Agnieszka Zwolak

Quality of Life in Patients with Type 2 Diabetes in Poland – Comparison with the General Population Using the EQ-5D Questionnaire

BACKGROUND Complications of type 2 diabetes (T2D) lead to increased mortality and reduced quality of life (QOL). OBJECTIVES The aim of the study was to compare health-related quality of life (HRQoL) in Polish patients with type 2 diabetes (T2D) and in a matched sample from the general population. MATERIAL AND METHODS Data on HRQoL came from two non-interventional studies: a prospective study of patients with T2D and an EQ-5D study of Polish general population norms. The HRQoL analysis was conducted in four separate age groups: 32-44, 45-54, 55-64 and over 65 years old. We analyzed both subjective and objective assessment of HRQoL (EQ VAS and EQ-5D index) and the presence of restrictions within five dimensions of the EQ-5D descriptive part. RESULTS A total of 274 patients with T2D and 214 representatives from the study of population norms were included. EQ VAS was systematically lower in diabetic patients as compared to the general population and decreased with age (68.2 vs 83.9, 62.4 vs 79.2; 54.9 vs 78.1, 50.2 vs 69.8 in consecutive age groups). A similar relationship was observed with the EQ-5D index. The largest mean differences were observed among subjects aged 55-64 years (EQ VAS: 23.2, EQ-5D index: 0.085). In three domains, i.e. self-care, usual activities and anxiety/depression, patients with diabetes who were over 45 years of age reported significantly more problems than respondents from the general population. CONCLUSIONS Both subjective and objective HRQoL in patients with T2D was lower than in respondents similar in age from the general population. Compared with type 2 diabetic populations from other countries, Polish patients are characterized by relatively high HRQoL objective assessment and very low subjective assessment.

Validation of the Polish version of Diabetes Quality of Life - Brief Clinical Inventory (DQL-BCI) among patients with type 2 diabetes.

Introduction The aim of the study was to develop a Polish version of the Diabetes Quality of Life Brief Clinical Inventory (DQL-BCI) and to perform validating evaluation of selected psychometric aspects. Material and methods The translation process was performed in accordance with generally accepted international principles of translation and cultural adaptation of measurement tools. Two hundred and seventy-four subjects with type 2 diabetes completed the Polish version of DQL-BCI, the generic EQ-5D questionnaire and the diabetes-specific DSC-R. The examination provides information about the reliability (internal consistency, test-retest) and the construct validity of the studied tool (the relationship between the DQL-BCI score and EQ-5D and DSC-R scales, as well as selected clinical patient characteristics). Results Cronbachs α (internal consistency) for the translated version of DQL-BCI was 0.76. Test-retest Pearson correlation coefficient was 0.96. Spearmans coefficient correlation between DQL-BCI score and EQ-5D index and EQ-VAS were 0.6 (p = 0.0000001) and 0.61 (p = 0.0000001) respectively. The correlation between scores of the examined tool and DSC-R total score was –0.6 (p = 0.0000001). Quality of life was lower among patients with microvascular as well as macrovascular complications and with occurring hypoglycemic episodes. Conclusions The result of this study is the Polish scale used to test the quality of life of patients with diabetes, which includes the range of problems faced by patients while maintaining a patient-friendly form. High reliability of the scale and good construct validity qualify the Polish version of DQL-BCI as a reliable tool in both research and individual diagnostics.

Biomarkers of alcohol misuse: recent advances and future prospects

Alcohol abuse and dependence are highly prevalent in many cultures and contribute considerably to the global burden of health and social issues. The current inability to accurately characterise long-term drinking behaviours is a major obstacle to alcoholism diagnosis and treatment. Therefore, it is of great importance to develop objective diagnostic tools to discern subjects with excessive alcohol use and alcoholism or to confirm abstinence. Research over past years has revealed several biochemical compounds with considerable potential for accurate reflection of alcohol intake. This review will address the issue of alcohol biomarker definition, the types of molecules used as so-called traditional biomarkers, and the compounds that can serve as novel biomarker candidates or components of biomarker panels.

Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences

Objectives Mechanisms of immune regulation in alcoholic liver disease (ALD) are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed. Materials and Methods 147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort. Conclusions We conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury.

Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholine but Not by Alpha Ketoglutarate

Introduction and Aims Toll-like receptor 4 and proinflammatory cytokines play a central role in the progression of nonalcoholic fatty liver disease. We investigated IL-1, IL-6 and TNFα production and toll-like receptor 4 in both—obese and lean patients with non-alcoholic fatty liver disease who met different sets of metabolic syndrome criteria and linked the results with the disease burden. Materials and Methods 95 subjects were divided into four groups depending on the following criteria: presence or absence of metabolic syndrome and/or non-alcoholic fatty liver disease, glucose tolerance (prediabetes or normoglycemia) and BMI value (obese or lean). We determined the levels of IL-1β, IL-6, TNFα, and monocyte toll-like receptor 4 expression in fresh blood as well as in blood cultures treated with lipopolysaccharide with or without metformin, alphaketoglutarate or phosphatidylcholine supplementation. Results The blood leukocytes of patients with non-alcoholic fatty liver disease are hypersensitive to lipopolysaccharide treatment and produce elevated levels of pro-inflammatory cytokines in response to ex vivo treatment with lipopolysaccharide. Moreover, they overexpress toll-like receptor-4. Hyperreactivity was typical mainly for obese patients with non-alcoholic fatty liver disease together with metabolic syndrome and decreased with the severity of disease. Metformin was the most effective in attenuation of hyperreactivity in all groups of patients with non-alcoholic fatty liver disease, but in obese patients the effectiveness of metformin was weaker than in lean. The reduction of cytokine level by metformin was accompanied by the decrease in toll-like receptor-4 expression. phosphatidylcholine also attenuated hyperreactivity to lipopolysaccharide but mainly in obese patients. Alpha ketoglutarate did not modulate cytokines’ level and toll-like receptor 4 expression in non-alcoholic fatty liver disease patients. Conclusions Metformin and phosphatidylcholine attenuated lipopolysaccharide induced toll-like receptor 4 overexpression and overproduction of pro-inflammatory cytokines; however, their efficacy depended on combined presence of non-alcoholic fatty liver disease, metabolic syndrome and obesity.

Peripheral blood dendritic cells in alcoholic and autoimmune liver disorders

Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N = 26) and primary biliary cirrhosis (N = 20). DCs isolated from the peripheral blood of recruited participants were stained with monoclonal antibodies against blood dendritic cell antigens (BDCAs) and estimated using the flow cytometry. Myeloid DCs were defined as BDCA-1+/CD19− cells, and lymphoid DCs as BDCA-2+/CD123+ cells. Total numbers of circulating DCs in subjects with some liver diseases were markedly lower than in the healthy participants (p = 0.03). There was a significantly lower percentage of circulating BDCA-2+/CD123+ (p = 0.02), and a tendency for the percentage of circulating BDCA-1+/CD19− cells to decrease in patients with liver diseases compared to the controls (p = 0.09). These results may suggest that decreased numbers of DCs may be responsible for reduced adaptive immune responses and increased susceptibility to infections and cancer development observed in patients exposed to alcohol. Moreover, numerical abnormalities of DCs may contribute to the breakdown of self-tolerance, a feature of autoimmune diseases.

Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease—Ex Vivo Studies

Background Toll-like receptor 4 (TLR4) contributes to the development of NAFLD (nonalcoholic fatty liver disease) and MetS (metabolic syndrome). It is unclear whether anti-diabetic metformin affects TLR4 expression on blood monocytes, thereby protecting or improving inflammatory parameters. Therefore, we investigated TLR4 in patients with NAFLD meeting different sets of MetS criteria and linked the results with the disease burden. Methods 70 subjects were characterized and divided into three groups: (I) healthy individuals, (II) nonobese with NAFLD and without MetS, and (III) prediabetic, obese with NAFLD and MetS. We determined the concentrations of IL-1β, IL-6, TNFα, and monocyte TLR4 levels in fresh blood as well as in blood cultures with or without metformin supplementation. Results The characteristics of the study groups revealed a significant association between NAFLD and BMI, MetS and inflammatory parameters, and TLR4. In ex vivo studies, 100 μM of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1β and TNFα production. A stepwise multiple regression analysis highlighted a strong effect of metformin on attenuation of the link between TLR4 and NAFLD, and TNFα. Conclusion We concluded that, by attenuation of the blood monocyte TLR4 level, metformin reduced their inflammatory potential—critical after recruitment these cells into liver. However, this finding should be confirmed after in vivo metformin administration.

Primary hyperparathyroidism due to parathyroid cancer — a diagnostic and management challenge

Parathyroid carcinoma (PC) is a rare endocrine malignancy and the cause of primary hyperparathyroidism. It is usually associated with a high rate of local and distant recurrence. Laboratory findings and clinical symptoms may be similar to those in parathyroid adenoma. The histological features of PC may also be non-specific and the affected gland is often indistinguishable from a benign lesion. The proper diagnosis is commonly made months to years later when the disease recurs or metastases are present. Therefore, parathyroid carcinoma still remains a diagnostic and management challenge for many physicians. However, there are some features that, in combination, may help in diagnosis. Surgery still remains the only curative treatment, even in metastatic disease. In advanced, non-operable subjects, managing hypercalcaemia and controlling a tumour are the main goals. Morbidity is caused by hypercalcaemia rather than metastases. A multidisciplinary approach with experienced endocrinologists, pathologists, radiologists, nuclear medicine doctors, oncologists, and surgeons is needed to optimize patient outcome.

Catecholamine crisis as a first manifestation of familial bilateral pheochromocytoma caused by RET proto-oncogene mutation in codon C 634R

INTRODUCTION Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disorder caused by mutation in the RET proto-oncogene. MEN 2A includes medullary carcinoma of the thyroid, pheochromocytoma, and primary hyperparathyroidism. The authors present a case study of three family members with bilateral pheochromocytoma in the course of MEN 2A, a catecholamine crisis being the first manifestation of the syndrome in one of them. Case 1: A 30-year-old man without a history of hypertension or any other chronic medical problems was admitted to the Emergency Department because of a hypertensive crisis that was followed by cardiac arrest. A later diagnosis revealed bilateral pheochromocytoma and RET proto-oncogene mutation in codon 634. The patient underwent bilateral adrenalectomy and total thyroidectomy; the latter confirmed the presence of medullary carcinoma. Case 2: The patient underwent right adrenalectomy with the removal of a pheochromocytoma at the age of sixteen. Ten years later, a suspicion of pheochromocytoma in the remaining left adrenal was raised. Mutation in the RET proto-oncogene was confirmed as well. The patient first underwent left adrenalectomy and then she had total thyroidectomy. Postoperative histopathological examinations revealed pheochromocytoma and medullary carcinoma. Case 3: Radiological and biochemical examination confirmed pheochromocytoma. Therefore, the two adrenals were removed. As mutation in codon 634 was detected, the patient underwent total thyroidectomy as well. The presence of medullary carcinoma was confirmed. CONCLUSIONS Pheochromocytoma is a rare and potentially lethal disease if a catecholamine crisis develops. Its recognition requires further investigation towards genetic syndromes, particularly MEN 2A.

Parathyroid cancer - difficult diagnosis - a case report.

Parathyroid cancer is a rare disorder of unclear etiology that is difficult to diagnose and treat. It is most often diagnosed incidentally based on multi-organ non-specific symptoms of hypercalcemia as a consequence of parathyroid hormone oversecretion. We present a case of a male with primary hyperparathyroidism who was diagnosed with parathyroid cancer ectopically located in the mediastinum only after the third surgery. However, due to chronic hypercalcemia, problems with localization and a bad clinical condition, the patient was not able to undergo a radical resection and one year after the first pathological fracture died. Taking into consideration the whole clinical picture we want to emphasize the need to apply comprehensive differential diagnosis of hypercalcemia and localization diagnosis of parathyroid tissue with a use of MIBI scintigraphy accompanied by the computed tomography and magnetic resonance imaging, as the most specific diagnostic tools employed in this pathology.