Hypertriglyceridemia and Other Risk Factors of Chronic Kidney Disease in Type 2 Diabetes: A Hospital-Based Clinic Population in Greece.

AIMS/INTRODUCTION: Several reports indicate an increasing prevalence of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Hyperglycemia and hypertension are the main risk factors for CKD development and progression. However, despite the achievement of recommended targets for blood glucose and blood pressure (BP), the residual risk of diabetic chronic kidney disease (DCKD) remains relatively high. The aim of this study is to examine dyslipidemia and other major risk factors to provide support for the prevention and treatment of DCKD. MATERIALS AND METHODS: Participants are from the Redit-2-Diag study that examines 1759 subjects within a period of 6 months. DCKD severity is staged according to KDIGO criteria. RESULTS: An increase in hemoglobin A1c (1 unit) and systolic blood pressure (1 mm Hg) increases the probability of being classified into a higher CKD stage by 14% and 26%, respectively. Moreover, an increase of triglycerides by 88.5 mg/dL increases the risk of classification to a worse CKD stage by 24%. CONCLUSIONS: Elevated triglycerides, systolic blood pressure, and poor glycemic control increase the risk of CKD in T2DM and should be addressed in the treatment strategies.

Chronic Diabetic Complications: Current Challenges and Opportunities.

The Special Issue, "Chronic Diabetic Complications: Current Challenges and Opportunities", is rich in scientific content, covering a wide field of diabetic complications via both original studies and reviews [...].

Antidiabetic and Other Therapies Used in Subjects with Diabetes and Chronic Kidney Disease in a Hospital-Based Clinic Population in Greece.

(1) Background: Type 2 diabetes mellitus (T2DM) is the main cause of chronic kidney disease (CKD). In Greece, in a population from hospital-based diabetes clinics (n = 1759), the overall prevalence of diabetic chronic kidney disease (DCKD) was 45% including mild, moderate, and severe CKD. The aim of this study was to describe and analyze how T2DM patients with mild-to-severe CKD are managed by diabetologists in Greece and assess the achievement rates in glycemic, blood pressure and low-density lipoprotein-cholesterol (LDL-C) control. (2) Methods: This cross-sectional multicenter study took place from June 2015 to March 2016 and collected data from diabetes centers in public hospitals all over Greece. (3) Results: With regard to the anti-diabetes treatment, most participants were on metformin, DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors and insulin. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were the most prescribed medications for hypertension. For the management of dyslipidemia, most participants were on statins. For patients with DCKD, the levels of HbA1c, blood pressure and LDL-C were 7.2%, 137.7/76.9 mmHg and 95.9 mg/dL, respectively (mean values). (4) Conclusions: The outcomes of this study suggest that management of DCKD can be further improved and should be enhanced. These results may contribute to the whole health care system in Greece. In addition, the better understanding of therapeutic strategies used by diabetologists treating these patients offers educational benefits to primary care physicians, which can result in an overall more successful and efficient management of subjects with T2DM and DCKD.

From Recession to Depression? Prevalence and Correlates of Depression, Anxiety, Traumatic Stress and Burnout in Healthcare Workers during the COVID-19 Pandemic in Greece: A Multi-Center, Cross-Sectional Study.

The COVID-19 pandemic has the potential to adversely affect the mental health of healthcare workers (HCWs). The public healthcare system in Greece was already facing serious challenges at the outset of the outbreak following years of austerity and an escalating refugee crisis. This multi-center, cross-sectional study aims to assess the levels and associated risk factors of anxiety, depression, traumatic stress and burnout of frontline staff in Greece. A total of 464 self-selected HCWs in six reference hospitals completed a questionnaire comprising sociodemographic and work-related information and validated psychometric scales. The proportion of HCWs with symptoms of moderate/severe depression, anxiety and traumatic stress were 30%, 25% and 33%, respectively. Burnout levels were particularly high with 65% of respondents scoring moderate/severe in emotional exhaustion, 92% severe in depersonalization and 51% low/moderate in personal accomplishment. Predictive factors of adverse psychological outcomes included fear, perceived stress, risk of infection, lack of protective equipment and low social support. The psychological burden associated with COVID-19 in healthcare professionals in Greece is considerable, with more than half experiencing at least mild mental health difficulties. Findings signal the need for immediate organizational and individually tailored interventions to enhance resilience and support wellbeing under pandemic conditions.

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

INTRODUCTION: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA1c), blood pressure and lipid control achievement rates in the routine care setting in Greece. METHODS: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA1c measurements in the previous year and an HbA1c target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year. RESULTS: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA1c, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively. CONCLUSIONS: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.

The prevalence of diabetic chronic kidney disease in adult Greek subjects with type 2 diabetes mellitus: A series from hospital-based diabetes clinics.

AIMS: To examine the prevalence of diabetic chronic kidney disease (DCKD) and its risk factors in adult Greek subjects with type 2 diabetes mellitus (T2DM) in a population from hospital-based diabetes clinics. METHODS: This is a cross-sectional multicentre study based on data collected from Greek hospital-based diabetes clinics from June 2015 to March 2016. DCKD severity was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines. Multivariate analyses assessed the associations between DCKD and its potential risk factors. RESULTS: Among the entire population (n = 1759), the overall prevalence of DCKD was 45% including mild, moderate and severe CKD. Older age, male gender, body-mass index, lack of exercise and diabetes duration were significantly associated with DCKD. CONCLUSIONS: In Greece, DCKD in T2DM is highly prevalent. It is significantly associated with demographic and lifestyle parameters, as well as T2DM complications, suggesting that further efforts to prevent DCKD should be addressed to subjects with specific characteristics.

The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in Greece.

AIM: To investigate the prevalence of hypoglycaemia during sulfonylurea (SU) treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on glycaemic control, treatment adherence and quality of life (QoL). PATIENTS AND METHODS: This was a retrospective cross-sectional study. We included 383 T2DM patients ≥30 years old on treatment with SU in monotherapy or in combination with metformin for at least 6 months. Patients were requested to fill in retrospective questionnaires on hypoglycaemia experience, adherence, weight gain and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). RESULTS: HbA1c<7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of those with HbA1c <7% and 44.1% (98/222) of those with HbA1c ≥7%. Glycaemic control was achieved by 43.1% (94/218) of patients without hypoglycaemia and 50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs. moderate vs. severe) of hypoglycaemia were significantly associated with impaired global treatment satisfaction (p=0.002 and p<0.0001 respectively) and HFS-II Worry scale scores (both p<0.0001), while lower QoL (EQ-5D (UK) Index) was related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence was associated with increased (none/mild vs. moderate/severe) hypoglycaemia severity in univariate analysis (p=0.019). CONCLUSION: A high prevalence of patient treated with SU reported hypoglycaemia in Greek healthcare settings with negative effects on treatment satisfaction, patient worry and adherence. Severity of hypoglycaemic symptoms was associated with reduced glycaemic control.

Fetuin-A levels and free leptin index are reduced in patients with chronic lymphocytic leukemia: a hospital-based case-control study.

There are limited data on fetuin-A, soluble leptin receptor (sOB-R) and free leptin index (FLI) in patients with chronic lymphocytic leukemia (CLL). The aim of this study was to compare circulating fetuin-A, sOB-R levels and FLI between 95 patients with CLL and 95 matched controls, as well as among different stages of CLL. Circulating fetuin-A was significantly lower in cases than controls (241.9 ± 99.2 vs. 288.8 ± 127.7 µg/mL; p = 0.005). Although circulating sOB-R levels were similar between groups, FLI was lower in cases than controls (0.45 ± 0.42 vs. 0.67 ± 0.57; p = 0.003). Furthermore, lower fetuin-A or FLI, but not sOB-R, were independently associated with CLL (p < 0.05), particularly among overweight/obese individuals. Fetuin-A, s-OB-R and FLI were similar between different stages of CLL severity, or between symptomatic and asymptomatic disease. In conclusion, circulating fetuin-A and FLI, but not sOB-R, were lower in patients with CLL than controls, a finding warranting further investigation.

The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data "The HERCULES Study".

Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control (Hba1c > 7%) versus patients with adequate control (Hba1c = 7%) (€ 7,783 versus € 6,366, resp.; P = 0.017). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, OR = 3.46 (95% CI: 1.10-10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients.

Circulating fetuin-A in patients with pancreatic cancer: a hospital-based case-control study.

CONTEXT: A proteomic analysis has proposed fetuin-A (alpha-2-HS-glycoprotein) as a new potential marker for pancreatic cancer (PC). OBJECTIVE: Circulating fetuin-A levels in patients with PC. METHODS: Serum fetuin-A was measured in 81 cases with PC and 81 matched controls before the initiation of any treatment. RESULTS: Serum fetuin-A was not independently associated with the presence of PC. Although there was a trend with higher fetuin-A levels across PC stages, comparisons of fetuin-A in patients within different PC prognostic stages revealed no differences. CONCLUSIONS: Circulating fetuin-A was similar between patients and controls and was not associated with the disease severity.

Long-acting basal insulin analogs: latest developments and clinical usefulness.

All patients with type 1 diabetes mellitus need insulin treatment permanently, and many patients with type 2 diabetes will require insulin therapy. Basal insulin analogs are increasingly used in the treatment of diabetes, with the aim of offering a better replication of the pattern of basal endogenous secretion of insulin. Their flatter pharmacodynamic profile, with a much lower peak of action, their slow and continuous absorption into the systemic circulation, and prolonged duration, more closely duplicate the endogenous insulin secretion leading to physiological basal glycemic control and affording more flexible treatment with fewer hypoglycemia episodes. The basal analogs represent the most significant advances in 'basal insulin' supplementation, and can be used in different insulin regimens achieving the same clinical effectiveness over conventional insulins, with benefits in terms of hypoglycemia and less weight gain, and may be an option for patients with problematic hypoglycemia despite optimization of conventional insulin therapy. At present, there are no data on micro- or macrovascular endpoints, and indeed it is unlikely that these will become available, at least in the foreseeable future. The evidence for basal insulin analogs affecting the risk of cancer is limited, and overriding diabetes indications rather than putative cancer concerns should remain the principal consideration when selecting therapy in patients with diabetes.

Insulin analogs versus human insulin in type 2 diabetes.

Oral hypoglycaemic agents become less effective as beta cell function declines. Thus many patients with type 2 diabetes will ultimately require treatment with insulin. There are two main approaches to starting insulin: (a) as a basal supplement with an intermediate to long-acting preparation (NPH, glargine or detemir) plus oral agents; (b) as a premixed insulin regimen. Almost all the studies have shown similar glucose control with both NPH and the new insulin analogs. Further analyses between these insulins have documented significant reductions in hypoglycaemia especially at night with the insulin analogs. The weight gain is an important issue in patients with diabetes. It appears that insulin detemir studies have reported weight neutrality or less weigh gain or even weight loss. However, most insulin glargine studies have reported a weight gain. On the other hand insulin analogs have the important disadvantage of high cost. It is important to take in to account all the above factors such as cost, weight gain, number of insulin injections and hypoglycaemia while prescribing insulin.

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case-control study in Greece.

AIM: Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. METHODS: Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined. RESULTS: Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01-0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls. CONCLUSION: Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study.

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case-control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.

Association of thyroid disease and thyroid autoimmunity with multiple myeloma risk: a case-control study.

Thyroid disease has been associated with lymphohematopoietic cancer (LHC). No previous study using clinical, sonographic and laboratory data has explored whether thyroid disease and specifically autoimmune thyroid disease (ATD) is associated with multiple myeloma (MM) risk. 73 patients with incident primary MM and 73 hospital controls admitted for non-neoplastic and non-infectious conditions, matched on gender and age were studied between 2001 and 2007. Blood samples were collected. All subjects were submitted to clinical, ultrasound and laboratory thyroid evaluation. The prevalence of clinical thyroid disease in MM patients was significantly higher than in controls (p = 0.002). ATD was associated with increased risk of MM, adjusting for age, gender, body mass index and familial history of LHC [OR = 5.68, 95% confidence interval (CI): 1.69-19.13]. Controlling for the above variables, an individual suffering from any thyroid disease more than 10 years has about 2.41 times more likely the risk to develop MM than an individual without any thyroid disease (OR = 2.41, 95% CI: 1.35-4.29). Also, adjusting for age, gender, BMI and family history of LHC, a familial history of thyroid disease is associated with increased risk of MM (OR = 3.23, 95% CI: 1.25-8.31). Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with plasma cell transformation.

Clinical study on the serum carcinoembryonic antigen, CA 19-9, CA 50 and alpha-fetoprotein levels in patients with myelodysplastic syndromes.

The present study aimed to determine the serum carcinoembryonic antigen (CEA), CA 19-9, CA 50 and alpha-fetoprotein (alpha-FP) levels between patients with myelodysplastic syndromes (MDS) at diagnosis and controls to clarify their potential clinical significance. A case-control investigation was conducted over a three year period, covering 95 MDS cases and 95 age- and gender-matched controls. Mean serum CEA levels were significantly higher (P = 0.0002) in MDS patients at diagnosis than in hospital controls. Adjusting for age, gender, tobacco consumption, serum CA 19-9, CA 50 and alpha-FP levels, there is statistically significant evidence that serum CEA values are associated with increased risk of MDS (odds ratio = 2.33, 95% confidence interval = 1.56 - 3.49). Six patients with MDS developed malignancies 4-9 months after the diagnosis of myelodysplasia. Serum CEA could be used as marker together with other important diagnostic tools for evaluating an underlying or developing malignancy in patients suffering from MDS.

Spontaneous peritonitis caused by Leminorella grimontii.

A case of spontaneous peritonitis caused by Leminorella grimontii in a 63-year-old man with cirrhosis is reported. To our knowledge, L. grimontii has never been reported as a cause of spontaneous bacterial peritonitis. The patient responded to antimicrobial therapy. Clinical and therapeutic implications are discussed.