from this large cohort indicate that, in type 2 diabetic subjects, a single UAE value, thought to be encumbered with high intra-individual variability, is an accurate predictor of nephropathy stage for clinical and epidemiological purposes