Abstract Uncontrolled hyperglycemia in hospitalized patients with or without a previous diagnosis of diabetes is associated with adverse outcomes and longer lengths of hospital stay. It is estimated ...that one-third of hospitalized patients will experience significant hyperglycemia, and the cost associated with hospitalization for patients with diabetes accounts for half of all health care expenditures for this disease. Optimizing glycemic control should be a priority for all health care providers in the inpatient setting. Appropriate management strategies should include identification of appropriate glycemic targets, prevention of hypoglycemia, initiation of appropriate basal-plus-bolus insulin regimens, and planning for the transition from inpatient to outpatient therapy before hospital discharge.
Type 1 diabetes mellitus (T1DM) results from a highly specific immune-mediated destruction of pancreatic β cells, resulting in chronic hyperglycemia. For many years, one of the mainstays of therapy ...for patients with T1DM has been exercise balanced with appropriate medications and medical nutrition. Compared to healthy peers, athletes with T1DM experience nearly all the same health-related benefits from exercise. Despite these benefits, effective management of the T1DM athlete is a constant challenge due to various concerns such as the increased risk of hypoglycemia. This review seeks to summarize the available literature and aid clinicians in clinical decision-making for this patient population.
PubMed searches were conducted for "type 1 diabetes mellitus AND athlete" along with "type 1 diabetes mellitus AND exercise" from database inception through November 2015. All articles identified by this search were reviewed if the article text was available in English and related to management of athletes with type 1 diabetes mellitus. Subsequent reference searches of retrieved articles yielded additional literature included in this review.
The majority of current literature available exists as recommendations, review articles, or proposed societal guidelines, with less prospective or higher-order treatment studies available. The available literature is presented objectively with an attempt to describe clinically relevant trends and findings in the management of athletes living with T1DM.
Managing T1DM in the context of exercise or athletic competition is a challenging but important skill for athletes living with this disease. A proper understanding of the hormonal milieu during exercise, special nutritional needs, glycemic control, necessary insulin dosing adjustments, and prevention/management strategies for exercise-related complications can lead to successful care plans for these patients. Individualized management strategies should be created with close cooperation between the T1DM athlete and their healthcare team (including a physician and dietitian).
Abstract
Context:
Fatty liver disease is one of the most common forms of chronic liver disease. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of fatty liver.
...Objective:
Determine the relationship between fatty liver and aldosterone in a large cohort study.
Design:
Community-based, observational cohort study of African Americans.
Setting:
The original Jackson Heart Study cohort enrolled African American participants from the Jackson, Mississippi, metropolitan area in Hinds, Madison, and Rankin Counties.
Participants:
Our study population consisted of 2507 Jackson Heart Study participants (1625 women and 882 men) who had liver attenuation measured per computed tomography scans, had aldosterone measurements, and were not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or mineralocorticoid receptor antagonists.
Intervention:
There was no intervention.
Main outcome measure:
Liver attenuation on computed tomography scans.
Results:
Univariate regression analysis demonstrated a statistically significant correlation between aldosterone levels and liver attenuation. Each doubling of aldosterone was associated with 1.08 Hounsfield unit decrease (95% confidence interval, 1.47 to −0.69, P < 0.001). A multivariable model adjusted for body mass index, age, alcohol intake, and homeostatic model assessment of insulin resistance determined that the association was statistically significant only for women.
Conclusion:
Our data demonstrate a positive association between aldosterone levels and fatty liver in African American women.
Aldosterone has been implicated in fatty liver. Population-based studies supporting this are lacking. In an African American cohort, we demonstrate an association between aldosterone and fatty liver.
Mutant forms of thyroid hormone receptor (TR) with dominant negative activity are frequently found in human hepatocellular carcinoma (HCC). Interestingly, the v-erbA oncogene, known to exert a ...dominant-negative effect on the expression of thyroid hormone (T3)-responsive genes, led to the development of HCC in a transgenic mouse model. Thus it is possible that the oncogenic activity of v-erbA in hepatocytes may be mediated by its dominant negative activity on T3-responsive genes. Microarray analysis was used to identify genes differentially expressed in murine hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to T3. The Affymetrix GeneChip Mouse Genome 430 2.0 array consisted of over 39,000 transcripts representing well-known genes. We have identified twenty T3-responsive genes that are negatively regulated by v-erbA at 3 h, and eighteen genes at 24 h, such as follistatin, activin βC, thrombomodulin, Six1, Rasgrp3 and Ndrg2, as well as genes that are regulated by v-erbA only, such as angiopoietin 1 and Igfr2. We have identified T3 responsive genes that are dysregulated by v-erbA. These genes are known to be involved in carcinogenesis. Our studies may provide insight into the potential role of mutant forms of TR in the pathogenesis of HCC.
Retinoic acid (RA) modulates the expression of genes involved in embryogenesis, development and differentiation processes in vertebrates. The v-erbA oncogene is known to exert a dominant-negative ...effect on the expression of RA-responsive genes. v-erbA belongs to a superfamily of transcription factors called nuclear receptors, which includes the retinoic acid receptors (RARs) responsible for mediating the effects of retinoic acid. While RA inhibits cell proliferation and promotes cell differentiation and apoptosis in a variety of tissues, v-erbA seems to play a role in oncogenesis, namely in the development of hepatocellular carcinoma (HCC) in a transgenic mouse model.
In order to study the effect of v-erbA on RA-responsive genes, we used microarray analysis to identify genes differentially expressed in murine hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to RA for 3 h or 24 h. We have identified RA-responsive genes that are affected by v-erbA, as well as genes that are regulated by v-erbA alone. We have found that v-erbA can affect gene expression in the presence of RA and at the level of basal transcription. We have also identified a number of v-erbA-responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC.
This article is aimed at providing a practical up-to-date review of the precipitating factors, diagnosis, management and secondary prevention of hyperglycemic emergencies (diabetic ketoacidosis (DKA) ...and hyperglycemic hyperosmolar state (HHS) to assist critical care physicians and hospitalists caring for these patients. Limitations of various guidelines include implementation in settings with an infrastructure different from that specified in the guidelines of a respective country, state, region or community. Appropriate individualized acute management of these conditions typically results in satisfactory clinical outcomes and may decrease the mortality rate from up to 20% in type 2 diabetics with hyperglycemic hyperosmolar state vs less than 2% in patients with DKA. DKA may be the first manifestation of type 1 diabetes and can also occur in type 2 diabetics depending on the state of insulin sufficiency/secretion. For type 1 diabetics, the transition period from adolescence to adulthood is particularly critical to prevent repetitive hospital admissions. Hyperglycemic emergencies are usually preventable but do depend on patient compliance and adherence as well as medical infrastructure. Patients of all ages should be both appropriately educated and assured continuous access to health care to prevent recurrences of these conditions.
Retinoic acid (RA) exerts profound effects on multiple aspects of vertebrate development, homeostasis and cellular differentiation. Although the liver is a major target organ for RA, no data exist on ...global expression of RA-responsive genes in hepatocytes. Therefore, the aim of this study was to characterize RA-responsive genes in a simple system, by using a non-transformed hepatic cell line that is able to express sufficient amounts of endogenous retinoic acid receptors (RARs). For this purpose we used the murine non-transformed hepatocyte cell line AML12.
We performed analyses using a cDNA microarray containing 39,000 murine genes. We identified 15 genes that were up-regulated ≥
2 fold while 3 were down-regulated ≥
2 fold after 3 h treatment with all-trans RA. Following 24 h all-trans RA treatment, 26 genes were up-regulated ≥
2 fold, whereas 48 genes were down-regulated ≥
2 fold. For some of the genes not previously known to be regulated by RA, we confirmed the regulation by RA using real time PCR.
Our data in AML12 cells provide a simple and physiologically relevant system to study RA action, without the influence of neoplastic transformation or artificial RAR over-expression. Furthermore, our data describe novel RA responsive genes and provide insight into the role of RA in important processes such as cholesterol metabolism, bile acid secretion, and oncogenesis, among others, that can be tested in future experiments in vivo.
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