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Current Diabetes Reviews 2020The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the...
BACKGROUND
The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan.
OBJECTIVE
Discuss the pathophysiology of type 2 DM in children and adolescents.
METHODS AND RESULTS
This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores the complexity in disease progression.
CONCLUSION
A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.
Topics: Adolescent; Child; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Pediatric Obesity; Risk Factors
PubMed: 29879890
DOI: 10.2174/1573399814666180608074510 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2023Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest... (Review)
Review
Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest anti-hyperglycemic drugs. They reduce blood glucose levels by inhibiting renal glucose reabsorption in the early proximal convoluted tubule. Various randomized trials showed that SGLT2i have cardio-protective and reno-protective action. SGLT2i also affect body composition. They usually decrease body fat percentage, visceral and subcutaneous adipose tissue. However, regarding the muscle mass, there are conflicting findings some studies showing detrimental effects and others showed neutral or beneficial effects. This issue is extremely important not only because of the wide use of SGLT2i around globe; but also skeletal muscle mass consumes large amounts of calories during exercise and is an important determinant of resting metabolic rate and skeletal muscle loss hinders energy consumption leading to obesity. In this systematic review, we extensively reviewed the experimental and clinical studies regarding the impact of SGLT2i on muscle mass and related metabolic alterations. Importantly, studies are heterogeneous and there is unmet need to highlight the alterations in muscle during SGLT2i use.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sarcopenia; Glucose; Sodium; Symporters
PubMed: 37862820
DOI: 10.1016/j.clnu.2023.10.004 -
Cureus Oct 2022The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations... (Review)
Review
The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations in the treatment of heart failure, the prognosis is still poor. To identify, evaluate, and summarize the findings of all relevant studies of a drug that is equally efficacious but rather cost-effective, empagliflozin compared to the other sodium-glucose cotransporter-2 (SGLT2) inhibitors was studied. It is licensed by the Food and Drug Administration (FDA), acts by preventing the reabsorption of glucose from the kidney, and exhibits promising advantages in heart failure. We systematically explored PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) for randomized controlled trials (RCTs) and observational studies related to cardiovascular and renal outcomes of empagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). After performing scoping search and search strategy, studies were screened for quality assessment using the Cochrane risk of bias assessment tool. We screened 60 articles by titles, abstract, and exclusion and inclusion criteria, after which eight final randomized controlled trials (RCTs) with 18,659 participants treated with empagliflozin and placebo were used for the systematic review. This systematic review's objective is to investigate and explore the full range of empagliflozin's effects and advantages on cardiac structure, function, and hemodynamics and renal function in patients with heart failure with reduced ejection fraction (EF) in order to better understand the drug's effects and related mechanisms.
PubMed: 36348895
DOI: 10.7759/cureus.29896 -
Nutrients Jun 2018Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence... (Review)
Review
Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence linking hypomagnesemia to clinical consequences in these specific populations. After a brief summary of the main mechanisms involved in Mg regulation and of Mg status in end-stage renal disease, the review focuses on the relationship between hypomagnesemia and cardiovascular risk in kidney transplant recipients. A body of evidence in recent studies points to a negative impact of hypomagnesemia on post-transplant diabetes mellitus (PTDM) and cardiovascular risk, which currently represent the main threat for morbidity and mortality in kidney transplantation. Deleterious biological mechanisms induced by hypomagnesemia are also discussed. While data analysis enables us to conclude that hypomagnesemia is linked to the development of PTDM, studies prospectively evaluating the impact of hypomagnesemia correction after kidney transplantation are still lacking and needed.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Magnesium; Magnesium Deficiency; Renal Elimination; Renal Reabsorption; Risk Factors; Treatment Outcome
PubMed: 29882768
DOI: 10.3390/nu10060729 -
Journal of the American Society of... Nov 2023Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the...
SIGNIFICANCE STATEMENT
Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the diagnostic workup of patients with electrolyte disorders. In this systematic review, we investigated the presence of electrolyte disorders in patients with mitochondrial cytopathies to determine the relevance of mitochondrial mutation screening in this population. Our analysis demonstrates that electrolyte disorders are commonly reported in mitochondrial cytopathies, often as presenting symptoms. Consequently, more clinical attention should be raised for mitochondrial disease as cause for disturbances in electrolyte homeostasis. Further prospective cohort studies are required to determine the exact prevalence of electrolyte disorders in mitochondrial cytopathies.
BACKGROUND
Electrolyte reabsorption in the kidney has a high energy demand. Proximal and distal tubular epithelial cells have a high mitochondrial density for energy release. Recently, electrolyte disorders have been reported as the primary presentation of some mitochondrial cytopathies. However, the prevalence and the pathophysiology of electrolyte disturbances in mitochondrial disease are unknown. Therefore, we systematically investigated electrolyte disorders in patients with mitochondrial cytopathies.
METHODS
We searched PubMed, Embase, and Google Scholar for articles on genetically confirmed mitochondrial disease in patients for whom at least one electrolyte is reported. Patients with a known second genetic anomaly were excluded. We evaluated 214 case series and reports (362 patients) as well as nine observational studies. Joanna Briggs Institute criteria were used to evaluate the quality of included studies.
RESULTS
Of 362 reported patients, 289 had an electrolyte disorder, with it being the presenting or main symptom in 38 patients. The average number of different electrolyte abnormalities per patient ranged from 2.4 to 1.0, depending on genotype. Patients with mitochondrial DNA structural variants seemed most affected. Reported pathophysiologic mechanisms included renal tubulopathies and hormonal, gastrointestinal, and iatrogenic causes.
CONCLUSIONS
Mitochondrial diseases should be considered in the evaluation of unexplained electrolyte disorders. Furthermore, clinicians should be aware of electrolyte abnormalities in patients with mitochondrial disease.
Topics: Humans; Mitochondrial Myopathies; Kearns-Sayre Syndrome; Mitochondrial Diseases; Mitochondria; DNA, Mitochondrial; Water-Electrolyte Imbalance
PubMed: 37678265
DOI: 10.1681/ASN.0000000000000224 -
The Cochrane Database of Systematic... Oct 2021Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations... (Review)
Review
BACKGROUND
Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations significantly, nor does it always normalize linear growth. Some clinical trials suggest that combining recombinant human growth hormone therapy with conventional treatment improves growth velocity, phosphate retention, and bone mineral density, but some clinical trials suggest that it appears to aggravate the pre-existent disproportionate stature of such children. This is an updated version of a previously published review.
OBJECTIVES
To determine whether recombinant human growth hormone therapy for children with X-linked hypophosphatemia is associated with changes in longitudinal growth, mineral metabolism, endocrine function, renal function, bone mineral density, body proportions, and also with any adverse effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and the reference lists of identified trials and other reviews. We also undertook some additional handsearching of relevant journals and conference proceedings. Date of the most recent search: 12 January 2021 SELECTION CRITERIA: All randomized controlled studies or quasi-randomized controlled studies comparing growth hormone (alone or combined with conventional treatment) with either placebo or conventional treatment alone in children with X-linked hypophosphatemia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for risk of bias and extracted data from eligible studies. GRADE criteria were used to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included two studies (20 participants) in the review. In one cross-over study, results showed that recombinant human growth hormone therapy may improve the height standard deviation (SDS) score (z score), but we are unsure whether the intervention was the reason behind a transient increase in serum phosphate and tubular maximum for phosphate reabsorption. In the second, parallel study, treatment may also have improved the height SDS from baseline in the rhGH group compared to the control group, although no significant difference was seen between groups after three years, MD 0.50 SDS (95 % CI -0.54 to 1.54) (low-certainty evidence). The treatment was possibly well-tolerated during both studies with only transient adverse effects seen in three participants (low-certainty evidence). We are uncertain whether growth hormone improves serum phosphate levels or change in TmP/GFR (very low-certainty evidence). The treatment may make little or no difference to alkaline phosphatase levels (low-certainty evidence).
AUTHORS' CONCLUSIONS
We do not have enough high-certainty evidence to recommend the use of recombinant human growth hormone therapy in children with X-linked hypophosphatemia.
Topics: Body Height; Child; Cross-Over Studies; Familial Hypophosphatemic Rickets; Growth Hormone; Human Growth Hormone; Humans
PubMed: 34618915
DOI: 10.1002/14651858.CD004447.pub3 -
Nephrology, Dialysis, Transplantation :... Sep 2018Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major...
Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5-10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.
Topics: Acute Kidney Injury; Humans; Kidney; Magnetic Resonance Imaging; Practice Guidelines as Topic; Renal Artery; Renal Circulation; Spin Labels
PubMed: 30137581
DOI: 10.1093/ndt/gfy180 -
Cardiology and Therapy Dec 2016Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drugs that have been extensively investigated for the treatment of hyperglycemia in type 2... (Review)
Review
UNLABELLED
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drugs that have been extensively investigated for the treatment of hyperglycemia in type 2 diabetes mellitus (T2DM). These drugs reduce hyperglycemia by blocking renal glucose reabsorption, thereby promoting increased renal glucose excretion. Beyond glycemic control, these drugs have other beneficial effects on cardiovascular (CV) risk factors. The present review discusses the potential role of SGLT2 inhibitors in treating CV complications (acute and chronic) associated with T2DM.
FUNDING
AstraZeneca Pharma India Ltd.
PubMed: 27539303
DOI: 10.1007/s40119-016-0069-z -
Journal of Diabetes Research 2020Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose...
Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. . A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). . Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with NaKATPase activity impacting on glucose transport. . Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.
Topics: Animals; Glucose; Humans; Insulin; Kidney Tubules, Proximal; Sodium-Glucose Transport Proteins
PubMed: 32377524
DOI: 10.1155/2020/8492467 -
Biometals : An International Journal on... Apr 2017Past research has shown the importance of zinc in several metabolic processes, such as the glucidic metabolism. The present systematic review aims to discuss zinc's... (Review)
Review
Past research has shown the importance of zinc in several metabolic processes, such as the glucidic metabolism. The present systematic review aims to discuss zinc's participation in the glycemic control of type 2 diabetes mellitus (DM2) patients. In order to accomplish that, a systematic search was performed in the Pubmed database using the following indexed and theme-related descriptors: "zinc" AND "type 2 diabetes mellitus", AND MeSH terms related to glycemic control combined with the boolean operator OR. In total, 1078 articles were retrieved from the research, of which 15 articles of original studies conducted with DM2 patients were included, with three being about the effect of mineral supplementation and 12 reporting observational studies. The main findings of these studies consisted of low body contents of zinc and high excretion of zinc in urine. Hyperglycemia was one of the mechanisms that caused these alterations owing to its interference in zinc reabsorption via renal cells. Another evidence was the negative correlation between the glycated hemoglobin percentage (%HbA1c) and the plasma zinc levels. Additionally, it has been observed that zinc supplementation in DM2 patients has improved glycemic control, since the %HbA1c significantly reduced in these individuals. This present review shows the positive effect of adequate zinc levels on glycemic control, whether it is through dietetic ingestion or supplementation, since its role in insulin homeostasis is clear.
Topics: Blood Glucose; Cations, Divalent; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Intestinal Absorption; Zinc
PubMed: 28138861
DOI: 10.1007/s10534-017-9996-y