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Special Issue "Carbohydrate and Insulin Metabolism in Chronic Kidney Disease"

A special issue of Medicina (ISSN 1010-660X).

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editors

Guest Editor
Prof. Dr. Domenico Santoro

Associate Professor of Nephrology, Unit of Nephrology and Dialysis, Department of Internal Medicine Via Consolare Valeria, 98124 Messina, Italy
Website | E-Mail
Interests: clinical nephrology; glomerulonephritis; dialysis; vascular access; mineral bone disorders and vitamin D; anemia in chronic kidney disease
Guest Editor
Prof. Dr. Giuseppina Russo

Assistant Professor of Internal Medicine, Metabolic Unit, Department of Clinical and Experimental Medicine Via Consolare Valeria, 98124 Messina, Italy
Website | E-Mail
Interests: diabetes; diabetic kidney disease; gender medicine; macrovascular disease; lipid metabolism; homocysteine; genetics

Special Issue Information

Dear Colleagues,

The prevalence of diabetes mellitus (DM) in the general population is continuously increasing, and it has been estimated that the number of diabetic subjects will reach 592 million worldwide by the end of 2035. DM is a metabolic disease that causes renal failure, and renal failure increases insulin resistance.

Thus, the kidney has a major role in glucose metabolism, and the complex relationship between diabetes and the kidney has been only recently unveiled thanks to the advance of new hypoglycaemic treatments. In patients with chronic renal failure (CRF), the accumulation of uremic toxins and increased parathyroid hormone levels causes and increased need for insulin secretion. Moreover, anemia caused by CRF has an impact on insulin resistance, and the correction of anemia by erythropoietin has been shown to improve glucose metabolism and insulin sensitivity in the body. Another consequence of CRF is a reduced insulin secretion, which is due to complications of renal failure such as metabolic acidosis, elevated levels of parathyroid hormone, and decreased level of vitamin D. However, despite a reduced insulin secretion and increased insulin resistance, most non-diabetic patients with renal failure do not have hyperglycemia unless they are genetically predisposed.

The relationship between DM and the kidney changes according to the stage of renal disease, and different mechanisms intervene altering insulin and carbohydrate metabolism in advanced stages of CRF. Indeed, when the glomerular filtration rate (GFR) become less than 15ml/min, the renal clearance of insulin decreases, which is clinically important in the treatment of patients with diabetes. Thus, the decreased insulin degradation may drastically reduce the need for administration of insulin in DM patients with advanced CRF, even resolving glucose abnormalities in type 2 DM. On the other hand, this may increase the risk of hypoglycemia, rendering diabetes treatment particularly challenging in these patients.

Finally, when patients with CRF start renal replacement therapy both with hemodialysis, or peritoneal dialysis, the insulin requirements further change, mainly due to increased appetite and food intake resulting from the attenuation of uremic symptoms.

Notably, increased evidence has been recently focused on clarifying different morphological renal lesions associated with diabetes, especially the non-albuminuric phenotype. There is still an ongoing debate on the prevalence and the role of different forms of kidney disease in diabetic subjects, other than diabetic kidney disease.

Furthermore, the epidemiology of diabetic kidney disease changed overtime, mainly because of the ageing of the population and the better available therapeutic strategies, leading to a greater number of DM subjects who are at-target for glucose and blood pressure control. However, in spite of these ameliorated treatments, many DM subjects still develop renal impairment, because of the occurrence of other independent risk factors, such as atherogenic dislipidemia. To date, renal impairment represented a demanding task in diabetic patients, because of the limited therapeutic options available and the higher burden of associated complications, including cardiovascular disease. In the last decades, the appearance of new class of hypoglycaemic drugs opened new avenues for safely treating diabetes in subjects with CRF, or even preventing its occurrence and/or progression.

This Special Issue will deal with several aspects of the management of diabetes and its renal complications, as specified below. 

Prof. Dr. Domenico Santoro
Prof. Dr. Giuseppina Russo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Diabetic kidney disease
  • Microalbuminuria
  • Gender
  • Carbohydrate metabolism
  • Low protein diet in diabetic nephropathy
  • Ageing
  • SGLT2 GLP1-RAs

Published Papers (7 papers)

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Research

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Open AccessArticle
Nutritional Aspects in Diabetic CKD Patients on Tertiary Care
Medicina 2019, 55(8), 427; https://doi.org/10.3390/medicina55080427
Received: 22 May 2019 / Revised: 22 July 2019 / Accepted: 29 July 2019 / Published: 1 August 2019
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Abstract
Background and objectives: Diabetes is largely prevalent in the chronic kidney disease (CKD) population. Both conditions have metabolic and nutritional abnormalities that affect body composition and the presence of diabetes makes the dietary management of CKD patients more difficult. The aim of [...] Read more.
Background and objectives: Diabetes is largely prevalent in the chronic kidney disease (CKD) population. Both conditions have metabolic and nutritional abnormalities that affect body composition and the presence of diabetes makes the dietary management of CKD patients more difficult. The aim of this study was to assess peculiar nutritional and functional aspects of diabetic patients in an adult/elderly CKD population, and their predictive significance. Materials and methods: This prospective cohort study included 144 out-patients aged >55 years, affected by stage 3b-4 CKD, on tertiary care clinic; 48 (40 males) were type 2 diabetics and 96 (80 males) were nondiabetics. The two groups have similar age, gender, and residual renal function (30 ± 9 vs. 31 ± 11 mL/min×1.73). All patients underwent a comprehensive nutritional and functional assessment and were followed for 31 ± 14 months. Results: Diabetic CKD patients showed higher waist circumference and fat body mass, lower muscle mass, and lower number of steps per day and average daily METs. Meanwhile, resting energy expenditure (REE), as assessed by indirect calorimetry, and dietary energy intake were similar as well as hand-grip and 6 min walking test. Diabetic patients did not show a greater risk for all-cause mortality and renal death with respect to nondiabetics. Middle arm muscle circumference, phase angle, serum cholesterol, and serum albumin were negatively related to the risk of mortality and renal death after adjustment for eGFR. Conclusions: CKD diabetic patients differed from nondiabetics for a greater fat mass, lower muscle mass, and lower physical activity levels. This occurred at the same REE and dietary energy intake. The outcome of diabetic or nondiabetic CKD patients on tertiary care management was similar in terms of risk for mortality or renal death. Given the same residual renal function, low levels of muscle mass, phase angle, serum albumin, and cholesterol were predictive of poor outcome. Overall, a malnutrition phenotype represents a major predictor of poor outcome in diabetic and nondiabetic CKD patients. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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Review

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Open AccessReview
Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach
Medicina 2019, 55(7), 382; https://doi.org/10.3390/medicina55070382
Received: 4 June 2019 / Revised: 2 July 2019 / Accepted: 12 July 2019 / Published: 16 July 2019
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Abstract
Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin–angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in [...] Read more.
Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin–angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin–angiotensin–aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
Open AccessReview
Role of Vitamin D Status in Diabetic Patients with Renal Disease
Medicina 2019, 55(6), 273; https://doi.org/10.3390/medicina55060273
Received: 29 April 2019 / Revised: 3 June 2019 / Accepted: 8 June 2019 / Published: 13 June 2019
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Abstract
Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will [...] Read more.
Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron’s function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
Open AccessReview
SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects
Medicina 2019, 55(6), 268; https://doi.org/10.3390/medicina55060268
Received: 26 April 2019 / Revised: 30 May 2019 / Accepted: 6 June 2019 / Published: 11 June 2019
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Abstract
The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that [...] Read more.
The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes (glomerular filtration rate and albuminuria) were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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Open AccessReview
GLP-1 Receptor Agonists and Kidney Protection
Medicina 2019, 55(6), 233; https://doi.org/10.3390/medicina55060233
Received: 21 March 2019 / Revised: 18 April 2019 / Accepted: 30 May 2019 / Published: 31 May 2019
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Abstract
Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular [...] Read more.
Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular filtration rate (GFR). Apart from renin–angiotensin–aldosterone system (RAAS) inhibitors, no other drugs are currently available as therapy for diabetic kidney disease (DKD). Glucagon-like peptide-1 receptor (GLP-1R) agonists are a new class of anti-hyperglycemic drugs which have been demonstrated to prevent the onset of macroalbuminuria and reduce the decline of GFR in diabetic patients. These drugs may exert their beneficial actions on the kidneys through blood glucose- and blood pressure (BP)-lowering effects, reduction of insulin levels and weight loss. Clinical benefits of GLP-1R agonists were acknowledged due to data from large randomized phase III clinical trials conducted to assess their cardiovascular(CV) safety. These drugs improved renal biomarkers in placebo-controlled clinical studies, with effects supposed to be independent of the actions on glycemic control. In this review, we will focus on the actions of GLP-1R agonists on glucose metabolism and kidney physiology, and evaluate direct and indirect mechanisms through which these drugs may confer renal protection. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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Open AccessReview
IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review
Received: 10 December 2018 / Revised: 11 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
Cited by 2 | PDF Full-text (554 KB) | HTML Full-text | XML Full-text
Abstract
Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is [...] Read more.
Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is a receptor for IL-33, expressed selectively on a subset of Th2 cells, mediating some of their functions. The IL-33/ST2 axis plays an important role in several acute and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Different disorders are related to the activity of IL-33, ST2, or their axis, including cardiovascular disease or renal disturbances. Therefore, in the present work, a literature review was conducted, covering the period from 1 January 2000 to 30 November 2018, in PubMed, ScienceDirect, and Google Scholar database, to assess the involvement of the IL-33/ST2 axis in diabetic kidney disease. 6 articles directly dealing with the argument were identified, highlighting a clear link between IL-33/ST2 axis and diabetic kidney disease or related nephropathy. Overall, the involvement of ST2 seems to be more predictive than IL-33, especially in investigating the deterioration of kidney function; however, both compounds are pivotal in the field of renal diseases. Future studies are required to confirm the scientific evidences on larger and more heterogeneous cohorts. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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Other

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Open AccessCase Report
Nephrology Consultation for Severe SGLT2 Inhibitor-Induced Ketoacidosis in Type 2 Diabetes: Case Report
Medicina 2019, 55(8), 462; https://doi.org/10.3390/medicina55080462
Received: 18 June 2019 / Revised: 6 August 2019 / Accepted: 8 August 2019 / Published: 10 August 2019
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Abstract
Euglycemic diabetic ketoacidosis (euDKA) related to sodium-glucose cotransporter 2 inhibitor (SGLT2-I), despite being reported as consistent, though infrequent, adverse effect in all trials on SGLT2-I in type 2 diabetes mellitus (T2D), still remains poorly known in the real world. On the other hand, [...] Read more.
Euglycemic diabetic ketoacidosis (euDKA) related to sodium-glucose cotransporter 2 inhibitor (SGLT2-I), despite being reported as consistent, though infrequent, adverse effect in all trials on SGLT2-I in type 2 diabetes mellitus (T2D), still remains poorly known in the real world. On the other hand, the use of this new class of antihyperglycemic agents is expected to increase based on the recent solid evidence of remarkable cardiorenal protection. Therefore, improving awareness on risk factors, diagnosis, and treatment of euDKA is essential to allow correct implementation of SGLT2-I in clinical practice. We here report a T2D patient admitted to the emergency department and then transferred to the nephrology-dialysis unit because of severe euglycemic diabetic ketoacidosis (euDKA) related to sodium-glucose cotransporter 2 inhibitor (SGLT2-I). In our patient, a concurrent acute kidney injury at presentation, initially attributed to excessive use of nonsteroid anti-inflammatory agents, and the absence of severe hyperglycemia led to delayed diagnosis and proper therapy. The detailed description of decision-making process for diagnosis and therapy, and the analysis of precipitating factors as well, discloses the helpful contribution of nephrologist to optimize prevention and management of euDKA. Full article
(This article belongs to the Special Issue Carbohydrate and Insulin Metabolism in Chronic Kidney Disease)
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