Syndrome X (hypertension, obesity, hyperlipidemia, hyperinsulinemia)

S Y N D R O M E ‘X’

Medical Director, BREAKSPEAR HOSPITAL, Hertfordshire, England

The principal features of syndrome X are hypertension, abnormal glucose tolerance, increased VLDL triglyceride levels, decreased HDL cholesterol levels, obesity and hyperinsulinaemia/insulin insensitivity. These are all cardiovascular risk factors (CAD). Hyperinsulinaemia is the common factor, linked with each of the six risk factors, and reflects decreased insulin sensitivity.

Hypertension: Many epidemiological studies have found a positive association between hyperinsulinaemia and hypertension. Hyperinsulinaemia can increase sympathetic neural activity and, as a consequence, blood pressure. Increased insulin levels have been associated with increased circulating catecholamine concentration.

Dyslipidaemia: Increased very low-density lipoprotein triglyceride and decreased HDL cholesterol concentrations are features of syndrome X and non-insulin dependent diabetes mellitus (NIDDM). An elevated LDL/HDL ratio has been shown to be predictive of CAD in diabetic subjects. Increased VLDL triglyceride in NIDDM is primarily due to increase in hepatic synthesis. VLDL triglyceride production rates are correlated with insulin levels. Insulin has a direct stimulatory effect on hepatic VLDL triglyceride synthesis.

A combination of hyperinsulinaemia and decreased insulin sensitivity, particularly at the liver, is required for the sustained increase in circulating VLDL triglyceride levels to develop in syndrome X. Impaired adipose tissue insulin sensitivity in NIDDM and the increase adipose tissue mass in obesity are responsible for the increase on circulating, non-esterified fatty acid levels in these conditions, and this increases the supply of substrate for hepatic VLDL triglyceride synthesis.

Lipoprotein lipase is the principal enzyme involved with catabolism of VLDL triglyceride. There is a deficiency of lipoprotein lipase in NIDDM. Decreased HDL cholesterol levels in NIDDM are due to an increased rate of clearance, primarily mediated by hepatic lipase. Fasting insulin levels correlate with the rate of HDL cholesterol clearance. There is an inverse correlation between circulating HDL cholesterol levels and whole body insulin resistance.

The association with hypertriglyceridaemia with insulin insensitivity: Acute elevation of triglyceride levels can induce insulin insensitivity. Circulating non-esterified fatty acid (NEFA) and triglyceride levels change simultaneously. An increase in circulating NEFA levels will impair insulin sensitivity, and vice versa.

Central obesity: Upper body obesity and lower body fat distribution are features of male and female sexes, respectively. An increased waist to hip ratio is a useful index of upper body obesity. Increased visceral fat stores can be distinguished from those with increased abdominal subcutaneous fat. Only the former have an association with increased plasma triglycerides and blood glucose levels, following an oral glucose load, and are associated with Syndrome X, NIDDM, hypertension, decreased plasma HDL cholesterol and increased plasma triglyceride levels.

Insulin insensitivity is a feature of obesity but peripheral insulin insensitivity is more marked in obese subjects with upper versus lower body fat distribution.

Other cardiovascular risk factors: There is a direct atherogenic role of insulin.

An increase in the circulating levels of plasminogen activator inhibitor 1 (PAI-1) activity is a CAD risk factor.

_ Dietary composition and intake
_ Physical exercise
_ Endocrine status

_ Weight loss
_ Medium protein and restricted carbohydrate diet
_ Increase in physical activity, exercise.
_ Nutriceuticals – vanadium, chromium, vitamin E.
_ Endocrine evaluation (hormone therapy – which may include testosterone).

The giants of nutritional medicine included people who recognized that refining foods resulted in ill-health. The causes of Syndrome ‘X’ are, in my opinion, two fold:  the decline in testosterone with age, and sugar and refined carbohydrates. We need to review our Western society’s dietary requirements and habits and revert to wholesome unrefined food.

Walker M and Alberti K G M M, Syndrome X, The Medical School, University of Newcastle upon Tyne, UK.

Headache 1998 Jun;38(6):483, What can we learn syndrome X?

Daly ME et al, Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications, Am J Clin Nutr 1997 Nov;66(5):1072-85.