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1.
Minerva Pediatr ; 62(6): 551-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21042267

ABSTRACT

AIM: In 32 juvenile patients suffering from insulin dependent diabetes we observed a carnitine imbalance (increase in acylcarnitine and reduction of free carnitine), which was higher in patients with the highest levels of glycosylated hemoglobin. Parallel to that, in patients with the most prominent carnitine imbalance, there was the highest increase in the postprandial lactic acid level and the highest increase in the lactate/pyruvate ratio, without relating to ketosis. In addition, we observed a decrease in free carnitine related to the length of time after appearance of diabetes. METHODS: This was a prospective study of a cohort of 32 children and young adolescents with insulin dependent diabetes mellitus. All patients were on insulin treatment. Plasma concentrations of total, free and acyl-Carnitine were evaluated in 12 hours fasting blood samples and before the morning administration of insulin. Blood glucose, cholesterol, triglycerides, and lactate, pyruvate, beta-hydroxybutyrate and free fatty acid levels were measured. RESULTS: The postprandial highest increase of the lactate and lactate/pyruvate ratio observed in patients with the highest degree of carnitine imbalance, namely with poorliest regulated diabetes, raises the question of a coincidental mitochondrial dysfunction. On the ground of our own data, such a claim cannot be substantiated for our patients. In contrast we suggest that the role of other factors like increased gluconeogenesis, degree of ketosis need to be sought. CONCLUSION: In order to clarify the role of carnitine in the pathophysiology of disease we need also data from other tissues. Carnitine in the peripheral blood reflects only the 1% of the total body carnitine ; furthermore, patients with diabetes exhibit changes in carnitine status not only in the peripheral blood but also in other body tissues, mainly in muscles.


Subject(s)
Carnitine/blood , Diabetes Mellitus, Type 1/blood , Lactic Acid/blood , Adolescent , Child , Child, Preschool , Female , Humans , Male , Prospective Studies
2.
Exp Clin Endocrinol Diabetes ; 118(1): 38-46, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19834879

ABSTRACT

BACKGROUND: CD40 signalling has been associated with the pathogenesis of autoimmune diseases and diseases with low-grade chronic inflammation. OBJECTIVE: To investigate, early in the course of type 1 diabetes (T1DM) patients, the expression of CD40 system components, as well as to explore the association of plasma and urine concentrations of CD40 with known inflammatory markers in T1DM. METHODS: Plasma, urine and peripheral blood mononuclear cells (PBMCs) from 70 T1DM patients without clinically detected chronic complications and 40 healthy controls (HCs) were examined using ELISA, western-blot, semi-quantitative RT-PCR and DNA-sequencing. RESULTS: Patients had significantly higher plasma soluble CD40 (sCD40) levels associated with higher Interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9) and CRP levels compared with healthy controls. This difference was also evident between poorly and well-controlled diabetic patients. The elevated plasma sCD40 levels do not appear to be due to diminished renal excretion since sCD40 concentrations in the urine were also elevated, suggesting an increased CD40 production. An upregulation of PBMCs' CD40 was evident in T1DM patients associated with higher sCD40, IL-6 and CRP levels. Furthermore, the main CD40 isoform (isoform-I) was solely expressed in poorly controlled diabetics' PBMCs, who also demonstrated cellular CD40 upregulation, higher plasma CD40, CRP, IL-6 and MMP-9 levels compared with the well-controlled diabetics and the control group, who co-expressed type I and II isoforms. CONCLUSIONS: Homeostatic dysregulation of CD40 and its association with inflammatory markers in T1DM patients, especially in those with poor glycaemic control, implies a pathophysiological role of CD40 in the low-grade inflammatory process in T1DM.


Subject(s)
CD40 Antigens/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/immunology , Gene Expression Regulation , Inflammation/metabolism , Leukocytes, Mononuclear/metabolism , RNA, Messenger/metabolism , Adolescent , Alternative Splicing , Biomarkers/blood , C-Reactive Protein/analysis , CD40 Antigens/blood , CD40 Antigens/genetics , CD40 Antigens/urine , Cells, Cultured , Child , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/metabolism , Disease Progression , Female , Greece , Humans , Hyperglycemia/blood , Inflammation/blood , Inflammation/complications , Insulin/administration & dosage , Insulin/therapeutic use , Interleukin-6/blood , Male , Matrix Metalloproteinase 9/blood , Protein Isoforms/blood , Protein Isoforms/genetics , RNA, Messenger/chemistry
3.
Diabet Med ; 21(4): 380-2, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15049943

ABSTRACT

The lipoprotein lipase coding gene sequence was analysed on a 10-year-old girl with new-onset Type 1 diabetes mellitus (DM), ketoacidosis and severe hypertriglyceridaemia (TG > 112.9 mmol/l), revealing that the patient was a compound heterozygote for two mutations, D9N in exon 2 and S447X in exon 9. Although these two mutations usually do not considerably impair lipolytic enzyme activity, the combination of both in this patient may play a role in the development of severe hypertriglyceridaemia.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetic Ketoacidosis/blood , Triglycerides/blood , Child , Diabetes Mellitus, Type 1/genetics , Diabetic Ketoacidosis/genetics , Family Health , Female , Heterozygote , Humans , Lipoprotein Lipase/deficiency , Mutation/genetics , Pedigree
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