A 58-year-old man is hospitalized due to sudden onset of chest pain. Blood pressure is 160/110 mm Hg and pulse is 90/min. BMI is 26.9 kg/m2. A baseline ECG shows nonspecific ST-segment and T-wave abnormalities, and serial troponin measurements are normal. The patient's fasting plasma glucose level is 160 mg/dL, although he has not been diagnosed previously with diabetes mellitus. Serum triglyceride level is elevated, and the HDL level is low. Which of the following additional findings would be most suggestive of increased insulin resistance in this patient?
This patient has hypertension and likely type 2 diabetes mellitus. The primary defects in the pathophysiology of type 2 diabetes include defective insulin secretion from pancreatic beta cells and insulin resistance in peripheral tissues. Insulin resistance is caused by a number of genetic (eg, insulin receptor and postreceptor mutations) and environmental factors (eg, lack of physical activity, obesity).
An adipose body habitus is commonly associated with insulin resistance and type 2 diabetes. In particular, excess visceral fat (surrounding internal organs) correlates much more strongly with insulin resistance than does subcutaneous fat. Measurement of waist circumference or waist-to-hip ratio is an effective indirect assessment of visceral fat, especially in patients who are overweight (BMI 25-29.9 kg/m2) or mildly obese (BMI 30-34.9 kg/m2). A waist circumference >102 cm (40 in) in men and >88 cm (35 in) in women is associated with a higher risk of insulin resistance.
The association of insulin resistance, increased visceral adiposity (ie, increased waist circumference), hypertension, and serum lipid abnormalities (high triglyceride levels, low HDL levels) is known as metabolic syndrome (sometimes called syndrome X). Patients with metabolic syndrome have increased rates of cardiovascular events and warrant careful risk factor management.
(Choice A) Insulin suppresses gluconeogenesis and promotes glycogen synthesis in the liver. In patients with insulin resistance, the inhibitory effect of insulin on gluconeogenesis is reduced, leading to increased hepatic glucose production.
(Choice B) High LDL levels are an independent risk factor for atherosclerotic heart disease in patients with diabetes, but are not directly associated with increased insulin resistance. In contrast, insulin resistance is associated with high triglyceride and low HDL levels.
(Choice C) High urinary excretion of ketones suggests absolute insulin deficiency, as seen in type 1 diabetes, rather than insulin resistance. Patients with type 2 diabetes and insulin resistance typically have high circulating insulin levels that are more than adequate to suppress ketone formation.
(Choice D) Skeletal muscle is a major repository for ingested glucose due to insulin-mediated glucose uptake. In patients with insulin resistance, decreased glucose uptake in skeletal muscle leads to reduced glycogen synthesis and higher blood glucose levels.
Educational objective:
Visceral obesity as measured by waist circumference or waist-to-hip ratio is an important predictor of insulin resistance.