MetabolicEffect – Metabolic Rehab

MetabolicEffect – Metabolic Rehab

Type 2 diabetes is a well-recognized risk factor for cerebrovascular disease. In this issue of Stroke, Thacker et al¹demonstrate 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.^2–5

The 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.⁶However, 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, although the effect appears to be substantially mediated by coexistent cardiovascular risk factors.^7,8 Importantly, not all obese patients exhibit these complications; ∼25% of those with obesity lack additional evidence for the metabolic syndrome. That is, they do not have hypertension, dyslipidemia, hyperglycemia, or evidence of vascular inflammation, insulin resistance, or endothelial dysfunction that typically characterize this condition.⁹ Adipose tissue topography may explain some of these differences because patients with so-called uncomplicated obesity may have fat distributed preferentially to more metabolically quiescent sites, such as arms, legs, and buttocks,⁹as opposed to the more metabolically active centripetal sites, including liver and omentum. It is not surprising, therefore, that waist-to-hip ratio (a reflection of central obesity) has a closer association with stroke risk than body mass index (odds ratio adjusted for risk factors including diabetes and body mass index=3.0; 95% confidence interval, 2.1–4.2).¹⁰