preventing metabolic side effects of thiazide diuretics with kmgcitrate

Conditions: Hypertension

Summary: chlorthalidone (ctd) may produce various metabolic disturbances, including hypokalemia, activation of renin-angiotensin- aldosterone (raa) system, oxidative stress, dyslipidemia, fibroblast growth factor 23 (fgf23) synthesis, and magnesium depletion. these factors may interact with each other to contribute to the development of insulin resistances and metabolic syndrome. smaller studies have suggested that potassium magnesium citrate (kmgcit) can ameliorate ctd- induced metabolic side effects independent of correction of hypokalemia. this study will tests if kmgcit ameliorates ctd induced metabolic effects independent of correction of hypokalemia.

ctd- induced metabolic side effects were though to be dependent on hypokalemia, but subsequent studies suggested that ctd - induced side effects were independent from hypokalemia. on the other hand, magnesium depletion has been linked to increased renin-angiotensin- aldosterone (raa) system, the development of metabolic syndrome and insulin resistance with magnesium supplementation ameliorating these effects. participants will participate in a double-blinded, parallel design study. after baseline evaluation participants will take chlorthalidone (ctd) alone for 2-3 weeks. they will then be randomized to two equal groups to take kmgcit powder or potassium chloride (kcl) powder along with ctd for 4 months. we speculate that mg depletion is responsible for hepatic fat deposition, which then produces insulin resistance. co-administration of kmgcit powder would avert magnesium (mg) depletion, block hepatic fat deposition by restoring normal mg status and direct intestinal binding of fat, thereby ameliorating insulin resistance. to test this hypothesis, we shall quantitate muscle mg status and hepatic fat content by magnetic resonance spectroscopy (mrs) before and after kmgcit. change in fasting glucose, insulin resistance, serum potassium, fgf23, and aldosterone will be compared between kcl and kmgcit groups after 4 months.

Eligibility criteria:
inclusion criteria: • treated or untreated stage i hypertension exclusion criteria: * diabetes mellitus, * renal impairment (serum creatinine \> 1.4 mg/dl), * any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary heart disease, * chronic regular nsaid use, * allergy to thiazide diuretics, * gastro-esophageal reflux disease (gerd) requiring treatment with acid reducing agents or antacid more than once a week, * esophageal-gastric ulcer or history of gastrointestinal bleeding, * chronic diarrhea, vomiting, * excessive sweating, * unprovoked hypokalemia (serum k \ 5.3 mmol/l), * abnormal liver function test (aspartate transaminase (ast) or alanine transaminase (alt) above upper limit of normal range), * subjects on any potassium supplement on a regular basis for any reason, such as patients with primary aldosteronism, * pregnancy, * history of major depression, bipolar disorder, or schizophrenia, * history of substance abuse, * gout, * metabolic alkalosis, with serum bicarbonate \> 32 meq/l, * severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day. * patient with claustrophobia will not have mri but can still participate in the study without mri * metal implants will not have mri but can still participate in the study without mri

Keywords: hypokalemia isoprostanes insulin resistance aldosterone hepatic fat muscle magnesium liver fat