Thiazide diuretics have been used to reduce calcium nephrolithiasis recurrence as it is tolerated well, inexpensive and reduces calcium excretion in urine. It has been linked with increased risk of diabetes mellitus (DM) in the presence of hypertension (ALLHAT study), however its long-term side-effects when used for stone prevention have not been studied. There is also a correlation between hypertension and insulin resistance, therefore hypertensive patients may be more sensitive to the hyperglycaemic effects of thiazide diuretics. The aim of this study is to assess risk of new onset DM in renal calculi patients in relation to thiazide use and hypertension. Using ICD-9 codes, patients with their first diagnosis of renal calculi between 1984 to 2011 from Olmsted County were studied. A symptomatic stone event must be present; this includes documentation of stone passage, visualisation of stone in ureter / renal pelvis, flank / abdominal pain, visible haematuria or urinary tract infection caused by urease splitting organism. Those with uric acid stones, already taking thiazide diuretics or started within 90 days of first stone presentation, pre-existing DM or those diagnosed with DM within 90 days of first presentation of renal calculi, were excluded. Onset of DM was determined by fasting glucose level higher than 126mg/dl on at least two consecutive separate readings or when anti-diabetic medications were commenced. Onset of hypertension was determined by two systolic blood pressure (BP) readings of ≥140mmHg, or two diastolic BP ≥90mmHg or when diagnosed with hypertension by a doctor. Two thousand three hundred and fifty patients fulfilled the study criteria, 332 were on thiazide diuretics during follow-up, of which 84 were using it for stone prophylaxis. One hundred and sixty-three DM events were detected during follow-up. Those with hypertension receiving thiazide diuretics were at higher risk of developing DM. When thiazide diuretics were purely used for stone prophylaxis in those who do not develop hypertension, there was no increased risk of developing DM. The authors recognise there are limitations to this study as the population of Olmsted County is mostly caucasian and length of thiazide diuretic therapy was unknown. 

Thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus.
Singh P, Knoedler JJ, Krambeck AE, et al.
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