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Clinical Gems

Our clinical gems come from the top selling medical books, and text books because knowledge is everything when it comes to diabetes.

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #121: The Insulin Resistance Syndrome Part 2

Concept of ectopic fat as a cause of tissue insulin resistance: It appears that individuals prone to T2DM (based in part on their nonmodifiable characteristics) show a greater propensity to accumulate visceral or ectopic fat for a given weight. Interestingly this characteristic, in turn, may be a downstream consequence of “impaired” subcutaneous fat storage capacity, the mechanisms of which deserve further research. As an extreme example of this concept, lipodystrophic individuals have an impaired ability to store subcutaneous fat and, as a consequence, they accumulate fat in visceral and ectopic tissues and so have marked insulin resistance.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #120: The Insulin Resistance Syndrome Part 1

What is insulin resistance? Broadly, insulin resistance can be defined as an abnormal biologic response to insulin; insulin, whether endogenous or exogenous in origin, has limited ability to reverse a hyperglycemic metabolic state.Thus a person with insulin resistance is, almost inevitably, progressing towards developing frank type 2 diabetes (T2DM) if an intervention (usually lifestyle) is not implemented. Due to the very close link between diabetes and insulin resistance, no formal clinical definition of insulin resistance has emerged.We will discuss the potential clinical use of the insulin resistance syndrome and the metabolic syndrome later in the chapter. For now, we focus on investigation of insulin resistance as a useful entity for research concepts, and in particular discuss its biologic consequences by describing its associated risk factor perturbations.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #119: Diabetes and Sleep Apnea Part 9

OSA management: OSA should be treated promptly and the aim of treatment is to reduce the morbidity and mortality associated with this condition. Weight loss and positional treatment (i.e., avoiding the position in which most episodes occur, which is usually the supine position) are important aspects of treatment. As with all obesity-related disorders, weight loss (regardless of the means) can result in significant improvements in OSA. In a randomized controlled trial of intensive lifestyle intervention in 264 patients with OSA and T2DM (the Sleep AHEAD study), weight loss of 11 kg on average in the treatment group resulted in a reduction in the AHI of about 10 events per hour.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #118: Diabetes and Sleep Apnea Part 8

Other OSA comorbidities: Road traffic accidents -- Several cross-sectional studies using driving simulators showed worse driving performance and increased risk of road traffic accidents in patients with OSA. In a sample of 913 employed adults whose motor vehicle accident history was obtained from a statewide database covering the period 1988–1993, men with OSA were more likely to have at least one accident in 5 years compared to those without OSA.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #117: Diabetes and Sleep Apnea Part 7

OSA and diabetes-related complications: Recently, there has been increasing interest in the association between OSA and diabetes-related complications. There is one cross-sectional published study regarding the association between OSA and macrovascular complications in T2DM, but several studies have examined the association between microvascular complications and OSA in T2DM. Most of these studies are cross-sectional in nature but more recently prospective studies proving causality have been published. Many of these studies fail to adjust for many of the possible confounders.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #116: Diabetes and Sleep Apnea Part 6

OSA and incident T2DM: Several studies have examined whether having OSA increases the individual’s risk of developing T2DM, in particular whether obesity is a major risk factor for both conditions and whether OSA has been associated with IR and prediabetes as described earlier. Several cross-sectional studies found a higher prevalence of T2DM in patients with OSA despite adjusting for confounders, particularly age and obesity; these studies are reviewed in. Whether OSA is a predictor of T2DM has been examined in a small number of longitudinal studies that used a variety of methods to diagnose OSA (from symptoms to polysomnography), and to diagnose T2DM (from self-reported to OGTT).

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #115: Diabetes and Sleep Apnea Part 5

OSA and beta-cell function: While the impact of OSA in IR has been studied extensively, the impact of OSA on beta-cell function has received little attention, despite being an essential part of the pathogenesis of T2DM and prediabetes. A small number of animal studies showed that intermittent hypoxia increases beta-cell death, and results in beta-cell dysfunction, although the intermittent hypoxia used in this study is far greater than that which occurs in humans with OSA.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #114: Diabetes and Sleep Apnea Part 4

OSA and glucose metabolism: OSA and dysglycemia have similar risk factors (namely obesity) and hence it is not surprising that these conditions co-exist. However, not all obese patients have both conditions and many patients have one and not the other. Hence, understanding this association and the mechanisms that underpin this relationship is important to understand the pathogenesis of OSA and T2DM. There are many studies that have examined the association between snoring, as a surrogate marker of OSA, and different aspects of glucose metabolism; here, however, we will mainly focus on studies that validated the presence and severity of OSA using more accurate methods.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #113: Diabetes and Sleep Apnea Part 3

OSA pathophysiology: OSA is a very complex disorder, and although obesity and fat deposition around the neck plays an important role, there are many other important players that contribute to the development of this condition. The human upper airway is a unique multipurpose structure involved in performing a variety of tasks such as speech, swallowing, and the passage of air for breathing. The airway, therefore, is composed of numerous muscles and soft tissue but lacks rigid or bony support. Most notably, it contains a collapsible portion that extends from the hard palate to the larynx, which allows the upper airway to change shape and momentarily for speech and swallowing during wakefulness; but this feature also provides the opportunity for collapse at inopportune times such as during sleep.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #112: Diabetes and Sleep Apnea Part 2

OSA epidemiology and risk factors: The prevalence of OSA varies considerably between studies, mainly due to differences in the population studied, study designs, and the method and criteria used to diagnose OSA. A prevalence of 4% in men and 2% in women has traditionally been quoted in many populations. The prevalence from three well-conducted studies with similar design from Wisconsin, Pennsylvania, and Spain showed an OSA prevalence of 17–26% in men and 9–28% in women and a prevalence of 9–14% and 2–7% for men and women with moderate to severe OSA. These studies used a two-stage sampling design which allows some degree of estimate of the “self-selection” bias which is usually a significant problem in OSA studies.

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