Type 2 Diabetes And Thiazide Diuretics
Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors) In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension. Cardiovascular diseaseDiureticHypertensionSGLT2 inhibitorThiazideType 2 diabetes This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications This is a preview of subscription content, log in to check access No sources of funding were used to assist in the preparation of this manuscript. No conflicts of interest are directly relevant to the content of this manuscript. A.J. Scheen has received lecturer/scientific advisor/clinical investigator fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, NovoNordisk, Sanofi, and Servier. Human and Animal Rights and Informed Consent This article does not contain any stud Continue reading >>
- Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study
- New type of diabetes discovered - Could YOU be showing symptoms of type 1.5 NOT type 2?
- Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes
Diuretic-related Side Effects: Development And Treatment
Please confirm that you would like to log out of Medscape.If you log out, you will be required to enter your username and password the next time you visit. Log out Cancel Diuretic-Related Side Effects: Development and Treatment Prolonged thiazide diuretic therapy can lead to glucose intolerance and may occasionally precipitate diabetes mellitus.[ 4 , 5 , 54 , 55 ] Short-term metabolic studies, epidemiologic studies, and a variety of clinical trials suggest a connection between ongoing thiazide diuretic use and the development of type 2 diabetes. However, it should be noted that interpretation of these studies is confounded by multiple factors including: differing definitions of new-onset diabetes, small numbers of patients, inadequate comparison groups, relatively limited periods of follow-up, selection criteria that limited the generalizability of the findings, and study designs that prohibited valid comparisons among antihypertensive drug classes.[ 56 ] Moreover, in a review of all the placebo-controlled hypertension trials with diuretics, there was only an approximate 1% increase in new-onset diabetes compared with placebo.[ 57 ] Hyperglycemia and carbohydrate intolerance have been linked to diuretic-induced hypokalemia. K+ deficiency is known to inhibit insulin secretion by cells; however, diuretic-induced changes in glucose metabolism are not conclusively related to altered K+ homeostasis, and impaired glucose tolerance occurs even when thiazide-type diuretics in relatively low doses are combined with K+ -sparing agents. The glucose intolerance seen with diuretic therapy can deteriorate further with an increase in sympathetic nervous system activity, which also decreases peripheral glucose utilization. Diuretic-associated glucose intolerance appears to be dose-rel Continue reading >>
Thiazide Diuretic Agent
Ruben Vardanyan, Victor Hruby, in Synthesis of Best-Seller Drugs , 2016 Thiazides and thiazide-like diuretics inhibit Na+/Cl cotransporter located on the apical membrane of the early segment of the distal convoluted tubule. They have been widely prescribed for more than 60 years for the treatment of hypertension and various edematous states. Some members of this series retain significant carbonic anhydrase inhibitory activity. They are mild diuretics and effective antihypertensives. Since the introduction of the first representatives of thiazides into medicinal practice in the mid-1950s, decades of criticism and controversy about them has not ceased. But 60 years later, they still remain one of the most important classes of drugs. The thiazide diuretics emerged from efforts to synthesize more potent carbonic anhydrase inhibitors by structural variations of sulfanilamides. A newly synthesized compound, 6-chloro-7-sulfamoyl-2H-l,2,4-benzothiadiazine 1,1-dioxide, displayed much weaker activity as a carbonic anhydrase suppressant than acetazolamide (21.1.1), but it produced a remarkable sodium and chloride excretion with relatively little bicarbonate output. The compound was named chlorothiazide (21.3.1) and became the prototype for a series of effective thiazide series diuretics that include hydrochlorothiazide (21.3.2), hydroflumethiazide (21.3.3), trichlormethiazide (21.3.4), mebutizide (21.3.5), cyclopenthiazide (21.3.6), cyclothiazide (21.3.7), bendroflumethiazide (21.3.8), polythiazide (21.3.9), and methycyclothiazide (21.3.10) (Fig. 21.4.). Thiazide diuretics were the first well-established and tolerated, efficient antihypertensive drugs. As diuretics they are usually used in combination with a loop diuretic to augment the diuresis in patients with refractory edema. Continue reading >>
Diuretics May Increase Diabetes Risk By Lowering Blood Potassium Levels
Diuretics may increase diabetes risk by lowering blood potassium levels Posted on Nov 25, 2008, 6 a.m. By Rich Hurd New research suggests that depleted blood potassium levels could help to explain why people prescribed diuretics for the treatment of high blood pressure are at increased risk of type 2 diabetes. New research suggests that depleted blood potassium levels could help to explain why people prescribed diuretics for the treatment of high blood pressure are at increased risk of type 2 diabetes. Tariq Shafi and colleagues examined data from 3,790 non-diabetic participants in the Systolic Hypertension in Elderly Program (SHEP), a study designed to determine the risk versus benefit of treating people age 60 years or older with the thiazide diuretic chlorthalidone. Previous research has shown that treatment with thiazide diuretics causes potassium levels to drop and increases patients' risk of developing type 2 diabetes by as much as 50%, although whether the drop in blood potassium was linked to the increased risk of diabetes was uncertain. Results of this study suggest that the increased risk of type 2 diabetes associated with thiazide diuretics is indeed linked to their action on blood potassium levels. In fact, results showed that for each 0.5 milliequivalent-per-liter (MEq/L) decrease in serum potassium, there was a 45% increased risk of diabetes . Thiazides are effective at treating high blood pressure and are inexpensive, however their association with diabetes has led many doctors to prescribe other, more expensive, drugs. However, according to Dr Shafi, the study findings suggest that thiazides can be used safely as long as doctors monitor and regulate blood potassium levels. The authors speculate that potassium supplement may prevent thiazide-induced diab Continue reading >>
Drugs That Can Worsen Diabetes Control
One of the main goals of any diabetes control regimen is keeping blood glucose levels in the near-normal range. The cornerstones of most plans to achieve that goal include following a healthy diet, getting regular exercise, and taking insulin or other medicines as necessary. However, it’s not uncommon for people with diabetes to have other medical conditions that also require taking medicines, and sometimes these drugs can interfere with efforts to control blood glucose. A few medicines, including some commonly prescribed to treat high blood pressure and heart disease, have even been implicated as the cause of some cases of diabetes. This article lists some of the medicines that can worsen blood glucose control, the reasons they have that effect, the usual magnitude of the blood glucose changes, as well as the pros and cons of using these drugs in people who have diabetes. Where the problems occur To understand how various medicines can worsen blood glucose control, it helps to understand how insulin, the hormone responsible for lowering blood glucose, works in the body. Insulin is released from the beta cells of the pancreas in response to rising levels of glucose in the bloodstream, rising levels of a hormone called GLP-1 (which is released from the intestines in response to glucose), and signals from the nerve connections to the pancreas. The secretion of insulin occurs in two phases: a rapid first phase and a delayed second phase. Both of these phases are dependent on levels of potassium and calcium in the pancreas. Insulin acts on three major organs: the liver, the muscles, and fat tissue. In the liver, insulin enhances the uptake of glucose and prevents the liver from forming new glucose, which it normally does to maintain fasting glucose levels. In muscle and f Continue reading >>
Why Do Thiazides Decrease Polyuria In Diabetes Insipidus?
I was reviewing the treatment of diabetes insipidus the other day, and was reminded of the paradoxical effect of thiazide diuretics on urine output in diabetes insipidus. How does this work? The traditional thinking is that thiazide-induced blockade of the Na-Cl cotransporter in the distal tubule leads to a decrease in GFR. This decrease is compensated by an increase in proximal tubule sodium and water uptake. Because less water and solute are then delivered to the collecting duct, less water is lost as urine. However, some studies suggest that chronic use of thiazides does not result in a decrease in extracellular fluid volume: cardiac output returns to normal several weeks after initiating therapy, and infusion of salt-free dextran does not increase blood pressure. Studies in rats with central DI have also shown that replacement of renal sodium losses does not prevent the antidiuretic effect of thiazides. Experiments by Kim et al. suggest that thiazides may serve to upregulate aquaporin channels and ENaC subunits. In rates with lithium-induced nephrogenic DI, HCTZ reversed lithium-induced downregulation of AQP2. It also caused an increase in the abundance of ENaC channels. While these results are specific to Li-induced renal effects, they may at least partially explain how a thiazide can serve to decrease polyuria in patients with diabetes insipidus. Continue reading >>
Many therapeutic agents can predispose to or precipitate diabetes, especially when pre-existing risk factors are present, and these may cause glucose control to deteriorate if administered to those with existing diabetes. They may act by increasing insulin resistance, by affecting the secretion of insulin, or both. For convenience, these agents may be subdivided into widely used medications that are weakly diabetogenic, and drugs used for special indications that are more strongly diabetogenic. Examples of the former include antihypertensive agents and statins, and examples of the latter include steroids, antipsychotics and a range of immunosuppressive agents. There are also a number of known beta cell poisons including the insecticide Vacor, alloxan and streptozotocin. Introduction A wide range of therapeutic agents may affect glucose tolerance, and the list of known or suspected drugs is lengthy. This entry summarizes evidence concerning the agents most frequently implicated. Widely used medications A number of drugs used to reduce cardiovascular risk also predispose to the development of diabetes. These include the thiazide diuretics, beta-blockers and statins. It should however be appreciated that these are commonly offered to individuals who are at increased risk of diabetes by virtue of risk factors such as obesity and hypertension, and that risk association does not necessarily mean causation. Thiazides: Thiazide diuretics revolutionized the treatment of hypertension in the 1960s, but were soon noted to increase the risk of diabetes. Subsequent experience showed that that this risk is greatly reduced by low-dose therapy, whose benefits therefore outweigh its risks. The thiazides have a weak inhibitory effect upon release of insulin from the beta cell. This eff Continue reading >>
- American Diabetes Association® Releases 2018 Standards of Medical Care in Diabetes, with Notable New Recommendations for People with Cardiovascular Disease and Diabetes
- Leeds diabetes clinical champion raises awareness of gestational diabetes for World Diabetes Day
- Diabetes doctors: Which specialists treat diabetes?
Thiazide-induced Hypokalemia May Mediate Increased Diabetes Risk
Thiazide-Induced Hypokalemia May Mediate Increased Diabetes Risk by Todd Neale Todd Neale, Staff Writer, MedPage Today Explain to interested patients that this study found that hypokalemia associated with thiazide diuretic use appears to mediate the increased risk of diabetes with the drugs. Point out that the researchers said randomized trials are needed to determine whether treating hypokalemia can mitigate the increased diabetes risk with thiazide diuretics. BALTIMORE, Nov. 25 -- Thiazide diuretic-induced decreases in serum potassium levels appear to be at least partially responsible for the link between the hypertension drugs and diabetes, researchers here found. Among older patients participating in a placebo-controlled blood pressure lowering trial with chlorthalidone, each 0.5-mEq/L decrease in serum potassium was associated with a 45% increased risk of diabetes (P<0.001), Tariq Shafi, M.D., of Johns Hopkins, and colleagues reported online in Hypertension: Journal of the American Heart Association. Through the first year of the trial, the increased risk of diabetes in the treatment group was attenuated by 40.7% after controlling for changes in serum potassium, which indicated a significant mediating effect, the researchers said. "This study shows us that as long as physicians monitor and regulate potassium levels, thiazides could be used safely," Dr. Shafi said. "It could be as simple as increasing the consumption of potassium-rich foods like bananas and oranges and/or reducing salt intake, both of which will keep potassium from dropping," he said. However, the researchers noted, the effect of potassium supplementation on diabetes risk needs to be evaluated in randomized trials. Although past studies have shown that the use of thiazide diuretics was associated w Continue reading >>
Interactions Between Acarbose Oral And Antidiabetics-thiazides
2 Answers - How Do Thiazides Decrease Urine Volume In Diabetes Insipidus?
How do thiazides decrease urine volume in Diabetes insipidus? Thiazides are Diuretics that act on Distal Convoluted Tubule and inhibit the NaCl cotransporter in the luminal membrane, thus decreasing the Cl and Na+ reabsorption. It has paradoxical antidiuretic action in Diabetes Insipidus (DI) An initial reduction of sodium reabsorption in the distal tubule increases sodium excretion and causes extracellular fluid volume contraction. As a result, the glomerular filtration rate decreases and the proximal tubular sodium and water reabsorption increases. Consequently, less water and sodium are delivered to the collecting tubules and, as a result, less water is excreted. Thiazides work upon the nephrons in kidney usually on the proximal part of the distal tubule. They increase the Sodium excretion and urine volume a by interference with transfer across cell membranes. The result is a reduction in blood volume. Changes in cardiac output and extracellular fluid volume are transient and, in the long-term, the major haemodynamic effect is a reduction in peripheral resistance due to subtle alterations in the contractile responses of vascular smooth muscle. Diabetes insipidus (DI) is a temporary or chronic disorder characterized by the excretion of excessive quantities of very dilute, but otherwise normal urine. In brief thiazides reduce polyuria and increase urine osmolality in DI. Continue reading >>
Thiazide Diuretics And Risk Of Diabetes Mellitus - General Practice Notebook
thiazide diuretics and risk of diabetes mellitus in the ALLHAT study, the first-line use of a thiazide diuretic, an angiotensin-converting enzyme (ACE) inhibitor, or a calcium-channel blocker (CCB) for hypertension was similarly effective in reducing the risk of major cardiovascular (CV) events CCBs were less effective in preventing heart failure than thiazide diuretics, whereas development of diabetes (defined as fasting blood glucose levels [FGs] above 6.9mmol/l) was more frequent with thiazide diuretics than with CCBs a post-hoc subgroup analysis considered non-diabetic patients in ALLHAT who were randomised to initially receive chlortalidone (n=8,419), amlodipine (n=4,958), or lisinopril (n=5,034) (2) after two years, mean FGs were raised in all groups by 0.47mmol/l, 0.31mmol/l and 0.19mmol/l, respectively more cases of incident diabetes, when defined by a 6.9mmol/l FG threshold, were detected in the chlortalidone group - however, absolute differences between groups in incident diabetes were small (chlortalidone 9.3%, amlodipine 7.2%, lisinopril 5.6%) risk of developing diabetes was lower for lisinopril (odds ratio [OR] 0.55, 95%CI 0.43 to 0.70, P<0.001) or amlodipine (OR 0.73, 95%CI 0.58 to 0.91, P=0.008) compared with chlortalidone was no significant association between FG changes at two years and any of the study endpoints (death, CV disease or end-stage renal disease), whether analysed for all treatments combined or for chortalidone alone findings support the results from the 14-year follow-up of SHEP (3) and suggest that, even if diabetes does occur during the treatment of hypertension with thiazide diuretics, this does not create any greater cardiovascular risk possible that that the raised FGs that occur with thiazide diuretics arise from mechanisms that are Continue reading >>
Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures. There are four types of DI, each with a different set of causes. Central DI (CDI) is due to a lack of the hormone vasopressin (antidiuretic hormone). This can be due to damage to the hypothalamus or pituitary gland or genetics. Nephrogenic diabetes insipidus (NDI) occurs when the kidneys do not respond properly to vasopressin. Dipsogenic DI is due to abnormal thirst mechanisms in the hypothalamus while gestational DI occurs only during pregnancy. Diagnosis is often based on urine tests, blood tests, and the fluid deprivation test. Diabetes mellitus is a separate condition with an unrelated mechanism, though both can result in the production of large amounts of urine. Treatment involves drinking sufficient fluids to prevent dehydration. Other treatments depend on the type. In central and gestational disease treated is with desmopressin. Nephrogenic disease may be treated by addressing the underlying cause or the use of a thiazide, aspirin, or ibuprofen. The number of new cases of diabetes insipidus each year is 3 in 100,000. Central DI usually starts between the ages of 10 and 20 and occurs in males and females equally. Nephrogenic DI can begin at any age. The term "diabetes" is derived from the Greek word meaning siphon. Signs and symptoms Excessive urination and extreme thirst and increased fluid intake (especially for cold water and sometimes ice or ice water) are typical for DI. The symptoms of excessive urination Continue reading >>
Paradoxical Antidiuretic Effect Of Thiazides In Diabetes Insipidus: Another Piece In The Puzzle
Diabetes insipidus (DI) is a temporary or chronic disorder characterized by the excretion of excessive quantities of very dilute, but otherwise normal urine. The disease results either from impaired synthesis and secretion of antidiuretic hormone (ADH, vasopressin) by the hypothalamus and posterior pituitary, respectively (central DI), or from an unresponsiveness of the kidneys to the hormone itself (nephrogenic DI) (1–3⇓⇓). The renal water transport defect is located in the collecting system (i.e. the connecting tubule – CNT and the collecting duct – CD) in which vasopressin normally controls the expression and cell surface targeting of the apical water channel aquaporin-2 (AQP2) (4). The CNT and CD are also the site of amiloride-sensitive sodium reabsorption via the epithelial sodium channel (ENaC) (5). Sodium transport across ENaC may osmotically drive transepithelial water reabsorption. Consistently, both AQP2 and ENaC are regulated by vasopressin via V2-receptor-dependent cAMP production (4,5⇓). While exogenous application of vasopressin efficiently corrects the reduced AQP2 expression and the urinary concentration defect in central DI (4), the treatment of nephrogenic DI is usually less obvious and may include different approaches such as dietary sodium restriction, prostaglandin synthesis inhibitors, potassium-sparing diuretics and/or thiazide diuretics (3,6⇓). The use of diuretics for the treatment of a polyuric disease appears paradoxical, but the beneficial effect of thiazides has now been proven for more than 45 yr. In 1959, Crawford and Kennedy showed in a seminal paper that thiazides reduce polyuria and increase urine osmolality in DI (7). Since then, thiazides have become an important component in the therapeutic repertoire for treatment of D Continue reading >>
Treatment Of Nephrogenic Diabetes Insipidus
INTRODUCTION Nephrogenic diabetes insipidus (nephrogenic DI) results from partial or complete resistance of the kidney to the effects of antidiuretic hormone (ADH). As a result, patients with this disorder are not likely to have a good response to hormone administration (as desmopressin [dDAVP]) or to drugs that increase either the renal response to ADH or ADH secretion. Nephrogenic DI can be hereditary or acquired. In adults, a concentrating defect severe enough to produce polyuria due to nephrogenic DI is most often due to chronic lithium use or hypercalcemia and less frequently to other conditions that impair tubular function, such as Sjögren's syndrome . Release of ureteral obstruction is often associated with a diuresis, but this is short lived and does not require specific therapy other than maintenance fluids. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis", section on 'Prognosis and recovery of renal function'.) Hereditary nephrogenic DI, which is largely an X-linked disease, may also be seen by internists since early recognition and treatment in infancy has led to survival to adulthood [2,3]. In addition, affected women may be carriers with few or no symptoms until pregnancy or other stress. In infants with hereditary nephrogenic DI, treatment is aimed at minimizing the polyuria and avoiding hypernatremia and volume depletion. In adults, therapy is usually aimed at correcting the underlying disorder or discontinuing an offending drug. In hypercalcemic patients, for example, normalization of the plasma calcium concentration usually leads to amelioration of polyuria. By contrast, lithium-induced nephrogenic DI may be irreversible if the pati Continue reading >>
Thiazide Diuretics Alone Or With Beta-blockers Impair Glucose Metabolism In Hypertensive Patients With Abdominal Obesity
Thiazide Diuretics Alone or with Beta-blockers Impair Glucose Metabolism in Hypertensive Patients with Abdominal Obesity 1 University of Missouri-Columbia School of Medicine, Department of Medicine 3 Department of Diabetes and Cardiovascular Center 1 University of Missouri-Columbia School of Medicine, Department of Medicine 3 Department of Diabetes and Cardiovascular Center 1 University of Missouri-Columbia School of Medicine, Department of Medicine 2 Department of Physiology and Pharmacology 3 Department of Diabetes and Cardiovascular Center 1 University of Missouri-Columbia School of Medicine, Department of Medicine 2 Department of Physiology and Pharmacology 3 Department of Diabetes and Cardiovascular Center Corresponding Author: James R. Sowers, M.D, ASCI, FAHA, FACP, Professor of Medicine, Physiology and Pharmacology, D109 HSC Diabetes Center, One Hospital Drive, Columbia, MO 65212, Telephone (573) 884-0769, FAX (573) 884-5530, [email protected] The publisher's final edited version of this article is available free at Hypertension See the article " IMPACT OF ABDOMINAL OBESITY ON INCIDENCE OF ADVERSE METABOLIC EFFECTS ASSOCIATED WITH ANTIHYPERTENSIVE MEDICATIONS " in Hypertension, volume 6 onpage61. See other articles in PMC that cite the published article. Randomized clinical trials in patients with hypertension and other cardiovascular disease (CVD) risk factors have shown that anti-hypertensive therapy with thiazide diuretics and beta-blockers is associated with increased incidence of new onset diabetes and other metabolic abnormalities ( 1 , 2 ). There is growing evidence that those patients with central obesity and other components of the cardiometabolic syndrome are especially prone to new onset diabetes ( 1 5 ). In persons with abdominal obesity, h Continue reading >>