scholarly journals The Use of Biochemical Parameters Instead of MRI for the Prediction of Pancreatic Iron Loading Among Patients with β-Thalassemia Major

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1356-1356
Author(s):  
Munevver Bas ◽  
Fatma Gumruk ◽  
Tuncay Hazirolan ◽  
A. Murat Tuncer ◽  
Mualla Cetin ◽  
...  

Abstract Patients with β-thalassemia major (BTM) are prone to morbidities and mortalities of iron accumulation as a consequence of transfusional iron overload and increased intestinal iron absorption. The use of cardiac and hepatic T2* measurements to pr edict the amount of iron accumulation in these organs have been studied extensively and was suggested to be used reliably. However, although the use of MRI for the assessment of iron status in other organs such as pancreas is possible, it may not be practical to screen all organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we studied fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results among patients with BTM, to detect the correlations of these measurements with pancreas, cardiac and hepatic T2* or R2* MRI values. Patients with BTM from a single center were included in the study between February 2013 and January 2014. All patients were above seven years of age, and were on regular erythrocyte transfusion programme. Only the patients who were compliant to iron chelation treatments were included in the study. Patients with hepatitis B or C, and/or cirrhosis were excluded. The study included a total of 37 patients who fulfilled the inclusion and exclusion criteria. Cardiac, hepatic T2* and pancreas T2* and R2* MRI was applied with 1.5 T (Siemens, Symphony, Erlangen, Germany) device. Simultaneous to MRI, fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results were obtained. HOMA-B was calculated as: insulin (μU/ml) x 20/glucose (mg/dl) - 3.5 and the normal range is 130-400. HOMA-IR was calculated as: insulin (μU/ml) x glucose (mg/dl) / 22,5 and the normal range is 0.8-1.6. Insulin resistance is defined as HOMA-IR value above 1.6. Two patients had a diagnosis of diabetes mellitus. The mean age of patients participating in the study was 20.8 ± 6.3 years (7.1-36.8). Of the study group, 43.3 % was above 20 years of age. According to BMI assessments, 32 (86.5%) of the patients had normal BMI, whereas 5 (13.5%) were underweight. Insulin resistance was found in 7.4% of the patients. Fasting blood glucose has been shown to increase with decreases of pancreatic T2* values, which was indicative of increase in fasting glucose levels in parallel to increased pancreatic iron accumulation (r= -0,55, p=0.016). Also there was a statistically significant positive correlation between fasting insulin and pancreatic R2* values. (r= 0.59, p= 0.01). A positive correlation was found between fasting insulin levels and pancreas R2* measeures, indicating increase in fasting insulin levels, paralleling the pancreatic iron accumulation. Correlation analysis was perfromed for cardiac and hepatic T2*, pancreas T2*, R2* and simultaneously calculated HOMA-IR and HOMA-B values and a negative correlation was found between liver T2* and HOMA-IR values (r=-0.54, p=0.004). A negative correlation was found between pancreas R2* ile cardiac T2* (r=-0.67, p=0.02), indicating increased pancreatic iron loading in parallel with cardiac iron accumulation. In centers where T2*/R2* MRI fascilities are unavailable, fasting insulin, fasting glucose, HOMA-IR measurements may be used to predict pancreatic iron overload. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron loaded liver. Additionally, disorders of glucose metabolism should be taken as a sign for the need to exercise caution in terms of cardiac iron overload and just vice versa patients with cardiac iron loading should be examined thoroughly for consequences of pancreatic iron loading. These biochemical tests may be used dynamically and more frequently throughout the control visits, whereas MRI is ordered at most once or twice a year which may cause a delay for the earlier diagnosis. Disclosures No relevant conflicts of interest to declare.

2011 ◽  
Vol 301 (2) ◽  
pp. E402-E408 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Jinrui Cui ◽  
Yii-Der I. Chen ◽  
Willa A. Hsueh ◽  
Xiuqing Guo ◽  
...  

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (−0.35, P < 0.0001), M (−0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for insulin resistance.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
So-Yun Yi ◽  
Lyn M Steffen ◽  
James G Terry ◽  
Daniel A Duprez ◽  
Brian Steffen ◽  
...  

Background: - Excess added sugar (AS) intake was shown to promote insulin resistance in skeletal muscle in animal studies, while sugar sweetened beverage (SSB) intake was associated with insulin resistance and lipids in skeletal muscle in humans. However, SSBs account for only 40% of AS intake. US adults consume excessive AS from foods and beverages relative to the 2015-2020 Dietary Guidelines recommendation which limit AS intake to <10% of energy intake per day. We evaluated the hypothesis that AS intake is adversely associated with glucose metabolism, insulin, and lean muscle attenuation (MA) in Black and white men and women aged 18-30 years at baseline (Y0). Methods: - After exclusions for diabetes defined as MD diagnosis, insulin or oral agent use, fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%, outlying energy intake, and missing 2-hour glucose, 2,016 adults were included in the analyses. Dietary intake was assessed by Diet History at Y0, Y7 and Y20. At Y25 follow-up, participants free of diabetes underwent a fasting blood draw for glucose, insulin, and triglycerides, an oral glucose tolerance test for 2-hour post-challenge glucose, and an abdominal CT scan for lean MA (an indicator of muscle quality). AS intake was averaged across Y0, Y7, and Y20 and divided into tertiles. General linear regression models estimated the associations across tertiles of AS intake with 2-hour glucose, fasting glucose, insulin, and triglycerides, and lean MA adjusted for potential confounders. Results: - AS intake (Table) was positively associated with 2-hour glucose and fasting insulin and triglycerides (p trend =0.004, 0.04, and 0.01, respectively) and inversely associated with lean MA (p trend =0.02). AS intake was not associated with fasting glucose (p trend =0.57). Conclusions: - Among adults free of diabetes, greater long-term AS intake was associated with higher 2-hour glucose and fasting insulin and triglycerides, and lower muscle quality. Our findings are consistent with the US Dietary Guidelines for Americans recommendation to limit AS intake.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1086-1086
Author(s):  
Vasilios Berdoukas ◽  
Mammen Puliyel ◽  
Adam Bush ◽  
Thomas Hofstra ◽  
Bhakti P. Mehta ◽  
...  

Abstract Abstract 1086 Recurrent blood transfusion results in significant iron overload that can cause serious organ damage and death if not properly treated. Liver iron concentration (LIC) is the best indicator of total body iron status and can be measured non-invasively by magnetic resonance imaging (MRI). In the past, it was recommended that LIC assessments by liver biopsy begin after about 6 years of age (yo). MRI is also an excellent way to monitor iron cardiomyopathy, which remains a major cause of death in chronically transfused patients. To understand how rapidly iron overload develops, we reviewed the 1316 MRI iron studies we have performed since 2002 and summarized the LIC and cardiac R2* in a subset of 127 subjects who had their first MRI studies before 10 yo. Because of the known serious pitfalls in the assessment of total body iron by measurement of ferritin, LIC is measured by MRI in our center as standard of care in all patients on chronic transfusion soon after the start of iron chelation therapy. Most children less than 6 years of age require general anesthesia for this procedure. In some older children cooperation can be achieved by distraction techniques. Thirty three percent had sickle cell disease (SCD), 33% thalassemia major (TM), 11% Blackfan Diamond anemia (DBA), 3% congenital dyserythropoietic anemia (CDA), and 8.6% had other transfusion dependent anemias (OTRAN) and 11.4% had studies done not related to transfusion. This paper will focus on the 114 subjects whose MRI was done to evaluate transfusion related iron overload. The median age at first MRI was 6 years with 25% having their first study before 3.7and 10% before 2.1 yo. The median LIC was 9.8 mg/g dry weight (dw) and 10% of subjects had a first LIC > 22 mg/g dw. Only 2.5% had evidence of cardiac iron (T2* < 20ms). The median LICs (mg/g dw) were 8.9 for SCD, 11.8 for TM, 13 for DBA, 6.1 for CDA, and 8.7 OTRAN and were not statistically different. The minima ranged from 0.6 in OTRAN to 4.2 for CDA and the maxima ranged from 25 in CDA to 39.7 for SCD. There was significant iron loading even when we restricted the analysis to 27 subjects with a first MRI at < 3.5 yo; SCD (2.3 median (med), 2.8 maximum (max)), TM (14.6 med, 35 max), DBA (13 med, 15 max),CDA (6.6 med, 25 max) and OTRAN (5.8 med, 11 max). There were 4 subjects who had evidence of cardiac iron loading. Two had DBA with T2* of 18 ms and 16 ms at 2.5 and 3.7 years of age respectively. A third DBA subject had a T2* of 20 ms at only 4.6 yo. Two TM subjects had a T2* of 15 ms at 6.6 and 9.1 yo respectively. These data indicate that there is significant elevation in LIC by the age of 3.5 years with a median LIC of 11 mg/g dw and 25% of subjects having a LIC > 15 mg/g dw. These are very high levels of iron loading. Furthermore, 2.5% of subjects in this age already have evidence of cardiac iron loading. On the basis of such findings, direct measurement of liver iron by MRI is essential as soon as possible after the start of regular transfusions and cardiac iron should be measured early in high risk children with Diamond Blackfan anemia and thalassemia major. Disclosures: Berdoukas: ApoPharma Inc.: Consultancy. Carson:ApoPharma Inc.: Honoraria; Novartis Inc: Speakers Bureau. Wood:Novartis: Research Funding; Ferrokin Biosciences: Consultancy; Cooleys Anemia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Coates:Novartis Inc: Speakers Bureau.


2016 ◽  
Vol 7 (8) ◽  
pp. 3390-3401 ◽  
Author(s):  
Damiana D. Rosa ◽  
Łukasz M. Grześkowiak ◽  
Célia L. L. F. Ferreira ◽  
Ana Carolina M. Fonseca ◽  
Sandra A. Reis ◽  
...  

Kefir supplementation in rats with induced metabolic syndrome was able to lower fasting glucose, fasting insulin levels, and reduce insulin resistance.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1751
Author(s):  
Saroj Khatiwada ◽  
Virginie Lecomte ◽  
Michael F. Fenech ◽  
Margaret J. Morris ◽  
Christopher A. Maloney

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.


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.


2016 ◽  
Vol 43 (4) ◽  
pp. 117
Author(s):  
Caroline Mulawi ◽  
Bambang Tridjaja ◽  
Maria Abdulsalam ◽  
Zakiudin Munasir

Background Diabetes mellitus is a common complication in pa-tients with thalassemia major. Iron overload plays an important roleby damaging the pancreatic β-cell and the liver cell, with the con-sequences of insulin deficiency and insulin resistance. Family his-tory of diabetes mellitus is one of the critical factors for the devel-opment of glucose metabolism derangement. However, the patho-genesis of glucose metabolism derangement remains unclear.Objective To evaluate the prevalence of impaired glucose toler-ance, diabetes mellitus, and insulin resistance in patients with β-thalassemia major treated in the Thalassemia Outpatient Clinic,Department of Child Health, Cipto Mangunkusumo Hospital,Jakarta.Methods This was a descriptive cross sectional study conductedin May 2002. Forty-eight subjects aged 10 to 18 years, grouped bytotal volume of transfusions and family history of diabetes mellitus,underwent an oral glucose tolerance test (OGTT), serum transfer-rin saturation, and insulin level examinations. Insulin resistancewas calculated from fasting plasma glucose and insulin concen-trations using the homeostasis model assessment (HOMA).Results One of 48 patients (2%) had impaired glucose toleranceat the age of 17 years. Diabetes mellitus occurred in three of 48patients (6%) at the age of 15.5 years in one patient and 18 yearsin two patients. Family history of diabetes mellitus was found in 2patients with diabetes mellitus and in the only one with impairedglucose tolerance. Insulin resistance was not detected in this study.Conclusion The prevalence of glucose metabolism derangementin patients with thalassemia major was low. No insulin resistancewas found in this study


2019 ◽  
Vol 8 (6) ◽  
pp. 817 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Shih-Che Hua ◽  
Chia-Hsuin Chang ◽  
Wei-Yi Kao ◽  
Hsiao-Lin Lee ◽  
...  

(1) Background: Overt and subclinical hypothyroidism has been associated with increased cardiometabolic risks. Here we further explore whether thyroid function within normal range is associated with cardiometabolic risk factors in a large population-based study. (2) Methods: We screened 24,765 adults participating in health examinations in Taiwan. Participants were grouped according to high-sensitive thyroid-stimulating hormone (hsTSH) level as: <50th percentile (0.47–1.48 mIU/L, the reference group), 50–60th percentile (1.49–1.68 mIU/L), 60–70th percentile (1.69–1.94 mIU/L), 70–80th percentile (1.95–2.3 mIU/L), 80–90th percentile (2.31–2.93 mIU/L), and >90th percentile (>2.93 mIU/L). Cardiometabolic traits of each percentile were compared with the reference group. (3) Results: Elevated hsTSH levels within normal range were dose-dependently associated with increased body mass index, body fat percentage, waist circumferences, blood pressure, hemoglobin A1c (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high homeostasis model of assessment of beta-cell (HOMA-β), triglycerides, total cholesterols, fibrinogen, and uric acids (p-for-trend <0.001), but not with fasting glucose levels. The association remained significant after adjustment of age, sex, and lifestyle. As compared to the reference group, subjects with the highest hsTSH percentile had significantly increased risk of being overweight (adjusted odds ratio (adjOR): 1.35), increased body fat (adjOR: 1.29), central obesity (adjOR: 1.36), elevated blood pressure (adjOR: 1.26), high HbA1c (adjOR: 1.20), hyperinsulinemia (adjOR: 1.75), increased HOMA-IR (adjOR: 1.45), increased HOMA-β (adjOR: 1.40), hypertriglyceridemia (adjOR: 1.60), hypercholesterolemia (adjOR: 1.25), elevated hsCRP (adjOR: 1.34), increased fibrinogen (adjOR: 1.45), hyperuricemia (adjOR: 1.47), and metabolic syndrome (adjOR: 1.42), but significant risk of low fasting glucose (adjOR: 0.89). Mediation analysis indicates that insulin resistance mediates the majority of the association between thyroid hormone status and the metabolic syndrome. (4) Conclusion: Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability.


Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2973-2978 ◽  
Author(s):  
Leila J. Noetzli ◽  
Susan M. Carson ◽  
Anne S. Nord ◽  
Thomas D. Coates ◽  
John C. Wood

Abstract High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.


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