Glucose metabolism disorders influence anticarcinogenic function of natural killer (NK) cells. The aim of this study was to evaluate the number and cytotoxic activity of NK cells in type 2 diabetic (T2D) patients with negative family history of cancer, type 2 diabetic subjects with newly diagnosed untreated colon cancer (T2DCC) and patients without type 2 diabetes with newly diagnosed, untreated colon cancer (CC). Incubation tests were performed in 18 T2D patients, treated with diet and oral antidiabetic agents, 16 T2DCC; cT1-4N0M0 (c-clinical diagnosis based on computed tomography, colonoscopy and histopathology) treated with diet and oral antidiabetic agents and 16 normoglycemic CC; cT1-4N0M0. Control group included 18 metabolically healthy (with normal fasting glucose and normal glucose tolerance) subjects (HS) with negative family history of cancer, matched by age, BMI and waist circumference. Peripheral blood mononuclear cells were isolated by means of gradient centrifugation. The K562 human erythroleukemia cell line served as the standard target for human NK cytotoxicity assay. The T2D revealed an increased number of NK cells (13.56 ± 5.9 vs 9.50 ± 4.8 %; p < 0.05) when compared with HS, yet these cells had a decreased activity (3.3 ± 2.5 vs 9.4 ± 3.6 %; p < 0.01). The CC demonstrated a decreased activity (2.9 ± 1.8 %; p < 0.01) but a similar number (8.82 ± 3.7 %; not significant) of NK cells when compared to HS. The T2DCC NK cells were characterized by trace cytotoxic activity (1.1 ± 0.7 %; p < 0.01) and nearly three times greater amount (21.24 ± 7.5 %; p < 0.01) when compared to T2D. Type 2 diabetes and CC are associated with disadvantageous alterations of NK cells, leading to impairment in their cytotoxic activity. The impaired activity of NK cells in T2D can be involved in the increased carcinogenic risk and can promote a higher incidence of CC.
BackgroundType 2 diabetes (T2D) and colon cancer (CC) are numbered among the most common diseases in the world. The decreased activity of natural killer (NK) cells previously revealed in both mentioned pathological states may be correlated with impaired expression of GLUT4 as the major insulin-dependent glucose transporter in these cells.MethodsThe aim of this study was to evaluate GLUT4 expression and NK cells number in subjects with T2D and/or CC in comparison with control group. We evaluated 78 individuals divided into four groups: (1) patients with CC and T2DM, (2) patients with CC, (3) patients with T2DM (4) healthy control. GLUT4 expression on the surface of NK cells was measured using flow cytometry and phenotyping of NK cell was performed by immunofluorescent method.ResultsSubjects with diabetes had the highest GLUT4 expression (21.35 ± 7.2 %) in comparison with other groups (P < 0.01). The mean values of GLUT4 expression in group with CC and in patients with both T2D and CC were similar (1.4 ± 0.4 % vs 1.5 ± 1.0 %; respectively). These values were significantly lower than in control group (12.6 ± 2.9 %; P < 0.01). In patients with T2D and CC the number of NK cells (20.15 ± 6.6 %) was significantly higher than in other groups, i.e. in group with T2D (14.08 ± 5.7 %), in group with CC (9.21 ± 3.6 %) and in control group (9.48 ± 4.7 %), respectively (P < 0.01).ConclusionsIt seems that there is a need to pay more attention to the high incidence of colon cancer among patients with type 2 diabetes. Decreased GLUT4 expression observed on NK cells in patients with colon cancer may be responsible for dysfunction of these cells and the higher carcinogenic risk in type 2 diabetic subjects.
A b s t r a c tBackground: Hypoglycaemia is a condition that occurs when blood glucose levels fall below 3.9 mmol/L (70 mg/dL), while hypoglycaemic coma is usually associated with glycaemia around 1.1 mmol/L (20 mg/dL). Recurrent severe hypoglycaemia may result in permanent neurological disorders and also has a negative impact on the cardiovascular system. Aim:To evaluate the causes of severe hypoglycaemia in elderly patients with type 2 diabetes and coexistence of cardiovascular history. Methods:We analysed retrospectively the history of 33 elderly patients with type 2 diabetes and coexistence of cardiovascular history, who were admitted to our clinic due to severe hypoglycaemia with loss of consciousness. The mean age of the patients was 76.0 ± 11.1 years, and the mean duration of diabetes was 12.0 ± 9.8 years. Glycated haemoglobin (HbA1c) was measured and the prevalence of cardiovascular diseases and therapeutic procedures were evaluated. Results:In the group of patients with severe hypoglycaemia, the mean value of HbA1c was 6.3 ± 1.2% (44 ± 13.1 mmol/mol), which indicates a mean glucose value below 7.8 mmol/L (140 mg/dL). Ischaemic heart disease was diagnosed in 18 patients (eight had a history of myocardial infarction), and 22 patients had arterial hypertension. Severe hypoglycaemia requiring hospitalisation in elderly patients with type 2 diabetes and coexistence of cardiovascular history was related to insulin or sulfonylurea therapy. Conclusions:A low HbA1c level indicates inappropriate intensification of therapy and was associated with high risk of severe hypoglycaemic episodes in older people. The majority of severe hypoglycaemic episodes were observed in sulphonylurea or insulin-treated type 2 diabetic patients.
Introduction. Diabetes is a growing social and epidemiological problem. Accordingly, the incidence of complications associated with diabetes can cause a persistent high percentage of diseases of the cardiovascular system, kidney and nervous systems, and impaired vision. Objective. The aim of the study was to evaluate the incidence of immunological markers in patients with type 1 diabetes and those with type 2 diabetes: the anti-GAD, ANA, AMA, ASMA, APCA and LKM, compared to healthy people. Another objective of the study was to evaluate the correlation between their presence and the degree of metabolic control in both groups. Materials and methods. The study comprised 100 subjects aged 25-75 years with a body mass index (BMI) between 20-30 kg / m2, hospitalized in the Department of Internal Diseases, Diabetology and Endocrinology, at the Medical University of Warsaw, with previously diagnosed diabetes who were assigned to one of 2 groups (50 subjects with type 1 diabetes and 50 subjects with type 2 diabetes). The control group consisted of 21 healthy individuals without the diagnosis of diabetes and a prediabetic state. All the study participants had the examined antibodies determined along with the panel of biochemical tests and neurological examination for diabetic neuropathy and fundus examination. Results. Anti-GAD antibodies were present in both groups of patients. Their presence was found in 30% of people with type 1 diabetes and in 16% of people with diabetes type 2. The presence of ANA antibodies was found in 24% of people with type 1 diabetes and 22% of people with type 2 diabetes. There was no correlation between the presence of ANA antibodies ANA and duration of diabetes. In the group of patients with type 1 diabetes, there was a correlation between the presence of ANA and the incidence of diabetic polyneuropathy. ASMA and APCA antibodies occurred with equal frequency in both studied groups (4% vs. 10%). There were no antibodies of AMA or anti-LKM in any of the patients. Conclusions. Marking of ANA antibodies in patients with type 1 diabetes may be a marker used to isolate a group of patients at risk of developing diabetic neuropathy. The presence of anti-GAD in type 2 diabetes may be a LADA marker which specifically marks the group of patients with type 2 diabetes, in whom there is a faster metabolic death of beta cells. The current classification of diabetes is vague, and in the near future it should be modified based on specific patient characteristics, phenotypic appearance, as well as the results of additional tests. Determination of antibodies AMA, ASMA, APCA and anti-LKM does not seem to be significant in the diagnosis of diabetes and its chronic complications.
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