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.

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.

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.

Beta cell stress in a 4-year follow-up of patients with type 2 diabetes: A longitudinal analysis of the BetaDecline Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a progressive deterioration in beta cell function and loss of glycaemic control. Clinical predictors of beta cell failure are needed to guide appropriate therapy. METHODS: A prospective evaluation of a large set of potential predictors of beta cell stress, measured as change in the proinsulin/insulin (PI/I) ratio, was conducted in a cohort of 235 outpatients with T2DM on stable treatment with oral hypoglycaemic agents or diet followed up for ~4 years (median value 3.9 years; interquartile range 3.8-4.1 years). RESULTS: Overall, metabolic control deteriorated over time, with a significant increase in glycated haemoglobin (HbA1c; P < .0001), proinsulin (P < .0001), and PI/I ratio (P = .001), without significant changes in the homeostatic model assessment of insulin resistance. Multivariate regression analysis showed that for each 1% (10.9 mmol/mol) increase from baseline in HbA1c, the risk of beta cell stress increased by 3.8 times; for each 1% (10.9 mmol/mol) incremental increase in HbA1c during the study, risk of beta cell stress increased by 2.25 times that at baseline. By contrast, baseline anthropometric and clinical variables, lipid profile, inflammatory markers (PCR, IL-6), non-esterified fatty acids, and current therapies did not independently influence PI/I ratio variation during follow-up. CONCLUSIONS: In this cohort of patients with T2DM, beta cell function progressively deteriorated despite current therapies. Among a large set of clinical and biochemical predictors, only baseline HbA1c levels and their deterioration overtime were associated with higher beta cell stress over time.

Diabetic kidney disease in the elderly: prevalence and clinical correlates.

BACKGROUND: Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, < 60 mL/min/1.73 m2) and albuminuria (Alb+) are essential for the diagnosis of DKD, but their association with clinical variables and quality of care may be influenced by ageing. METHODS: Here we investigated the association of clinical variables and quality of care measures with eGFR+ and Alb+ in 157,595 T2DM individuals participating to the Italian Association of Clinical Diabetologists (AMD) Annals Initiative, stratified by age. RESULTS: The prevalence of eGFR+ and Alb+ increased with ageing, although this increment was more pronounced for low eGFR. Irrespective of age, both the eGFR+ and Alb + groups had the worst risk factors profile when compared to subjects without renal disease, showing a higher prevalence of out-of target values of HbA1c, BMI, triglycerides, HDL-C, blood pressure and more complex cardiovascular (CVD) and anti-diabetic therapies, including a larger use of insulin In all age groups, these associations differed according to the specific renal outcome examined: male sex and smoking were positively associated with Alb+ and negatively with eGFR+; age and anti-hypertensive therapies were more strongly associated with eGFR+, glucose control with Alb+, whereas BMI, and lipid-related variables with both abnormalities. All these associations were attenuated in the older (> 75 years) as compared to the younger groups (< 65 years; 65-75 years), and they were confirmed by multivariate analysis. Notably, Q-score values < 15, indicating a low quality of care, were strongly associated with Alb+ (OR 8.54; P < 0.001), but not with eGFR+. CONCLUSIONS: In T2DM patients, the prevalence of both eGFR and Albuminuria increase with age. DKD is associated with poor cardiovascular risk profile and a lower quality of care, although these associations are influenced by the type of renal abnormality and by ageing. These data indicate that clinical surveillance of DKD should not be unerestimated in old T2DM patients.

The place of frailty and vulnerability in the surgical risk assessment: should we move from complexity to simplicity?

Due to aging of the world population, older patients accessing health services are becoming continuously more frequent. This has increased the interest in assessing frailty and vulnerability in all specialties and general medicine. Although the term frailty has been recognized for over 30 years, there is not yet a universally recognized definition, and different care providers assess frailty and vulnerability with dissimilar tools, from very complex to very simple validated scales. Being treated with respect and dignity at the right time and place is the key message, as well as after undergoing a global evaluation both in urgency/emergency and in programmed surgery for all older surgical patients. Filling the gap will improve the results of any clinical intervention, both medical and surgical. Anesthesiologists, surgeons, hospitalists, and any member of the team of care providers must be trained into geriatric syndromes.

Multiple fractures and impaired bone metabolism in Wolfram syndrome: a case report.

Wolfram Syndrome (WS) is a rare and lethal disease characterized by optic atrophy, diabetes mellitus, diabetes insipidus, and hearing loss. To date, osteoporotic related fractures have not been reported in affected patients. Here, we describe the case of a man affected by WS complicated by several bone fragility fractures. A 50-year-old Caucasian man was hospitalized because of tibia and fibula fractures. His clinical features included diabetes mellitus, diabetes insipidus, optic atrophy and deafness that were consistent with an unrecognized WS diagnosis, which was confirmed by the identification of a specific mutation in gene WFS1 encoding wolframin. Bone mineral density by phalangeal quantitative ultrasound demonstrated severe osteoporosis, with high serum levels of surrogate markers of bone turn-over. Previously unidentified rib fractures were also detected. To the best of our knowledge, this is the first report of osteoporotic related fractures in a patient affected by WS. Although no effective treatments are currently available to delay the progression of the disease, this case report suggests to evaluate fracture risk in the diagnostic work-up of WS.

Calcifediol improves lipid profile in osteopenicatorvastatin-treated postmenopausal women.

BACKGROUND: Low vitamin D serum levels have been associated with unfavourable lipid profile and poorer response to atorvastatin. Aims of this study were to test the effects of 25-hydroxyvitamin D3 (calcifediol) compared to parental vitamin D3 (cholecalciferol) supplementation on modifications of plasma 25(OH)D levels and lipid profile. MATERIALS AND METHODS: Fifty-seven postmenopausal women (aged 59.03 ± 6.73 years) who were at low risk of fracture and with basal plasma 25(OH)D < 30 ng/mL were included if they were on atorvastatin treatment prescribed as appropriate. Recruited women were randomized to receive oral calcifediol or cholecalciferol, both at a dose of 140 µg according to a weekly regimen. RESULTS: At baseline, 25(OH)D was negatively associated with BMI (r = -0.37; P = 0.004), total cholesterol (r = -0.31; P = 0.01) and LDL-C (r = -0.32; P = 0.02). After 24 weeks, 25(OH)D increased significantly in both groups (P < 0.001), although higher levels were obtained with calcifediol as compared with cholecalciferol (P < 0.001). Only in the calcifediol group, a significant reduction of LDL-C (P = 0.01) and an increase of HDL-C (P = 0.02) were obtained, even after adjustment for age, and baseline BMI, 25(OH)D and lipid levels (P < 0.05). The percentage changes in 25(OH)D levels were associated with the variations of LDL-C (r = -0.44; P = 0.01) and HDL-C levels (r = 0.30; P = 0.10). CONCLUSION: Calcifediol administration in osteopenic and dyslipidemic postmenopausal women with low 25(OH)D improves lipid profile when added to an ongoing atorvastatin treatment.

Sexual dysfunction at the onset of type 2 diabetes: the interplay of depression, hormonal and cardiovascular factors.

INTRODUCTION: Several data have emphasized the importance of early diagnosis of erectile dysfunction (ED) and meticulous cardiovascular investigation in the type 2 diabetic mellitus (T2DM) patients. AIM: To estimate the prevalence of ED and its associated determinants in a sample of male patients with new or recently diagnosed T2DM. METHODS: The SUBITO-DE study is an observational, multicenter, prospective study involving 27 Italian diabetes centers. Male patients recently diagnosed with T2DM were consecutively interviewed by their attending physician at the diabetes care centers and asked whether they had experienced a change in their sexual function or found it unsatisfactory. Those responding positively were then invited to participate in the study. MAIN OUTCOME MEASURE: Several hormonal and biochemical parameters were studied. RESULTS: A nonselected series of 1,503 patients was interviewed, 499 of which (mean age, 58.8 ± 8.8 years) entered the study, yielding a final enrolment rate of 33.3%. ED was classified as mild in 19.4%, mild-to-moderate in 15.4%, moderate in 10.4%, and severe in 21.6% of patients, respectively. In addition, premature ejaculation, delayed ejaculation, and hypoactive sexual desire (HSD) were comorbid in 28.3%, 32.9%, and 58.4%, respectively. Finally, hypogonadism, showed an estimated prevalence of almost 20%. Both organic (at least one chronic DM-associated complication) and psychological factors (severe depressive symptoms) increased the risk of ED. Severe depressive symptoms were also associated with ejaculatory problems, HSD, and hypogonadism. CONCLUSIONS: A high prevalence of sexual dysfunction in men with recently diagnosed T2DM was detected. Early diagnosis of ED could help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of sexual dysfunction should become a part of routine care in the management of T2DM patients.

MTHFR C677T polymorphism, folate status and colon cancer risk in acromegalic patients.

BACKGROUND: Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. PURPOSE: We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. METHODS: Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T MTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. RESULTS: Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFR C677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95% CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95% CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. CONCLUSIONS: In this cohort of acromegalic patients, CRT risk is increased in 677TT MTHFR patients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.

Vitamin D reduces musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P < 0.05] and exhibited lower inflammatory markers (P < 0.005 vs. placebo). Our data demonstrate that cholecalciferol at a dose of 300,000 IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

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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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.

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.

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.

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.