scholarly journals Relationship between Reduced BCL-2 Expression in Circulating Mononuclear Cells and Early Nephropathy in Type 1 Diabetes

2005 ◽  
Vol 18 (4) ◽  
pp. 625-635 ◽  
Author(s):  
F. Cipollone ◽  
F. Chiarelli ◽  
A. Iezzi ◽  
M.L. Fazia ◽  
C. Cuccurullo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Vitamin E ◽  
Glycemic Control ◽  
Mononuclear Cells ◽  
Diabetic Patients ◽  
Down Regulation ◽  
Inflammatory Status

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.

scholarly journals Metabolic Syndrome in Type 1 Diabetes: Association with diabetic nephropathy and glycemic control (the FinnDiane study)

Diabetes Care ◽  
2005 ◽  
Vol 28 (8) ◽  
pp. 2019-2024 ◽  
Author(s):  
L. M. Thorn ◽  
C. Forsblom ◽  
J. Fagerudd ◽  
M. C. Thomas ◽  
K. Pettersson-Fernholm ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycemic Control

scholarly journals Circulating and cell-bound antibodies increase coxsackievirus B4-induced production of IFN-α by peripheral blood mononuclear cells from patients with type 1 diabetes

2002 ◽  
Vol 83 (9) ◽  
pp. 2169-2176 ◽  
Author(s):  
Didier Hober ◽  
Wassim Chehadeh ◽  
Jacques Weill ◽  
Christine Hober ◽  
Marie-Christine Vantyghem ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Coxsackievirus B4 ◽  
Blood Mononuclear Cells

Increased levels of IFN-α have been found in patients with type 1 diabetes who have detectable levels of coxsackievirus B4 (CVB4) RNA in their blood. The IFN-α-inducing activity of CVB4 in vitro is weak but can be enhanced by human IgGs. Therefore, it was investigated in vitro whether a preferential IFN-α response of peripheral blood mononuclear cells (PBMCs) to CVB4 exists in patients with type 1 diabetes (n=56) compared with healthy subjects (n=20) and whether antibodies play a role. In patients, the levels of IFN-α obtained after stimulation by PBMCs with CVB4 were higher (P=0·008), an individual IFN-α response by PBMCs to CVB4 was more frequent (P=0·0004) and increased levels of IFN-α were observed in CVB4-infected whole blood cultures. The IFN-α-inducing activity of patients plasma and IgGs mixed with CVB4 and then added to PBMCs was high in comparison with healthy subjects (P<0·001) and was inhibited by preincubating the cells with anti-FcγRII, anti-FcγRIII and anti-CAR (coxsackievirus and adenovirus receptor) antibodies. The strong IFN-α responsiveness of PBMCs to CVB4 suggested that IgGs bound to the cell surface might play a role. A short 56 °C incubation of PBMCs from patients responsive to CVB4 generated supernatants, which, when added to cells, exhibited IFN-α-enhancing activity in combination with CVB4, whereas those of controls did not. Specific antibodies for FcγRI, FcγRII and CAR inhibited this activity. These studies demonstrate that CVB4, through interactions with circulating and/or cell-bound IgGs, can strongly induce the production of IFN-α by PBMCs from patients with type 1 diabetes.

scholarly journals Human Mesenchymal Stem Cells Modulate Cellular Immune Response to Islet Antigen Glutamic Acid Decarboxylase in Type 1 Diabetes

2010 ◽  
Vol 95 (8) ◽  
pp. 3788-3797 ◽  
Author(s):  
Maria M. Zanone ◽  
Enrica Favaro ◽  
Ilaria Miceli ◽  
Giorgio Grassi ◽  
Elisa Camussi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Acid Decarboxylase ◽  
Diabetic Patients ◽  
Human Mscs ◽  
T Helper ◽  
Ifn Γ ◽  
Islet Antigen ◽  
Helper Type

Context: Mesenchymal stem cells (MSCs) exert an immunosuppressive effect on the immune system. However, studies on the immunomodulatory potential of MSCs in type 1 diabetes are lacking. Objective: We aimed to evaluate whether human MSCs may inhibit in vitro pancreatic islet antigen-specific T cell activation in type 1 diabetes. Design: Human MSCs were isolated and characterized. Peripheral blood mononuclear cells (PBMCs) were obtained from nine type 1 diabetic patients at disease onset and 13 healthy control subjects. IFN-γ, IL-10, and IL-4 enzyme-linked immunospot responses of lymphocytes incubated with glutamic acid decarboxylase 65 (GAD65) were investigated in PBMC cultures and PBMC/MSC cocultures. Levels of prostaglandin E2 (PGE2), IFN-γ, IL-4, and IL-10 in supernatants were measured by ELISA. PGE2 inhibition experiments with NS-398 and indomethacin were also performed. Results: Five diabetic patients were identified with a positive PBMC IFN-γ response to GAD65 and negative IL-10 and IL-4 response. PBMC/MSC cocultures resulted in a significant decrease in the number of spots and in detection of IL-4-secreting cells. PGE2 inhibitors abrogated the immune-suppressive effect, indicating an involvement of PGE2 production, and the constitutive production of PGE2 by MSCs was enhanced in PBMC/MSC coculture. Moreover, in GAD-responder patients, GAD-stimulated PBMC/MSC cocultures significantly decreased secretion of IFN-γ and IL-10 and increased secretion of IL-4. Conclusions: These results provide evidence that human MSCs abrogate in vitro a proinflammatory T helper type 1 response to an islet antigenic stimulus in type 1 diabetes. MSCs induce IL-4-producing cells, suggesting a possible switch to an antiinflammatory T helper type 2 signaling of T cells.

scholarly journals Effect of metabolic control on the in vitro proliferation of peripheral blood mononuclear cells in type 1 and type 2 diabetic patients

2006 ◽  
Vol 124 (4) ◽  
pp. 219-222 ◽  
Author(s):  
Maria Cristina Foss-Freitas ◽  
Norma Tiraboschi Foss ◽  
Eduardo Antonio Donadi ◽  
Milton Cesar Foss
Keyword(s):  
Metabolic Control ◽  
Mononuclear Cells ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
In Vitro Proliferation ◽  
Peripheral Blood Mononuclear ◽  
Type 2 Diabetic

CONTEXT AND OBJECTIVE: Diabetes mellitus is a clinical syndrome that frequently leads to the development of chronic complications and high susceptibility to infections. It is probably due to defective immunological defense, which may be related to metabolic control of the disease. The aim of this study was to evaluate the effect of metabolic control on immune-cell behavior in type 1 and type 2 diabetic patients. For this, the in vitro proliferation of peripheral blood mononuclear cells (PBMC) was analyzed in patients with inadequate and adequate metabolic control. DESIGN AND SETTING: Experimental/laboratory study at a university hospital. METHODS: Eleven type 1 and thirteen type 2 diabetic patients were studied, together with 21 healthy individuals divided in two groups (11/10), who were matched by sex and age with those diabetic patients. PBMC cultures stimulated with concanavalin-A (Con-A) were used to measure ³H-thymidine incorporation after 72 hours of cell culturing. For patients with inadequate metabolic control, culturing was performed on the first day of patient hospitalization and again after intensive treatment to achieve adequate control. RESULTS: The proliferation index for Con-A-stimulated cultures from type 1 diabetic patients was significantly greater than that for cultures from healthy individuals and type 2 diabetic patients, independent of metabolic control. A negative correlation between the proliferation cell index and body mass index and serum C-reactive protein levels was also observed. CONCLUSION: The increase in the proliferation capacity of type 1 diabetic T lymphocytes was probably not caused by hyperglycemia and/or insulinopenia related to inadequate metabolic control.

scholarly journals Evaluation of Microalbuminuria and Glycosylated Hemoglobin in the Assessment of Diabetes Control in Children with Type 1 Diabetes Mellitus Hospitalized with Diabetic Ketoacidosis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Saiprasad Onkareshwar Kavthekar ◽  
Vijay Tukaram Mali ◽  
Sachin Verma ◽  
Anil Bapurao Kurane ◽  
Nivedita Balasaheb Patil ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Hba1c Level ◽  
Glycosylated Hemoglobin ◽  
Duration Of Diabetes ◽  
Hba1c Control

Background: Microalbuminuria is thought to be an early predictor of impending diabetic nephropathy, while glycosylated hemoglobin (HbA1c) is a biochemical marker of long-term glycemic control in children with type 1 diabetes mellitus (T1DM). Objectives: The study aimed to evaluate the prevalence of microalbuminuria and its association with HbA1c on admission and duration of diabetes. Also, changes in HbA1c level on admission and three months after admission were studied to assess diabetes control in children with T1DM. Methods: This prospective study was conducted among 38 children (< 18 years) diagnosed with TIDM presenting with clinical signs, symptoms, and biochemical parameters of DKA. The presence of microalbuminuria, HbA1c level, and the number of past episodes of DKA were recorded. HbA1c level was again estimated after three months. The resultant data was tabulated and analyzed statistically (P < 0.05). Results: Microalbuminuria and poor HbA1c control were observed in 18% and 60% of the sample population, respectively. A significant association was found between HbA1c > 9% (P = 0.032) and the duration of diabetes > 4 years (P = 0.032) and microalbuminuria. Significant improvement in glycemic control was noted from the time of admission to three months after admission (9.76 ± 2.77 vs. 7.75 ± 1.28; P = 0.00012). A significant difference was observed between past DKA episodes according to HbA1c control (P < 0.001). Conclusions: Microalbuminuria assessment is needed in T1DM children, especially those with HbA1c > 9% and duration of diabetes > four years, to evaluate diabetic nephropathy. Good glycemic control can be achieved with effective insulin therapy accompanied by appropriate counseling and regular follow-up.

scholarly journals Diabetes mellitus type 1 in children and adolescents in Moscow. Data from the Moscow Segment of the Federal Register of Diabetic Patients 2015–2020

2021 ◽  
Vol 67 (6) ◽  
pp. 113-123
Author(s):  
E. E. Petryaykina ◽  
D. N. Laptev ◽  
I. G. Vorontsova ◽  
N. A. Demidov ◽  
Yu. А. Ryapolova
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Children And Adolescents ◽  
Incidence Rates ◽  
Diabetic Coma ◽  
Simultaneous Increase ◽  
Diabetic Patients ◽  
Federal Register

BACKGROUND: Therapy for type 1 diabetes mellitus (T1DM) is still largely an unsolved clinical problem. Despite the introduction into clinical practice of modern insulin preparations, devices for its administration, as well as continuous monitoring of glucose levels, the goals of therapy are often not achieved. At the same time, the International Diabetes Federation (IDF) notes an increase in the prevalence and incidence of T1DM in children and adolescents in the world. The Federal Register of Diabetes Mellitus (FRDM) is a dynamically updated database of patients with diabetes, which allows assessing prevalence and incidence rates, achievement of glycemic control goals and the incidence of diabetes complications.AIM: analyze the epidemiological data of T1DM (prevalence, morbidity) in children and adolescents (patients from birth to 18 years of age) in Moscow according to the FRSD data and to assess their dynamics, as well as the dynamics of achieving the goals of glycemic control and the incidence of T1DM complications in 2015-2020.MATERIALS AND METHODS: The object of the study is a sample from the database of the Moscow segment of the FRDM of a cohort of patients with type 1 diabetes under 18 years of age who were registered for the period 01.01.2015-01.01.2021. Epidemiological prevalence and incidence rates are calculated per 100,000 of the relevant population.RESULTS: the number of children and adolescents with type 1 diabetes in Moscow as of 01.01.2021 was 4024 people (2962 children and 1062 adolescents). Over the period from 2015 to 2020, there was an increase in the prevalence of T1DM (possibly due to an increase in the quality of data registration in the FRSD) and a decrease in the incidence of both children and adolescents. There was also a decrease in the level of HbA1c and the proportion of patients with HbAc1> 8.0% among children with T1DM. Both children and adolescents with T1DM showed a decrease in the incidence of diabetic coma and ketoacidosis with a simultaneous increase in the incidence of severe hypoglycemia, as well as a decrease in the incidence of retinopathy and nephropathy. However, the incidence of neuropathy decreased among children and increased among adolescents.CONCLUSION: The data obtained on the dynamic management of adolescents with T1DM are the basis for considering the development of a profile program for their dynamic observation, taking into account the need for psychological and social support for patients and their families.

Gastrointestinal symptoms in pediatric patients with type 1 diabetes mellitus

2020 ◽  
Vol 33 (2) ◽  
pp. 185-190
Author(s):  
Suna Selbuz ◽  
Ayşe Derya Buluş
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Abdominal Pain ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Pediatric Patients ◽  
Stool Examination ◽  
Diabetic Patients ◽  
Gi Symptoms

AbstractBackgroundVarious gastrointestinal (GI) symptoms are associated with diabetes. Common GI complaints associated with the manifestation of the disease include abdominal pain, diarrhea, nausea, bloating and vomiting. There have been very few studies examining GI problems of pediatric patients with type 1 diabetes mellitus (T1DM). The aims of this study were to find out the prevalence of GI symptoms in pediatric patients with T1DM and to determine the correlation among such symptoms, duration of diabetes and glycemic control.MethodsOne hundred and thirty-seven (median age 13.2 years, female 45.3%) patients with T1DM were examined. Demographic features, GI symptoms, signs and physical examination findings of the patients were recorded by pediatric gastroenterology specialists for the differential diagnosis and exclusion of other etiologies. Complete blood count, blood glucose, lipid profile, electrolytes, amylase, lipase, celiac antibodies and glycated hemoglobin (HbA1c) levels were evaluated and stool examination was performed. Endoscopy was performed on the patients who had refractory GI complaints. Gastric emptying (GE) time was evaluated using GE scintigraphy.ResultsOverall, 74 (54%) patients had ≥1 GI complaints. Patients often reported gastroesophageal reflux (32.8%) and abdominal pain (18%). The most significant findings in terms of GI symptoms were determined when patients were classified according to the glycemic control status. Reflux and dyspeptic symptoms were significantly more common in poorly or very poorly controlled diabetic patients (p=0.003 and p=0.004, respectively).ConclusionsDiabetes can affect the entire GI tract, and GI symptoms are common in pediatric patients. We recommend that T1DM patients be evaluated for GI symptoms.

scholarly journals Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

2021 ◽  
Vol 22 (13) ◽  
pp. 7032
Author(s):  
Ornella Bosco ◽  
Barbara Vizio ◽  
Gabriella Gruden ◽  
Martina Schiavello ◽  
Bartolomeo Lorenzati ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Platelet Activation ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Potential Contribution ◽  
Atherosclerotic Cardiovascular Disease

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.

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