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Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12787pmid: 25998863
Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of healthcare dollars annually. Since the advent of the obesity epidemic, insulin resistance (IR) and diabetes have become common clinical findings in patients with ALD; and the development of IR predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin‐sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12880pmid: 26335600
Obesity is a phenotype resulting from a series of causative factors with a variable risk of complications. Etiologic diversity requires personalized prevention and treatment. Imaging procedures offer the potential to investigate the interplay between organs and pathways underlying energy intake and consumption in an integrated manner, and may open the perspective to classify and treat obesity according to causative mechanisms. This review illustrates the contribution provided by imaging studies to the understanding of human obesity, starting with the regulation of food intake and intestinal metabolism, followed by the role of adipose tissue in storing, releasing, and utilizing substrates, including the interconversion of white and brown fat, and concluding with the examination of imaging risk indicators related to complications, including type 2 diabetes, liver pathologies, cardiac and kidney diseases, and sleep disorders. The imaging modalities include (1) positron emission tomography to quantify organ‐specific perfusion and substrate metabolism; (2) computed tomography to assess tissue density as an indicator of fat content and browning/ whitening; (3) ultrasounds to examine liver steatosis, stiffness, and inflammation; and (4) magnetic resonance techniques to assess blood oxygenation levels in the brain, liver stiffness, and metabolite contents (triglycerides, fatty acids, glucose, phosphocreatine, ATP, and acetylcarnitine) in a variety of organs.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12842pmid: 26250623
Advances in the technological qualities of imaging modalities for assessing human body composition have been stimulated by accumulating evidence that individual components of body composition have significant influences on chronic disease onset, disease progression, treatment response, and health outcomes. Importantly, imaging modalities have provided a systematic method for differentiating phenotypes of body composition that diverge from what is considered normal, that is, having low bone mass (osteopenia/osteoporosis), low muscle mass (sarcopenia), high fat mass (obesity), or high fat with low muscle mass (sarcopenic obesity). Moreover, advances over the past three decades in the sensitivity and quality of imaging not just to discern the amount and distribution of adipose and lean tissue but also to differentiate layers or depots within tissues and cells is enhancing our understanding of distinct mechanistic, metabolic, and functional roles of body composition within human phenotypes. In this review, we focus on advances in imaging technologies that show great promise for future investigation of human body composition and how they are being used to address the pandemic of obesity, metabolic syndrome, and diabetes.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12807pmid: 26132277
Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function and with structural abnormalities in the brain. With an aging population and a growing epidemic of diabetes, central nervous system–related complications of diabetes are expected to rise and could have challenging future public health implications. In this review, we will discuss the brain structural and functional changes that have been associated with type 1 and type 2 diabetes. Diabetes duration and glycemic control may play important roles in the development of cognitive impairment in diabetes, but the exact underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood. Future research is needed to better understand the natural history and the underlying mechanisms, as well as to identify risk factors that predict who is at greatest risk of developing cognitive impairment. This information will lead to the development of new strategies to minimize the impact of diabetes on cognitive function.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12758pmid: 25877817
MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms and thereby affect many cellular processes and disease states. Over 2,000 human mature miRNAs have been identified, and at least 60% of all human protein‐coding genes are known to be regulated by miRNAs. MicroRNA biogenesis involves classical transcription regulation and processing by key ribonucleases, as well as other protein factors and epigenetic mechanisms. Diabetic nephropathy (DN), a severe microvascular complication frequently associated with diabetes mellitus, is a major cause of renal failure. Although several mechanisms of regulation of key renal genes implicated in DN pathogenesis have been identified, a greater understanding is needed to develop better treatment modalities. Recent studies show that miRNAs induced in renal cells in vivo and in vitro under diabetic conditions can promote the accumulation of extracellular matrix proteins related to fibrosis and glomerular dysfunction. In this review, we highlight the significance of the expression of miRNAs in various stages of DN and emerging approaches to exploit them as biomarkers for early detection or novel therapeutic targets to prevent progression of DN.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12844pmid: 26250784
Diabetes self‐care is a critical aspect of disease management for adults with diabetes. Since family members can play a vital role in a patient's disease management, involving them in self‐care interventions may positively influence patients’ diabetes outcomes. We systematically reviewed family‐based interventions for adults with diabetes published from 1994 to 2014 and assessed their impact on patients’ diabetes outcomes and the extent of family involvement. We found 26 studies describing family‐based diabetes interventions for adults. Interventions were conducted across a range of patient populations and settings. The degree of family involvement varied across studies. We found evidence for improvement in patients’ self‐efficacy, perceived social support, diabetes knowledge, and diabetes self‐care across the studies. Owing to the heterogeneity of the study designs, types of interventions, reporting of outcomes, and family involvement, it is difficult to determine how family participation in diabetes interventions may affect patients’ clinical outcomes. Future studies should clearly describe the role of family in the intervention, assess quality and extent of family participation, and compare patient outcomes with and without family involvement.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12939pmid: 26448515
The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high‐risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes‐related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three‐ to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes‐related morbidity and mortality at younger ages.
Powers, Alvin C.; Ahima, Rexford S.
doi: 10.1111/nyas.12950pmid: 26495771
Diabetes affects 29 million Americans and is associated with billions of dollars in health expenditures and lost productivity. Robust evidence has shown that lifestyle interventions in people at high risk for diabetes and comprehensive management of cardiometabolic risk factors like glucose, blood pressure, and lipids can delay the onset of diabetes and its complications, respectively. However, realizing the “triple aim” of better health, better care, and lower cost in diabetes has been hampered by low adoption of lifestyle interventions to prevent diabetes and poor achievement of care goals for those with diabetes. To achieve better care, a number of quality improvement (QI) strategies targeting the health system, healthcare providers, and/or patients have been evaluated in both controlled trials and real‐world programs, and have shown some successes, though barriers still impede wider adoption, effectiveness, real‐world feasibility, and scalability. Here, we summarize the effectiveness and cost‐effectiveness data regarding QI strategies in diabetes care and discuss the potential role of quality monitoring and QI in trying to implement primary prevention of diabetes more widely and effectively. Over time, achieving better care and better health will likely help bend the ever‐growing cost curve.
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