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Insulin Metabolism In Ckd

Carbohydrate And Insulin Metabolism In Chronic Kidney Disease

Carbohydrate And Insulin Metabolism In Chronic Kidney Disease

INTRODUCTION Uremia is typically associated with impaired glucose metabolism. Some patients have hyperglycemia in response to oral and intravenous glucose loads, while others are able to maintain normoglycemia by raising plasma insulin levels. Studies utilizing the euglycemic and hyperglycemic clamp techniques suggest that several disturbances in carbohydrate handling may be present. Tissue insensitivity to insulin is of primary importance, but alterations in insulin degradation and insulin secretion also may contribute [1-3]. The variable severity of these changes in individual patients explains the variable plasma levels of insulin and glucose that may be seen both fasting and following a glucose load. This topic will review the changes in carbohydrate and insulin metabolism that occur in chronic kidney disease (CKD) and the clinical implications of these abnormalities in nondiabetics. The impact of these changes on the management of hyperglycemia in diabetic patients with end-stage renal disease (ESRD) is discussed separately. (See "Management of hyperglycemia in patients with type 2 diabetes and pre-dialysis chronic kidney disease or end-stage renal disease".) NORMAL RENAL HANDLING OF INSULIN The kidney plays a central role in the metabolism of insulin in normal subjects [1,2,4]. Insulin has a molecular weight of 6000 and is therefore freely filtered. Of the total renal insulin clearance, approximately 60 percent occurs by glomerular filtration and 40 percent by extraction from the peritubular vessels. Insulin in the tubular lumen enters proximal tubular cells by carrier-mediated endocytosis and is then transported into lysosomes, where it is metabolized to amino acids [5]. The net effect is that <1 percent of filtered insulin appears in the final urine. The renal c Continue reading >>

Management Of Diabetes Mellitus In Patients With Chronic Kidney Disease

Management Of Diabetes Mellitus In Patients With Chronic Kidney Disease

Abstract Glycemic control is essential to delay or prevent the onset of diabetic kidney disease. There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7 % but this target is adjusted based on the needs of the patient. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events. Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed. Introduction Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease (CKD) and kidney failure. Diabetic nephropathy affects approximately 20–40 % of individuals who have diabetes [1], making it one of the most common complications related to diabetes. Screening for diabetic nephropathy along with early intervention is fundamental to delaying its progression in conjunction with providing proper glycemic control. Given the growing population that is now affected by diabetes and thus, nephropathy, knowledge regarding the safe use of various anti-hyperglycemic agents in those with nephropathy is of importance. In addition, attention to modification of cardiovascular disease (CVD) risk factors is essential. Altogether, knowledge regarding the prevention and management of diabetic nephropathy, along with other aspects of diabetes care, is part of the comprehensive care of any patient with diabetes. Review Recommendations for nephropathy screening in diabetes Patients with diabetes should be screened on an annual basis for nephropathy. I Continue reading >>

Carbohydrate Metabolism In Renal Failure.

Carbohydrate Metabolism In Renal Failure.

Abstract Hyperglycemia and impaired glucose tolerance are well known phenomena occurring in patients with renal failure. In contrast to true diabetic subjects, an elevated ratio of insulin to glucose during the glucose tolerance test is consistently observed indicating a peripheral insulin insensitivity. Among the possible reasons, a disturbance at the cellular level seems to be most likely. There is some evidence of reduced peripheral glucose utilization on the one hand and increased hepatic glucose output--probably by stimulation of gluconeogenesis--on the other. Agents that have been suggested to be involved in these alterations of carbohydrate metabolism in uremia are hormones, electrolytes, pH, and "toxic" metabolic intermediates or end-products. Of these, an increase in insulin antagonistic hormones; among them growth hormone, catecholamines, and glucagon, seems to be of most significance. Although for the individual hormones no equivocal correlation with glucose intolerance has been proved, the interaction of all of them may result in a preponderance of insulin antagonism thus leading to an apparent insulin resistance. Continue reading >>

Insulin Sensitivity Of Muscle Protein Metabolism Is Altered In Patients With Chronic Kidney Disease And Metabolic Acidosis

Insulin Sensitivity Of Muscle Protein Metabolism Is Altered In Patients With Chronic Kidney Disease And Metabolic Acidosis

Article Outline An emergent hypothesis is that a resistance to the anabolic drive by insulin may contribute to loss of strength and muscle mass in patients with chronic kidney disease (CKD). We tested whether insulin resistance extends to protein metabolism using the forearm perfusion method with arterial insulin infusion in 7 patients with CKD and metabolic acidosis (bicarbonate 19 mmol/l) and 7 control individuals. Forearm glucose balance and protein turnover (2H-phenylalanine kinetics) were measured basally and in response to insulin infused at different rates for 2 h to increase local forearm plasma insulin concentration by approximately 20 and 50 μU/ml. In response to insulin, forearm glucose uptake was significantly increased to a lesser extent (-40%) in patients with CKD than controls. In addition, whereas in the controls net muscle protein balance and protein degradation were decreased by both insulin infusion rates, in patients with CKD net protein balance and protein degradation were sensitive to the high (0.035 mU/kg per min) but not the low (0.01 mU/kg per min) insulin infusion. Besides blunting muscle glucose uptake, CKD and acidosis interfere with the normal suppression of protein degradation in response to a moderate rise in plasma insulin. Thus, alteration of protein metabolism by insulin may lead to changes in body tissue composition which may become clinically evident in conditions characterized by low insulinemia. Insulin resistance is a well-known complication of chronic kidney diseases (CKD).1., 2., 3., 4., 5., 6., 7. Although not clinically remarkable, insulin resistance appears to be strongly implicated in the pathogenesis of hypertension, accelerated atherosclerosis, and cardiovascular events.8., 9., 10. Besides its effects on glucose and lipid Continue reading >>

Comparison Of Insulin Resistance In The Various Stages Of Chronic Kidney Disease And Inflammation

Comparison Of Insulin Resistance In The Various Stages Of Chronic Kidney Disease And Inflammation

Objective: In this study, we compared predialysis and dialysis patients with the controls in terms of insulin resistance and evaluated the association with inflammation that is a risk factor for cardiovascular disease. Materials and methods: A total of 134 non-diabetic patients with controls (n = 33), predialysis (n = 29) and dialysis patient group (n = 72) were included in the study. Fasting blood glucose, insulin, C-peptide, albumin, CRP (C-reactive protein) and homocysteine plasma levels were simultaneously analyzed in all the patients. HOMA-IR index was calculated to show existence of insulin resistance. Results: Mean insulin and HOMA-IR index values were found to be higher in the predialysis and dialysis patient groups than in the control group (p = 0.019, p = 0.014; respectively). When three groups were compared in terms of C-peptide levels; these values were found to be statistically significantly higher in the predialysis patients than in controls (p = 0.017) and in the dialysis group than in the predialysis patients and controls (p = 0.0001, p = 0.0001; respectively). CRP and homocysteine levels were found to be statistically higher (p = 0.0001, p = 0.0001; respectively), while albumin levels were significantly lower (p = 0.0001) in the dialysis patient group. Conclusion: In our study, we demonstrated that insulin resistance was higher in patients in the various stages of chronic kidney disease compared to healthy population. We found that insulin resistance, C-peptid and inflammation related cardiovascular risk factors increased. Continue reading >>

Diabetes, Metabolism And The Kidney

Diabetes, Metabolism And The Kidney

The kidney is a highly metabolic organ that requires large numbers of mitochondria to perform tasks such as maintain acid–base homeostasis and reabsorb nutrients. It also has a key role in maintaining glucose homeostasis and is adversely affected by hyperglycaemia and insulin resistance in the setting of diabetes mellitus. This collection of Reviews, commentaries and original research articles from across the Nature group of journals covers a range of areas related to the topic of diabetes, metabolism and the kidney, including the roles of mTOR complexes and NAD+ metabolism, the role of the kidney in maintaining glucose homeostasis, the effects of insulin resistance on the kidney and vasculature, the epidemiology and mechanisms of diabetic nephropathy, and potential therapeutic targets for renal protection. The content of this collection has been chosen by the editors of Nature Reviews Nephrology. Image credit: Patricia Toth McCormick/Moment/Getty Continue reading >>

Management Of Diabetes Mellitus In Individuals With Chronic Kidney Disease: Therapeutic Perspectives And Glycemic Control

Management Of Diabetes Mellitus In Individuals With Chronic Kidney Disease: Therapeutic Perspectives And Glycemic Control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. Key words: Type 2 Diabetes Mellitus; Chronic Kidney Disease, Diabetic Kidney Disease; Renal Failure; Diabetes Treatment; Oral Antidiabetic Drugs Continue reading >>

Insulin Resistance In Chronic Kidney Disease: New Lessons From Experimental Models

Insulin Resistance In Chronic Kidney Disease: New Lessons From Experimental Models

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease, and this increase in disease burden cannot be solely explained by traditional cardiovascular risk factors. In the 1980s, DeFronzo et al., using the ‘gold standard’ euglycemic hyperinsulinemic clamp technique, found evidence of insulin resistance (IR) in CKD patients [1]. They suggested that the site of this resistance lies in the binding of insulin to its receptor and can be reversed by dialysis. It is now well established that the decline of renal function is associated with the development of IR with impaired insulin-induced glucose utilization of peripheral target tissues. Since this seminal study, there has been a renewed interest in IR in CKD, especially as IR is an independent risk factor for cardiovascular morbidity and mortality in patients with CKD [2]. Although the underlying causes of IR in CKD remain unclear, understanding the mechanisms is pivotal. In obesity and diabetes, emerging studies suggest an interconnected network linking innate immunity and inflammation to metabolic diseases, and the major role of adipose tissue and intestinal flora in the control of energy metabolism and insulin sensitivity [3, 4]. During the last two decades, several cellular and animal models have enabled us to better understand the mechanisms underlying IR in CKD. The field has progressed rapidly with the availability of tools such as high-resolution mass spectrometry, 16S rRNA gene sequencing, metabolomic and metagenomic sequencing enabling even broader insights into the composition of uraemia retention molecules (URMs) and gut microbiota. There is strong evidence that there is an increased colonic generation or absorption of bacterial URMs in CKD [5–7]. Moreover, specific factors that are produce Continue reading >>

Carbohydrate Metabolism

Carbohydrate Metabolism

Glucose metabolism has been studied extensively in the fetus and newborn, both in animal models and in humans, and several reviews have been published. Our ability to study glucose metabolism has improved significantly because of the availability of (1) the chronic fetal preparation in large animals, in which fetal blood sampling and physiologic monitoring can be done without causing major changes in the state of the fetus; (2) stable, nonradioactive isotopic tracers; and (3) molecular biology techniques and transgenic animals. In this chapter, glucose metabolism in the fetus and newborn is discussed, and recent developments are emphasized. Throughout the chapter, emphasis is placed on the available data in humans, supplemented when necessary with animal data. Carbohydrate Metabolism Glucose metabolism in AKI again is affected both by unspecific mechanisms mediated by the acute disease state and specific effects of acute uremia. A major finding is insulin resistance [39]. Plasma insulin concentrations are elevated, maximal insulin-stimulated glucose uptake by skeletal muscle is decreased and muscular glycogen synthesis is impaired [40]. A second feature of glucose metabolism in AKI is accelerated hepatic gluconeogenesis mainly from conversion of amino acids released during protein catabolism [20]. Hepatic extraction of amino acids and their conversion to glucose and urea production are all increased in AKI. As discussed earlier, in contrast to the non-uremic state and CKD, hepatic gluconeogenesis cannot be suppressed completely by exogenous glucose infusions in AKI. Metabolic acidosis also affects glucose metabolism in AKI by further deteriorating glucose tolerance [41]. Alterations in glucose and protein metabolism in AKI are interrelated, and several factors activatin Continue reading >>

Urea Impairs Β Cell Glycolysis And Insulin Secretion In Chronic Kidney Disease

Urea Impairs Β Cell Glycolysis And Insulin Secretion In Chronic Kidney Disease

Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis. Continue reading >>

Diabetes,dysglycemia; And Chronic Kidney Disease By Prof Alaa Wafa

Diabetes,dysglycemia; And Chronic Kidney Disease By Prof Alaa Wafa

1. Dysglycemia and CKD BY Alaa Wafa MD. Associate Professor of internal medicine Diabetes & Endocrine unit. Mansoura university 8th international HD course UNC 15/12/2015 2. AGENDA 2 Background of Dysglycemia and CKD Pathophysiology of Dysglycemia and CKD Glycemic control and CKD Insulin therapy and CKD Conclusions 3. TEAMWORK- the power of a multidisciplinary approach Patient and family Nephrologist Nurse Clinician Diabetes Educator Pharmacist Registered Dietitian Social Work 4. Diabetes: The Most Common Cause of ESRD Primary Diagnosis for Patients Who Start Dialysis Diabetes 50.1% Hypertension 27% Glomerulonephritis 13% Other 10% United States Renal Data System. Annual data report. 2000. No. of patients Projection 95% CI 1984 1988 1992 1996 2000 2004 2008 0 100 200 300 400 500 600 700 r2=99.8% 243,524 281,355 520,240 No.ofdialysispatients (thousands) ©2006. American College of Physicians. All Rights Reserved. 5. Rate of kidney diseases in Egypt is 36.4* with about 5.19% deaths *Per 100,000 disease/by-country/ accessed 2012 Oct. 6. Dysglycemia The Dysglycemia of diabetes includes two components: • (1) sustained chronic hyperglycemia that exerts its effects through both excessive protein glycation and activation of oxidative stress • (2) acute glucose fluctuations (glycemic variability). Glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as both upward (postprandial glucose increments) and downward (interprandial glucose decrements) changes activate the oxidative stress. 6 7. Glucose variability Multiple fluctuations of glycemia in the same individual within-day or day-to-day, or even over longer periods of time; that is, week to-week or visit-to-visit. The concept of glucose variab Continue reading >>

Effect Of Insulin Resistance In Chronic Kidney Disease

Effect Of Insulin Resistance In Chronic Kidney Disease

1Imperial College Kidney and Transplant Institute, Hammersmith Hospital, Imperial College London, London, UK 2Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran *Corresponding Author: Andrew H Frankel Imperial College Kidney and Transplant Institute Hammersmith Hospital Imperial College London London, UK Tel: +98 912 188 1096 E-mail: [email protected] Citation: Frankel AH, Kazempour-Ardebili S (2016) Effect of Insulin Resistance in Chronic Kidney Disease. Endocrinol Metab Syndr 5:255. doi:10.4172/2161-1017.1000255 Copyright: © 2016 Frankel AH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Endocrinology & Metabolic Syndrome Abstract Insulin resistance accompanies many well-established cardiovascular risk factors, such as obesity, hypertension, dyslipidaemia and type 2 diabetes. Since cardiovascular disease (CVD) is the leading cause of death in patients with end stage renal disease (ESRD), insulin resistance is thought to play a role in the morbidity and mortality associated with ESRD. This paper reviews the available information on insulin resistance in patients with impaired kidney function as well as those on renal replacement therapy in the form of maintenance hemodialysis. Potential mechanisms for the dynamic changes in insulin resistance, which occur through the different stages of kidney disease, are also discussed. We hypothesize that stabilizing insulin sensitivity may have a positive effect on improving outcome in ESRD subjects Continue reading >>

Role Of The Kidney In Insulin Metabolism And Excretion

Role Of The Kidney In Insulin Metabolism And Excretion

The role of the kidneys in insulin metabolism and excretion is reviewed. Removal of these organs from animals prolongs the half-life of injected labeled or unlabeled insulin. Similar findings, reversible by transplantation, are noted in patients with severe renal disease. After injection of insulin-I-131 into a peripheral vein, the concentration of radioactivity in the renal cortex of rats is nine times greater than any other tissue and 21 per cent of the administered dose is present in the kidneys at fifteen minutes. In contrast to other organs, an increase in the injected dose results in a greater proportion being localized to the kidneys. The concentration of insulin in renal venous blood is 30 to 40 per cent lower than the arterial level, and the quantity of insulin removed by the kidneys over twentyfour hours is 6 to 8 U. The renal clearance of insulin in man is approximately 200 ml. per minute. There is both direct and indirect evidence that insulin is filtered at the glomerulus and almost completely reabsorbed and degraded by cells lining the proximal convoluted tubules. This mechanism accounts for 50 to 60 per cent of the renal uptake of insulin, the remaining 40 to 50 per cent being removed from the postglomerular peritubular capillaries. The amount of insulin excreted in the urine is less than 2 per cent of the filtered load and the urinary clearance is 0.1-0.5 ml. per minute. This clearance is constant over a wide range of serum levels and is thus a useful reflection of the mean serum level over a period of time. These observations explain the fall in insulin requirements of diabetic patients who develop renal failure. Furthermore, the severe hypoglycemia which occasionally occurs in elderly subjects with uremia following the administration of oral sulfonylur Continue reading >>

Alvestrand, A. (1997) Carbohydrate And Insulin Metabolism In Renal Failure. Kidney International Supplement, 62, S48-s52.

Alvestrand, A. (1997) Carbohydrate And Insulin Metabolism In Renal Failure. Kidney International Supplement, 62, S48-s52.

has been cited by the following article: KEYWORDS: Chronic Kidney Disease; End-Stage Renal Disease; Inflammation; Malnutrition ABSTRACT: Malnutrition is a major issue in patients with chronic kidney disease (CKD), adversely affecting morbidity, mortality, functional activity and patients’ quality of life. Our knowledge of the pathogenic mechanisms of malnutrition in patients with CKD, including endstage renal disease, has been improved. This has led to the development of clinical practice guidelines for nutritional care in CKD which provide a framework for the nutritional issues facing patients and physiccians. Extensive research in the field of nutrition in patients with CKD has resulted in the formation of general guidelines, although some uncertainties still exist on some of the best therapeutic or preventive options in uremic malnutrition. It is important to search actively for malnutrition since early diagnosis and treatment can improve the prognosis for CKD patients and reduce the monetary costs connected with treatment. Continue reading >>

Insulin And Its Role In Chronic Kidney Disease.

Insulin And Its Role In Chronic Kidney Disease.

Abstract The body's resistance to the actions of insulin (type II diabetes defect) results in compensatory increased production and secretion by the pancreas and leads to hyperinsulinemia in order to maintain euglycemia. When insulin secretion cannot be increased adequately (type I diabetes defect) to overcome insulin resistance in maintaining glucose homeostasis, hyperglycemia and glucose intolerance ensues. Insulin resistance and glucose intolerance has been well recognized in patients with advanced chronic kidney diseases (CKD). The etiology may involve uremic toxins from protein catabolism, vitamin D deficiency, metabolic acidosis, anemia, poor physical fitness, inflammation, and cachexia. Glucose and insulin abnormalities in nondiabetic CKD patients are implicated in the pathogenesis of hyperlipidemia and may represent important risk factors for accelerated atherosclerosis in these patients. Insulin secretion inadequacy has been associated with growth retardation in adolescents with CKD. Normal adolescents demonstrate an increase in insulin secretion as they go into puberty. It seems that the puberty growth spurt in adolescents both with normal health and renal failure may require increased insulin secretion as one of its hormonal requirements. Finally, insulin resistance has been associated with CKD. Whether insulin resistance is an antecedent of CKD or a consequence of impaired kidney function has been a subject of debate. The goal of this review was to provide an update of the literature on insulin pathophysiology in CKD, current understanding of its mechanisms, and epidemiological association of insulin resistance and CKD. Continue reading >>

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