Even Silent Hypoglycemia Induces Cardiac Arrhythmias

  1. Simon J. Fisher2,3
  1. 1Division of Endocrinology and Diabetes, Department of Pediatrics, Washington University, St. Louis, MO
  2. 2Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University, St. Louis, MO
  3. 3Department of Cell Biology and Physiology, Washington University, St. Louis, MO
  1. Corresponding author: Simon J. Fisher, sfisher{at}

While many studies have shown that intensive glycemic control can prevent the microvascular complications of diabetes, the benefits of intensive glycemic control in preventing macrovascular complications, including heart attacks, strokes, and overall mortality, have been less clear. Intensive glycemic control almost always increases the frequency and severity of hypoglycemic episodes. What remains unclear is whether hypoglycemia directly contributes to, or is merely associated with, the increased mortality noted in recent large trials (e.g., Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR], Control of Hyperglycaemia in Paediatric intensive care [CHiP], Action to Control Cardiovascular Risk in Diabetes [ACCORD]) (13). In the intensive care setting, noniatrogenic hypoglycemia serves as a harbinger of mortality, but it is unlikely to be a direct cause of mortality (4). By contrast, in the outpatient setting, insulin-induced hypoglycemia can be lethal. Among people with diabetes, the mortality rate due to hypoglycemia has been reported to be as high as 10% (5). Indeed, insulin-induced hypoglycemia has been considered responsible for nocturnal deaths in diabetic patients (6), and has been documented to be associated with the “dead-in-bed” syndrome (7). Therefore in the outpatient setting, the microvascular benefits of intensive glycemic control in people with diabetes have to be weighed against the apparent increased mortality associated with iatrogenic hypoglycemia.

The mechanism(s) by which hypoglycemia may increase mortality remains unknown. In patients with cardiac disease, hypoglycemia has been associated with ischemic chest pain (8). Hypoglycemia also increases markers of thrombosis and inflammation, potentially increasing the risk of acute thrombotic events or accelerating development of atherosclerosis (9). Although hypoglycemia-associated …

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