Review and Evaluation of European National Clinical Practice Guidelines for the Treatment and Management of Active Charcot Neuro-Osteoarthropathy in Diabetes Using the AGREE-II Tool Identifies an Absence of Evidence-Based Recommendations.

Background: Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO. Aim: The aim of this study is to review European national diabetes CPGs for the diagnosis and management of active CNO and to assess their methodological rigor and transparency. Methods: A systematic search was performed to identify diabetes national CPGs across Europe. Guidelines in any language were reviewed to explore whether they provided a definition for active CNO and recommendations for diagnosis, monitoring, and management. Methodological rigor and transparency were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool, which comprises 23 key items organized within six domains with an overall guideline assessment score of ≥ 60% considered to be of adequate quality to recommend use. Each guideline was assessed by two reviewers, and inter-rater agreement (Kendall's W) was calculated for AGREE-II scores. Results: Seventeen CPGs met the inclusion criteria. Breadth of CNO content varied across guidelines (median (IQR) word count: 327; Q1 = 151; Q3 = 790), and 53% provided a definition for active CNO. Recommendations for diagnosis and monitoring were provided by 82% and 53%, respectively, with offloading being the most common management recommendation (88%). Four guidelines (24%) reached threshold for recommendation for use in clinical practice (≥ 60%) with the scope and purpose domain scoring highest (mean (SD): 67%, ± 23%). The remaining domains had average scores ranging between 19% and 53%. Inter-rater agreement was strong (W = 0.882; p < 0.001). Conclusions: European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.

A Single Center, Randomized Controlled Trial on the Efficacy of Topical Application of ReGenerating Tissue Agents (RGTA) Technology in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus. Clinical data from the use of ReGenerating Tissue Agents (RGTA) technology in patients with DFUs are scarce. The objective of this randomized controlled study was to evaluate the efficacy of RGTA technology in the management of DFUs. Patients with chronic, neuroischemic diabetic foot ulcers were randomized 1:1 to the control group, that received the standard of care, and to the intervention group, that additionally received RGTA twice per week. The duration of the intervention was 12 weeks. Skin biopsies for histological and immunohistochemical analyses from a sample of participants were also performed. About 31 patients completed the study. Five (31.2%) patients in the intervention group achieved complete healing at the end of the intervention period versus 0 patients in the control group (P = .043), [RR: 0.688 (95% CI: 0.494-0.957)]. The intervention group had more ulcers with at least 80% healing of their surface [10 (66.7%) versus 2 (13.3%), P = .008, RR: 0.385 (95% CI: 0.183-0.808)], higher absolute surface reduction [1.5 (0.7, 5.2) versus 0.6 (0.3, 1.0), P = .026] and higher percentages of surface reduction [94 (67, 100) versus 40 (26, 75), P = .001] at the end of the intervention period. More patients in the intervention group achieved at least 50% healing at the fourth week of the study [9 (64.3%) versus 2 (14.3%) P = .018, RR: 0.417 (95% CI: 0.200-0.869)]. Immunohistochemical analyses were performed in a sample of participants that revealed higher expression of CD163, COL3 and VEGFR in the intervention group. The adverse effects were similar between the 2 groups. The data from the present study suggest that the adjunction of RGTA technology in the management of diabetic foot ulcers is a safe practice that promotes wound healing.

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity.

BACKGROUND: Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients. METHODS: This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors. RESULTS: Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls. CONCLUSIONS: The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.

What is New on Diabetic Neuropathy? Insights from the 2023 ADA and EASD Conferences.

Diabetic neuropathy is a common complication of diabetes; yet its pathophysiology is still incompletely understood and until today, there is no specific treatment against it. In the two 2023 large congresses on diabetes (American Diabetes Association, ADA, European Association for the Study of Diabetes, EASD), several high-level studies have been presented. They have attempted to delineate the pathophysiology of DN, the characteristics of affected patients, and future potential treatments. We herein review the presented studies on diabetic neuropathy at these diabetes congresses and discuss the needs for future research on this topic.

Monoclonal Gammopathy of Undetermined Cardiovascular Significance; Current Evidence and Novel Insights.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by the presence of low levels of a monoclonal protein in the serum and a low percentage of clonal plasma cells in the bone marrow. MGUS may progress to multiple myeloma or other plasma cell disorders at a rate of 1% annually. However, MGUS may also have adverse effects on the cardiovascular system independent of its malignant potential. Emerging data have shown that MGUS is associated with cardiovascular disease. The mechanisms underlying this association are not fully understood but may involve genetic abnormalities, vascular calcification, cryoglobulinemia, cold agglutinin disease, autoantibodies and the direct or indirect effects of the monoclonal protein on the vascular endothelium. Herein, we review current evidence in this field and we suggest that patients with MGUS may benefit from regular cardiovascular risk assessment to prevent severe cardiovascular complications, in parallel with close hematological follow-up to monitor potential disease progression.

Highlights from the 82nd ADA Scientific Sessions and the 58th EASD Meeting on Diabetic Neuropathy.

Diabetic neuropathy is one of the commonest diabetic complications. It affects 30-50% of people with diabetes mellitus (DM) and may cause severe pain and foot ulcers. Distal symmetric polyneuropathy and diabetic autonomic neuropathy are the main manifestations of diabetic neuropathy. The American Diabetes Association's (ADA) 82nd Scientific Sessions took place in June 2022 in New Orleans, Louisiana, and the 58th European Association for the Study of Diabetes (EASD) Annual Meeting was held in September 2022 in Stockholm, Sweden. Herein, we describe interesting studies in the field of diabetic neuropathy presented in these two meetings.

Obesity and multiple myeloma: Emerging mechanisms and perspectives.

Obesity is a global pandemic that has been associated with the development of breast, endometrial, large intestine, renal, esophageal, and pancreatic cancer. Obesity is also involved in the development of cardiovascular disease and type 2 diabetes mellitus. Recently, an increase in the incidence of obesity-related cancers has been reported. Multiple myeloma (MM) is the second most common hematological malignancy, after lymphoma. The aim of this review is to examine the epidemiological data on obesity and MM, assess the effect of obesity on MM outcomes, evaluate the possible mechanisms through which obesity might increase the incidence of MM and provide the effects of obesity management on MM. Current evidence indicates that obesity may have an impact on the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM and increase the prevalence of MM. However, data regarding the effect of obesity on MGUS incidence are controversial; further studies are needed to examine whether obesity affects the development of MGUS or the progression of MGUS to MM. In addition, obesity affects MM outcomes. Increased BMI is associated with decreased survival in patients with MM, while data regarding the effect of obesity on newly diagnosed MM subjects and autologous stem cell transplantation are limited. Interestingly, the obesity paradox may also apply to patients with relapsed/refractory MM who are overweight or obese, because they may have a survival advantage. The pathophysiological pathways linking obesity to MM are very complicated and include bone marrow adipose tissue; adipokines, such as adiponectin, leptin, resistin, and visfatin; inflammatory cytokines and growth factors, such as TNF-α and IL-6; hormones including insulin and the insulin-like growth factor system as well as sex hormones. In terms of the effect of pharmacological management of obesity, orlistat has been shown to alter the proliferation of MM cells, whereas no data exist on glucagon-like peptide-1 receptor agonists, naltrexone/bupropion, or phentermine/topiramate. Bariatric surgery may be associated with a reduction in the incidence of MM, however, further studies are needed.

Impact of Glucagon-like peptide 1 receptor agonists on peripheral arterial disease in people with diabetes mellitus: A narrative review.

Peripheral arterial disease (PAD) is a common macrovascular complication of diabetes mellitus (DM). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are among the latest class of antidiabetic medications that stimulate insulin synthesis and secretion and have been used for the management of type 2 DM. Apart from the effect on glycaemic control, GLP-1RAs also have a robust impact on weight reduction and have shown favorable effects on cardiovascular morbidity and mortality in cardiovascular outcome trials (CVOTs). The aim of this review was to examine the impact of GLP1-RAs on PAD among people with DM based on CVOTs, randomized controlled trials, observational studies as well as systematic reviews and meta-analyses. Data from retrospective studies and meta-analyses have shown superiority of these agents in comparison with other antidiabetic medications such as sodium-glucose cotransporter type 2 inhibitors and dipeptidyl peptidase-4 inhibitors in terms of PAD-related events. Nevertheless, data from CVOTs regarding the impact of GLP-1RAs on PAD are scarce and hence, safe conclusions regarding their effects cannot be drawn. Further prospective studies are needed to examine the impact of GLP-1RAs on PAD-related incidents including major adverse limb events, lower limb amputations and revascularization procedures.

The Performance and Interrater Agreement of Vibration Perception for the Diagnosis of Loss of Protective Sensation in People With Diabetes Mellitus.

This study examined the performance of VibraTip for the diagnosis of loss of protective sensation (LOPS) and the interrater agreement of different neurological modalities performed by 3 health care professionals, a consultant diabetologist, a diabetes specialist nurse, and a podiatrist. Diagnosis of LOPS was based on 10-g Semmes Weinstein monofilament testing performed by a consultant diabetologist (reference method), while examination with a 128-Hz tuning form was also performed. The performance of VibraTip for the diagnosis of LOPS was examined using the receiver operating characteristic curves analysis. Interrater agreement was determined by weighted kappa (κ) statistics. Diagnosis of LOPS (%) was 37.5%. Receiver operating characteristic curve analysis showed that VibraTip examination versus 10-g monofilament, both performed by a consultant, could diagnose LOPS (P < .001). Sensitivity, specificity, positive predictive value, and negative predictive value of VibraTip versus 10-g monofilament, both performed by a consultant (value, 95% confidence interval), was 0.705 (0.591-0.803), 0.836 (0.758-0.897), 0.733 (0.642-0.808), and 0.816 (0.757-0.863), respectively. The interrater agreement among the health care professionals for 10-g monofilament, VibraTip, and 128-Hz tuning fork in neurological assessment was good with κ > 0.61. VibraTip can be used as a screening tool for the detection of LOPS. There was good overall agreement in the results of neurological examination using 10-g monofilament, 128-Hz tuning fork, and VibraTip among health care professionals.

The necessity of administrating antibiotic prophylaxis to patients with diabetes mellitus prior to oral surgical procedures-a systematic review.

BACKGROUND AND AIMS: Μany studies suggest the use of antibiotic prophylaxis (AP) as an appropriate preventive measure for patients with diabetes mellitus (DM) due to the increased possibility of an impaired wound healing and infections after surgical procedures in the oral cavity. Existing recommendations regarding antibiotic prophylaxis before surgical procedures are not definitive and are based on expert opinions. The purpose of this study was to review the available scientific data about the necessity of administrating AP as a preventive measure prior to oral surgical procedures. METHOD: PubMed®, Scopus® και Cochrane Central Register of Controlled Trials (CENTRAL) were used as databases to search for published research. All articles were initially identified and classified based on the title and subsequently on their abstract. For the next level the full scientific paper was read and evaluated. RESULTS: Overall, 22 articles were included in the study, of which 2 were systematic reviews, 2 cohort studies, 2 case-control studies, 1 case series, 8 case reports and 7 professional association publications. CONCLUSIONS: In the scientific literature, there is a wide range of recommendations and inconsistency regarding the need to administer AP prior to surgical dental operations in patients with DM, while there is no scientific evidence demonstrating its' effectiveness as a precautionary measure. Both blood glucose level measurements and recent HbA1c measurement should be evaluated before any dental procedure. Poor regulation may result to life-threatening infections after tooth extraction. AP is recommended prior to the placement of dental implant. Randomized, controlled, clinical trials with large number of participants and greater variety of surgical dental procedures are needed.

Radiologically suspected COVID-19-associated organizing pneumonia responding well to corticosteroids: A report of two cases and a review of the literature.

Organizing pneumonia (OP) is a type of diffuse interstitial lung disease, which may be induced in the context of several clinical conditions, such as drug reactions, infections, autoimmune diseases and cancer. Coronavirus disease 2019 (COVID-19)-associated OP has been reported as a late-stage consequence of the infection or a histological form of COVID-19-associated pneumonia. Autopsies and postmortem lung biopsies have demonstrated that the majority of patients with COVID-19-associated pneumonia develop secondary OP, and COVID-19-associated pneumonia and OP have common radiological features. The diagnosis of COVID-19-associated OP should be suspected in patients with severe acute respiratory syndrome coronavirus 2 infection who exhibit clinical deterioration despite optimal care, or who have aggravating symptoms following an initial recovery. The use of corticosteroids is a typical treatment for OP. However, to date, at least to the best of our knowledge, there are a few reports regarding the role of corticosteroids in COVID-19-associated pneumonia; thus, the optimal time for administration, the dose and treatment duration have not yet been determined. The present study presents two cases of patients with COVID-19, who exhibited clinical deterioration following the initial phase of infection and with radiological characteristics of OP who received corticosteroids and had a favorable outcome. The early diagnosis of COVID-19-associated OP may lead to targeted treatment, decreased requirements for ventilatory support and an improved survival rate.

Diabetes mellitus and multiple myeloma; common features of two distinct entities.

Diabetes mellitus (DM) has attained the status of a global pandemic. Cardiovascular disease (CV) was the leading cause of morbidity in people with type 2 DM, however, a transition from CV to cancer as the leading contributor to DM related death has been observed lately. Multiple myeloma (MM) is the second most common haematological malignancy. Obesity is a common risk factor for both DM and MM. Although data are limited, studies have shown that DM might be associated with increased risk for the development of MM. The presence of DM might affect the course of patients with MM, since hyperglycemia may have an impact on both the efficacy and the adverse effects of antimyeloma therapy. In parallel, DM and MM share common clinical presentations, such as nephropathy, neuropathy, and CV. In terms of antidiabetic medications, metformin might present a synergistic effect with antimyeloma drugs and also prevent some of the adverse effects of these drugs; pioglitazone might have favourable effects when given as add on treatment in people with relapsed or refractory MM. No clinically important interactions have been observed between antidiabetic agents and the most commonly used antimyeloma drugs. Further data are needed to examine the effect of all classes of antidiabetic medication on MM and its complications. A baseline assessment of risk factors for glucose intolerance and close monitoring of glucose levels during therapy is strongly suggested for patients with MM.

Low concentrations of bisphenol A promote the activation of the mitochondrial apoptotic pathway on Beta-TC-6 cells via the generation of intracellular reactive oxygen species and mitochondrial superoxide.

Τhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine-disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells. Herein, we examined the effect of low doses of BPA on pancreatic beta cell viability and apoptosis and we tried to elucidate the mechanisms involved in these processes. Beta-TC-6 (ATCC® CRL-11506™) cells were cultured with a medium containing the following dilutions of BPA: 0.002, 0.02, 0.1, 0.2, 2 µΜ up to 72 h. We examined the viability and adenosine triphosphate (ATP) levels of cells. Then, we measured apoptosis, cell cycle, and insulin levels. We quantified the levels of proteins implicated in the mitochondrial pathway of apoptosis; and finally, we quantified the intracellular reactive oxygen species and mitochondrial superoxide. We found that the exposure of Beta-TC-6 cells to BPA results in a decrease in cell viability, ATP levels, and an increase in insulin levels. We found an increase in apoptosis levels and a decrease in cell cycle levels. In addition, we provide evidence of the levels of apoptotic proteins. Finally, we found an increase in the cellular reactive oxygen species and mitochondrial superoxide production. Exposure to low concentrations of BPA triggers the mitochondrial pathway of apoptosis via the generation of intracellular reactive oxygen species and mitochondrial superoxide on Beta-TC-6 cells in a dose-dependent way.

Favorable outcomes of patients with sickle cell disease hospitalized due to COVID-19: A report of three cases.

Sickle cell disease (SCD) is one of the most frequent and severe monogenic disorders, affecting millions of individuals worldwide. SCD represents a fatal hematological illness, characterized by veno-occlusive events and hemolytic anemia. Hemolytic anemia is caused by abnormal sickle-shaped erythrocytes, which induce parenchymal destruction and persistent organ damage, resulting in considerable morbidity and mortality. During the coronavirus disease 2019 (COVID-19) pandemic, patients with SCD were characterized as a 'high-risk' group due to their compromised immune system, caused by functional hyposplenism, as well as systemic vasculopathy. COVID-19 is characterized by endothelial damage and a procoagulant condition. The present study describes the clinical features, management and outcomes of 3 patients with SCD who were hospitalized due to COVID-19, who all had favorable outcomes despite the complications.

Immunogenicity of SARS-CoV-2 BNT162b2 Vaccine in People with Diabetes: A Prospective Observational Study.

The mRNA-based BNT162b2 vaccine has demonstrated high efficacy against severe SARS-CoV-2. However, data regarding immune response in people with diabetes mellitus (DM) after vaccination with the BNT162b2 vaccine are limited. In this prospective observational study, we examined humoral immune response in participants with and without DM after vaccination with the BNT162b2 mRNA vaccine. A total of 174 participants (58 with and 116 without diabetes, matched for age) were included. Antibodies were measured 21 days after the first dose, 7−15 days after the second dose, and 70−75 days after the second and before the third dose of the vaccine. Antibodies were measured by an anti-SARS-CoV-2 receptor-binding domain IgG (Abs-RBD-IgG) assay by a chemiluminescent microparticle immune assay; values > 50 AU/mL are considered protective from severe disease. Almost 17% of participants with DM did not develop adequate humoral immune response to the BNT162b2 mRNA vaccine after the first dose; however, it was high and similar after the second dose in both participants with and without DM and remained so almost 2 months after the second dose of the vaccine. Geometric mean values of Abs-RBD-IgG were not significantly different between participants with and without DM during the study. At least two doses of the BNT162b2 vaccine are necessary to ensure adequate and sustainable immune response in people with DM.

Role of diabetes mellitus in the clinical course and outcome of SARS-CoV-2 infected patients.

PURPOSE: Our aim was to study patients with diabetes mellitus and SARS-CoV-2-infection diagnosed during the first pandemic wave in Greece. METHODS: Cases were retrieved from the national database of SARS-CoV-2 infections. RESULTS: We studied 2624 SARS-CoV-2 infected cases, including 157 with diabetes. Patients with diabetes more often had other comorbidities (68.8 vs. 24.1%; p-value < 0.001). Among patients with diabetes, 149 (94.9%) developed symptomatic disease (COVID-19) compared to 1817 patients (73.7%) without diabetes (p-value < 0.001). A total of 126 patients with diabetes and COVID-19 were hospitalized and 41 died (27.5% case-fatality rate compared to 7.5% among patients without diabetes; p-value < 0.001). Patients with diabetes more often were hospitalized, developed complications, were admitted to the intensive care unit (ICU), received invasive mechanical ventilation, and died compared to patients without diabetes (p-values < 0.001 to 0.002 for all comparisons). Multivariate logistic regression analyses revealed that diabetes, having other comorbidities, and older age were significantly associated with higher risk for hospitalization, ICU admission, invasive mechanical ventilation, and death, and that obesity was significantly associated with higher risk for hospitalization, ICU admission, and mechanical intubation, while female gender protected against these outcomes. CONCLUSION: COVID-19 is associated with increased rates of serious morbidity and adverse outcome in patients with diabetes and represents a severe illness for them.

The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression.

AIMS: The aim of this systematic review and meta-analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID-19 patients. METHODS: A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID-19 was conducted on 26 March 2021. Comprehensive Meta-Analysis software was used for the quantitative assessment of data and random-effects model was applied. To investigate the association between the dose of vitamin D and the outcomes of interest, meta-regression analysis was performed. RESULTS: Two thousand and seventy-eight patients from nine studies with data on mortality were included (583 received vitamin D supplementation, while 1495 did not). Sixty-one (10.46%) individuals in the treated group died, compared to 386 (25.81%) in the non-treated group (odds ratio [OR]: 0.597; 95% CI: 0.318-1.121; p = 0.109). Eight hundred and sixty patients from six studies with data on ICU admission were included (369 received vitamin D supplementation, while 491 did not). Forty-five (12.19%) individuals in the treated group were admitted to ICU, compared to 129 (26.27%) in the non-treated group (OR: 0.326; 95% CI: 0.149-0.712; p = 0.005). No significant linear relationship between vitamin D dose and log OR of mortality or log OR of ICU admission was observed. CONCLUSION: This meta-analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID-19 patients. Further research is urgently needed to understand the benefit of vitamin D in COVID-19.

The Role of Diabetes and Hyperglycemia on COVID-19 Infection Course-A Narrative Review.

It was previously reported that subjects with diabetes mellitus (DM) are more vulnerable to several bacterial or viral infections. In the era of coronavirus disease 2019 (COVID-19) pandemic, it is reasonable to wonder whether DM is a risk factor for COVID-19 infection, too. It is not yet clear whether DM increases the risk for contracting COVID-19 infection or not. However, patients with DM when infected are more likely to develop severe or even fatal COVID-19 disease course than patients without DM. Certain characteristics of DM patients may also deteriorate prognosis. On the other hand, hyperglycemia per se is related to unfavorable outcomes, and the risk may be higher for COVID-19 subjects without pre-existing DM. In addition, individuals with DM may experience prolonged symptoms, need readmission, or develop complications such as mucormycosis long after recovery from COVID-19; close follow-up is hence necessary in some selected cases. We here present a narrative review of the literature in order to set light into the relationship between COVID-19 infection and DM/hyperglycemia.

Association of cardiovascular factors in diabetic patients with non-alcoholic fatty liver disease.

PURPOSE: To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. RESULTS: Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3 kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). CONCLUSION: Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasive techniques, were associated with severity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.