Chlorthalidone, a first-line thiazide-type diuretic used in the treatment of hypertension, has been shown to cause “persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients”, according to a study titled “Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients” which was published in the April 2009 edition of The Journal of Clinical Endocrinology & Metabolism.

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Over three months, 23 undedicated hypertensive patients were given either chlorthalidone or spironolactone. Their sympathetic nervous system activity (or SNA and often a contributor to high blood pressure) was measured at baseline, 1 months and 3 months. They found that after just 1 month, SNA activity was increased by 23% in the chlorthalidone users with no change in the spironolactone patients and it remained elevated for 3 months after stopping the treatment. There was also a statistically significant increase in insulin resistance in chlorthalidone users. Overall reductions in blood pressure were comparable between the two groups.

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http://jcem.endojournals.org/cgi/content/abstract/94/4/1361