AIMS: Glycaemic variability (GV) has been hypothesized to increase the risk of diabetes complications; however, results of clinical studies are contradictory. The effect of GV on cell phenotypes has been investigated in vitro showing that GV may have more deleterious effect on cells that high glucose itself. However, methodology used to study GV in vitro differs significantly between studies and does not reflect in vivo situation. Therefore we aimed to establish clinically relevant an in vitro experimental approach for the study of GV that reflects intra-day glucose fluctuations of subjects with type 1 diabetes mellitus (T1DM) and of healthy subjects and to test how low and high GV affect expression of genes that protects cells from hyperglycaemia-induced damage. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured 24h in medium with different glucose profiles: high GV, low GV and GV of healthy subjects-profiles created according to CGM of T1DM patients and healthy subjects. These profiles were compared to commonly used 5.5 and 25mmol/l glucose concentrations. Gene expression was determined using quantitative PCR. RESULTS: Our results showed general down-regulation of enzymes that are involved in the protection against hyperglycaemia-induced intracellular changes in both low and high GV compared to normal glycaemia similarly to the decrease induced by continuous hyperglycaemia. Gene expressions did not differ between high and low GV. CONCLUSION: Our data indicate that GV may have similar or even greater effect than continuous hyperglycaemia on the expression of several genes relevant to pathogenesis of diabetes microvascular complications.

• MeSH
• Apoptosis drug effects   MeSH
• Biomarkers metabolism   MeSH
• Diabetes Mellitus, Type 1 complications   drug therapy   physiopathology   MeSH
• Human Umbilical Vein Endothelial Cells drug effects   metabolism   MeSH
• Glucose adverse effects   MeSH
• Hyperglycemia etiology   pathology   MeSH
• Hypoglycemia etiology   pathology   MeSH
• Blood Glucose metabolism   MeSH
• Cells, Cultured MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• RNA, Messenger genetics   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Cell Proliferation drug effects   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• In Vitro Techniques MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

V následující kazuistice uvádíme případ 54letého nemocného s diabetem 2. typu původně léčeného derivátem sulfonylurey hospitalizovaného pro těžkou a protrahovanou hypoglykemickou epizodu. Vlastní léčba hypoglykemie proběhla bez pozoruhodností, ale pátrání po příčině rozvoje hypoglykemie bylo diferenciálně diagnosticky velmi zajímavé. Některé klinické příznaky malabsorpčního syndromu byly u nemocného kombinovány s déletrvajícími subfebriliemi a při známém hematoonkologickém onemocnění nemocného bylo pátráno po možné infekční příčině průjmů či progrese základního onkologického onemocnění. Provedená kultivační vyšetření a zobrazovací metody tyto alternativy vyloučily. Pro přítomnou anemii a gastrointestinální obtíže byla provedena endoskopie horního GITu s nálezem lymfostázy v tenkém střevě. Diferenciální diagnó-za intestinální lymfangiektázie nabízela možnost aktivně probíhajícího lymfomu, kterým pacient trpěl, ale onkologický nález nemocného se jevil jako stabilizovaný. Další možností diferenciální diagnózy byla Whippleova choroba, která byla histologickým vyšetřením vzorku tkáně sliznice i metodou PCR potvrzena. Vznik hypoglykemické epizody při zavedené léčbě diabetu 2. typu souvisel s rozvojem malabsorpčního syndromu při Whippleově chorobě, který podmínil pokles hmotnosti nemocného a současné razantní snížení inzulínové rezistence nemocného. Za této situace původně adekvát-ně nastavená léčba diabetu vedla u nemocného k rozvoji hypoglykemie. Malabsorpční syndrom na podkladě lymfangiektázie střevní sliznice u osoby již léčené pro maligní lymfom vyžadoval vyloučení progrese tohoto onemocnění, ale současně při známém imunodeficitu nemocného a přítomnosti seronegativní artritidy nutil k zamyšlení i nad možností Whippleovy choroby.

In the following case report we present a case of a 54years old patient with type 2 diabetes mellitus, who was formerly treated with sulphonylurea derivate and hospitalized for severe and prolonged hypoglycemic episode. The treatment of hypoglycemia itself was unremarkable but the search for the cause of hypoglycemia was very interesting from the differential diagnostic point of view. Some clinical signs of malabsorption syndrome were combined with prolonged subfebrile temperatures and because of a known patient’s hematooncology disease it was searched for a possible infective cause of diarrhea or for a progression of the underlying oncology disease. The cultivation and imaging methods ruled out these possibilities. Because of anemia and gastrointestinal problems the endoscopy of upper gastrointenstinal tract was performed with a finding of lymphostasis in the small intestine, the differential diagnosis of intestinal lymphangiectasia offered the possibility of active lymphoma, which the patient suffered from, but the patient’s oncology status appeared to be stable. Other differential diagnostic possibility was the Whipple’s disease that was proved both by histology of mucosal tissue sample and by PCR. The occurrence of hypoglycemic episode during the established treatment of type 2 diabetes mellitus was associated with the development of the malabsorption syndrome in Whipple’s disease that caused the weight loss and simultaneously the significant decrease of the insulin resistance in the patient. In this situation the previously adequate treatment of diabetes mellitus led to hypoglycemic episode in the patient. The malabsorption syndrome caused by the lymphangiectasia of the intestinal mucosa in the patient, who was already treated for the malignant lymphoma, required the exclusion of the progression of the lymphoma, but in the known immunodeficiency and the presence of the seronegative arthritis it simultaneously forced to consider the possibility of the Whipple’s disease.

• MeSH
• Diabetes Mellitus, Type 2 drug therapy   complications   MeSH
• Diagnosis, Differential MeSH
• Lymphoma, Large B-Cell, Diffuse MeSH
• Weight Loss MeSH
• Hypoglycemia * etiology   chemically induced   MeSH
• Arthritis, Infectious etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malabsorption Syndromes etiology   MeSH
• Diarrhea etiology   MeSH
• Lymphangiectasis, Intestinal diagnosis   physiopathology   pathology   MeSH
• Intestinal Mucosa pathology   MeSH
• Intestine, Small pathology   MeSH
• Whipple Disease * diagnosis   drug therapy   physiopathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH