scholarly journals Relation of Pancreatic Iron Overload Detected By MRI with Disorders of Glucose Metabolism and Results of Liver, Cardiac and Pitutiary MRI Among Transfusion Dependent Thalassemia (TDT) Patients in Turkey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2350-2350
Author(s):  
Zeynep Karakas ◽  
Cihangir Sevimli ◽  
Nurdan Gul ◽  
Rana Comert ◽  
Memduh Dursun

Abstract The relationship between pancreatic iron overload and glucose dysregulation has not been well defined and need further investigation. Pancreas iron load measurements are also necessary to understand how hepatic, pancreatic, and cardiac iron burden prospectively modulate the evolution of diabetes in transfusion dependent thalassemia (TDT). Aim: This study aims to evaluate the presence of pancreatic iron overload among TDT patients in Turkey based on the MRI R2* and T2* results as well as to determine its association to Fasting blood glucose (FBG), insulin, fructosamine, Homa-IR, C-peptide, ferritin, liver, cardiac and hypophysis MRI R2* results. Material and Methods: This study was conducted at the Thalassemia Center in Istanbul University, Istanbul Medical Faculty. Forty-one TDT patients included the study with a mean age of 29.9±9,9 (median 29) years old, ranging from 11 to 45 years old. Pancreatic, liver, cardiac and hypophsis MRI's were conducted using 1.5 Tesla Philips MRI machine in the Department of Radiology. Pancreatic MRI R2* results < 30 Hz were considered normal, 30-100 Hz as mild, and > 100 Hz as moderate to severe pancreatic siderosis. Pancreatic MRI T2 results >26 ms were is normal, < 10 ms is severe iron overload as presented at literature. Correlations between pancreatic MRI R2* results and FBG, insulin, fructosamine, Homa-IR, C-peptide, ferritin, cardiac and hypophysis MRI R2* were evaluated using the Pearson correlation, Man Whitney U test. Results: Laboratory findings of glucose metabolism and MRI's of liver, pancreas, hypophsis and cardiac iron are shown at Table 1. There were no significant relationship between fasting blood glucose, insülin, C-peptid level, fructosamine, Homa-IR, ferritin and Pancreas T2* and R2* results (p>0.05). There was significant correlation between liver and pancreas MRI T2* and R2* results. (p<0.01). There was no significant correlation between hypophysis global R2, cardiac R2*, Pancreas T2* and, Pancreas R2* measurements (p>0.05). Fourteen patients were found to have normal pancreatic MRI R2* (34,1%) while 19 patients have normal pancreatic MRI T2 (46.3%). It is reported that T2 is irrelevant to age and sex, and R2 can be related to age-related fatty degeneration. There was significant pancreatic iron burden in 31.7% of patients (R2*>100 Hz), of whom only 1 patient was under 18 years of age.There were 22 (53.6%) patients with T2* <26 ms and had iron overload, 13 (31.7%) had T2 <10 ms and had significant iron overload. Almost three-quarters of patients (n:13, 31.7%) had moderate to severe pancreatic iron load on both T2* and R2* measurements. Thirteen patients with significant pancreatic iron overload had 3 severe hypophysis, 1 moderate, 2 severe cardiac siderosis. and had no serious liver iron burden. This shows that the treatment of chelation first led to liver, then heart and pituitary, respectively, and finally pancreatic iron burden and demonstrates the importance of pancreas MR in assessing the body iron load. Discussion:The lack of correlation between pancreatic and cardiac MRI R2* are in contrast to another demonstrating that pancreatic iron load are good predictors of cardiac iron load. This is due to the fact that our patients are followed up with cardiac MR and taken to the intensive chelation programs of the patients who detect iron in the heart. Previous studies also report that while pancreatic R2* may be sensitive for glucose dysregulation, most patients may still have no symptoms and normal blood glucose, indicating the presence of a preclinical iron burden. Pancreatic MRI R2* can detect pancreatic iron accumulation at a much earlier stage. Lack of excessive iron load in liver of our patient can be explain low glucose metabolism disorder despite high pancreatic iron overload. Disclosures No relevant conflicts of interest to declare.

2016 ◽  
Vol 38 (4) ◽  
pp. 155
Author(s):  
Elsi Kelana ◽  
Ellyza Nasrul ◽  
Rismawati Yaswir ◽  
Desywar Desywar

AbstrakResistensi insulin merupakan penurunan respons biologis jaringan terhadap insulin dalam kadar normal. Pada DM tipe 2 terjadi resistensi dan gangguan sekresi insulin. Terdapat indeks baru 20/(C-peptide puasa x glukosa darah puasa) untuk menilai resistensi sekaligus gangguan sekresi insulin. Penelitian bertujuan membuktikan korelasi indeks 20/(C-peptide puasa x glukosa darah puasa) dengan HOMA-IR untuk menilai resistensi insulin pada DM tipe 2 di RSUP. Dr. M. Djamil Padang. Dengan menggunakan sampel darah dari pasien, kadar glukosa darah puasa, insulin puasa dan C-peptide puasa ditentukan. Data yang diperoleh kemudian dianalisis menggunakan korelasi Pearson. Hasil penelitian menunjukkan rerata kadar glukosa puasa 9,83 (3,53) mmol/L [177 (63,54) mg/dL], insulin puasa 10,58 (3,61) μU/L, dan C-peptide puasa 0,97 (0,29) nmol/L dan terdapat korelasi yang sangat kuat dan bermakna secara statistik (p<0,0001) antara indeks 20/(C-peptide puasa x glukosa darah puasa) dengan HOMA-IR (r= -0,838). Dapat disimpulkan bahwa indeks 20/(C-peptide puasa x glukosa darah puasa) dan HOMA–IR berkorelasi kuat untuk menilai resistensi insulin pada DM tipe 2 di RSUP. Dr. M. Djamil Padang.AbstractInsulin resistance is a decrease of biological response of the tissues to the normal level of insulin. In type 2 diabetes, there is resistance and impaired of insulin secretion. There is a new index available to assess resistance and impaired of insulin secretion all at once, with the formula 20/(fasting C-peptide x fasting blood glucose). This study aimed to prove the correlation of this new index to the HOMA-IR (Homeostasis model assesment of insulin resistance) in type 2 diabetes at Dr.M.Djamil Padang hospital. Level of fasting glucose, fasting insulin and fasting C-peptide of blood were measured, followed by statistical data analysis using Pearson correlation test.The result showed the mean of fasting blood glucose, fasting insulin and fasting C-peptide were 9.83 (3.53) mmol/L[177 (63.54) mg/dl], 10.58 (3.61) μU/L, and 0.97 (0.29) nmol/L respectively.There was a strong and statistically significant correlation (p<0.0001) found between the new index and the HOMA-IR ( r= -0.838). To be concluded, the index 20/(fasting C-peptide x fasting blood glucose) and HOMA-IR was strongly correlated to assess insulin resistance in type 2 diabetes at Dr. M. Djamil Padang hospital.


2017 ◽  
Vol 2 (4) ◽  
pp. 49-50
Author(s):  
Alvaro Muriel ◽  
Nicole Chamorro ◽  
Alin Abreu ◽  
William Jubiz

Presentamos una mujer de 42 años quien consultó por parestesia lingual y ganancia de 10 Kg de peso, sin síntomas clásicos de hipoglucemia, a quién se le encontró una glucemia en ayunas de 46 mg/dl (2,6 mmol/L) con insulina y péptido C concomitantes de 10,2 µU/ml (73,2 pmol/L) y 2,14 ng/dl (79,2 nmol/L) respectivamente. Hallazgos similares fueron encontrados en una segunda ocasión. La resonancia magnética del páncreas mostró una lesión de 1,7 x 1,3 cm dependiente del reborde superior del cuerpo, la cual fue extirpada vía laparoscopia. Patología reveló un tumor neuroendocrino con inmunohistoquímica positiva para insulina, cromogranina y sinaptofisina. La parestesia lingual desapareció y la glucosa se normalizó. La tríada de Whipple no siempre está presente en pacientes con hipoglucemia, mientras que la parestesia lingual debe considerarse para la evaluación de estos pacientes.Abstract We report on a 42 years old female who consulted because of lingual paresthesia and 10 kg weight gain but without classic symptoms of hypoglycemia, who had a fasting blood glucose of 46 mg/dl (2.6 mmol/L) with a concomitant insulin a C-peptide of 10.2 µU/ml (73.2 pmol/L) and 2.14 ng/dl (79.2 nmol/L) respectively. Similar findings were obtained on a second occasion. Magnetic resonance of the pancreas revealed a 1.7 x 1.3 cm lesion dependent of the superior border of the body which was removed by laparoscopy. Pathology showed a neuroendocrine tumor with positive immmunohistochemistry for insulin, chromogranin and synaptophysin. Lingual paresthesia disappeared and blood glucose was normalized. Patients with lingual paresthesia should be evaluated for hypoglycemia even in the absent of a classic Whipple triad.


2018 ◽  
Vol 24 (27) ◽  
pp. 3223-3231 ◽  
Author(s):  
Luyao Li ◽  
Shiyao Xu ◽  
Tingting Guo ◽  
Shouliang Gong ◽  
Chuan Zhang

Objective: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes. Methods: Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks. Mouse body weights and fasting blood glucose levels were measured, and intestinal short-chain fatty acids were measured by gas chromatography. A series of methods was used to analyse the number of primary harmful bacteria in the faeces, and high-throughput sequencing was used to sequence the changes in intestinal flora. Results: The weight of the mice decreased after dapagliflozin gavage, and fasting blood glucose was significantly lower than that in the control group (P < 0.001). Acetic acid and butyric acid contents in the intestinal tracts of the mice increased, and the growth of harmful microorganisms, such as Clostridium perfringens, enterococci, Enterobacteriaceae, and intestinal enterococci, was inhibited. Blautia is a species found in the experimental group and was significantly different from the control and blank groups as determined by the LDA score from highthroughput sequencing. Conclusion: Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase short-chain fatty acid content, regulate the intestinal microecological balance of the body and promote blood glucose and energy homeostasis.


2019 ◽  
Vol 19 (8) ◽  
pp. 1148-1156 ◽  
Author(s):  
Ifeanacho Mercy Onuekwuzu ◽  
Ikewuchi Catherine Chidinma ◽  
Ikewuchi Jude Chigozie

Objective:Traditionally prepared infusions and decoctions are commonly used in the management of diabetes mellitus, in southern Nigeria; one of such is the aqueous extract of the sclerotia of Pleurotus tuberregium (“usu” milk). In this study, the effects of the extract on the body weights, tissue/ organ weights, fasting blood glucose, blood/plasma lipid profiles and atherogenic indices were investigated in normal and alloxan-induced diabetic rabbits.Methods:Diabetes mellitus was induced by the injection of alloxan (120 mg/kg body weight) via the marginal ear vein. The extract was administered orally at 100, 200 and 300 mg/kg to normal and diabetic rabbits; while metformin was administered at 50 mg/kg. The crude extract was analyzed by gas chromatography, coupled to flame ionization detector.Results:Thirty-one known flavonoids were detected, consisting mainly of isoquercetin (28.5%), luteolin (24.3%), quercetin (18.8%) and kaempferol (11.3%). Sitosterol (82.0%) and stigmasterol (12.5%) were the most abundant of the seven phytosterols detected. Compared to the diabetic control, the treatment significantly (p<0.05) lowered the weights of the kidney and liver, as well as the levels of blood glucose and triglyceride, plasma VLDL, LDL and non-HDL cholesterol, atherogenic index of plasma, cardiac risk ratio, atherogenic coefficient and Castelli’s risk index II. It, however, significantly (p<0.05) increased plasma HDL cholesterol, without significantly affecting blood total cholesterol levels.Conclusion:This study showed that the extract was hypoglycemic, and improved lipid profile and atherogenic indices, thus highlighting its cardioprotective potential, thereby supporting its use in the management of diabetes mellitus.


2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olubanke O. Ogunlana ◽  
Babatunde O. Adetuyi ◽  
Miracle Rotimi ◽  
lohor Esalomi ◽  
Alaba Adeyemi ◽  
...  

Abstract Background Diabetes, a global cause of mortality in developing countries is a chronic disorder affecting the metabolism of macromolecules and has been attributed to the defective production and action of insulin characterized by persistent hyperglycemic properties. This global disorder harms organs of the body such as the liver, kidney and spleen. Medicinal plants such as Hunteria umbellate have been shown to possess hypoglycemic, antioxidative and anti-diabetic properties owing to the high concentration of active phytochemical constituents like flavonoids and alkaloids. The present study seeks to evaluate the hypoglycemic activities of ethanolic seed extract of Hunteria umbellate on streptozotocin-induced diabetes rats. Methods Thirty (30) female experimental rats were randomly divided into five groups with six rats per group and were administered streptozotocin (STZ) and Hunteria umbellate as follows. Group 1 served as control and was given only distilled water, group 2 rats were administered 60 mg/kg STZ; Group 3 was administered 60 mg/kg STZ and 100 mg/kg metformin; group 4 rats were administered 60 mg/kg STZ and 800 mg/kg Hunteria umbellate, group 5 rats 60 mg/kg STZ and 400 mg/kg Hunteria umbellate. The fasting blood glucose level of each rat was measured before sacrifice. Rats were then sacrificed 24 h after the last dose of treatment. Results The results showed that Hunteria umbellate significantly reversed STZ-induced increase in fasting blood glucose and increase in body and organs weight of rats. Hunteria umbellate significantly reversed STZ-induced decrease in antioxidant enzyme in liver, kidney and spleen of rats. Hunteria umbellate significantly reversed STZ-induced increase in oxidative stress markers in liver, kidney and spleen of rats. Conclusion Collectively, our results provide convincing information that inhibition of oxidative stress and regulation of blood glucose level are major mechanisms through which Hunteria umbellate protects against streptozotocin-induced diabketes rats.


Author(s):  
Minsoo Kang ◽  
Sun Kyoung Han ◽  
Suhyun Kim ◽  
Sungyeon Park ◽  
Yerin Jo ◽  
...  

Abstract Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.


2021 ◽  
Vol 10 (23) ◽  
pp. 5561
Author(s):  
Antonella Meloni ◽  
Laura Pistoia ◽  
Maria Rita Gamberini ◽  
Paolo Ricchi ◽  
Valerio Cecinati ◽  
...  

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.


1997 ◽  
Vol 82 (12) ◽  
pp. 4167-4170 ◽  
Author(s):  
Constantine Tsigos ◽  
Dimitris A. Papanicolaou ◽  
Ioannis Kyrou ◽  
Ruby Defensor ◽  
Constantine S. Mitsiadis ◽  
...  

Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.


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