Metabolic Rehabilitation

See related article, page 3347.Type 2 diabetes is a well-recognized risk factor for cerebrovascular disease. In this issue of Stroke , Thacker et al1 demonstrate that earlier abnormalities in carbohydrate metabolism, insulin resistance, and impaired glucose tolerance are also associated with increased risk for cerebral ischemic events. These findings are reliable and timely, and they have immediate implications for the design of the next generation of stroke prevention trials.Abnormal carbohydrate metabolism comprises a spectrum of disorders characterized by impaired energy utilization. Early manifestations include obesity, decreased insulin sensitivity, impaired fasting glucose, and impaired glucose tolerance. The latter 2 conditions are often referred to as “prediabetes,” a stark description of their typically progressive nature. The most advanced manifestation, type 2 diabetes, results from the inexorable loss of insulin secretory capacity in the face of well-established insulin resistance. These metabolic states have become endemic in most countries as westernized lifestyles are adopted. In the United States alone, there are now 26 million individuals with diabetes and 79 million with prediabetes. Globally, the number of diabetic patients is now estimated to be 366 million.Clinicians who care for stroke patients know that metabolic disease is also prevalent in this population. Among patients with ischemic cerebrovascular disease, 18% to 30% are obese, 25% to 30% are insulin-resistant, 23% to 28% have impaired glucose tolerance, and 13% to 36% have diabetes.2–5The Figure illustrates a model of impaired glucose regulation and its potential causal relationship to stroke. Each of its cardinal manifestations (ie, obesity, insulin resistance, hyperglycemia, diabetes) have been associated with increased risk for stroke.6 However, the evidence is strongest for obesity and diabetes, possibly because these are easiest to measure and classify. Obesity (body mass index ≥30 kg/m2) doubles the risk for ischemic stroke, …