Prevalence of Diabetes Mellitus and Clinical Differences in Patients with Severe Osteoporosis and Fragility Fractures.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic diseases in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search for differences in clinical characteristics. Methods: This is a single-center retrospective, case-controlled study. A total of 589 patients attending CTO Bone Unit between 2 January 2010 and 31 May 2023, due to osteoporosis and fragility fractures, were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 12.7%. Compared to patients without DM, the median age at the time of first fracture was similar: 72 years ± 13.5 interquartile range (IQR) vs. 71 years ± 12 IQR; prevalence of combination of vertebral and hip fractures was higher (p = 0.008), as well as prevalence of males (p = 0.016). Bone mineral density (BMD) at all sites was higher in DM group; trabecular bone score (TBS), instead, was significantly lower (p < 0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and, therefore, might be used as a diagnostic tool in clinical practice.

Diabetic Polyneuropathy and Physical Activity in Type 1 Diabetes Mellitus: A Cross-Sectional Study.

BACKGROUND: The purpose of this study is to access whether a personal attitude to physical activity (PA) may influence the appearance of diabetic polyneuropathy (DPN) patients with well-controlled type 1 diabetes mellitus. METHODS: Ninety patients attending the diabetes technology outpatient clinic were enrolled. DPN was investigated according to the Toronto consensus diagnostic criteria. PA was assessed using the International Physical Activity Questionnaire. RESULTS: PA was low in 21.1%, moderate in 42.2% and high in 36.7% of patients. According to Toronto criteria, we defined two categories: the first one with DPN absent or possible (57 (63.3%)) and a second one with DPN certain or probable (33 (36.7%)). The χ2-test of the PA groups and the DPN categories showed a statistically significant difference (p < 0.001), with less neuropathy in patients belonging to the group of moderate/high PA. Exposure to a minimum of 600 MET minutes/week was protective factor against the onset of DPN (odd ratio 0.221, c.i. 0.068-0.720, p = 0.012). CONCLUSIONS: This study suggests that DPN is less present in type 1 diabetic patients with good metabolic control and a good personal habit of PA. Moderate-to-vigorous PA of at least 600 MET minutes/week might be a protective factor against DPN.

Risk Factors for Ulcer Recurrence in Diabetic Patients Managed by an Integrated Foot Care Protocol.

The aim of our study was to identify risk factors for the recurrence of diabetic foot ulcers (DFUs) in a selected population of patients in secondary prevention treated, according to International Guidelines, with an integrated foot care protocol by a referral diabetic foot clinic. A retrospective study was performed with the inclusion of selected outpatients with diabetes at higher risk for ulceration with a history of previous ulcer and/or amputation followed in our diabetic foot clinic between January 2015 and December 2021. According to the presence or absence of recurrence, patients were divided into 2 groups: ulcer recurrence and without ulcer recurrence. One hundred twenty-seven (127) patients were included, 47 patients (37%) developed an ulcer recurrence while 80 patients (63%) did not. The mean age was 71.7 years; 65% were male; 97% were affected by type 2 diabetes with a mean duration of 21.1 years, the mean HbA1c was 63 + 21 mmol/mol. Both groups of patients had foot deformities, such as claw and hammertoes; hallux valgus, and prominent metatarsal heads (MTHs). The presence of deformity was significantly associated with ulceration. The group with ulcer recurrence showed a higher rate of prominence MTHs in comparison to a group without ulcer recurrence. The MTHs resulted as the only independent predictor for recurrence. This study shows that the presence of the prominent MTH is a significant risk factor for ulcer recurrence in a selected population of diabetic foot patients treated in the best way with integrated foot care.

IL-6 Levels Influence 3-Month All-Cause Mortality in Frail Hospitalized Older Patients.

The multidimensional prognostic index (MPI) is a sensitive and specific prognosis estimation tool that accurately predicts all-cause mortality in frail older patients. It has been validated to assess the risk of 1-month to 2-year mortality in frail older patients during hospitalization and after hospital discharge. However, whether the MPI is a valid prognostic tool for follow-up periods of different lengths remains to be validated. To this end, we followed up 80 hospitalized patients (female=37, male 43) at least 75 years of age (mean age=82.6±4.4, range=75-94 years) to assess the 3-month all-cause mortality (mean follow-up=61.0 ± 31.7 months [range 4-90 days]). Accordingly, patients were subdivided into low (MPI-1, score 0-0.33), moderate (MPI-2, score 0.34-0.66) and high (MPI-3, score 0.67-1) mortality risk classes. Moreover, baseline biochemical, inflammatory and metabolic parameters, as well as anamnestic and clinical characteristics, were obtained. Although the MPI-3 score was significantly associated with 3-month all-cause mortality in univariate analysis (HR=5.79, 95%CI=1.77-18.92, p=0.004), a multivariate model indicated that only low albumin (HR=0.33, 95%CI=0.16-0.68, p=0.003) and high IL6 (HR=1.01, 95%CI=1.00-1.02, p=0.010) levels were significantly associated with 3-month all-cause mortality. In conclusion, we suggest that measurement of IL6 as well as albumin, rather than the MPI score, may help in providing tailored therapeutic interventions to decrease short term mortality in older hospitalized individuals.

2-hydroxycaproate predicts cardiovascular mortality in patients with atherosclerotic disease.

BACKGROUND AND AIMS: We aimed to identify novel biomarkers for cardiovascular mortality through a non-targeted metabolomics approach in patients with established atherosclerotic disease from the Tor Vergata Atherosclerosis Registry (TVAR). METHODS: We compared the serum baseline metabolome of 19 patients with atherosclerosis suffering from cardiovascular death during follow-up with the baseline serum metabolome of 20 control patients matched for age, gender, body mass index (BMI) and atherosclerotic disease status, who survived during the observation period. RESULTS: Three metabolites were significantly different in the cardiovascular mortality (CVM) group compared to controls: 2-hydroxycaproate, gluconate and sorbitol. 2-hydroxycaproate (otherwise known as alpha hydroxy caproate) was also significantly correlated with time to death. The metabolites performed better when combined together rather than singularly on the identification of CVM status. CONCLUSIONS: Our analysis led to identify few metabolites potentially amenable of translation into the clinical practice as biomarkers for specific metabolic changes in the cardiovascular system in patients with established atherosclerotic disease.

C-peptide: A predictor of cardiovascular mortality in subjects with established atherosclerotic disease.

AIM: Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease. METHODS: We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events. RESULTS: We performed a mean follow-up of 56 months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p < 0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors. CONCLUSION: C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker.

A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis.

OBJECTIVE: Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable. APPROACH AND RESULTS: We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1-118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence = 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82-63.36, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p < 0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 9%, p = 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI = 0.51 (p = 0.005). CONCLUSION: We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis.

Atherosclerosis severity but not undiagnosed diabetes predicts new cardiovascular events of subjects in secondary cardiovascular prevention.

OBJECTIVE: Undiagnosed diabetes (DM2), especially in individuals that have experienced a major atherosclerotic vascular event, could increase the risk of a second major cardiovascular (CV) event. The aim of this study was to evaluate the impact of type 2 diabetes (DM2), diagnosed after a major cardiovascular event, on subsequent CV disease in high risk individuals. METHODS: 411 subjects without known DM2 and with a history of a prior major CV event were followed for a second major CV event (fatal and nonfatal MI, fatal and nonfatal stroke or any arterial revascularization procedure). At baseline, each individual underwent a physical, biochemical examination, an OGTT and dosed A1c. In addition, patients were classified as having monovascular or polyvascular disease. The average follow-up duration was 31 months. RESULTS: The incidence of second CV events was 10.70 per 100 person-years (114 events/1066 person-years). The diagnosis of occult DM2 was not associated with major CV events, either using A1c values ≥6.5%, fasting glucose ≥126 mg/dL or 2 h post-load glucose ≥200 mg/dL. Polyvascular disease was the only significant predictor of a second major CV event (HR 2.60, 95% CI 1.72-3.95) after adjustment for age, BMI, smoking status, systolic blood pressure, high-density and low-density lipoprotein cholesterol and high sensitivity C-reactive protein. CONCLUSION: DM2 that was newly diagnosed after established vascular atherosclerotic disease did not increase the risk of new major CV events. In our population only the polyvascular disease was able to identify the subjects at high risk for a second major cardiovascular event.

Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects.

OBJECTIVE: To investigate the effect of pioglitazone on endothelial and adipose tissue dysfunction in newly detected IGT patients with CAD. METHODS AND DESIGN: Participants (n=25) were randomized to treatment with either placebo or pioglitazone (30 mg/day) for 12 weeks. Before and after treatment we evaluated endothelial function (flow-mediated dilation--FMD--of the brachial artery), circulating adipose and inflammatory markers (adiponectin isoforms, TNF-alpha, and high sensitivity-CRP), and insulin sensitivity (euglycemic hyperinsulinemic clamp). RESULTS: No significant changes were observed in subjects (n=12) treated with placebo. By contrast, subjects (n=13) treated with pioglitazone had significant improvement in FMD (10.8±5.3 vs 13.3±3.6%, p<0.01), accompanied by increased high molecular weight adiponectin (HMW-Ad) (1.7±1.2 vs 4.8±3.6 µg/ml, p<0.05) and decreased TNF-alpha (4.3±1.9 vs 3.2±1.2 pg/ml, p<0.05) associated to an increased glucose disposal (4.8±1.9 vs 5.4±2.0 mg kg(-1) min(-1), p<0.05). A multiple regression analysis indicated that increasing of HMW-Ad after pioglitazone predicted increased FMD. CONCLUSION: Pioglitazone significantly improves endothelial and adipose tissue dysfunction in pre-diabetic patients with CAD.

Occult impaired glucose regulation in patients with atherosclerosis is associated to the number of affected vascular districts and inflammation.

OBJECTIVE: The role of inflammatory adipokines has clear mechanistic effects in the promotion of both DM2 and cardiovascular diseases (CVDs), but it is unknown to what extent atherosclerosis-related inflammation might promote defects of glucose metabolism. The purpose of this study was to test the hypothesis that in subjects with atherosclerotic vascular disease and no previous medical record of type 2 diabetes mellitus (DM2), the diagnosis of occult impaired glucose regulation (IGR) is related to the severity of atherosclerosis, measured as the single or combined presence of an history of coronary artery disease (CAD), carotid atherosclerosis (Car-ATS) and peripheral artery disease (PAD). METHODS: In a population of 551 subjects (440 men and 111 women) with a previous history of atherosclerosis, we investigated the presence of IGR (including both impaired glucose tolerance and DM2). To test the correlation between conventional and non-conventional risk factors for cardiovascular disease and diabetes we used logistic and regression analysis models. RESULTS: IGR was more prevalent in patients with a documented vascular disease in two or three vessel districts compared with patients with only one symptomatic district (p=0.016). Among classic risk factors we found that waist circumference was correlated neither to IGR nor to symptomatic vascular disease extension. By contrast, adiponectin level was independently associated to vascular and glucose regulation status (p=0.012 and p<0.001, respectively). CONCLUSION: In subjects affected by atherosclerotic vascular diseases, the presence of impaired glucose regulation is associated to the number of vascular districts affected and to a reduced adiponectin level.

Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: relations with eating patterns and circulating concentrations of cortisol and thyroid hormones.

The present study was designed to investigate the relations between plasma ghrelin concentrations, eating patterns, and circulating concentrations of cortisol and thyroid hormones in women with anorexia nervosa, bulimia nervosa, and binge-eating disorder. The patterns of disordered eating behavior were assessed using the Eating Attitudes Test (EAT-26) and the Bulimia Test-Revised (BULIT-R). In women with eating disorders, but not in healthy control women, plasma ghrelin concentrations were negatively correlated with body mass index (BMI) and plasma concentrations of thyreotropin (TSH), free T3 and free T4, and positively correlated with plasma concentrations of cortisol. The ghrelin concentrations of women with binge-eating and purging behavior were significantly lower than those of women with anorexia nervosa, restricting type, and there was a negative relation between the frequency and severity of binge-eating and purging behavior, as measured by the BULIT-R total score, and ghrelin concentrations. In a multivariate regression model controlling for the confounding effects of body mass index (BMI) and age, higher ghrelin concentrations were correlated with lower BULIT-R total scores. The results of this study did not confirm the hypothesis advanced in previous studies that ghrelin concentrations are higher in patients with binge-eating/purging forms of eating disorders. Based on these data, we suggest that, in women with eating disorders, ghrelin concentrations best reflect nutritional status rather than specific patterns of disordered eating behavior.