Bloodletting Ameliorates Insulin Sensitivity and Secretion in Parallel to Reducing Liver Iron in Carriers of HFE Gene Mutations
To clarify the pathogenesis of diabetes associated with mutations of the hemochromatosis (HFE) gene, 17 carriers, 9 normal glucose tolerant (NGT) and 8 diabetic, were evaluated in an interventional trial. At enrollment and after a 2-year bloodletting period, euglycemic-hyperinsulinemic clamp, oral glucose tolerance test (OGTT), liver histology (nonalcoholic fatty liver disease activity score [NAS]), and liver iron content (LIC) were assessed. NGT subjects had significantly higher baseline insulin sensitivity (P <or= 0.001), secretion, and insulinogenic index (calculated from the OGTT) (P <or= 0.0001 for both) and lower LIC (P = 0.004) and NAS (P = 0.02) than diabetic patients. Baseline LIC correlated negatively with insulin secretion (NGT r(0) = -0.676, P <or= 0.0001; diabetes r(0) = -0.589, P = 0.02) and insulin sensitivity (M value) (NGT r(0) = -0.597, P = 0.009; diabetes r(0) = -0.535, P = 0.03) and positively with NAS (diabetes r(0) = 0.649, P = 0.007) and triglycerides (NGT r(0) = 0.563, P = 0.015). At month 24, circulating iron was reduced by 179 +/- 26% in NGT and 284 +/- 54% in diabetic subjects. Insulin secretion (NGT 20 +/- 4%; diabetes 33 +/- 7%) and insulin sensitivity (NGT 25 +/- 5%; diabetes 18 +/- 3%) increased. LIC decreased in both groups (NGT 126 +/- 42%; diabetes 61 +/- 13%), and NAS ameliorated (NGT 65.1 +/- 6.5 vs. 38.1 +/- 6.83; P <or= 0.0001; diabetes 2.1 +/- 10.7 vs. 69.9 +/- 10; P <or= 0.0001). Iron depletion ameliorates insulin secretion and sensitivity in NGT and diabetic carriers of HFE gene mutations. This amelioration occurs in parallel with decreased LIC and improved NAS. These results justify glucose tolerance testing and prophylactic iron depletion in asymptomatic carriers as well.
[Show abstract] [Hide abstract] ABSTRACT: Background: Wet cupping (Hejamah) has been used as alternative treatment for several diseases. Objectives: Materials and methods: 16 participants were treated with hejamah for 2 consecutive months. Blood pressure was measure before and 30 minutes after the treatment. Blood samples were collected from all participants before and 48 hours after hejamah and all participants were fasting for 12 hours before sample collection. Results: Fasting blood glucose was significantly decreased before the treatment in the second month only. The levels of serum triglycerides significantly decreased after the first treatment and remained low in the 2nd month. There was no significant difference between the different time points in total cholesterol except for the 48 hours of the second month compared to the samples collected before the procedure of the same month. There was a significant decrease in LDL and significant increase in HDL following hejamah therapy (P<0.05). Significant decrease in sodium and significant increase in potassium 48 hours following treatment with hejamah was observed in the 2 months (P<0.05). Conclusions: The performance of hejamah during fasting state could represent a useful complementary method for the regulation of diastolic blood pressure and prevention/treatment of risk factors associated with cardiovascular diseases. Further studies are required to explore the role of hejamah in controlling blood pressure and prevention of cardiovascular diseases.0Comments 0Citations
- "Bloodletting has been shown to increase the insulin sensitivity , which is a major risk factor for the development of metabolic syndrome if impaired. In a constant line, Ranaei-siadat and his colleagues measured the venous blood concentrations of several molecules before and after five times of cupping (one time per month) in young healthy males (20-27 years). "
[Show abstract] [Hide abstract] ABSTRACT: In patients with metabolic syndrome, body iron overload exacerbates insulin resistance, impairment of glucose metabolism, endothelium dysfunction and coronary artery responses. Conversely, iron depletion is effective to ameliorate glucose metabolism and dysfunctional endothelium. Most of its effectiveness seems to occur through the amelioration of systemic and hepatic insulin resistance. In a study published by BMC Medicine, Michalsen et al. demonstrated a dramatic improvement of blood pressure, serum glucose and lipids after removing 550 to 800 ml of blood in subjects with metabolic syndrome. This effect was apparently independent of changes in insulin resistance, in contrast to previous cross-sectional and cohort studies investigating the association between iron overload, insulin resistance and cardiovascular disease. Despite drawbacks in the study design, its findings may lead the way to investigations aimed at exploring iron-dependent regulatory mechanisms of vascular tone in healthy individuals and patients with metabolic disease, thus providing a rationale for novel preventive and therapeutic strategies to counteract hypertension. Please see related article: http://www.biomedcentral.com/1741-7015/10/540Comments 3Citations
- "They might be unable to compensate for hypovolemia as healthy donors do. Indeed, most previous evidence were from cohort and cross-sectional studies of healthy donors , and from high-ferritin T2DM patients and carriers of hereditary hemocromatosis in whom blood volume was restored to normal at each procedure [7,10]. "
[Show abstract] [Hide abstract] ABSTRACT: Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial. In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR). SBP decreased from 148.5 ± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P < 0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction. In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS. ClinicalTrials.gov: NCT01328210 Please see related article: http://www.biomedcentral.com/1741-7015/10/53.0Comments 49Citations
- "In a small safety study on blood donation, phlebotomy resulted ina significant decrease in serum glucose and blood lipids in patients with diabetes . Iron reduction by phlebotomy also enhanced insulin sensitivity in patients with ironinduced insulin resistance and in carriers of the hemochromatosis gene . Notably, in these studies, the amount of removed blood was larger than in our study and the study period was longer. "
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