Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN.

The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials.

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.

Current Position of Gliclazide and Sulfonylureas in the Contemporary Treatment Paradigm for Type 2 Diabetes: A Scoping Review.

The increasing burden of type 2 diabetes (T2D), in relation to alarming rise in the prevalence; challenges in the diagnosis, prevention, and treatment; as well as the substantial impact of disease on longevity and quality of life, is a major concern in healthcare worldwide. Sulfonylureas (SUs) have been a cornerstone of T2D pharmacotherapy for over 60 years as oral antidiabetic drugs (OADs), while the newer generation SUs, such as gliclazide modified release (MR), are known to be associated with low risk of hypoglycemia in addition to the cardiovascular neutrality. This scoping review aimed to specifically address the current position of gliclazide MR among other SUs in the contemporary treatment paradigm for T2D and to provide a practical guidance document to assist clinicians in using gliclazide MR in real-life clinical practice. The main topics addressed in this paper include the role of early and sustained glycemic control and use of SUs in T2D management, the properties of gliclazide MR in relation to its effectiveness and safety, the use of gliclazide therapy in special populations, and the place of SUs as a class and gliclazide MR specifically in the current T2D treatment algorithm.

Impact of lipodystrophy on health-related quality of life: the QuaLip study.

BACKGROUND: Lipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits. RESULTS: Eighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive-compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive-compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects. CONCLUSIONS: Lipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy.

Many Faces of Adrenal Lesions in a Large Patient Cohort: What Has Changed Over the Last Two Decades?

OBJECTIVE: To review the presentation characteristics, clinical and hormonal evaluations, and histopathological results of patients with adrenal lesions over a 21-year period and evaluate the changes across the two decades. METHODS: This single-center, retrospective study included 1003 patients with adrenal lesions who presented to our department between 2000 and 2021. Clinical, metabolic, hormonal, radiological, and pathological data of the patients were collected. RESULTS: Forty-seven percent of the lesions were non-functioning adrenal adenomas. Possible autonomous and autonomous cortisol secretion were detected in 22.2% of the patients. The percentages of the patients diagnosed with pheochromocytoma, primary hyperaldosteronism, adrenal Cushing syndrome, adrenocortical carcinoma, and adrenal metastasis were 7.4%, 4.8%, 4.7%, 0.9%, and 5.6%, respectively. Adrenalectomy was performed in 31.3% of the patients. Functional adrenal lesions were the leading cause of surgery (46.5%), followed by large size and/or suspicious imaging features (38.6%). Among the patients referred to surgery due to large size (≥6 cm), the diagnosis in 19% was metastasis, and in 12.1%, it was primary adrenocortical carcinoma. In patients with adrenal lesions with a size of 4-6 cm and suspicious imaging properties, the rates of metastasis and primary adrenocortical carcinoma were 44.4% and 4.8%, respectively. From the first to the second decade, major differences in presentation characteristics were increased detection of bilateral lesions and increased prevalence of possible autonomous and autonomous cortisol secretion. CONCLUSIONS: Adrenal lesions are common in the adult population, and while it is important to avoid overtreatment, hormone secretion, and malignancy should not be overlooked.

The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.

Prevalence of Gastrointestinal Symptoms and Clinical Outcomes in Hospitalized Coronavirus Disease 2019 Patients: A Single-Center Study from Turkey.

BACKGROUND: In patients with coronavirus disease 2019, the gastrointestinal symptoms have been reported increasingly in addition to the respiratory system symptoms. The studies show that the prevalence of gastrointestinal system symptoms and how the gastrointestinal system contributes to the severity and prognosis of the disease is still not clear. This study aims to find the prevalence of gastrointestinal symptoms and the correlation between the gastrointestinal symptoms and the clinical results in hospitalized patients diagnosed with coronavirus disease 2019. METHODS: This study retrospectively analyzes patients diagnosed with coronavirus disease 2019 and hospitalized in the pandemic unit between March 2020 and August 2020 and compares their demographic and clinical characteristics, laboratory and radiologic findings, coronavirus disease 2019 treatments received, the clinical course of the disease, and the gastrointestinal symptoms. RESULTS: In our study, we included 322 patients diagnosed with coronavirus disease 2019 and hospitalized; 39 patients (12.1%) were admitted to the hospital with at least one gastrointestinal symptom (nausea and vomiting, diarrhea, abdominal pain, and the loss of taste). Nausea and vomiting are the most common gastrointestinal symptoms with a prevalence of 7.1%, followed by diarrhea with 2.8%, the loss of taste with 2.2%, and abdominal pain with 1.5%. The mean age and D-dimer levels of the patients showing gastrointestinal symptoms were lower than those who did not have any gastrointestinal symptoms. We did not find a significant correlation between the presence of the gastrointestinal symptoms and the severity of the disease, treatment received, risk of acute respiratory distress syndrome and septic shock, admission to the intensive care unit, the need for mechanical ventilation, the mortality rate or the length of hospitalization in the medical floor or the intensive care unit. CONCLUSION: In this study, we observed that 12.1% of coronavirus disease 2019 patients apply to the hospital due to gastrointestinal symptoms. Furthermore, the gastrointestinal symptoms do not seem to affect the severity and the course of the disease, it is important to identify coronavirus disease 2019 patients showing unusual symptoms such as the gastrointestinal symptoms at an early stage to protect healthcare professionals from infection risk.

Higher rate of COVID-19 mortality in patients with type 1 than type 2 diabetes: a nationwide study.

INTRODUCTION: COVID-19 disease has a worse prognosis in patients with diabetes, but comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM. MATERIAL AND METHODS: A nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n = 149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n = 163), T2DM (n = 33,478) and those without diabetes (n = 115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation, and mortality. RESULTS: The patients with T1DM had higher mortality than the age- and gender-matched patients with T2DM (n = 489) and those without diabetes (n = 489) (p < 0.001). After further adjustment for the HbA1c, and microvascular and macrovascular complications, the odds of mortality (OR: 3.35, 95% CI: 1.41-7.96, p = 0.006) and ICU admission and/or mechanical ventilation (OR: 2.95, 95% CI: 1.28-6.77, p = 0.011) were significantly higher in patients with T1DM compared to those with T2DM. Older age (OR: 1.06, 95% CI: 1.01-1.12, p = 0.028) and lymphopaenia (OR: 5.13, 95% CI: 1.04-25.5, p = 0.045) were independently associated with mortality in patients with T1DM. CONCLUSIONS: Patients with T1DM had worse prognosis of COVID-19 compared to T2DM patients or those without diabetes. These cases should be cared for diligently until more data become available about the causes of increased COVID-19 mortality in T1DM.

Clinical Characteristics and Outcomes of COVID-19 Patients with Overweight and Obesity: Turkish Nationwide Cohort Study (TurCObesity).

PURPOSE: While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. METHODS: A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. RESULTS: A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04-3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02-1.05; p<0.001) were associated with a higher intubation/mechanical ventilation rate but only obesity was associated with increased mortality (OR, 95% CI: 2.56, 1.40-4.67; p=0.002). Old age, male gender, chronic kidney disease, and high C reactive protein levels were independently associated with COVID-19 mortality in overweight or obese patients. CONCLUSIONS: COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study.

INTRODUCTION: To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population. RESULTS: A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39-1.08; p = 0.099). CONCLUSIONS: The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.

Clinical outcomes of non-diabetic COVID-19 patients with different blood glucose levels: a nationwide Turkish study (TurCoGlycemia).

PURPOSE: New coronavirus disease 2019 (COVID-19) has a worse prognosis in patients with diabetes. However, there are insufficient data about the effect of hyperglycemia on COVID-19 prognosis in non-diabetic patients. This study aimed to investigate the relationship between random blood glucose levels measured at the time of diagnosis and prognosis of COVID-19 disease in non-diabetic patients. METHODS: A nationwide retrospective cohort of non-diabetic patients with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. The patients were stratified into three groups according to blood glucose levels which were <100 mg/dL in group-1, in the range of 100-139 mg/dl in group-2, and the range of 140-199 mg/dl in group-3. Clinical characteristics and outcomes were compared among the groups. The primary outcome was mortality. RESULTS: A total of 12,817 non-diabetic patients (median age [IQR]: 44 [25] years, females: 50.9%) were included. Patients in group-2 (5%) and group-3 (14%) had higher mortality rates than patients in group-1 (2.1%). The rates of hospitalization, hospital stays longer than 8 days, intensive care unit (ICU) admission, ICU stay more than 6 days, and mechanical ventilation were also significantly higher in group-3 patients. Likewise, glucose levels in the range of 140-199 mg/dL were an independent associate of mortality and composite of ICU admission and/or mechanical ventilation. CONCLUSION: Hyperglycemia at the time of COVID-19 diagnosis is associated with poor prognosis in non-diabetic patients. Clinicians should be more careful in the treatment of non-diabetic COVID-19 patients with hyperglycemia.

The clinical outcomes of COVID-19 infection in patients with a history of thyroid cancer: A nationwide study.

BACKGROUND: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection. DESIGN AND METHODS: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease. RESULTS: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group. CONCLUSIONS: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.

Use of Insulin Degludec/Insulin Aspart in the Management of Diabetes Mellitus: Expert Panel Recommendations on Appropriate Practice Patterns.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (IDeg), which provides long-lasting basal insulin coverage, and insulin aspart (IAsp), which targets post-prandial glucose. This expert panel aimed to provide a practical and implementable guidance document to assist clinicians in prescribing IDegAsp in the diabetes management with respect to different patient populations including children and adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) as well as pregnant, elderly and hospitalized patients and varying practice patterns (insulin-naive, insulin-treated, switching from basal, basal bolus and premix regimens). The experts recommended that IDegAsp can be used in insulin-naive T2D patients with poor glycemic control (HbA1c >8.5%) despite optimal oral antidiabetic drugs (OADs) as well as in insulin-treated T2D patients by switching from basal insulin, basal-bolus therapy or premixed insulins in relation to lower risk of nocturnal hypoglycemia, fewer injections and lower intraday glycemic variability, respectively. The experts considered the use of IDegAsp in children with T2D as a basal bolus alternative rather than as an alternative to basal insulin after metformin failure, use of IDegAsp in adult T1D patients as a simplified basal bolus regimen with lesser nocturnal hypoglycemia, fewer injections and better fasting plasma glucose control and in children with T1D as an alternative insulin regimen with fewer injection to increase treatment adherence. The proposed expert opinion provides practical information on use of IDegAsp in different patient populations and practice patterns to assist clinicians, which seems to compensate the need for easily implementable guidance on this novel insulin regimen.

Clinical characteristics and outcomes of COVID-19 in patients with type 2 diabetes in Turkey: A nationwide study (TurCoviDia).

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been reported to be associated with a more severe course in patients with type 2 diabetes mellitus (T2DM). However, severe adverse outcomes are not recorded in all patients. In this study, we assessed disease outcomes in patients with and without T2DM hospitalized for COVID-19. METHODS: A nationwide retrospective cohort of patients with T2DM hospitalized with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. Multivariate modeling was used to assess the independent predictors of demographic and clinical characteristics with mortality, length of hospital stay, and intensive care unit (ICU) admission and/or mechanical ventilation. RESULTS: A total of 18 426 inpatients (median age [interquartile range, IQR]: 61 [17] years; males: 43.3%) were investigated. Patients with T2DM (n = 9213) were compared with a group without diabetes (n = 9213) that were matched using the propensity scores for age and gender. Compared with the group without T2DM, 30-day mortality following hospitalization was higher in patients with T2DM (13.6% vs 8.7%; hazard ratio 1.75; 95% CI, 1.58-1.93; P < .001). The independent associates of mortality were older age, male gender, obesity, insulin treatment, low lymphocyte count, and pulmonary involvement on admission. Older age, low lymphocyte values, and pulmonary involvement at baseline were independently associated with longer hospital stay and/or ICU admission. CONCLUSIONS: The current study from the Turkish national health care database showed that patients with T2DM hospitalized for COVID-19 are at increased risk of mortality, longer hospital stay, and ICU admission.

Associations Between Bioavailable Vitamin D and Remnant Cholesterol in Patients With Type 2 Diabetes Mellitus.

Introduction In circulation, 99% vitamin D is transported by binding to vitamin D binding protein (VDBP) and albumin. Vitamin D at free form and vitamin D binding to albumin are defined as bioavailable vitamin D. Vitamin D deficiency is associated with atherogenic lipid profile and insulin resistance. Remnant cholesterol is defined as the cholesterol component of triglyceride-rich lipoproteins and contributes to the atherosclerotic burden. The aim of this study was to investigate the association between bioavailable vitamin D and remnant cholesterol in patients with type 2 diabetes mellitus (T2DM). Methods A total of 198 T2DM patients and 208 non-diabetic subjects underwent biochemical measurements of lipid profiles, 25(OH)D, VDBP, CRP and albumin levels. Their demographic characteristics (age, sex) were questioned. Subjects with thyroid, kidney and liver dysfunction and using lipid-lowering therapy were not included in the study. The diagnosis of T2DM was made according to the American Diabetes Association ADA 2016 criteria. Classification of vitamin D levels was done according to the Endocrine Society. Bioavailable vitamin D concentrations were calculated. Results High-density lipoprotein cholesterol (HDL), 25(OH)D, free vitamin D and bioavailable vitamin D levels were significantly lower in diabetic patients than in non-diabetic patients while triglyceride, remnant cholesterol and CRP levels were found to be significantly higher. VDBP was positively correlated with CRP and remnant cholesterol in diabetic patients, but not in non-diabetic patients. Cut-off values were determined from non-diabetics as 3.56 ng/mL for bioavailable vitamin D and 26.56 mg/dL for remnant cholesterol. Logistic regression analysis in the control group showed that the odds ratio for increasing remnant cholesterol above the cut-off value was determined as 2.01 for low bioavailable vitamin D and 1.1 for elevated CRP. However, in T2DM there was no significant relationship. In all subjects, low bioavailable vitamin D increased the remnant cholesterol above the cut-off by 2.18-fold independent of the presence of T2DM. However, there was no significant risk to increase remnant cholesterol, considering a total 25(OH) D deficiency in all groups. Conclusions Low bioavailable vitamin D was found to be a risk factor for elevated remnant cholesterol. This relationship was not detected in patients with T2DM. We believe that the inflammation observed in Diabetes Mellitus may increase the concentrations of VDBP and a decrease in bioavailable vitamin D levels. Therefore, measuring VDBP and calculating the bioavailable vitamin D may provide additional information about the actual vitamin D status.

Unexpectedly lower mortality rates in COVID-19 patients with and without type 2 diabetes in Istanbul.

AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for severe COVID-19. Our aim was to compare the clinical outcomes of patients with and without T2DM during the first hit of COVID-19 in Istanbul. METHODS: A retrospective population-based study was conducted including all consecutive adult symptomatic COVID-19 cases. Patients were confirmed with rt-PCR; treated and monitored in accordance with standard protocols. The primary endpoints were hospitalization and 30-day mortality. RESULTS: Of the 93,571 patients, 22.6% had T2DM, with older age and higher BMI. Propensity Score matched evaluation resulted in significantly higher rates of hospitalization (1.5-fold), 30-day mortality (1.6-fold), and pneumonia (1.4-fold). They revealed more severe laboratory deviations, comorbidities, and frequent drug usage than the Non-DM group. In T2DM age, pneumonia, hypertension, obesity, and insulin-based therapies were associated with an increased likelihood of hospitalization; whereas age, male gender, lymphopenia, obesity, and insulin treatment were considerably associated with higher odds of death. CONCLUSIONS: COVID-19 patients with T2DM had worse clinical outcomes with higher hospitalization and 30-day mortality rates than those without diabetes. Compared to most territories of the world, COVID-19 mortality was much lower in Istanbul, which may be associated with accessible healthcare provision and the younger structure of the population.

Magnetic resonance spectroscopy to assess hepatic steatosis in patients with lipodystrophy.

BACKGROUND/AIMS: Lipodystrophy is a rare metabolic disorder characterized by near total or partial lack of subcutaneous adipose tissue and associated with insulin resistance. We aimed to evaluate the efficacy of magnetic resonance spectroscopy imaging (MRS) to explore the fat content of the liver in patients with lipodystrophy and to determine the relationship between the liver fat accumulation and clinical presentations of lipodystrophy. MATERIALS AND METHODS: Between July 2014 and February 2016, 34 patients with lipodystrophy were assessed by MRS for quantification of hepatic steatosis. All patients had metabolic abnormalities associated with insulin resistance. Metabolic parameters and the MRS findings were analyzed to identify potential correlations between the liver fat content and disease severity. RESULTS: The MRS fat ratios (MRS-FR) were markedly higher, indicating severe hepatic steatosis in lipodystrophy. Patients with generalized and partial lipodystrophy had comparable levels of MRS-FRs, although patients with generalized lipodystrophy were significantly younger. Patients with genetically based lipodystrophy had elevated MRS-FR compared to those with acquired lipodystrophy (p=0.042). The MRS-FR was positively correlated with liver enzyme alanine aminotransferase (p=0.028) and serum adiponectin (p=0.043). CONCLUSION: Our data suggest that MRS might be an effective, noninvasive imaging method to quantify hepatic fat content in patients with lipodystrophy. Further studies are needed to validate the technique and threshold values which would allow accurate comparison of data acquired by different machines and centers.

Predictors and histopathological characteristics of non-diabetic renal disorders in diabetes: a look from the tubulointerstitial point of view.

BACKGROUND: Prevalence and characteristics of non-diabetic renal diseases (NDRD) in patients with type 2 diabetes mellitus is different between populations, and seems to be largely dependent on biopsy policies. AIM: To investigate clinical clues for NDRD in patients with type 2 diabetes mellitus and to analyse renal prognosis of patients based on pathological diagnosis. METHODS: We retrospectively searched medical records of 115 patients with type 2 diabetes who underwent a renal biopsy between 2004 and 2018. Patients were divided into three groups as diabetic nephropathy (DN), NDRD + DN or NDRD based on histopathological examination. RESULTS: Thirty-six (31.3%) patients had DN, 33 (28.7%) had DN + NDRD and 46 (40%) had NDRD. The absence of diabetic retinopathy, recent onset of diabetes, abnormal disease chronology, and blood haemoglobin was associated with the presence of NDRD in univariate analysis. Abnormal disease chronology which was defined as the presence of acute proteinuria and/or acute kidney injury that are unexpected to be related to evolution of diabetic nepropathy (odds ratio 4.65, 95% confidence interval 1.44-15.00; P = 0.010) and absence of diabetic retinopathy (odds ratio 3.44, 95% confidence interval 1.32-8.98; P = 0.012) were independently associated with the presence of NDRD in multivariate analysis. Focal segmental glomerulosclerosis was the most frequent type of NDRD. Diseases that affect tubulointerstitial area were more prevalent in the DN + NDRD group compared to the NDRD group (P = 0.001). Renal survival, which was defined as evolution to end-stage renal disease, was 59.5 ± 14.4 months, 93.7 ± 11.7 months and 87.2 ± 2.6 months for DN, DN + NDRD and NDRD groups, respectively (P = 0.005). CONCLUSIONS: Renal biopsy is essential in certain clinical conditions as diagnosis of NDRD is vital for favourable renal survival. DN may facilitate superimposed tubular injury in the presence of toxic insults.