Tiziana Filardi

Assessment of fracture risk by the FRAX algorithm in men and women with and without type 2 diabetes mellitus: a cross-sectional study.

The FRAX algorithm is a diffuse tool to assess fracture risk, but it has not been clinically applied in European patients with diabetes. We investigated FRAX‐estimated fracture risk in patients with type 2 diabetes mellitus (DM), compared with concomitantly enrolled control subjects.

Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes

Objective: Endothelial dysfunction (ED) plays a role in diabetic cardiovascular complications. Hyperglycemia increases cytockines involved in vascular inflammation. Inhibition of phosphodiesterase type 5 (PDE5) exerts a relaxation on corpora cavernosa and has cardioprotective properties. The effect of chronic sildenafil treatment, on ED markers and metabolic parameters in a non-randomized study on men with type 2 diabetes (T2DM), was investigated. Research design and methods: Twenty-eight T2DM patients (61.2 ± 7.8 years, hemoglobin A1c (HbA1c) 7.9 ± 1.3%, duration of diabetes 11.5 ± 7.8 years) were treated with sildenafil 100 mg/d for 3 months. Baseline and postprandial glycemia, insulin, HbA1c, HOMA index, lipids, glomerular filtration rate, homocysteine were assessed at each visit. P-selectin (CD62P), CD14/42b, CD14/41, ICAM (CD54), PECAM (CD31) and CD11b/CD18, were evaluated, after monocyte isolation with flow-cytometry, before and after treatment. Results: After 3 months, sildenafil decreased P-selectin (p < 0.05), post-prandial glycemia (p < 0.01), HbA1c (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and increased high-density lipoprotein (p < 0.05). Conclusions: PDE5 inhibition, in T2DM patients, reduces the endothelial function marker P-selectin and exerts a beneficial effect on glycometabolic control.

IgA Anti-transglutaminase Autoantibodies at Type 1 Diabetes Onset Are Less Frequent in Adult Patients and Are Associated With a General Celiac-Specific Lower Immune Response in Comparison With Nondiabetic Celiac Patients at Diagnosis

OBJECTIVE To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis. RESEARCH DESIGN AND METHODS IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb+ DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis. RESULTS A total of 12.8% DM1 sera were IgA-tTGAb+, with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb+ DM1 compared with nondiabetic CD patients. CONCLUSIONS Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis.

Metabolic and cardiovascular response to exercise in patients with type 1 diabetes

PurposePhysical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population.MethodsThis observational study included 17 T1DM patients and 17 matched healthy volunteers. Cardiopulmonary exercise test (CPET) was conducted on an electronically-braked cycle ergometer. Blood samples were collected for evaluation of glycemia and lactate levels.ResultsMean oxygen uptake at peak exercise (VʹO2,peak) was significantly lower in T1DM subjects (V′O2,peak T1DM 2200 ± 132ml/min vs VʹO2,peak Healthy subjects of 2659 ± 120 ml/min p = 0.035). Cardiovascular response analysis did not show statistically significant differences. Respiratory exchange ratio (RER) was significantly higher in healthy subjects at peak exercise and at the first minute of recovery (p = 0.022, p = 0.024). Peak exercise lactate levels were significantly higher in healthy subjects. There was no statistical correlation between CPET results and diabetes-related parameters.ConclusionsPatients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.

Linking type 2 diabetes and gynecological cancer: an introductory overview

Abstract Type 2 diabetes (T2D) is a chronic disease with a growing prevalence and a leading cause of death in many countries. Several epidemiological studies observed an association between T2D and increased risk of many types of cancer, such as gynecologic neoplasms (endometrial, cervical, ovarian and vulvar cancer). Insulin resistance, chronic inflammation and high free ovarian steroid hormones are considered the possible mechanisms behind this complex relationship. A higher risk of endometrial cancer was observed in T2D, even though this association largely attenuated after adjusting for obesity. A clear relationship between the incidence of cervical cancer (CC) and T2D has still not be determined; however T2D might have an impact on prognosis in patients with CC. To date, studies on the association between T2D and ovarian cancer (OC) are limited. The effect of pre-existing diabetes on cancer-specific mortality has been evaluated in several studies, with less clear results. Other epidemiological and experimental studies focused on the potential role of diabetes medications, mainly metformin, in cancer development in women. The correct understanding of the link between T2D and gynecologic cancer risk and mortality is currently imperative to possibly modify screening and diagnostic-therapeutic protocols in the future.

Two-hour postload glycemia is associated to an increased risk of NAFLD in healthy subjects with family history of type 2 diabetes: a case control study

Nonalcoholic fatty liver disease (NAFLD) includes steatosis and nonalcoholic steatohepatitis (NASH), which can be complicated by cirrhosis and hepatocellular carcinoma [1]. NAFLD affects over 30 % of the general population and is associated with type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome [2, 3]. NAFLD prevalence in T2DM patients is about 70 % using ultrasonography (US) [4]. NAFLD and T2DM share insulinresistance, which in the liver increases gluconeogenesis and glycogenolysis, resulting in hyperglycemia. The pancreatic beta islet cells adapt to hyperglycemia by increasing insulin secretion. Hyperinsulinemia upregulates several lipogenic transcription factors, promoting hepatic lipid synthesis [5]. The association between NAFLD and T2DM seems to be the result of a “common soil” [3]. Several studies showed that NAFLD predicts T2DM and vice versa, and that each condition may act as a progression factor for the other [4]. There is evidence of a high risk of NASH and its progression to hepatocellular carcinoma in T2DM patients [6]. Conversely, recent studies showed that NAFLD not only predicts diabetes [7], but also contributes to poor glycemic control and chronic complications [8]. Despite its clear link with T2DM, the association of NAFLD with family history of diabetes has been poorly investigated. A recent cross-sectional study in nondiabetic individuals with NAFLD demonstrated that family history of diabetes increased the risk of NASH and fibrosis [9]. The aim of this study was to evaluate the prevalence of NAFLD in healthy first degree relatives of T2DM patients (T2DM-rel) and in healthy subjects without family history of T2DM and to assess the risk factors associated with NAFLD development.