Journal of Clinical Medicine

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14 pages, 706 KiB

Open AccessArticle

Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

by Haoyong Yu, Weiping Jia and ZengKui Guo

J. Clin. Med. 2014, 3(3), 1050-1063; https://doi.org/10.3390/jcm3031050 - 22 Sep 2014

Cited by 30 | Viewed by 8696

Abstract

Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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11 pages, 233 KiB

Open AccessArticle

The Impacts of Obesity and Metabolic Abnormality on Carotid Intima-Media Thickness and Non-Alcoholic Fatty Liver Disease in Children from an Inland Chinese City

by Xiao-Yue Wang, Xiang-Hua Zhang, Chao Hua Yao, Hong-Hui Zhu and Liang Zhang

J. Clin. Med. 2014, 3(1), 323-333; https://doi.org/10.3390/jcm3010323 - 20 Mar 2014

Cited by 1 | Viewed by 7245

Abstract

The Chinese inland, where low child obesity and overweight rates were reported in earlier studies, has recently experienced rapid economy changes. This may impact children’s health. In the present study, we investigated the obesity rate, metabolic health status, and their impacts on carotid [...] Read more.

The Chinese inland, where low child obesity and overweight rates were reported in earlier studies, has recently experienced rapid economy changes. This may impact children’s health. In the present study, we investigated the obesity rate, metabolic health status, and their impacts on carotid intima-media thickness (IMT) and non-alcoholic fatty liver disease (NAFLD) among children from Yueyang, an inland city of China. We found that the obesity rate was about 5% for both 7- and 11-year olds. Overweightness rates were 9.5% and 11.5% for the 7- and 11-year olds, respectively. Clinical and laboratory examinations revealed significant differences among different weight groups in the 11-year old volunteers, which were absent in the 7-year olds. Further statistical analysis showed that: age, BMI, blood pressure, triglyceride level, and metabolic abnormality were positively correlated to carotid IMT; triglyceride level, obesity, male, and the number of metabolic abnormalities were independent risk factors for NAFLD in these children. Our study suggests that: childhood overweightness and obesity are now epidemic in Yueyang, which have contributed to increased carotid IMT and may also increased NAFLD incidents; and serum triglyceride level is a critical factor in the development of childhood NAFLD. Thus, childhood metabolic health warrants further vigorous research in the inland of China. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

14 pages, 216 KiB

Open AccessArticle

Associations between U.S. Adult Obesity and State and County Economic Conditions in the Recession

by Qi Zhang, Rajan Lamichhane and Youfa Wang

J. Clin. Med. 2014, 3(1), 153-166; https://doi.org/10.3390/jcm3010153 - 27 Jan 2014

Cited by 10 | Viewed by 6374

Abstract

This study examines the association between state and county unemployment rates and individuals’ body weight status during the latest recession in the U.S. We used the U.S. Behavioral Risk Factor Surveillance System (BRFSS) data in 2007, 2009 and 2011, which were collected from [...] Read more.

This study examines the association between state and county unemployment rates and individuals’ body weight status during the latest recession in the U.S. We used the U.S. Behavioral Risk Factor Surveillance System (BRFSS) data in 2007, 2009 and 2011, which were collected from 722,692 American adults aged 18 or older. Overweight and obesity were defined as body mass index (BMI) ≥25, and ≥30, respectively. Multivariate linear and logistic regressions were applied to assess the association between BMI, risks of overweight and obesity, and state and county unemployment rates. State unemployment rates were negatively associated with individual BMI across years, while county unemployment rates were significantly positively associated with BMI and obesity rates in all years (p < 0.05). However, the scale of the positive relationship was reduced in 2009 and 2011. Stratified analyses were conducted among adults with employment and without employment. The unemployed group’s body weight status was not related to state- and county-level economic conditions in most times. In the pooled analyses with all three years’ data, the relationship between unemployment rates and body weight status were consistently reduced after the recession of 2008–2009. Our results indicated that macroeconomic conditions at different levels can have different associations with individuals’ obesity risk across time. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

Review

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14 pages, 195 KiB

Open AccessReview

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

by Moira S. Lewitt, Mairi S. Dent and Kerstin Hall

J. Clin. Med. 2014, 3(4), 1561-1574; https://doi.org/10.3390/jcm3041561 - 22 Dec 2014

Cited by 92 | Viewed by 19040

Abstract

The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to [...] Read more.

The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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21 pages, 2038 KiB

Open AccessReview

Obesity as an Early Symptom of the AMIS Syndrome

by W. Wayne Lautt and Hui Helen Wang

J. Clin. Med. 2014, 3(4), 1178-1198; https://doi.org/10.3390/jcm3041178 - 28 Oct 2014

Cited by 4 | Viewed by 6727

Abstract

We review evidence that the AMIS (Absence of Meal-induced Insulin Sensitization) syndrome describes a paradigm fundamental to development of obesity. The hypoglycemic response to a pulse of insulin is doubled after a meal as a result of Hepatic Insulin Sensitizing Substance (HISS), released [...] Read more.

We review evidence that the AMIS (Absence of Meal-induced Insulin Sensitization) syndrome describes a paradigm fundamental to development of obesity. The hypoglycemic response to a pulse of insulin is doubled after a meal as a result of Hepatic Insulin Sensitizing Substance (HISS), released from the liver to act selectively on muscle, heart and kidney. In the absence of HISS action, the hypoglycemic response to insulin is the same as in the fasted state, and only half of what it should be. Postprandial hyperglycemia ensues, with compensatory hyperinsulinemia, resultant hyperlipidemia and elevated free radical stress. Storage of nutrient energy shifts from glycogen in muscle to fat. Chronic AMIS results in adiposity, occurs with age, is accelerated with sucrose supplement, and prevented by a synergistic antioxidant. Exercise reverses AMIS, as do pharmaceuticals that mimic the “feeding signals”. The AMIS syndrome develops as a sequence of pathologies based on the consequences of absence of HISS action, including adiposity as the earliest symptom. Cardiac dysfunction, hypertension, hypercholesterolemia, and fatty liver are related to lack of HISS action. The AMIS syndrome hypothesis is mechanistic-based and accounts for the major pathologies associated with prediabetes, obesity, diabetes and metabolic syndrome. AMIS can be diagnosed, prevented and treated. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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21 pages, 1013 KiB

Open AccessReview

Importance of Beta Cell Function for the Treatment of Type 2 Diabetes

by Yoshifumi Saisho

J. Clin. Med. 2014, 3(3), 923-943; https://doi.org/10.3390/jcm3030923 - 14 Aug 2014

Cited by 46 | Viewed by 14281

Abstract

Type 2 diabetes (T2DM) is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, [...] Read more.

Type 2 diabetes (T2DM) is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, treatment of T2DM should aim to restore beta cell function. Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1) hypoglycemia; (2) body weight gain; (3) peripheral hyperinsulinemia and (4) postprandial hyperglycemia, which are all associated with inappropriate insulin supplementation, again underpinning the important role of endogenous and physiological insulin secretion in the management of T2DM. This review summarizes the current knowledge on beta cell function in T2DM and discusses the treatment strategy for T2DM in relation to beta cell dysfunction. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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16 pages, 688 KiB

Open AccessReview

Consequences of Abdominal Adiposity within the Metabolic Syndrome Paradigm in Black People of African Ancestry

by Trudy Gaillard

J. Clin. Med. 2014, 3(3), 897-912; https://doi.org/10.3390/jcm3030897 - 13 Aug 2014

Cited by 9 | Viewed by 5533

Abstract

The metabolic syndrome (MetS) is a constellation of risk factors that are associated with increased risks for coronary heart disease and type 2 diabetes. Although the cause is unknown, abdominal adiposity is considered the underpinning of these metabolic alterations. Hence, increased abdominal adiposity [...] Read more.

The metabolic syndrome (MetS) is a constellation of risk factors that are associated with increased risks for coronary heart disease and type 2 diabetes. Although the cause is unknown, abdominal adiposity is considered the underpinning of these metabolic alterations. Hence, increased abdominal adiposity contributes to dyslipidemia, hyperglycemia, beta cell dysfunction, insulin resistance, hypertension and inflammation. The role of abdominal adiposity in the causation of metabolic alterations that lead to the clinical expression of the MetS has become a focus of active research. In addition, there are ethnic/racial differences in the manifestation of the MetS. Therefore, the focus of this current review is to: (1) explore the consequences of abdominal obesity within the MetS paradigm; and (2) discuss the impact of ethnicity/race on MetS in Black People of African Ancestry (PAA). Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

32 pages, 298 KiB

Open AccessReview

Gut-Brain Endocrine Axes in Weight Regulation and Obesity Pharmacotherapy

by Dante J. Merlino, Erik S. Blomain, Amanda S. Aing and Scott A. Waldman

J. Clin. Med. 2014, 3(3), 763-794; https://doi.org/10.3390/jcm3030763 - 15 Jul 2014

Cited by 9 | Viewed by 7804

Abstract

In recent years, the obesity epidemic has developed into a major health crisis both in the United States as well as throughout the developed world. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed [...] Read more.

In recent years, the obesity epidemic has developed into a major health crisis both in the United States as well as throughout the developed world. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to combat this alarming trend. This review focuses on the endogenous gut-brain signaling axes that regulate appetite under physiological conditions, and discusses their clinical relevance by summarizing the clinical and preclinical studies that have investigated manipulation of these pathways to treat obesity. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

17 pages, 658 KiB

Open AccessReview

Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus

by Robert V. Farese, Mackenzie C. Lee and Mini P. Sajan

J. Clin. Med. 2014, 3(3), 724-740; https://doi.org/10.3390/jcm3030724 - 7 Jul 2014

Cited by 2 | Viewed by 7410

Abstract

This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and [...] Read more.

This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and what our options are for restoring insulin signaling, and glucose/lipid homeostasis. A central theme in this review is that excessive hepatic activity of an archetypal protein kinase enzyme, “atypical” protein kinase C (aPKC), plays a critically important role in the development of impaired glucose metabolism, systemic insulin resistance, and excessive hepatic production of glucose, lipids and proinflammatory factors that underlie clinical problems of glucose intolerance, obesity, hepatosteatosis, hyperlipidemia, and, ultimately, type 2 diabetes. The review suggests that normally inherited genes, in particular, the aPKC isoforms, that were important for survival and longevity in times of food scarcity are now liabilities in times of over-nutrition. Fortunately, new knowledge of insulin signaling mechanisms and how an aberration of excessive hepatic aPKC activation is induced by over-nutrition puts us in a position to target this aberration by diet and/or by specific inhibitors of hepatic aPKC. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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17 pages, 712 KiB

Open AccessReview

Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by Lipotoxicity

by Julien Véret, Lara Bellini, Paola Giussani, Carl Ng, Christophe Magnan and Hervé Le Stunff

J. Clin. Med. 2014, 3(2), 646-662; https://doi.org/10.3390/jcm3020646 - 20 Jun 2014

Cited by 38 | Viewed by 10691

Abstract

Pancreatic β cells secrete insulin in order to maintain glucose homeostasis. However, various environmental stresses such as obesity have been shown to induce loss of secretory responsiveness in pancreatic β cells and pancreatic β cell apoptosis which can favor the development of type [...] Read more.

Pancreatic β cells secrete insulin in order to maintain glucose homeostasis. However, various environmental stresses such as obesity have been shown to induce loss of secretory responsiveness in pancreatic β cells and pancreatic β cell apoptosis which can favor the development of type 2 diabetes (T2D). Indeed, elevated levels of free fatty acids (FFAs) have been shown to induce β cell apoptosis. Importantly, the chronic adverse effects of FFAs on β cell function and viability are potentiated in the presence of hyperglycaemia, a phenomenon that has been termed gluco-lipotoxicity. The molecular mechanisms underlying the pathogenesis of gluco-lipotoxicity in pancreatic β cells are not completely understood. Recent studies have shown that sphingolipid metabolism plays a key role in gluco-lipotoxicity induced apoptosis and loss of function of pancreatic β cells. The present review focuses on how the two main sphingolipid mediators, ceramides and sphingoid base-1-phosphates, regulate the deleterious effects of gluco-lipotoxicity on pancreatic β cells. The review highlights the role of a sphingolipid biostat on the dysregulation of β cell fate and function induced by gluco-lipotoxicity, offering the possibility of new therapeutic targets to prevent the onset of T2D. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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19 pages, 485 KiB

Open AccessReview

Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

by Gayotri Goswami, Nataliya Shinkazh and Nichola Davis

J. Clin. Med. 2014, 3(2), 595-613; https://doi.org/10.3390/jcm3020595 - 18 Jun 2014

Cited by 10 | Viewed by 9971

Abstract

The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains [...] Read more.

The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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29 pages, 432 KiB

Open AccessReview

Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling

by Jing Pan, Rakeshwar S. Guleria, Sen Zhu and Kenneth M. Baker

J. Clin. Med. 2014, 3(2), 566-594; https://doi.org/10.3390/jcm3020566 - 4 Jun 2014

Cited by 24 | Viewed by 11678

Abstract

Diabetic cardiomyopathy (DCM), a significant contributor to morbidity and mortality in diabetic patients, is characterized by ventricular dysfunction, in the absence of coronary atherosclerosis and hypertension. There is no specific therapeutic strategy to effectively treat patients with DCM, due to a lack of [...] Read more.

Diabetic cardiomyopathy (DCM), a significant contributor to morbidity and mortality in diabetic patients, is characterized by ventricular dysfunction, in the absence of coronary atherosclerosis and hypertension. There is no specific therapeutic strategy to effectively treat patients with DCM, due to a lack of a mechanistic understanding of the disease process. Retinoic acid, the active metabolite of vitamin A, is involved in a wide range of biological processes, through binding and activation of nuclear receptors: retinoic acid receptors (RAR) and retinoid X receptors (RXR). RAR/RXR-mediated signaling has been implicated in the regulation of glucose and lipid metabolism. Recently, it has been reported that activation of RAR/RXR has an important role in preventing the development of diabetic cardiomyopathy, through improving cardiac insulin resistance, inhibition of intracellular oxidative stress, NF-κB-mediated inflammatory responses and the renin-angiotensin system. Moreover, downregulated RAR/RXR signaling has been demonstrated in diabetic myocardium, suggesting that impaired RAR/RXR signaling may be a trigger to accelerate diabetes-induced development of DCM. Understanding the molecular mechanisms of retinoid receptors in the regulation of cardiac metabolism and remodeling under diabetic conditions is important in providing the impetus for generating novel therapeutic approaches for the prevention and treatment of diabetes-induced cardiac complications and heart failure. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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27 pages, 541 KiB

Open AccessReview

The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

by Wei Chen and Guoxun Chen

J. Clin. Med. 2014, 3(2), 453-479; https://doi.org/10.3390/jcm3020453 - 7 May 2014

Cited by 64 | Viewed by 22134

Abstract

Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity’s impact on [...] Read more.

Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity’s impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol), regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA’s role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided. Full article

(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)

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