Current Diabetes Reviews - Volume 3, Issue 4, 2007

Hand-in-hand with obesity, the type 2 diabetes epidemic has become a major health problem in both developed and developing countries, with the estimated number of cases increasing from 170 million to 366 million worldwide by 2030 [1,2]. In the US, diabetes is the 6th leading cause of death and in some race/ethnic groups the predicted chance of developing diabetes among children born today is 40% [3, 4]. Proportionate with its impact on society, diabetes has also been the focus of years of both basic and clinical research. In particular, some of the most groundbreaking and important randomized controlled trials have been conducted among patients with diabetes. From the venerable UKPDS and DCCT studies to a plethora of cardiology trials, the evidence base for managing diabetes is considerable [5-10]. And the drug development process continues to yield new therapies from novel drug classes designed to treat the underlying pathophysiology of diabetes and associated metabolic derangements [11,12]. In the United States, an estimated 5.6% of total health expenditures are spent on biomedical research, more than any other country [13]. However, less than 0.1% of this effort is devoted to health services research. Measured another way, less than 1 cent is spent on evaluating health care delivery for every dollar spent on health care. Given this relative lack of funding for research specifically aimed at translating and implementing clinical advances into more effective clinical care, it should come as no surprise that most people with diabetes remain poorly controlled. In the U.S., fewer than 40% of patients with diabetes have HbA1c levels below goal and fewer than 5% meet all evidence-based goals of care [14-16]. Although future and ongoing scientific research developments hold tremendous promise for patients with diabetes, the fact remains that more effective use of existing therapies will have a much greater impact on diabetes control [17]. For example, as described by Woolf and Johnson in their seminal analysis “The Break-Even Point: When Medical Advances are less Important than Improving the Fidelity with which they are Delivered”, the next generation of cholesterol-lowering drugs would have to be three times more potent than today's statins to deliver the same population health benefits that would occur if everyone who currently needed a statin was prescribed one and took it regularly [18]. The barrier between clinical evidence and clinical practice has been described as a “quality chasm” by the Institute of Medicine [19]. Overcoming this barrier between evidence and practice is the goal of translation research. In this special issue of Current Diabetes Reviews, leading translational researchers review the current evidence for changing current diabetes care. This issue begins with a review of the Chronic Care Model as a conceptual framework for understanding the role of clinical care systems, clinicians, and patients in the process of diabetes management. The next four papers review specific elements within this framework: 1) Interventions to support patient self-management 2) Interventions using Health Information Technology, 3) The role of patient/provider communities linked via electronic personal health records, and 4) The transition between in-patient and outpatient care. The remainder of the issue focuses on the unique barriers faced by specific patient groups. Professor Arlene Brown addresses the role of race/ethnic disparities in diabetes care with an emphasis on patients, clinicians, health systems, and communities. Additional articles review the role of depression in diabetes, the link between neuroendocrine activity and diabetes, and how to apply the current evidence base to elderly patients with diabetes. This last topic introduces the key concept that translating evidence into practice requires a sophisticated understanding of the risks and benefits of therapy and discourages the notion of “one-size-fits-all” algorithmic medicine for this complex disease.

There is a significant gap between evidenced-based diabetes care and actual care delivery. The Chronic Care Model (CCM) was developed to bridge this gap and translate scientific knowledge directly to the care of patients. The CCM is a primary care based framework that identifies the essential elements of high quality chronic disease care. It includes attention to self-management support, delivery system design, decision support, information technology, community linkages, and the health care organization as a whole. This review will describe these elements and provide evidence for their use in improving diabetes care. Evidence for the CCM as a whole will also be presented.

More so than most other diseases, effective control of type 2 diabetes (DM) requires that patients are actively engaged in the self-management of their health. In this paper we define and characterize the elements of self-management and review the published literature for the evidence of the benefit of interventions that support patient self-management.

Current methods of analyzing the use of communication technologies in diabetes care improvement programs are limited by a poor understanding of the impact of technology on the delivery of care. We applied a standardized methodology using a functional framework to analyze 14 diabetes care improvement programs that used communications technology. Controlled trials and observational studies were selected after searching 5 electronic databases to identify care improvement programs for type 2 diabetes that used communications technology in the past 10 years with greater than 10 subjects. A 3-stage framework was used to analyze intervention elements: 1) functional components, 2) structural components, and 3) level of automation in program design. Using this methodology we found marked variability in operational design of programs and poor rationalization of choice of outcome metrics with program components. Although 11 of 14 studies showed significant declines in HbA1c, our analysis indicated that the causal pathways remain unclear. Recent systematic reviews have highlighted the difficulties in evaluating communication technology use in diabetes. The functional framework presented in this review provides a systems approach to the problem and represents a standardized methodology for analyzing communications technology use in diabetes care.

Wagner's modern construct for chronic care recognizes the primacy of ‘productive interactions’ among the patient, their personal community and the care provider team. No longer the only locus of care, the health system should operate within the context of and have access to the people and resources of the larger community involved in the patient's care. Shared medical visits in the care of patients with diabetes serve as a model for collaborative care inclusive of the patient community in complex chronic disease management. We describe the design considerations for a web-based personal health application iHealthSpace enabling multi-faceted connectivity and collaborative services needed to support shared medical visits for patients with diabetes in a large academic practice.

The epidemic of diabetes and results from several recent trials demonstrating the benefits of intensive glycemic control in the ICU setting have focused attention on inpatient glycemic control on general hospital wards, where over 25% of patients have diabetes. Current management of inpatient glycemia is haphazard, relying on corrective doses of insulin after hyperglycemia has occurred (the insulin “sliding scale”). Although data to guide evidence-based management of inpatient glycemia in non-critically ill patients are scant, the American College of Endocrinology and the American Diabetes Association have advocated more intensive therapy in the general inpatient setting, and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has followed suit, launching an initiative on inpatient glycemic control. Extrapolation from basic and clinical studies suggests that improved diabetes management in general medical settings is likely to be beneficial, though the appropriate intensity of glycemic control in non-ICU settings has yet to be determined. Independent of the acute impact of inpatient glycemia, inpatient diabetes management is also important because hospitalization offers an opportunity to optimize care upon discharge for patients with poorly controlled diabetes. Finally, systems-level strategies likely to improve inpatient diabetes management are reviewed.

Type 2 diabetes disproportionately affects socially disadvantaged groups, including racial and ethnic minority groups and low income and less educated persons [1-7]. Although effective therapies are available for managing diabetes and preventing or treating its complications, these therapies are underutilized, particularly among these socially disadvantaged groups [8-10]. Social disadvantage may affect diabetes outcomes through a number of different pathways, including access to care, the quality of care received, psychosocial characteristics, and neighborhood or community factors [11]. Because of the high prevalence of diabetes in socially disadvantaged persons, interventions to reduce racial/ethnic and social disparities in health may have a profound impact on the morbidity and mortality associated with diabetes. In this review, we will discuss evidence on interventions at the individual, provider, health care system, and community levels that have the potential to reduce diabetes disparities and highlight gaps in our understanding of social disparities and health for persons with diabetes.

Depression is a severe medical illness that can interfere with an individual's self-care behaviors. Depression is prevalent [1], burdensome [2], treatable [3], and costly [4]. Recognizing depression in diabetic individuals is critical because depression may play a role in worse control of diabetes and worse diabetes outcomes [5-10]. Depression also appears to increase the costs associated with treating diabetes [11]. A number of clinical trials have recently focused on whether treatment of depression can lead to improved diabetes outcomes [12-15]. In this review, we examine the present state of knowledge on the interaction of depression and diabetes, discuss the epidemiologic and physiologic evidence for the co-occurrence of these conditions, and describe the ways in which diabetes control is worsened by depression, how depression interferes with diabetes care, and how depression acts to increase costs in diabetics. We focus specifically on interventions to treat depression in patients with diabetes and suggest areas of future research and practice with respect to improving care and outcomes those suffering in the intersection of these diseases.

Obesity and type 2 diabetes continue to be major public health burdens with type 2 diabetes rising in epidemic proportions. Since known risk factors do not explain all of the variance in the population, it is important to identify novel risk factors that can lead to development of new preventive measures. Chronic psychological stress and depression are associated with type 2 diabetes but the mechanism remains unclear. Neuroendocrine changes induced by these stressors, specifically activation of the hypothalamic-pituitaryadrenal (HPA) axis and sympathetic nervous system (SNS), might provide a unifying explanation. The objectives of this review are (1) to summarize the metabolic impact of HPA axis and SNS dysfunction induced by depression and stress, (2) to summarize the relation of neuroendocrine parameters to risk factors for diabetes, (3) to discuss the limitations of assessing neuroendocrine function in populationbased and intervention studies, and (4) to summarize the evidence of the impact of stress reduction, by cognitive behavior therapy (CBT), on neuroendocrine factors and on outcomes in diabetes and obesity.

Modern diabetes care may benefit a significant proportion of adults living with diabetes; however, these benefits may not be consistently realized among the heterogeneous subpopulation of elderly patients over 65 years of age. There are three clinical constraints that have been proposed as important considerations for individualizing diabetes care among elderly patients. Life expectancy should be an important determinant of the intensity of glucose control because intensive control has been found to prevent complications only after extended periods of treatment. Therefore, patients with limited life expectancy may not benefit from intensive glucose control. The time and attention of health care providers should also be considered a constrained resource that can be optimally allocated to care for elderly diabetes patients. In the face of multiple chronic conditions and symptomatic complaints, patients and their providers should prioritize diabetes care within the context of a patient's overall health care plan. The complexity of chronic medications or polypharmacy is the final clinical constraint. Polypharmacy may increase the probability of adverse drug events and represent a significant burden on quality of life. More direct clinical investigation of elderly diabetes patients will be needed if we are to truly improve the quality of life of this growing subpopulation.

Recent findings from several groups demonstrate that ABC-A1 participates in the pathogenesis of the metabolic syndrome and type 2 diabetes. A variant of the ABC-A1 gene (R230C) is associated with the metabolic syndrome and its co-morbidities in Mexicans. Its presence is associated with an increased risk for obesity, the metabolic syndrome and type 2 diabetes. R230C is found exclusively in Amerindian and Amerindian-derived populations. Moreover, animal models confirm the participation of ABC-A1 in the pathogenesis of diabetes. Mice lacking AbcA1 specifically in beta cells had glucose intolerance at 8 weeks of age. The absence of ABC-A1 led to cholesterol accumulation within the beta cell plasma membrane, suggesting that cholesterol may play a role in the insulin secretory pathway. In conclusion, ABC-A1 may be more than a determinant of HDL-cholesterol. It may provide a link between components of the metabolic syndrome and atherosclerosis.

In diabetic patients the incidence of cardiovascular diseases (CVD) is higher compared with those without diabetes. This elevated incidence may be due to an increased prevalence of established risk factors, such as obesity, dyslipidemia and hypertension. However, several other determinants must be considered. Attention must be paid to the role that specific factors strictly related to diabetes, insulin- resistance and post-prandial hyperglycemia, play in the etiopathogenesis of CVD, as for example atherosclerosis. This review acknowledges the incidence of diabetes on cardiovascular diseases and atherosclerosis from endothelial dysfunction to plaque destabilization, suggesting that insulin resistance and postprandial hyperglycemia should be considered keys in the generation of these worst diabetic cardiovascular outcomes. It finds in hyperglycemia the primum movens that mediates the cascade of vascular damaging events from the beginning of ROS formation to plaque rupture, through increased inflammation. It also adds insights of why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complication of atherosclerosis in diabetic patients.

Earlier studies and reviews have shown an association between high fasting blood glucose levels (FBG) and increased mortality. Less is known about the association between low FBG and mortality. This study aimed at reviewing the literature on this topic. A search was performed primarily of Medline through PubMed, and secondarily by searching other databases and using the information from articles already found. Altogether 5 articles meeting the quality demands of the search were found, all supporting the association between low FBG and increased all-cause mortality, with multivariate adjusted hazard ratios between 1.2 and 3.2. Another 22 articles not fulfilling the quality criteria were studied, and actually no study contradicted this association. Most studies were focused on the relation between high FBG and mortality, and did not analyze the association between low FBG and mortality specifically, hence explaining the low number of conclusive articles focusing on this. Thus we conclude, that low FBG is associated with increased mortality, but the cause of this association is unclear. We hypothesize, that low FBG could be a marker of low fat-free mass and low nutrition intake. This topic needs further studies.

People with diabetes have a marked increase in morbidity and mortality. The American Diabetes Association has recommended evidence-based process and outcome measures to improve diabetes care. However, these are not met in the majority of patients under our current medical care system. There have been many (mostly unsuccessful) approaches to improving these outcomes including reminding patients about appointments, feeding back information on the patient to the physician, even when specific treatment recommendations for the individual patient were included, case management (when the case manager could not make treatment decisions), education of physicians and multifaceted quality improvement interventions in the practice setting. One approach has consistently been successful; case management when a nurse or pharmacist had the authority to make independent treatment decisions. In randomized clinical trials, Hb A1c levels were lowered approximately three times as much by nurses or pharmacists following approved detailed treatment algorithms (under the supervision of a physician) compared to usual care. Given the approaching epidemic of diabetes, our medical care system should strongly consider this approach to improving diabetes care to forestall the devastation of diabetic complications and the overwhelming costs of caring for these patients.