Dipeptidyl peptidase-4 inhibitors do not alter GH/IGF-I axis in adult diabetic patients.

PURPOSE: Incretin-based therapies have been introduced in clinical practice for type 2 diabetes mellitus (T2DM) treatment in the last few years. Current available medications of this class include glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. In addition to GLP-1, DPP-4 is able to inactivate many others peptides as hypothalamic growth hormone-releasing hormone (GHRH). The aim of this exploratory study was to evaluate, on adult diabetic patients, the impact of therapy with incretins, particularly DPP-4 inhibitors on GH/IGF-I axis. METHODS: 60 patients with T2DM were included in the study and they were divided into three groups (age and sex comparable) on the basis of their hypoglycemic drugs in the last 4 months: group 1 (17 patients, exenatide or liraglutide + metformin), group 2 (18 patients, sitagliptin or vildagliptin + metformin), group 3 (25 patients, metformin). Anthropometric data, glycemia, glycosylated hemoglobin (HbA1c), IGF-I and acid-labile subunit (ALS) were collected in all patients. RESULTS: Weight, waist circumference and BMI of group 1 were significantly higher (P < 0.05) compared to the other groups. Fasting plasma glucose and HbA1c of the group 1 were similar compared to those of group 3 (P ns) and higher compared to those of group 2 (P < 0.05). IGF-I absolute values, IGF-I SDS were not significantly different in the three groups. CONCLUSIONS: Our data evidence that DPP-4 inhibition does not influence significantly GH/IGF-I system, confirming what was observed in animal models. Further studies are needed to better characterize the properties of these molecules on endocrine system.

Impact of severe and symptomatic hypoglycemia on quality of life and fear of hypoglycemia in type 1 and type 2 diabetes. Results of the Hypos-1 observational study.

BACKGROUND AND AIMS: Hypoglycemia represents a relevant burden in people with diabetes. Consequences of hypoglycemia/fear of hypoglycemia on quality of life (QoL) and behaviors of patients with T1DM and T2DM were assessed. METHODS AND RESULTS: HYPOS-1 was an observational retrospective study. Fear of hypoglycemia (Fear of Hypoglycemia Questionnaire, FHQ), general health status (visual analog scale of EuroQol questionnaire, EQ5D-VAS) psychological well-being (WHO-5 well being index, WHO-5), diabetes related distress (Problem Areas in Diabetes 5, PAID-5), and corrective/preventive behaviors following hypoglycemia were compared between people with and without previous experience of severe and symptomatic hypoglycemia and by tertiles of FHQ scores. A multivariate analysis was performed to identify factors associated with the likelihood of being in the third tertile of FHQ score. Overall, 2229 patients were involved. Severe hypoglycemia had statistically significant and clinically relevant (measured as effect sizes) negative impact on EQ5D-VAS, WHO-5, PAID-5, and FHQ both in T1DM and T2DM. In T2DM, symptomatic episodes had similar impact of severe hypoglycemia. Moving from the first to the third FHQ tertile, lower scores of EQ-5D VAS and WHO-5, and higher levels of PAID-5 were found. Patients in the third tertile performed more frequently corrective/preventive actions that negatively impact on metabolic control. Previous hypoglycemia, insulin treatment, female gender, age, and school education were the independent factors associated with increased likelihood to be in the third tertile. CONCLUSION: Not only severe but also symptomatic hypoglycemia negatively affect patient QoL, especially in T2DM. Addressing fear of hypoglycemia should be a goal of diabetes education.

INtegration of care for reaching targetS In Diabetic patiEnts: Design of the INSIDE Study.

INTRODUCTION: Three Italian scientific associations of different specialties (AMD, Associazione Medici Diabetologi-for diabetologists; ANMCO,Associazione Nazionale Medici Cardiologi Ospedalieri-for cardiologists; SIMG, Società Italiana di Medicina Generale-for General Practitioners) designed this study to assess whether an integrated care organization comprising three different specialists can improve adherence and can achieve the guidelines targets in a population of individuals with type 2 diabetes, without established cardiovascular disease but at high risk (≥ 20% at 10 years according to the CUORE.ISS risk cards) compared with the current standards of care provided by the Italian National Health Service. METHODS: Thirty primary care centers (general practitioners, GPs), 30 cardiology centers and 30 diabetes centers have been selected by the scientific associations, disseminated in the national territory, on the basis of proven previous cooperation in other studies. Each primary care center will enroll 100 type 2 diabetic subjects, > 45 years old, with no established cardiovascular disease, but with a high risk due to the presence of at least one other risk factor besides diabetes over the cutoff [hypertension > 135/80 mmHg, LDL cholesterol > 70 mg/dl, tobacco smoke, first-degree familiarity for CHD (coronary heart disease), central obesity according the WHO criteria]. Fifteen of 30 selected primary care centers, chosen randomly, will continue the treatment of the 100 identified patients according to their "usual care," driven by Good Clinical Practice and by current guidelines (control group or "UC"-usual care), collecting all available clinical and instrumental data and transferring them to the electronic CRF. The remaining 15, after informed consent, will submit their 100 patients each in a specific integrated pathway, which entails the mandatory operational integration and exchange of information with the diabetes specialists and cardiologists pertaining to the same previously identified area. The integrated care path for the patients in the proband group (IC, integrated care) is based on application of the recommendations of the Italian Guidelines aimed at achieving the proposed targets for the main risk factors [LDL < 70 mg/dl; SBP < 130 mmHg; HbA1c (glycated hemoglobin) ≤ 7% (52 mmol/mol]. All the clinical data will be recorded on a shared electronic CRF. The trial will last 3 years: 6 months for the enrollment and randomization of the centers, 6 months for the enrollment of the probands and control subjects, and 2 years of follow-up. The study will be conducted according the Helsinki Declaration on human experimentation ethics. PLANNED OUTCOMES: The primary planned outcome is represented by the increase in the percentage of people that achieve the target values of at least two out of three of the considered risk factors [HbA1c, SBP (systolic blood pressure), LDL cholesterol] compared with the percentage actually achieved in the control group. The secondary outcomes are: (1) a MACE (major adverse cardiac event) composite: non-fatal myocardial infarction, non-fatal stroke, mortality from any cause and hospitalization for cardiovascular disease; (2) the number of early diagnoses of new onset complications; (3) evaluation of adverse events and safety of the probands and control patients; (4) comparative cost analysis and cost-effectiveness analysis.

Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study.

OBJECTIVE: Hypoglycemia is common in type 1 diabetes mellitus (T1DM). We aimed to update the incidence of severe and symptomatic hypoglycemia and investigate several correlated factors. METHODS: In this multicenter, observational retrospective study, the data of 206 T1DM patients from a sample of 2,229 consecutive patients seen at 18 diabetes clinics were analyzed. Sociodemographic and clinical characteristics, severe hypoglycemia in the past 12 months, and symptomatic hypoglycemia in the past 4 weeks were recorded with a self-report questionnaire and a clinical form during a routine visit. Poisson multivariate models were applied. RESULTS: A minority of patients accounted for the majority of both severe and symptomatic episodes. The incidence rate (IR) of severe hypoglycemia was 0.49 (0.40-0.60) events/person-years. The incidence rate ratio (IRR) was higher in patients with previous severe hypoglycemia (3.71; 2.28-6.04), neuropathy (4.16; 2.14-8.05), long duration (>20 years, 2.96; 1.60-5.45), and on polypharmacy (1.24; 1.13-1.36), but it was lower when a complication was present. The IR of symptomatic hypoglycemia was 53.3 events/person-years, with an IRR significantly higher among women or patients with better education, or shorter duration or on pumps. The IRR was lower in patients with higher BMI or neuropathy or aged more than 50 years. CONCLUSIONS: Fewer than 20 % of T1DM patients are free from hypoglycemia, with one in six having experienced at least one severe episode in the last year. The distribution is uneven, with a tendency of episodes to cluster in some patients. Severe and symptomatic episodes have different correlates and reflect different conditions.

Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement : Diabetes mellitus and thyroid disorders: recommendations for clinical practice.

Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management.