Association of free-living physical activity measures with metabolic phenotypes in type 2 diabetes at the time of diagnosis. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

Objective: Lifestyle is considered a major determinant of risk of type 2 diabetes (T2D). We investigated whether daily physical activity (DPA) is associated with beta-cell function (BF) and/or insulin sensitivity (IS) in patients with T2D at the time of diagnosis. Methods: In 41 subjects enrolled in the Verona Newly-Diagnosed Type 2 Diabetes Study we assessed: (1) IS, by euglycaemic insulin clamp; (2) BF, estimated by prolonged-OGTT minimal modeling and expressed as derivative and proportional control; (3) DPA and energy expenditure (EE), assessed over 48-hours monitoring by a validated wearable armband system. Results: Study participants (median[IQR]; age: 62 [53-67] years, BMI: 30.8 [26.5-34.3] Kg c5m-2, HbA1c: 6.7 [6.3-7.3]%; 49.7 [45.4-56.3] mmol/mol) were moderately active (footsteps/day: 7,773 [5,748-10,927]; DPA 653MET: 70 [38-125] min/day), but none of them exercised above 6 metabolic equivalents (MET). EE, expressed as EETOT (total daily-EE) and EE 653MET (EE due to DPA 653MET) were 2,398 [2,226-2,801] and 364 [238-617] Kcal/day, respectively. IS (M-clamp 630 [371-878] \u3bcmol/min/m2) was positively associated with DPA and EE, independent of age, sex and BMI (p<0.05). Among the DPA and EE parameters assessed, DPA 653MET and EETOT were independent predictors of IS in multivariable regression analyses, adjusted for age, sex, BMI (R2=16%, R2=19%, respectively; p<0.01). None of model-derived components of BF was significantly associated with DPA or accompanying EE. Conclusions Our study highlighted moderate levels of DPA and total EE as potential determinants of IS, but not BF, in T2D at the time of diagnosis. Intervention studies are needed to conclusively elucidate the effect of DPA on these features

Assessing attitudes towards insulin pump therapy in adults with type 1 diabetes: Italian validation of the Insulin Pump Attitudes Questionnaire (IT-IPA questionnaire)

Aims: The aim of the study was to adapt the German version of the insulin pump therapy (IPA) questionnaire to Italian (IT-IPA) and to evaluate its psychometric properties in adults with type 1 diabetes. Methods: We conducted a cross-sectional study, data were collected through an online survey. In addition to IT-IPA, questionnaires evaluating depression, anxiety, diabetes distress, self-efficacy, and treatment satisfaction were administered. The six factors identified in the IPA German version were assessed using confirmatory factor analysis; psychometric testing included construct validity and internal consistency. Results: The online survey was compiled by 182 individuals with type 1 diabetes: 45.6% continuous subcutaneous insulin infusion (CSII) users and 54.4% multiple daily insulin injection users. The six-factor model had a very good fit in our sample. The internal consistency was acceptable (Cronbach's α = 0.75; 95% IC [0.65-0.81]). Diabetes treatment satisfaction was positively correlated with a positive attitude towards CSII therapy (Spearman's rho = 0.31; p < 0.01), less Technology Dependency, higher Ease of Use, and less Impaired Body Image. Furthermore, less Technology Dependency was associated with lower diabetes distress and depressive symptoms. Conclusions: The IT-IPA is a valid and reliable questionnaire evaluating attitudes towards insulin pump therapy. The questionnaire can be used for clinical practice during consultations for shared decision-making to CSII therapy

Cutaneous squamous carcinoma in a patient with diabetic foot: an unusual evolution of a frequent complication

After basal cell carcinoma, the cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer worldwide, and, classically, arises from the upper coats of the epidermis of sun-exposed areas or from skin areas constantly exposed to a chronic inflammatory stimulus. The occurrence of cSCC seems to be linked to several factors, including exposure to sunlight (or other ultraviolet radiations), immunosuppression, chronic scarring conditions and some familial cancer syndromes. Although the majority of cSCCs are adequately eradicated by surgical excision, a subgroup of cSCC may be linked with an increased risk of recurrence, metastasis and death. The incidence of type 2 diabetes mellitus is constantly increasing worldwide. Importantly, diabetes mellitus is a strong risk factor for cancers (including cutaneous tumors) and is highly related with poor cancer outcomes. At present, in the literature, squamous cell carcinoma developing in association with diabetic foot ulcers has been already reported in some reports; however, additional data are needed to make the clinicians aware of this rare, although possible, complication. Therefore, we herein report an unusual case of an elderly man with T2DM and a positive oncological history, presenting a cSCC involving the skin overlying the first toe of left foot. The growing cSCC appeared approximately 3 years after the appearance of a diabetic ulcer

nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes

OBJECTIVE There is no information about the role of nonalcoholic fatty liver disease (NAFLD) in predicting the development of chronic kidney disease (CKD) in type 1 diabetes. RESEARCH DESIGN AND METHODS We studied 261 type 1 diabetic adults with preserved kidney function and with no macroalbuminuria at baseline, who were followed for a mean period of 5.2 years for the occurrence of incident CKD (defined as estimated glomerular filtration rate [eGFR] 2 and/or macroalbuminuria). NAFLD was diagnosed by ultrasonography. RESULTS At baseline, patients had a mean eGFR of 92 ± 23 mL/min/1.73 m 2 ; 234 (89.7%) of them had normoalbuminuria and 27 (10.3%) microalbuminuria. NAFLD was present in 131 (50.2%) patients. During follow-up, 61 subjects developed incident CKD. NAFLD was associated with an increased risk of incident CKD (hazard ratio [HR] 2.85 [95% CI 1.59–5.10]; P P P P = 0.002). CONCLUSIONS This is the first study to demonstrate that NAFLD is strongly associated with an increased incidence of CKD. Measurement of NAFLD improves risk prediction for CKD, independently of traditional cardio-renal risk factors, in patients with type 1 diabetes

Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (>140 and < 200 mg/dL), named AGT140

Diabetic foot complicated by vertebral osteomyelitis and epidural abscess

Vertebral osteomyelitis (or spondylodiscitis) is steadily increasing in Western countries and often results from hematogenous seeding, direct inoculation during spinal surgery, or contiguous spread from an infection in the adjacent soft tissue. We present the case of a 67-year-old white patient with type 2 diabetes who went to Hospital for high fever, back pain, and worsening of known infected ulcers in the left foot. Despite intravenous antibiotic treatment and surgical debridement of the foot infection, high fever and lower back pain continued. Bone biopsy and two consecutive blood cultures were positive for Staphylococcus aureus. A spinal magnetic resonance imaging (MRI) was performed, revealing serious osteomyelitis in L4 and L5 complicated by an epidural abscess. Contiguous or other distant focuses of infection were not identified. In this case, diabetic foot could be considered as a primary distant focus for vertebral osteomyelitis. Clinicians should consider vertebral osteomyelitis as a 'possible' diagnosis in patients with type 2 diabetes complicated by foot infection that is associated with fever and lower back pain. LEARNING POINTS: Vertebral osteomyelitis is increasing in Western countries, especially in patients with type 2 diabetes.The primary focus of infection is the genitourinary tract followed by skin, soft tissue, endocarditis, bursitis, septic arthritis, and intravascular access.Diabetic foot could be a rare primary focus of infection for vertebral osteomyelitis, and, however, vertebral osteomyelitis could be a serious, albeit rare, complication of diabetic foot.Clinicians should keep in mind the many potential complications of diabetic foot ulcerations and consider vertebral osteomyelitis as a "possible" diagnosis in patients with type 2 diabetes and foot ulcers associated with nonspecific symptoms such as lower back pain.Early diagnosis and correct management of vertebral osteomyelitis are crucial to improve clinical outcomes

Abstracts of 51st EASD Annual Meeting

Background and aims: Presence and frequency of beta cell (BC) dysfunction(BCD) and insulin resistance (IR) in patients with newly diagnosedtype 2 diabetes mellitus (NDT2D) are imperfectly known, becauseprevious studies used small cohorts and/or only surrogate indexes of BCfunction and IR.We sought to assess BC function and IR with state-of-artmethods in the VNDS.Materials and methods: In 712 GADA-negative, drug naïve, consecutiveItalian NDT2D patients we assessed: 1. standard parameters; 2. insulinsensitivity (IS) by the euglycaemic insulin clamp); 3. BC functionby state-of-art modeling of prolonged (5 hours) OGTT-derived glucose/C-peptide curves. Thresholds for BCD and IR were the 25th percentilesof BC function and IS assessed with the same methods of the VNDS inItalian subjects with normal glucose regulation of the GENFIEV (n=340)and GISIR (n=386) studies, respectively.Results: In the VNDS, 89.8% [95% C.I.: 87.6 - 92.0%] and87.8% [85.4 - 90.2] patients had BCD and IR, respectively. Patientswith only one defect were 19.7% [16.8 - 22.6]. IsolatedBCD and isolated IR were present in 10.9% [8.6 - 13.2] and8.9% [6.8 - 11.0] patients, respectively. Coexistence of BCDand IR was observed in 78.9% [75.9 - 81.9] of the patients.1.4% [0.5 - 2.3] of the patients had no detectable alterations inBC function and IS. Patients (19.7%) with only one metabolicdefect had lower BMI, fasting glucose, HbA1c, triglycerides andBC function, and higher HDL-cholesterol and IS than patientswith both BCD and IR (p<0.01 or less after Bonferroni’scorrection).Conclusion: In conclusion, in NDT2DM patients: 1. at least 75.9% haveboth BCD and IR; 2. At least 87.6% and 85.4% have BCD and IR,respectively; 3. At least 16.8% have only one defect and a significantlydifferent (milder) metabolic phenotype compared to patients with bothdefects. These findings may be relevant to therapeutic strategies centeredon the metabolic phenotype of the patient.Clinical Trial Registration Number: NCT00879801; NCT01526720Supported by: University of Veron

Left ventricular chamber dilation and filling pressure may help to categorise patients with type 2 diabetes

Type 2 diabetes may alter cardiac structure and function. Many patients with type 2 diabetes have diastolic dysfunction with preserved ejection fraction (EF). Recently, this latter measure was criticised. Thus, this research looked at the impact of left ventricular end-diastolic volume and E/e' ratio variations in patients with type 2 diabetes and preserved EF with the aim to recognise different clinical phenotypes

Long-Acting GLP-1 Receptor Agonist Exenatide Influence on the Autonomic Cardiac Sympatho-Vagal Balance

Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to treat type 2 diabetes. An increase of heart rate (HR) has been observed with their use. To elucidate the role of the cardiac sympatho-vagal balance as a possible mediator of the reported increase in HR, we performed power spectral analysis of HR variability (HRV) in patients receiving exenatide extended-release (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation at initiation of exenatide-ER and thereafter at 3 and at 6 months. To obtain spectral analyses of HRV, a computerized acquisition of 10 minutes of RR electrocardiogram intervals (mean values of ~700 RR intervals) were recorded both in lying and in standing positions. All patients showed a substantial increase of HR both in lying and in standing positions. Systolic blood pressure, body weight, and glycated hemoglobin A1c significantly decreased both at 3 and 6 months compared with basal levels. The low-frequency/high-frequency ratio varied from 3.05 \ub1 0.4 to 1.64 \ub1 0.2 (P &lt; 0.001) after 3 months and to 1.57 \ub1 0.3 (P &lt; 0.001) after 6 months in a lying position and from 4.56 \ub1 0.8 to 2.24 \ub1 0.3 (P &lt; 0.001) after 3 months and to 2.38 \ub1 0.4 (P &lt; 0.001) after 6 months in a standing position compared with basal values, respectively. HR variations, induced by exenatide-ER treatment, do not appear to be related to sympathetic autonomic tone. Of note, we observed a relative increase of vagal influence on the heart