Long-Term Influence of Locus of Control and Quality of Life on Metabolic Profile in Elderly Subjects with Type 2 Diabetes.

BACKGROUND: The Locus of Control (LOC) is a mental disposition indicating the individuals' belief that disease-related outcomes are under their own control (Internal), dependent on others (External), or dependent on chance (Chance). Quality of Life (QoL) and LOC may have complex effects on self-care activities and diabetes management in subjects with type 2 diabetes (T2D). The aim of the present study was to evaluate the predictive role of LOC and QoL scores on metabolic control in elderly T2D outpatients, secondly evaluating potential gender differences. METHODS: An extensive set of questionnaires was administered to a group of consecutive elderly T2D outpatients on oral glucose-lowering drugs attending a single diabetes center. Personal and clinical variables were analyzed at baseline (between 1 February and 31 March 2015) and after 6 years of follow-up. RESULTS: At baseline, study participants showed an overall good metabolic control. Diabetes Specific Quality of Life (DSQoL) scores indicated an overall good QoL in both genders, with a higher DSQoL satisfaction score in women. Both genders presented higher scores in the LOC-Internal domain, with men reaching higher scores in the LOC-External domain than women. At the 6-years follow-up, subjects with baseline higher LOC-External score presented better metabolic outcome. In the regression analysis, LOC-External score was an independent predictor of good metabolic control maintenance, but this result was only statistically significant in men. CONCLUSIONS: LOC scores may influence long-term glycemic control in elderly T2D patients on oral glucose-lowering drugs.

Comparative effectiveness of Glargine 300 U/mL vs. Degludec 100 U/mL in patients with type 2 diabetes switching from 1° generation basal insulins.

BACKGROUND AND AIMS: Data on second generation basal insulin (2BI) in people with type 2 diabetes (T2D) generated by clinical trials still need confirmation in real-world clinical settings. This study aimed at assessing the comparative effectiveness of 2BI [Glargine 300 U/mL (Gla-300) vs. Degludec 100 U/mL (Deg-100)] in T2D Italian patients switching from first generation basal insulins (1BI). METHODS AND RESULTS: This was a retrospective, non-inferiority, multicenter study. Patients switching to Gla-300 or Deg-100 from 1BI were 1:1 propensity score matched (PSM). Changes during 6 months in continuous endpoints were assessed through linear mixed models. Incidence rates (IR) of hypoglycemia (episodes per patient-months) were compared using Poisson regression. Each PSM cohort included 593 patients. HbA1c decreased from baseline (8.7%) to 6 months by -0.58% (95%CI -0.69;-0.47) in Gla-300 group and -0.50% (95%CI -0.61;-0.39) in Deg-100 group, confirming the non-inferiority of Gla-300 vs. Deg-100. No between-group differences emerged: FBG was reduced by about 20 mg/dl with both 2BI, mean dose of 2BI (24.5 U, 0.3 U/Kg at the first prescription) was suboptimally titrated during 6 months (+1.34 U in Gla-300 and + 1.76 U in Deg-100), body weight showed minor changes. IR of hypoglycemia <54 mg/dl was 0.32 (95%CI 0.21; 0.49) in Gla-300 group and 0.19 (95%CI 0.11; 0.33) in Deg-100 group (p = 0.14). CONCLUSION: In subjects with T2D, switching to 2BI from 1BI was associated with similar improvements in glycemic control, low hypoglycemia rates and no weight gain in real-life setting. Clinical inertia, represented by late treatment intensification and suboptimal titration, represents a major issue in Italy.

Comparative effectiveness and safety of glargine 300 U/mL versus degludec 100 U/mL in insulin-naïve patients with type 2 diabetes. A multicenter retrospective real-world study (RESTORE-2 NAIVE STUDY).

AIMS: This study assessed comparative effectiveness of glargine 300 U/mL (Gla-300) versus degludec 100 U/mL (Deg-100) in insulin-naïve patients with T2D. METHODS: This is a retrospective, multicenter, non-inferiority study based on electronic medical records. All patients initiating Gla-300 or Deg-100 were 1:1 propensity score-matched (PSM). Linear mixed models were used to assess the changes in continuous endpoints. Incidence rates (IR) of hypoglycemia were compared using Poisson's regression models. RESULTS: Nineteen centers provided data on 357 patients in each PSM cohort. HbA1c after 6 months (primary endpoint) decreased by - 1.70% (95%CI - 1.90; - 1.50) in Gla-300 group and - 169% (95%CI - 1.89; - 1.49) in Deg-100 group, confirming non-inferiority of Gla-300 versus Deg-100. Fasting blood glucose (BG) decreased by ~60 mg/dl in both groups; body weight remained unchanged. In both groups, the mean starting dose was 12U (0.15U/kg) and it was slightly titrated to 16U (0.20U/kg). IR (episodes per patient-months) of BG ≤70 mg/dl was 0.13 in Gla-300 group and 0.14 in Deg-100 group (p=0.87). IR of BG <54 mg/dL was 0.02 in both groups (p=0.49). No severe hypoglycemia occurred. CONCLUSION: Initiating Gla-300 or Deg-100 was associated with similar improvements in glycemic control, no weight gain and low hypoglycemia rates, without severe episodes during 6 months of treatment.

Multimorbidity and polypharmacy: a risk factor for older patients.

Invited commentary on Letter: Acta Biomed 2022; Vol. 93, N. 2: e2022136 DOI 10.23750/abm.v93i2.12855 https://mattioli1885journals.com/index.php/actabiomedica/article/view/12855.

2021- Pros and Cons in General Internal Medicine and Geriatrics.

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Temporal trends in intensification of glucose-lowering therapy for type 2 diabetes in Italy: Data from the AMD Annals initiative and their impact on clinical inertia.

AIMS: Clinical inertia negatively affects type 2 diabetes (T2DM) management. We evaluated changes in prescription patterns of hypoglycemic drugs during a 15 year-observation period in a large population of T2DM outpatients and their effect on metabolic control. METHODS: Data on all T2DM patients attending 258 Italian diabetes clinics between 2005 and 2019 were collected and analyzed for three 5-years periods. The addition of a second drug to metformin and the addition of a third agent to dual therapy were evaluated. RESULTS: During the observation period, 437.179 patients added a second drug to metformin. The intensification occurred earlier over time: patients had a shorter duration of disease and a better cardiovascular risk profile in the last five years, compared to previous periods. During the same period, 208.767 patients added a third agent to dual therapy. Duration of diabetes at the time of intensification decreased, and cardiovascular risk profile improved over time. Also HbA1c levels at the time of intensification decreased over time. CONCLUSIONS: in this large cohort of T2MD subjects during a long observation period an earlier treatment intensification and a better metabolic control were observed, suggesting an improved approach to clinical inertia.

Structured self-monitoring of blood glucose is associated with more appropriate therapeutic interventions than unstructured self-monitoring: A novel analysis of data from the PRISMA trial.

AIMS: To investigate the relationship between single therapeutic interventions and indicatorsofglycemic control in the PRISMA trial, a large study comparing the effects of intensive structured SMBG (ISM) vs. active control (AC) in non-insulin-treated type 2 diabetes (T2D). METHODS: Information was collected at four time points, corresponding to months 3, 6, 9, and 12 and visits 2, 3, 4, and 5, respectively. Data on therapeutic interventions, HbA1c levels and the number of hypoglycemic episodes at each visit were analyzed. RESULTS: Intensification of drug therapy occurred in 20.3% vs. 15.6%, and no change in 71.8% vs. 78.7% of visits for the ISM and AC groups, respectively. On the other hand, de-intensification and redistribution of drugs and/or drug dose occurred in a similar proportion of visits. Intensification of drug therapy in both groups was associated with significant reductions in HbA1c vs. the previous visit, while de-intensification of therapy led to a significant increase in HbA1c in the AC group only. CONCLUSIONS: Our data strongly support that structured SMBG has clinical value in reducing HbA1c in non-insulin-treated T2D and suggest that this clinical benefit may be mediated by more appropriate and timely changes in drug therapy.

Gender Differences in Diabetic Kidney Disease: Focus on Hormonal, Genetic and Clinical Factors.

Diabetic kidney disease (DKD) is one of the most serious complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Current guidelines recommend a personalized approach in order to reduce the burden of DM and its complications. Recognizing sex and gender- differences in medicine is considered one of the first steps toward personalized medicine, but the gender issue in DM has been scarcely explored so far. Gender differences have been reported in the incidence and the prevalence of DKD, in its phenotypes and clinical manifestations, as well as in several risk factors, with a different impact in the two genders. Hormonal factors, especially estrogen loss, play a significant role in explaining these differences. Additionally, the impact of sex chromosomes as well as the influence of gene-sex interactions with several susceptibility genes for DKD have been investigated. In spite of the increasing evidence that sex and gender should be included in the evaluation of DKD, several open issues remain uncovered, including the potentially different effects of newly recommended drugs, such as SGLT2i and GLP1Ras. This narrative review explored current evidence on sex/gender differences in DKD, taking into account hormonal, genetic and clinical factors.

PROS and CONS in general medicine and geriatrics, 2020.

In 2020 many researches were published concening non Covid pathologies. In the field of general medicine and geriatrics a look is given to oxygen therapeutic use, soft surgical treatments of benign prostatic hyperplasia, nonalcoholic steatohepatitis treatment, use of SGLT2 inhibitors in cardiac failure and a proposal for treatment of severe claudicatio intermittens.

Primum non nocere. The SARS-CoV-2 pandemic course in oldest.

Dramatic outcomes of Covid-19 pandemia in Italy, in particular in the North, must be discussed. Maybe a bad strategy and lack of timely intervention togheter with concurrent social events, comorbidities of oldest persons, bed rest, inadequate nutritional support and drugs' side effects and infection of health professionals  proved fatal for many.

Pros and Cons in general medicine and geriatrics, 2019.

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WHO Declares COVID-19 a Pandemic.

The World Health Organization (WHO) on March 11, 2020, has declared the novel coronavirus (COVID-19) outbreak a global pandemic (1). At a news briefing , WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, noted that over the past 2 weeks, the number of cases outside China increased 13-fold and the number of countries with cases increased threefold. Further increases are expected. He said that the WHO is "deeply concerned both by the alarming levels of spread and severity and by the alarming levels of inaction," and he called on countries to take action now to contain the virus. "We should double down," he said. "We should be more aggressive." [...].

Comparable efficacy with similarly low risk of hypoglycaemia in patient- vs physician-managed basal insulin initiation and titration in insulin-naïve type 2 diabetic subjects: The Italian Titration Approach Study.

AIMS: People with uncontrolled type 2 diabetes (T2DM) often delay initiating and titrating basal insulin. Patient-managed titration may reduce such deferral. The Italian Titration Approach Study (ITAS) compared the efficacy and safety of insulin glargine 300 U/mL (Gla-300) initiation and titration using patient- (nurse-supported) or physician-management in insulin-naïve patients with uncontrolled T2DM. MATERIALS AND METHODS: ITAS was a multicentre, phase IV, 24-week, open-label, randomized (1:1), parallel-group study. Insulin-naïve adults with T2DM for ≥1 year with poor metabolic control initiated Gla-300 after discontinuation of SU/glinides, and were randomized to self-titrate insulin dose (nurse-assisted) or have it done by the physician. The primary endpoint was change in HbA1c . Secondary outcomes included hypoglycaemia incidence and rate, change in fasting self-monitored plasma glucose, patient-reported outcomes (PROs), and adverse events. RESULTS: Three hundred and fifty five participants were included in the intention-to-treat population. At Week 24, HbA1c reduction from baseline was non-inferior in patient- vs physician-managed arms [least squares mean (LSM) change (SE): -1.60% (0.06) vs -1.49% (0.06), respectively; LSM difference: -0.11% (95% CI: -0.26 to 0.04)]. The incidence and rates of hypoglycaemia were similarly low in both arms: relative risk of confirmed and/or severe nocturnal (00:00-05:59 hours) hypoglycaemia was 0.77 (95% CI: 0.27 to 2.18). No differences were observed for improvement in PROs. No safety concerns were reported. CONCLUSIONS: In the T2DM insulin-naïve, SU/glinides discontinued population, patient-managed (nurse-assisted) titration of Gla-300 may be a suitable option as it provides improved glycaemic control with low risk of hypoglycaemia, similar to physician-managed titration.

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.

Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice.

INTRODUCTION: Following the US Food and Drug Administration (FDA) guidance on the evaluation of novel agents for the treatment of type 2 diabetes mellitus (T2DM), a number of cardiovascular outcomes safety trials (CVOTs) on sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been conducted. These trials show similarities in study design and definition of primary endpoints, but differ in their eligibility criteria. The aim of the present study was to investigate the generalizability of CVOTs on SGLT2i to Italian adults with T2DM; we estimated the proportions of this patient population who would be eligible for enrollment in EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), DECLARE-TIMI 58 (dapagliflozin), and VERTIS-CV (ertugliflozin) studies. METHODS: This observational, cross-sectional study was conducted in 222 Italian diabetes clinics. Data on 455,662 adult patients with T2DM seen during 2016 were analyzed against the published patient eligibility criteria for the four CVOTs. The current use of SGLT2i in potentially eligible patients was assessed. RESULTS: Among the population identified, the proportion of patients meeting major eligibility criteria was 11.7% for EMPA-REG OUTCOME, 29.4% for CANVAS, 55.9% for DECLARE-TIMI 58, and 12.8% for VERTIS-CV. Of the patients eligible for these CVOTs, only a minority (range 4.4-6.8%) was actually prescribed an SGLT2i. Compared with patients in the CVOTs, eligible patients in the real world showed older age and longer diabetes duration, lower BMI and HbA1c levels, lower prevalence of established cardiovascular and cerebrovascular disease, and higher rates of microvascular complications and peripheral arterial disease. CONCLUSION: The percentage of patients potentially eligible for treatment with SGLT2i varies as a reflection of different eligibility criteria applied in the trials. A large number of patients that could benefit from SGLT2i in terms of not only cardiovascular protection but also renal protection do not receive the treatment. FUNDING: AstraZeneca.

The Science of Choosing Wisely: should it be applied to any intervention for healthy and active longevity?

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Pros and Cons in General Medicine and Geriatrics - 2018.

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