Structure activity relationship of thiazide diuretics and diabetes

structure activity relationship of thiazide diuretics and diabetes

Thiazide is a type of molecule and a class of diuretics often used to treat hypertension (high converting enzyme (ACE) inhibitors in Australia due to their propensity to increase risk of diabetes mellitus type 2. with a similar action that do not have the thiazide chemical structure, such as chlorthalidone and metolazone. The relation between each treatment and new onset diabetes was evaluated using risk of new onset diabetes and use of β blockers, thiazide diuretics, The distinguishing feature of the marginal structural model is that inverse a function of all time dependent covariates listed in table 1, updated to their. Randomized trials suggest that thiazide diuretics and non-selective Keywords: beta-blockers, diabetes, diuretics, glycaemic control, meta-analysis .. There were no financial relationships with any organizations that might have an .. 2 diabetes: conflicting effects on blood pressure, endothelial function.

Several smaller studies have not observed a correlation between serum potassium and serum glucose level changes or insulin sensitivity after thiazide-type diuretic treatment, even though the mean serum potassium level decreased and fasting blood glucose level increased.

This recommendation has recently been endorsed by others. In addition, a recent cross-sectional study suggested that abdominal obesity may predispose patients to thiazide-induced hyperglycemia in association with potassium depletion. Fasting blood samples were collected at baseline before either treatmentbefore the additional drug was added, and after 9 weeks of combination therapy.

Complete details of the PEAR trial design and purpose have been previously published. All participants provided written informed consent, and the institutional review boards of participating study centers approved the study protocol. Study Participants Males and females with mild-to-moderate essential hypertension, of any race-ethnicity, and aged 17—65 years were eligible for participation.

Study participants were those with newly diagnosed hypertension, untreated hypertension, or known hypertension previously treated with fewer than three antihypertensive drugs potassium-sparing diuretics were not considered an antihypertensive drug.

After a washout period of at least 18 days, participants were screened for inclusion based on home and clinic blood pressure measurements. Eligible participants were those with an average seated diastolic blood pressure measurement above 85 mm Hg and systolic blood pressure measurement below mm Hg, measured at home over 1 week, and clinic measurements of seated diastolic blood pressure of 90— mm Hg and systolic blood pressure less than mm Hg.

Patients were excluded from the study if they had been treated with antihypertensive drugs but still had a clinic systolic blood pressure above mm Hg. Study Procedures Patients received hydrochlorothiazide Patients were included in the substudy only if they had completed at least 9 weeks of therapy with hydrochlorothiazide monotherapy.

Compliance was assessed based on pill counts from study drug blisterpacks. Use of potassium-sparing diuretic agents was not permitted.

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Potassium supplements were allowed at the discretion of the study physician for any serum potassium level and mandated for any patient with a serum potassium concentration below 3. Study participants who received any form of potassium supplementation at any time during the study were included in the primary analysis.

structure activity relationship of thiazide diuretics and diabetes

Fasting serum glucose, serum potassium, serum uric acid, and plasma insulin levels were obtained at baseline before hydrochlorothiazide therapy was started and after 9 weeks of therapy. All laboratory parameters were determined in a central laboratory at the Mayo Clinic.

structure activity relationship of thiazide diuretics and diabetes

Insulin resistance was assessed based on the homeostatic assessment model of insulin resistance HOMA-IRwhich incorporates fasting glucose and fasting insulin levels to arrive at a measure of insulin sensitivity. Sampling distribution of laboratory parameters was checked by Kolmogorov-Smirnovand test and QQ plot.

The Kolmogorov-Smirnovand test of p value of 0. These trials suggest that some beta-blockers can be used safely in people with diabetes, but at present the available information is conflicting.

A meta-analysis comparing the rates of cardiovascular events for people with diabetes taking atenolol compared with other antihypertensive drugs showed an increased risk ratio of 1. Randomized trials have shown that low dose diuretic treatment prevents major cardiovascular events in people with and without diabetes 15 However, thiazide diuretics have been linked to adverse metabolic effects, glucose intolerance and hyperglycaemia 17as well as incident diabetes Some studies have suggested that the use of diuretics in diabetes may be dangerous.

For example, a cohort study from reported that using diuretics to reduce hypertension in diabetes was associated with an increased risk of mortality Diuretics can also cause hypokalaemia 20which can cause reduced insulin secretion and an increased risk of diabetes 17 Information on whether these medications have adverse effects on glucose control in people with diabetes is hard to find.

Despite its importance in monitoring and care, this information has not to date been systematically assessed, making it difficult for clinicians to make informed decisions about how these medications should be used.

We have carried out a systematic review and meta-analysis to quantify the effects of beta-blockers and diuretics on glycaemic control and the incidence of adverse events in people with type 1 and type 2 diabetes. Methods Our review and protocol were registered, in advance of searching the literature, on the Prospero database registration number CRD In addition, we searched the ClinicalTrials. The Medline search strategy is shown in Supporting Information. All identified studies were screened independently by two reviewers JH and BF for eligibility.

We included placebo-controlled randomized trials of any duration in which the effects of either beta-blockers or diuretics on measures of glycaemic control in people with diabetes were assessed. We also included trials in which a diuretic or beta-blocker was added to another medication, provided that the other medication was the same in both the intervention and comparator arms.

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Two reviewers extracted data on study characteristics intervention and comparator medications and doses, length of follow-uppatient characteristics mean age, gender, BMI and diabetes durationstudy quality randomization and blinding 22and patient outcomes measures of glycaemic control from included trials.

The primary outcome was glycaemic control, measured as HbA1c, fasting blood glucose or hypoglycaemic episodes between intervention and control groups. Secondary outcomes were systolic blood pressure and adverse events.

We wrote to the authors of trials published in the past 10 years to request unpublished data.

The definitions of episodes of symptomatic hypoglycaemia reported in the methods of each paper were accepted as the criteria for our analysis including tremor, sweating, tachycardia, palpitation, and piloerection. We also extracted data on end point systolic blood pressure when it was reported. The quality of included studies was assessed, and studies in which randomization or double blinding were not stated were excluded in a sensitivity analysis to see whether this affected the results.

We assessed the potential risk of publication bias using Egger's test Statistical methods All analyses were carried out using Stata We pooled data on the mean difference between intervention and comparator groups in fasting blood glucose, HbA1c concentrations and systolic blood pressure reported at the end of the trial using a fixed effects inverse variance weighted meta-analysis.

HbA1c was only pooled in trials that lasted 8 weeks or longer. Numbers of hypoglycaemic events or other adverse events were pooled using the Mantel Haenszel method to calculate the risk ratio When total or mean numbers of adverse events per patient were reported, we calculated the number of events per patient-week in the trial, to enable pooling of the results.

Standard deviations were imputed in one trial in which they were not reported 23 by averaging standard deviations from all the included trials in which they were reported, as recommended in the Cochrane Handbook 22and the geometric mean was approximated to the mean.

Trials in which approximations were made were excluded in a sensitivity analysis. Prespecified sub-group analysis and meta-regression was used to assess whether selective and non-selective beta-blockers 2425 gave significantly different results from each other, and whether thiazide diuretics gave significantly different results from other diuretics.

Results We identified papers, of which were duplicate references resulting from searching multiple databases, leaving papers for review Figure 1.