Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography.

AIM: To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). METHODS: We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. RESULTS: Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (ß = 0.274, P = 0.008) and fasting insulin levels (ß = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (ß = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. CONCLUSION: Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.

Potential Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Cognitive Decline and Dementia in Diabetes Mellitus.

Dementia is a permanent illness characterized by mental instability, memory loss, and cognitive decline. Many studies have demonstrated an association between diabetes and cognitive dysfunction that proceeds in three steps, namely, diabetes-associated cognitive decrements, mild cognitive impairment (MCI; both non-amnesic MCI and amnesic MCI), and dementia [both vascular dementia and Alzheimer's disease (AD)]. Based on this association, this disease has been designated as type 3 diabetes mellitus. The underlying mechanisms comprise insulin resistance, inflammation, lipid abnormalities, oxidative stress, mitochondrial dysfunction, glycated end-products and autophagy. Moreover, insulin and insulin-like growth factor-1 (IGF-1) have been demonstrated to be involved. Insulin in the brain has a neuroprotective role that alters cognitive skills and alteration of insulin signaling determines beta-amyloid (Aß) accumulation, in turn promoting brain insulin resistance. In this complex mechanism, other triggers include hyperglycemia-induced overproduction of reactive oxygen species (ROS) and inflammatory cytokines, which result in neuroinflammation, suggesting that antidiabetic drugs may be potential treatments to protect against AD. Among these, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are the most attractive antidiabetic drugs due to their actions on synaptic plasticity, cognition and cell survival. The present review summarizes the significant data concerning the underlying pathophysiological and pharmacological mechanisms between diabetes and dementia.

CAPTURE: A cross-sectional study on the prevalence of cardiovascular disease in adults with type 2 diabetes in Italy.

BACKGROUND AND AIMS: The prevalence of type 2 diabetes (T2D) in Italy is increasing and cardiovascular disease (CVD) represents the leading cause of death in this population. CAPTURE was a multinational, multicentre, non-interventional, cross-sectional study assessing the prevalence of CVD, atherosclerotic CVD (AsCVD) and CVD subtypes among patients with T2D, across 13 countries. Here we report the results from Italy. METHODS AND RESULTS: Overall, 816 patients with T2D (median age, 69 years [interquartile range: 62-75]; median duration of diabetes, 11.2 years [interquartile range: 5.7-18.7]) were recruited during routine clinical visits at secondary care centres in Italy between December 2018-September 2019. The prevalence of CVD was estimated at 38.8%, largely accounted for by AsCVD (33.1%). The most prevalent CVD subtype was coronary heart disease (20.8%), followed by carotid artery disease (13.2%). Most patients (85.9%) were prescribed oral glucose-lowering agents (GLAs), particularly biguanide (76.7%). Insulin use was higher in patients with CVD (41.3%) than in patients without CVD (32.9%). Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were prescribed to 20.2% vs 14.6%, and 14.5% vs 16.6% of patients with CVD compared to those without CVD, respectively. CONCLUSION: The results show that, in Italy, more than one in three patients with T2D attending secondary care centres have CVD, 85% of whom have AsCVD, yet only a minority are treated with SGLT2is and GLP-1 RAs, in discordance with the recommendations of current national and international guidelines.

Immuno-Mediated Inflammation in Hypertensive Patients with 1-h Post-Load Hyperglycemia.

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kß (NF-kß), interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kß (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1ß (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kß. These results contribute to better characterizing cardiovascular risk in hypertensives.

Liver Stiffness in Obese Hypothyroid Patients Taking Levothyroxine.

Background and Objectives: Thyroid dysfunction is associated with non-alcoholic fatty liver disease, but its role in the progression of liver damage in obese patients remains unclear. In addition, several case reports have suggested the existence of a levothyroxine-induced liver injury, which has been poorly investigated. Our aim was to verify whether a difference in the prevalence of liver fibrosis exists in a population of obese individuals taking Levothyroxine. Materials and Methods: We conducted a cross-sectional study on a population of 137 obese individuals, of which 49 were on replacement therapy with Levothyroxine. We excluded those who had hypertriglyceridemia and diabetes mellitus. All participants underwent a liver stiffness assessment by transient elastography as well as biochemical measurements. In subjects with liver fibrosis, other cause of liver fibrosis were ruled out. Results: Participants taking Levothyroxine had a higher prevalence of liver fibrosis than those not taking Levothyroxine (30.6% vs. 2.3%; p < 0.001), and these results were obtained after we made an adjustment for age (Exp(B) = 18.9; 95% CI = 4.1−87.4; p < 0.001). The liver stiffness value differed significantly between groups (6.0 ± 3.6 and 5.1 ± 1.2, p = 0.033). Of those subjects taking Levothyroxine, there were no significant differences in the dose of medication (1.21 ± 0.36 vs. 1.07 ± 0.42; p = 0.240) and treatment duration (13.7 ± 7.43 vs. 11.13 ± 6.23; p = 0.380) between those with and without liver fibrosis. Conclusions: We found, for the first time, a greater prevalence of liver fibrosis in obese individuals taking Levothyroxine than in those not taking this medication. This finding needs to be confirmed by longitudinal population studies as well as by cellular studies.

An open-label trial on the efficacy and tolerability of naltrexone/bupropion SR for treating altered eating behaviours and weight loss in binge eating disorder.

PURPOSE: Binge eating disorder (BED) has a considerable clinical relevance by virtue of its high numerous psychiatric and medical comorbidities; among the latter, the most frequent is obesity. Available treatments for BED have shown frequent relapse of binges or weight regain in the long term. The new combination of naltrexone and bupropion sustained release (NB) has proved to be effective for weight loss among obese patients. As NB acts on hypothalamic and reward circuits, that seem involved in the pathogenesis and maintenance of BED symptoms, this study aims to evaluate the efficacy of NB in improving pathological eating behavior and losing weight in BED patients. METHODS: In this preliminary study, 23 obese-BED patients and a control group of 20 obese non-BED patients (respectively, Groups 1 and 2) who had previously undergone at least 5 unsuccessful weight-loss programs were treated with NB in addition to modified life style. Evaluation at t0 and after 16 weeks of treatment (t1) included anthropometric measurement, eating behavior assessment and psychopathological questionnaires (EDE-Q, BES, YFAS, BDI and STAI). RESULTS: A significant and similar weight loss (ΔBMI% ≈ 8%) was evident for both groups. Pathological eating behavior (i.e., binge, grazing, emotional eating, craving for carbohydrates, and post-dinner eating), BES score and YFAS severity significantly improved, especially among BED. NB was well tolerated and drop-out rate was low. CONCLUSION: Treatment with NB, in addition to a reduced-calorie diet and increased physical activity, seems an effective and well-tolerated option for improving pathological eating behavior and losing weight in obese-BED patients. LEVEL OF EVIDENCE: Level III case-control study.

Exploring the effects of DPP-4 inhibitors on the kidney from the bench to clinical trials.

Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non-insulin glucose-lowering agents, belonging to the incretin family, which are able to improve glycemic control with a favorable safety profile, since they are associated with a low risk of hypoglycemia, no weight gain, and good tolerability in patients with chronic renal failure. Some experimental and clinical studies suggest that these drugs may exert significant pleiotropic effects, in particular on chronic kidney disease (CKD) progression, but data from clinical trials are still controversial. In an effort to clarify the effects of DPP-4 inhibitors (DPP-4is) on diabetes-related renal damage, we performed a narrative review of available clinical trials and other experimental studies focusing on renal effects of DPP-4is. Currently, there is no conclusive evidence proving the usefulness of this drug class for improving diabetes-related renal damage. However, our literature review suggests that DPP-4is are safe and well tolerated in type 2 diabetes mellitus (T2DM) patients with CKD. More importantly, results from the reviewed studies indicate that DPP-4 inhibitor therapy may improve two major risk factors for diabetic nephropathy, such as hyperglycemia and albuminuria, resulting in potential renal benefits beyond glycemic control. Despite several limitations, the conclusions of our review corroborate previous evidence on the potential renal benefits of DPP-4is, highlighting the urgent need of future trials adequately powered and designed on hard renal outcomes to ascertain (or contradict) the therapeutic benefit of DPP-4is in T2DM and CKD patients.

Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes.

Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's and Alzheimer's disease); furthermore, also other antidiabetic drugs have proven efficacy in preclinical studies. Overall, promising results are already available and finding new intervention strategies represents a current need in this field of research.

Serum complement C3 strongly correlates with whole-body insulin sensitivity in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is characterised by an excess of cardiovascular diseases (CVD) risk, attributable to a synergy between under-diagnosed traditional risk factors (i.e. insulin resistance) and inflammatory disease activity. The aim of the present study was to evaluate the correlation between inflammatory measures and insulin sensitivity in RA patients. METHODS: Forty non-diabetic RA patients (19 males) were recruited. All patients underwent anthropometric measurements, laboratory evaluation and oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI) was calculated with the equation proposed by Matsuda et al., from dynamic values of glucose and insulin obtained during OGTT. RESULTS: In the univariate analysis, lnISI correlated inversely with age, BMI, waist circumference, sBP, ESR, lnCRP and complement C3, but not with disease duration, dBP or complement C4. In non-obese patients (BMI <30 kg/m2, n=28), only age, BMI, lnCRP and C3 maintained their correlation with lnISI. In a stepwise multiple regression using lnISI as the dependent variable and BMI, age, lnCRP and complement C3 as predictors, only BMI and C3 entered the equation and accounted for 38.2% of the variance in lnISI. In non-obese patients, only C3 entered the regression equation, accounting for 32.2% of the variance in lnISI. Using a ROC curve, we identified the best cut-off for complement C3 of 1.22 g/L that yielded a sensitivity of 67% and a specificity of 79% for classification of insulin resistant patients. CONCLUSIONS: In RA patients, complement C3 correlates strongly with insulin sensitivity, in both obese and non-obese individuals.

Vitamin D and 1-hour post-load plasma glucose in hypertensive patients.

BACKGROUND: A plasma glucose value ≥155 mg/dl for 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes and with subclinical organ damage. We designed this study to address if 25-hydroxyvitamin D [25(OH)D] circulating levels are associated with glucose tolerance status, and in particular with 1-hour post-load plasma glucose levels. METHODS: We enrolled 300 consecutive Caucasian hypertensive never-treated outpatients (160 men and 140 women, aged 52.9 ± 9.2 years). Subjects underwent OGTT and measurements of 25(OH)D and standard laboratory tests. Estimated glomerular filtration rate (e-GFR) was calculated by CKD-EPI formula and insulin sensitivity was assessed by Matsuda-index. RESULTS: Among participants, 230 were NGT, 44 had impaired glucose tolerance (IGT) and 26 had type-2 diabetes. According to 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into: NGT < 155 (n = 156) and NGT > 155 mg/dL (n = 74).NGT ≥ 155 had higher significant fasting and post-load glucose and insulin, parathyroid hormone and hs-CRP levels than NGT < 155. On the contrary, Matsuda-index, e-GFR, and 25(OH)D were significantly lower in NGT ≥ 155 than NGT < 155 subjects. In the multiple regression analysis, 25(OH)D levels resulted the major determinant of 1-h post-load plasma glucose in all population and in the four groups of glucose tolerance status. In the whole population, Matsuda-index, hs-CRP and e-GFR explained another 12.2%, 6.7% and 1.7% of its variation. CONCLUSIONS: Our data demonstrate a significant and inverse relationship between 25(OH)D levels and glucose tolerance status, particularly with 1-h post-load glucose.

Association between augmented levels of the gut pro-hormone Proneurotensin and subclinical vascular damage.

Elevated levels of the gut pro-hormone Proneurotensin (proNT) have been found to predict development of cardiovascular disease. However, it is still unknown whether higher proNT levels are associated with subclinical vascular damage. Herein, we investigated the relationship between higher proNT concentrations and augmented pulse pressure (PP) and carotid intima-media thickness (cIMT), indicators of increased arterial stiffness and subclinical atherosclerosis, respectively. Clinical characteristics, PP and cIMT were evaluated in 154 non-diabetic individuals stratified into tertiles according to fasting serum proNT concentrations. We found that, subjects with higher proNT levels exhibited a worse lipid profile and insulin sensitivity, increased C-reactive protein levels, along with higher values of PP and cIMT as compared to the lowest proNT tertile. Prevalence of elevated PP (≥ 60 mmHg) and subclinical carotid atherosclerosis (IMT > 0.9 mm) was increased in the highest tertile of proNT. In a logistic regression analysis adjusted for several confounders, subjects with higher proNT levels displayed a fivefold raised risk of having elevated PP values (OR 5.36; 95%CI 1.04-27.28; P = 0.05) and early carotid atherosclerosis (OR 4.81; 95%CI 1.39-16.57; P = 0.01) as compared to the lowest proNT tertile. In conclusion, higher circulating levels of proNT are a biomarker of subclinical vascular damage independent of other atherosclerotic risk factors.

Sex-based differences in the comprehensive geriatric assessment in elderly hospitalized patients with non-valvular atrial fibrillation.

Atrial fibrillation (AF) represents the most common supraventricular arrhythmia, with a prevalence of 1-3 % in the world population. Growing evidences show that AF plays an important role as a risk factor for the development of cognitive impairment (CoI) and dementia, depression and functional limitation. The purpose of the study is to evaluate, in a large cohort of elderly hospitalized patients with nonvalvular AF (NVAF) on direct oral anticoagulants (DOACs) therapy, the prevalence of CoI, depression, and functional limitation, and to assess the different variables that may be detrimental or protective on the risk of CoI or functional limitation. 1004 elderly patients were enrolled, 384 men and 620 women, with a mean age of 84±7.1 years. The two groups were comparable for the main study variables, except for age, prevalence of hypertension and CKD, which were higher in women, while ischemic heart disease was higher in men. In addition, the two groups differed in the CHA2DS2VASc score 5.3 ± 1.3 vs 4.2 ± 1.4 pts (p < 0.0001) and HAS-BLED score 2.5 ± 0.7 vs 2.3 ± 0.8 pts (p = 0.009) that were significantly higher in women. Our study revealed that in a cohort of elderly patients hospitalized with AF taking DOACs, CoI and disability are widely represented, and female sex increases the risk of being affected by CoI by about 3-fold, while improvement of functional limitations reduce this risk by about 15 %. In addition, CoI and depressive symptoms increase the risk of functional impairment about 2-fold and 28 % respectively, while antihypertensive and anti-diabetic therapy reduce this risk.

Influence of NUCB/Nesfatin-1 Polymorphism on Treatment Response to Naltrexone/Bupropion SR in Binge Eating Disorder and Obesity.

Background and Objectives: The NUCB2 gene and its polymorphisms were identified as novel players in the regulation of food intake, potentially leading to obesity (OBE) and altered eating behaviors. Naltrexone/bupropion SR (NB) showed good efficacy and tolerability for treating OBE and altered eating behaviors associated with binge eating disorder (BED). This prospective study investigates the influence of NUCB2 gene polymorphism on NB treatment response in OBE and BED. Materials and Methods: Body mass index (BMI), eating (EDE-Q, BES, NEQ, GQ, Y-FAS 2.0) and general psychopathology (BDI, STAI-S) were evaluated at baseline (t0) and after 16 weeks (t1) of NB treatment in patients with OBE and BED (Group 1; N = 22) vs. patients with OBE without BED (Group 2; N = 20). Differences were evaluated according to the rs757081 NUCB2 gene polymorphism. Results: NUCB2 polymorphism was equally distributed between groups. Although weight at t0 was higher in Group 1, weight loss was similar at t1 in both groups. BMI was not influenced by NUCB2 polymorphism. In Group 1, the CG-genotype reported significant improvement in eating psychopathology while the GG-genotype reported improvement only for FA. No differences were observed in Group 2. Conclusions: Patients diagnosed with BED and treated with NB exhibited a more favorable treatment response within the CG-genotype of the NUCB2 polymorphism.

Effect of dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist on weight loss in subjects with obesity.

The occurrence of obesity is an increasing issue worldwide, especially in industrialized countries. Weight loss is important both to treat obesity and to prevent the development of complications. Currently, several drugs are used to treat obesity, but their efficacy is modest. Thus, new anti-obesity treatments are needed. Recently, there has been increased interest in the development of incretins that combine body-weight-lowering and glucose-lowering effects. Therefore, a new drug that simultaneously coactivates both the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R) has been developed. Tirzepatide, the first in this class, improves glycemic control by increasing insulin sensitivity and lipid metabolism as well as by reducing body weight. Combining the activation of the two receptors, greater improvement of ß-cell function offers more effective treatment of diabetes and obesity with fewer adverse effects than selective GLP-1R agonists. In the present review, we discuss the progress in the use of GIPR and GLP-1R coagonists and review literature from in vitro studies, animal studies, and human trials, highlighting the synergistic mechanisms of tirzepatide.

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register.

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria.

Short term effect of sacubitril/valsartan on comprehensive geriatric assessment in chronic heart failure: a real life analysis.

Sacubitril/Valsartan (Sac-Val) has improved clinical prognosis in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF). Comorbidities have a crucial impact on clinical presentation and prognosis in HF patients. Cognitive impairment (CoI) and Depression are a very common comorbidity in patients with HF and is widely recognized as a specific determinant of chronic disability, and HF patients with poor physical functional performance in Short physical performance battery (SPPB) showed a worse prognosis. The aim of the present study was to evaluate the potential effects of Sac-Val on functional, humoral, and cognitive aspects, evaluated by performing comprehensive geriatric assessment (CGA), in a cohort of elderly HFrEF. We studied 61 patients (51 men and 10 women, mean age 76.4 ± 5.1 years) suffering from HFrEF. After 6 months follow-up, we observed a significant improvement in humoral and functional parameters of CGA, renal function, NTpro-BNP levels and echocardiographic parameters. In the whole population, multivariate analysis shows that changes of Cardiac Index, NT-proBNP and Respiratory rate contributed for 26.0%, 9.7% and 4.8% to GDS variability, respectively, and the whole model accounted for a 41.1% of GDS variation; moreover changes of Global longitudinal strain, estimated glomerular filtration rate, Cardiac Index and BMI contributed for 23.9%, 11.7%, 5.4% and 4.0% to SPPB variability, respectively, and the whole model accounted for a 45% of SPPB variation. This represents the first real-world study carried out in an elderly population suffering from chronic HFrEF with numerous comorbidities, in which treatment with Sac-Val for 6 months induced important improvements in clinical, humoral, hemodynamic, and functional outcomes, without adverse effects on cognitive performance.

Effects of continuous positive airway pressure on comprehensive geriatric assessment and cognitive function in elderly patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) can lead to cognitive impairment and depression affecting memory, attention, and executive functions. Continuous positive airway pressure (CPAP) treatment seems to be able to revert changes in brain networks and neuropsychological tests correlated to OSAS. The aim of the present study was to evaluate the effects of a 6-month treatment with CPAP on functional, humoral and cognitive parameters in a cohort of elderly OSAS patients with several comorbidities. We enrolled 360 elderly patients suffering from moderate to severe OSAS and indication for nocturnal CPAP. At baseline the Comprehensive Geriatric Assessment (CGA) revealed a borderline Mini-Mental State Examination (MMSE) score that improved after 6-month treatment with CPAP (25.3 ± 1.6 vs 26 ± 1.5; p < 0.0001), as well as the Montreal Cognitive Assessment (MoCA) showed a mild improvement (24.4 ± 2.3 vs 26.2 ± 1.7; p < 0.0001). Moreover, functionality activities increased after treatment, as documented by a short physical performance battery (SPPB) (6.3 ± 1.5 vs 6.9 ± 1.4; p < 0.0001). Reduction of the Geriatric Depression Scale (GDS) from 6.0 ± 2.5 to 4.6 ± 2.2 (p < 0.0001) was also detected. Changes of homeostasis model assessment (HOMA) index, oxygen desaturation index (ODI), sleep-time spent with saturation below 90% (TC90), peripheral arterial oxyhaemoglobin saturation (SpO2), apnea-hypopnea index (AHI) and estimation of glomerular filtration rate (eGFR), contributed, respectively, to 27.9%, 9.0%, 2.8%, 2.3%, 1.7% and 0.9% of MMSE variability for a total of 44.6% of MMSE variations. GDS score changes were due to the improvement of AHI, ODI and TC90, respectively, for 19.2%, 4.9%, 4.2% of the GDS variability, cumulative responsible for 28.3% of GDS modifications. The present real-world study shows that CPAP treatment is able to improve cognition and depressive symptoms in OSAS elderly patients.

Reactive hypoglycemia in binge eating disorder, food addiction, and the comorbid phenotype: unravelling the metabolic drive to disordered eating behaviours.

BACKGROUND: Impaired metabolic response such as blood glucose fast fluctuations may be hypothesized in binge eating disorder (BED) and food addiction (FA) by virtue of the repetitive consumption of highly processed food. Conversely, rapid changes in plasma glucose (i.e., hypoglycemia) may trigger craving for the same food products. The investigation of early glycemic disturbances in BED and FA could enhance the understanding of the metabolic mechanisms involved in the maintenance of the disorders. Present study investigated hypoglycemia events during a 5-h-long oral glucose tolerance test (OGTT) in people with BED, FA, and the comorbid phenotype. Further, the association between the severity of eating psychopathology and the variability in hypoglycaemia events was explored. METHODS: Two-hundred participants with high weight and no diabetes completed the extended OGTT and were screened for BED, FA, BED-FA, or no-BED/FA. The four groups were compared in hypoglycemia events, OGTT-derived measures, and eating psychopathology. The association between predictors (eating psychopathology), confounders (demographics, metabolic features), and the outcomes (hypoglycemia, early/late hypoglycemia, severe hypoglycemia, reactive hypoglycemia) was examined through logistic regression. RESULTS: Hypoglycemia in general, and reactive hypoglycemia were highly frequent (79% and 28% of the sample, respectively). Hypoglycemia events (< 70 mg/dL) were equally experienced among groups, whilst severe hypoglycemia (< 54 mg/dL) was more frequent in BED at the late stage of OGTT (5 h; χ2 = 1.120, p = .011). The FA and BED groups exhibited significantly higher number of reactive hypoglycemia (χ2 = 13.898, p = .003), in different times by diagnosis (FA: 210'-240'; BED: at the 270'). FA severity was the only predictor of early and reactive hypoglycemia. CONCLUSIONS: People with BED or FA are prone to experiencing reactive hypoglycemia; FA severity may predict early and symptomatic hypoglycemia events. This can further reinforce disordered eating behaviours by promoting addictive responses, both biologically and behaviourally. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.

Impairment in blood glucose control may be attended in binge eating disorder (BED) and food addiction (FA), two distinct eating disorders which are characterized by the recurrent consumption of highly palatable food rich in high-glucose index carbohydrates. Conversely, rapid changes in blood glucose, such as hypoglycemia, may intensify craving for high-calorie products, thus reinforcing pathological eating behaviours. This study investigated the presence of hypoglycemia events in people suffering from BED, FA, both, or no eating disorder, and explored whether the severity of eating behaviours correlated with a higher probability of having hypoglycemia. Results showed that people with BED and FA experienced more episodes of symptomatic hypoglycemia than those with obesity but no eating disorder. The severity of binge eating was associated with more severe hypoglycemia events, indicated by lower plasma glucose values. Lastly, people with severe FA were more prone to experiencing early post-meal hypoglycemia accompanied by symptoms. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.

Hyperkalemia in CKD: an overview of available therapeutic strategies.

Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin-angiotensin-aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels.