Cohort Of Diabetic Patients Research Articles

S-17-3: ANTIDIABETIC DRUG THERAPY AND SURVIVAL IN ELDERLY FRAIL PATIENTS. REAL-LIFE EVIDENCE FROM ITALY

Objective: Aim of the study was to evaluate the protective effect of antidiabetic drugs in a large cohort of unselected elderly diabetic patients differing for their clinical status and life expectancy. The evaluation focused, in particular, on a group of patients with a very low survival rate because frail patients are usually excluded from intervention trials, limiting evidence on treatment effectiveness. The protective effect of drug therapy, quantified by the reduction in all-cause mortality with increased adherence to antidiabetic agent therapy, was studied by stratifying patients according to their life expectancy. Design and method: The Lombardy (Italy) residents, aged > 65 years, who received > 2 consecutive prescriptions of antidiabetic agents during 2012 were identified and the date of the third prescription was defined as the index date. A case-control study was nested into the cohort of antidiabetic drug users. Death from any cause was the outcome of interest, and cases were cohort members who died during follow-up (up to 2018). For each case, a control was selected and matched for age, gender, and clinical profile. Conditional logistic regression was used to model the risk of outcome associated with four categories of adherence to antidiabetic drugs. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drugs. The analysis was stratified according to four categories of the clinical profile (good, intermediate, poor, and very poor) differing for life expectancies, as evaluated by a multisource comorbidity score able to accurately predict the risk of death. Results: Among the 276,336 patients in treatment with antidiabetic agents during 2012, 188,983 met the inclusion criteria and generated 49,219 deaths during follow-up, 49,201 of whom were matched to a control. The 6-year survival decreased from 85% to 52% from the group of patients with good to the group of patients with a very poor clinical status. Adherence to treatment was associated with a progressive decrease in the risk of mortality in all categories of clinical status. The reduction from lowest to highest adherence level was 36% (95% CI, 25–46%), 50% (44–56%), 38% (33–42%) and 26% (17–34%) from good to very poor clinical status (Figure). Conclusions: In a real-life context, adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the clinical status of the patients. However, in more frail patients, the benefit of treatment is less than in patients in good clinical condition.

Prognostic Relevance of Type 2 Diabetes and Metformin Treatment in Head and Neck Melanoma: Results from a Population-Based Cohort Study

Type 2 Diabetes (DM2) and the consecutively daily use of antidiabetic medication are characterized by a frequent prevalence worldwide and were shown to impact the initiation and progression of malignant diseases. While these effects were observed in a variety of malignancies, comprehensive data about the role of DM2 and antidiabetic drugs in the outcome of head and neck melanoma (HNM) patients are missing. This retrospective population-based cohort study included 382 HNM patients from Eastern Bavaria having received tumor resection to negative margins between 2010 and 2017. Recurrence-free survival (RFS) was evaluated with regard to DM2 and routine metformin intake. Statistical analysis was performed by uni- and multivariate analyses. The median follow-up time was 5.6 years. DM2 was diagnosed in 68 patients (17.8%), routine metformin intake was found in 39 cases (10.2%). The univariate survival analysis revealed impaired 5-year RFS in HNM patients with DM2 compared to non-diabetic controls (p = 0.016; 64.0% and 74.5%, respectively). The multivariate Cox regression substantiated this effect (HR = 1.980, 95% CI = 1.108-3.538, p = 0.021). In detail, the cumulative locoregional recurrence rate displayed the most far-reaching negative effect on the RFS of diabetic HNM patients (HR = 4.173, 95% CI = 1.628-10.697, p = 0.003). For metformin intake, a profound positive effect on the RFS in multivariate statistics was observed, both in the complete cohort (HR = 0.396, 95% CI = 0.177-0.884, p = 0.024) as well as in the cohort of diabetic HNM patients (HR = 0.352, 95% CI = 0.135-0.913, p = 0.032). This study emphasizes that DM2 is a relevant comorbid condition in HNM patients, impairing patient survival. Metformin intake was associated with a favorable outcome in HNM patients, providing possible therapeutic implications for future adjuvant treatment regimes.

Echocardiography Findings in a Cohort of Older Diabetic Patients with Diastolic Dysfunction: Do They Fall Under the Diabetic Cardiomyopathy Diagnosis?

ObjectivesOur main goal is to describe the echocardiography findings in older type 2 diabetic patients with diastolic dysfunction (DD) and contrast them with the diabetic cardiomyopathy criteria (1). MethodsWe assessed 201 echocardiography results in a private cardiology center in Guayaquil, Ecuador. We describe the mean±SD of continuous variables, and frequencies of categorical variables with cut-off points taken from the Spanish Society of Cardiac Imaging guidelines. We conducted Chi-square and linear regression analysis for further associations. ResultsThe mean age was 68.07±12.08, 75.6% were females, 92.5% had hypertension (HTN) and 79.1% had DD with a mean ejection fraction of 64.51±9.44. The mean interventricular septum width (IVSW) was 11.05±2.66mm. HTN showed no association with DD (p=0.929), however, an increased IVSW (p=0.47) and age >65yo (p<0.001) did. IVSW also showed a strong positive correlation with posterior wall width (PWW) (B=0.872, p<0.001), although PWW mean was normal (10.48±2.22mm). ConclusionThese diabetic patients had DD which was not related with HTN, but associated with age and increased IVSW. Diabetic cardiomyopathy (DCM) is defined as diastolic or systolic dysfunction in the absence of cardiovascular disease (CVD), therefore we couldn't classify them into this category because the majority had HTN. However, we found no association between DD and HTN, which raises the doubt for future research about whether CVD (eg, HTN) needs to be excluded or not for the diagnosis of DCM.

Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients.

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low-density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events. This cross-sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid-femoral pulse wave velocity (PWV). Patients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e-GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e-GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation. Our study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well-known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects.

Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19

IntroductionThe role of glycemic control, both prior and during hospitalization, on mortality from COVID-19 in diabetic patients is debated. Furthermore, it is not clear whether hyperglycemia has a direct effect or requires inflammatory mechanisms.ObjectiveTo identify predictors of clinical outcomes (in-hospital mortality, length of hospitalization, respiratory failure, need for intensive care), considering hyperglycemia, inflammation markers and clinical history.MethodsRetrospective observational study of 291 diabetic patients hospitalized with COVID-19 in the Spedali Civili di Brescia from February 1th 2020 to March 31th 2021, with also outpatient electronic records. Glucose, inflammatory parameters, creatinine were collected within 24 h after admission to the hospital. A causal mediation analysis allowed the estimation of the direct and indirect effects of hyperglycemia on mortality.ResultsGlucose at admission ≥ 165 mg/dL and reduced renal function were associated with an increased risk of in-hospital mortality and length of hospitalization (all p < 0.001), while an increase in inflammatory parameters was significantly associated with an increased risk of all outcomes. High basophil count was associated with reduced mortality (p < 0.001). Hyperglycemia had a direct effect on mortality (p < 0.001); the indirect, through inflammatory markers, was significant only for absolute neutrophil count, C-Reactive protein and procalcitonin (p = 0.007, p = 0.029, p = 0.042). Patients with microvascular complications and with chronic kidney disease showed higher mortality (p = 0.03, p = 0.01).ConclusionsHyperglycemia at admission, renal function and inflammatory parameters were found to be predictors of in-hospital mortality, while an increased basophil count was protective. Hyperglycemia had a direct effect on mortality, the indirect effect was only through few markers and markedly lower than the direct one.

Fluidic Device System for Mechanical Processing and Filtering of Human Lipoaspirate Enhances Recovery of Mesenchymal Stem Cells.

Adipose tissue is an easily accessible source of stem and progenitor cells that offers exciting promise as an injectable autologous therapeutic for regenerative applications. Mechanical processing is preferred over enzymatic digestion, and the most common method involves shuffling lipoaspirate between syringes and filtering to produce nanofat. Although nanofat has shown exciting clinical results, the authors hypothesized that new device designs could enhance recovery of stem/progenitor cells through optimization of fluid dynamics principles, integration, and automation. The authors designed and fabricated the emulsification and micronization device (EMD) and the filtration device (FD) to replace the manual nanofat procedures. Using human lipoaspirate samples, the EMD and the FD were optimized and compared to traditional nanofat using ex vivo measurements of cell number, viability, and percentage of mesenchymal stem cells and endothelial progenitor cells. The EMD produced results statistically similar to nanofat, and these findings were confirmed for a cohort of diabetic patients. Combining the FD with the EMD was superior to manually filtered nanofat in terms of both recovered cell percentages (>1.5-fold) and numbers (two- to three-fold). Differences were statistically significant for total mesenchymal stem cells and a DPP4 + /CD55 + subpopulation linked to improved wound healing in diabetes. The new EMD and the FD improved mechanical processing of human lipoaspirate in terms of mesenchymal stem cell enrichment and number compared to traditional nanofat. Future work will seek to investigate the wound healing response both in vitro and in vivo, and to refine the technology for automated operation within clinical settings. The new devices improved mechanical processing of human lipoaspirate in terms of stem cell enrichment and number compared to traditional methods. Future work will seek to validate wound healing response and refine the technology for automated operation within clinical settings.

Continuum of sensory profiles in diabetes mellitus patients with and without neuropathy and pain.

Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in patients with diabetes mellitus to study whether these could differentiate patients with and without pain and neuropathy. A standardized QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n=220) and non-painful distal symmetric polyneuropathy (nDSPN; n=219), diabetic patients without neuropathy (DM; n=23) and healthy non-diabetic subjects (n=37). Based on the QST findings, diabetic subjects were further stratified into four predefined prototypic phenotypes: sensory loss (SL), thermal hyperalgesia (TH), mechanical hyperalgesia (MH) and healthy individuals. Patients in the pDSPN group showed the greatest hyposensitivity ('loss of function'), and DM patients showed the lowest, with statistically significant increases in thermal, thermal pain, mechanical and mechanical pain sensory thresholds. Accordingly, the frequency of the SL phenotype was significantly higher in the pDSPN subgroup (41.8%), than expected (p &lt; 0.0042). The proportion of 'gain of function' abnormalities was low in both pDSPN and nDSPN patients without significant differences. There is a continuum in the sensory profiles of diabetic patients, with a more pronounced sensory loss in pDSPN group probably reflecting somatosensory nerve fibre degeneration. An analysis of 'gain of function' abnormalities (allodynia, hyperalgesia) did not offer a key to understanding the pathophysiology of spontaneous diabetic peripheral neuropathic pain. This article, using quantitative sensory testing profiles in large cohorts of diabetic patients with and without polyneuropathy and pain, presents a continuum in the sensory profiles of diabetic patients, with more pronounced 'loss of function' abnormalities in painful polyneuropathy patients. Painful diabetic polyneuropathy probably represents a 'more progressed' type of neuropathy with more pronounced somatosensory nerve fibre degeneration. The proportion of 'gain of function' sensory abnormalities was low, and these offer limited understanding of pathophysiological mechanisms of spontaneous neuropathic pain.

POS-126 BACTERIAL INFECTION RELATED GLOMERULONEPHRITIS IN PATIENTS WITH DIABETES MELLITUS

Patients with underlying Diabetes Mellitus are prone for various infections, thus making them susceptible to develop bacterial infection related glomerulonephritis (IRGN). There is paucity of data on the nature of infections, infecting organism, renal histology, role of immunosuppressants and long-term renal outcomes in the cohort of diabetic patients with IRGN.

P37. Postoperative hematocrit predicts postoperative complications in diabetic patients undergoing spinal deformity surgery

P37. Postoperative hematocrit predicts postoperative complications in diabetic patients undergoing spinal deformity surgery

Health Needs Assessment: Chronic Kidney Disease Secondary to Type 2 Diabetes Mellitus in a Population without Social Security, Mexico 2016-2032.

Health needs assessment is a relevant tracer of planning process of healthcare programs. The objective is to assess the health needs of chronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2 DM) in a population without social security in Mexico. The study design was a statistical simulation model based on data at the national level of Mexico. A stochastic Markov model was used to simulate the progression from diabetes to CKD. The time horizon was 16 years. The results indicate that in 2022, kidney damage progression and affectation in the diabetic patient cohort will be 34.15% based on the time since T2 DM diagnosis. At the end of the 16-year period, assuming that the model of care remains unchanged, early renal involvement will affect slightly more than twice as many patients (118%) and cases with macroalbuminuria will triple (228%). The need for renal replacement therapy will more than double (169%). Meanwhile, deaths associated with cardiovascular risk will more than triple (284%). We concluded that the clinical manifestations of patients with CKD secondary to T2 DM without social security constitute a double challenge. The first refers to the fact that the greatest health need is early care of CKD, and the second is the urgent need to address cardiovascular risk in order to reduce deaths in the population at risk.

Albuminuria in Patients with Type 2 Diabetes Mellitus: a Single Center Cross-Sectional Study

Introduction: Diabetes mellitus is one of the commonest non-communicable diseases in Nepal and is associated with long term microvascular and macro vascular complications. Detection of albumin in urine is the earliest recognizable feature in the development of proteinuric diabetic nephropathy. This study aims to study the prevalence as well the determinants of albuminuria in patient with Type 2 diabetes mellitus visiting the medical OPD of College of Medical Sciences-Teaching hospital. Methods: This was a cross-sectional study done from January to June 2022 among Type 2 diabetes patients presenting to medical OPD for the comprehensive diabetes management. Relevant epidemiological, clinical and laboratory data were obtained. Urine dipstick test was done to screen for albuminuria. The prevalence and determinants of albuminuria were studied. Results: Study among 360 patients with mean age of 58.5 + 10.9 years and the mean duration since the diagnosis of diabetes of 6.8 + 5.5 years, showed that the prevalence of albuminuria was 33.3%. Albuminuria in these patients was found to have significant association with age (P&lt;0.001), duration since diagnosis of diabetes (&lt;0.001) and HbA1c (P&lt;0.001). No significant association of albuminuria was found with gender (P=0.087), hypertension (P=0.063) and previous use of Angiotensin-converting enzyme inhibitors/ Angiotensin II receptor blockers. (P=0.217) Conclusions: Albuminuria is highly prevalent among our cohort of diabetic patients. Increasing age, longer duration since diagnosis of diabetes and higher HbA1c are the factors significantly associated with it.

The frailty risk trajectory associated with kidney and cardiovascular morbidities among patients with incident diabetes: A population-based study

Background and aimsFrailty denotes the increased vulnerability to stressors/insults associated with aging or diseases, and has high incidence in patients with diabetes mellitus (DM). We hypothesized that chronic kidney disease (CKD) and non-kidney morbidities in patients with newly diagnosed DM might modulate their risk of developing incident frailty. MethodsFrom the Longitudinal Cohort of Diabetes Patients, we identified 322,109 patients with newly diagnosed DM, and classified them into those without CKD, with CKD before and after DM. We used Kaplan-Meier analyses and Cox proportional hazard regression to analyze associations between CKD or non-kidney morbidities and the risk of incident frailty. We further analyzed the year-to-year trend of frailty risk brought by CKD or non-kidney morbidities. ResultsPatients with DM but without CKD (n = 249,752; 77.5%), with CKD prior to (n = 23,829; 7.4%), and after DM (n = 48,528; 15.1%) were enrolled. Those with CKD, regardless of onset timing, had a significantly higher risk of developing frailty than those without (for onset prior to DM, hazard ratio (HR) 1.235, 95% confidence interval (CI) 1.11–1.38; for onset after DM, HR 1.386, 95% CI 1.21–1.59). The risk was more prominent early after the diagnosis of DM was made. Patients with chronic obstructive pulmonary disease, liver, and cardiovascular morbidities all had a significantly higher risk of frailty than those without, with cerebrovascular accident carrying the most prominent risk elevation (HR 4.059, 95% CI 3.73–4.42). ConclusionsCKD regardless of onset timing relative to DM predicted a higher risk of incident frailty, while non-kidney morbidities including cardiovascular morbidities, similarly increased frailty risk among incident diabetic patients.

1505-PUB: Impact of Diabetes on Radiotherapy-Related Infection

Background and Purpose: Poor perioperative glucose control in diabetes patients is associated with infectious adverse effects (AEs) . Radical radiotherapy (RT) for head and neck (H&amp;N) cancer extensively destroys skin and the mucosa barrier function, and can be as invasive as surgery. In this study, the risk of radiation-induced acute infectious AEs was investigated in a cohort of diabetic patients given RT for H&amp;N cancer. Materials and Methods: Acute AEs associated with RT in diabetic patients treated between January 2017 and July 2021 at three institutions were retrospectively analyzed. Patients were included if they met the following criteria: confirmed diagnosis of type 1 or 2 diabetes mellitus, age &amp;gt; years, stable on glucose-lowering therapy before starting RT, and had undergone RT for pathologically proven malignancies. The endpoint was the rate of acute infectious AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: A total of 216 patients were eligible for the present study (median follow-up, 15.6 months; range, 1.3-33.3 months; median age, 72 years; range, 33-90 years) . The median glycated hemoglobin (A1c) value at the start of RT was 7.4% (range, 4.1%-12.7%) . Grade ≥ 3 acute infectious AEs that occurred in 31 (14.4%) patients included mucosal infection, pneumonia, and sepsis. Five patients died due to infectious AEs that developed during or after RT. Concurrent chemoradiotherapy (CCRT) (OR, 2.0; 95%CI, 0.9-4.6; P = 0.08) tended to be a predictor of severe infectious AEs. The frequency of glucose control by diabetologists during CCRT was significantly lower than during RT alone (P = 0.001) . Conclusions: The incidence of severe infectious AEs was high in the present cohort of irradiated diabetic patients with H&amp;N cancer compared with historical data. Patients with CCRT had a higher risk of AEs, which should be considered before irradiation. Therapeutic intervention for glucose control by diabetologists during CCRT may lead to fewer severe infectious AEs. Disclosure K. Ito: None.

The Effects of Sodium-Glucose Cotransporter-2 Inhibitors (SLGT-2i) on Cardiovascular and Renal Outcomes in Non-diabetic Patients: A Systematic Review.

Globally, cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of mortality. Despite medical advances, these illnesses are still underdiagnosed and undermanaged. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently emerged as a potential class of medications with promising cardiovascular and renal safety in non-diabetic patients. In this systematic review, we explored the outcomes of cardiovascular and renal protective effects utilizing SGLT-2i in three large randomized clinical trials with a cohort of both diabetes and non-diabetes patients. In these studies, data conferred that there is a significant reduction in heart failure (HF) hospitalization, as well as cardiovascular and all-cause mortality. Moreover, SGLT-2i impede the progression to and death from CKD. Additionally, we reviewed trials solely done on non-diabetics which demonstrated benefits in patients with established HF with reduced ejection fraction, though the fact that these studies had a smaller sample size. We also discussed some of the potential mechanisms of action of SGLT-2i on cardiovascular and renal outcomes that are beyond anti-hyperglycemic control. There is ongoing research involving a larger number of non-diabetes patients that may provide more information about the efficacy of these drugs besides anti-diabetic medications in the future. Finally, this is the first systematic review that has provided a perspective on the currently available trials, which offer evidence supporting the potential benefits of SGLT-2i on cardiovascular and renal outcomes in non-diabetic individuals.

Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study.

Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of tencytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n=777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n=69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5ml/min/1.73m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience.

Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients

PurposeRegistered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D).MethodsIn a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021.ResultsDuring the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide.ConclusionsReal-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Expressions of Serum lncRNAs in Diabetic Retinopathy - A Potential Diagnostic Tool.

With increasing incidence of diabetes worldwide, there is an ever-expanding number of patients with chronic diabetic complications such as diabetic retinopathy (DR), one of the leading causes of blindness in the working age population. Early screening for the onset and severity of DR is essential for timely intervention. With recent advancements in genomic technologies, epigenetic alterations in DR are beginning to unravel. Long non-coding RNAs (lncRNAs), which are key epigenetic mediators, have demonstrated implications in several (DR) related processes. Based on the previous research, we have developed a serum-based, multi-panel PCR test using 9 lncRNAs (ANRIL, MALAT1, WISPER, ZFAS1, H19, HOTAIR, HULC, MEG3, and MIAT) to identify and validate whether this panel could be used as a diagnostic and prognostic tool for DR. We initially used a cell culture model (human retinal endothelial cells) and confirmed that 25 mM glucose induces upregulations of ANRIL, HOTAIR, HULC, MALAT1, and ZFAS1, and downregulation of H19 compared to 5 mM glucose controls. Then as an initial proof-of-concept, we tested vitreous humor and serum samples from a small cohort of non-diabetic (N=10) and diabetic patients with proliferative retinopathy (PDR, N=11) and measured the levels of the 9 lncRNAs. Differential expressions of lncRNAs were found in the vitreous and serum of patients and showed significant correlations. We expanded our approach and assessed the same lncRNAs using samples from a larger cohort of diabetic (n= 59; M/F:44/15) and non-diabetic patients (n= 11; M/F:4/7). Significant increased lncRNA expressions of ANRIL, H19, HOTAIR, HULC, MIAT, WISPER and ZFAS1 were observed in the serum of diabetic patients (with varying stages of DR) compared to non-diabetics. No significant correlations were demonstrated between lncRNA expressions and creatinine or glycated hemoglobin (HbA1C) levels. Using ROC and further analyses, we identified distinct lncRNA phenotype combinations, which may be used to identify patients with DR. Data from this study indicate that a panel of serum lncRNAs may be used for a potential screening test for DR. Further large-scale studies are needed to validate this notion.

Does optimal HbA1c in diabetes differ according to drug treatment? An evaluation of national electronic database in Malta

Background and aimsA J-shaped relationship between HbA1c and mortality has been reported in subjects with type 2 diabetes. The postulated mechanism linking low HbA1c with increased mortality is increased hypoglycaemia risk. We tested this hypothesis by comparing the relationship between low HbA1c to mortality in patients on therapies with different hypoglycaemia risk. MethodsWe selected patients on any type of treatment for diabetes from a national electronic database (n = 25,743) and linked to other databases, including laboratory database and the national mortality register. ResultsWe observed a J–shaped or U–shaped association between HbA1c and all–cause mortality in the whole type 2 diabetes patient cohort as well as in patients on metformin monotherapy and in those on metformin-sulphonylurea combination therapy, but not in subjects on sulphonylurea monotherapy or in those on insulin. ConclusionsOur data confirm the J-shaped relationship between HbA1c and mortality in type 2 diabetes, but suggest that a low HbA1c is deleterious even in absence of hypoglycaemia and that subjects with type 2 diabetes might require a slightly elevated blood glucose for optimal outcome. Our data also suggest that the increased mortality associated with sulphonylureas cannot be mediated solely through increased hypoglycaemia risk.

602 Foot burns in diabetic patients: A single center experience

IntroductionThe most significant sequelae of foot burns in diabetic patients is a non-healing wound that results in a diabetic foot ulcer, which has been a predictor for need for amputation and mortality. Even minor amputations in patients with diabetes have a significant mortality rate. Our systemic review found that when 60% of a diabetic patient cohort with foot burns was managed by skin grafting, 29% subsequently required amputations, which is concerning. The practice at our regional burn center has been to manage patients with foot burns and diabetes non-operatively with daily dressing changes, and we believe that this may result in better functional outcomes, ambulatory status, and lower amputation rates.MethodsA retrospective review of patients with diabetes and foot burns admitted to an ABA verified regional burn center was conducted. The primary outcome was amputation. Secondary outcomes were ambulatory status, wound closure, and infection. Rank sum and fisher exact tests were performed to compare patient demographics, comorbidities, uncontrolled DM (A1c >9%), and burn characteristics between patients who were treated surgically and those who received daily wound care only. These associations were subsequently evaluated with odds ratios (OR) and 95% confidence intervals (CI). A multivariable logistic regression was performed to evaluate for possible differentiating factors that resulted in maintaining ambulatory status at completion of burn care. Statistical significance was defined as p< .05.ResultsOf 75 patients identified, median TBSA burned was 2% (IQR 2), and 61% (n=46) had full thickness burns. Mean A1c at admission was 9% (SD 2). In terms of management, 9% (n=7) were treated with debridement and/or skin grafting, and 9% (n=7) later required lower extremity amputations. Infection during first admission developed in 8% (n=6). At completion of burn care, 73% had normal or same ambulatory status, and older patients were less likely to maintain ambulatory status (p=.009, OR=0.92, 95% CI=0.86-0.98). Median time to wound closure was 95 (IQR 130) days, and 12% (n=9) of wounds never fully closed. Burn depth (second vs third degree), burn location (plantar burn vs other areas), uncontrolled DM, and surgical treatment did not result in a statistically significant difference in maintaining ambulatory status at completion of burn care.ConclusionsDiabetic patients with foot burns are best managed non-operatively with daily dressing changes, and should be allowed to heal secondarily. This may result in a longer time to close the wounds, but the amputation rates were much lower when compared to surgical management. However, 5% of our cohort developed diabetic foot ulcers at completion of burn care, which is a complex disease process that carries a dire prognosis.