Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.
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PMID:[Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus]. 2184 8

Hypertension is a major risk factor for coronary heart disease, stroke, heart failure and renal disease. The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 7 defined hypertension as a blood pressure of more than 140/90 mmHg and recommended to initiate treatment with a two-drug combination for stage 2 hypertension (blood pressure of 160-179/100-109 mmHg). The need for drug combinations is clear from a patient and physician perspective as they provide more effective blood pressure lowering, reduce pill burden, improve compliance and decrease hypertension-related morbidity and mortality. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Blockers of the renin-angiotensin system are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug-drug combinations of both principles, such as candesartan/hydrochlorothiazide, are highly effective in lowering blood pressure while providing improved compliance, a good tolerability and largely neutral metabolic profile. In this article, we review the literature for the role of candesartan-based therapy for hypertension, stroke, diabetes mellitus and heart failure.
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PMID:An overview of candesartan in clinical practice. 2187 42

High blood pressure in children and adolescents is a growing health problem that is often overlooked by physicians. Normal blood pressure values for children and adolescents are based on age, sex, and height, and are available in standardized tables. Prehypertension is defined as a blood pressure in at least the 90th percentile, but less than the 95th percentile, for age, sex, and height, or a measurement of 120/80 mm Hg or greater. Hypertension is defined as blood pressure in the 95th percentile or greater. A secondary etiology of hypertension is much more likely in children than in adults, with renal parenchymal disease and renovascular disease being the most common. Overweight and obesity are strongly correlated with primary hypertension in children. A history and physical examination are needed for all children with newly diagnosed hypertension to help rule out underlying medical disorders. Children with hypertension should also be screened for other risk factors for cardiovascular disease, including diabetes mellitus and hyperlipidemia, and should be evaluated for target organ damage with a retinal examination and echocardiography. Hypertension in children is treated with lifestyle changes, including weight loss for those who are overweight or obese; a healthy, low-sodium diet; regular physical activity; and avoidance of tobacco and alcohol. Children with symptomatic hypertension, secondary hypertension, target organ damage, diabetes, or persistent hypertension despite nonpharmacologic measures should be treated with antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, and calcium channel blockers are safe, effective, and well tolerated in children.
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PMID:High blood pressure in children and adolescents. 2296 55

Thiazide-induced potassium loss may contribute to new onset diabetes (NOD). KCNJ1 encodes a potassium channel and one study observed that a KCNJ1 single-nucleotide polymorphism (SNP) was associated with changes in fasting glucose (FG) during hydrochlorothiazide (HCTZ) treatment. We used linear regression to test association of KCNJ1 SNPs and haplotypes with FG changes during HCTZ treatment in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. We used logistic regression to test association of KCNJ1 variation with NOD in HCTZ-treated patients from the International Verapamil SR Trandolapril Study (INVEST). Multivariate regression analyses were performed by race/ethnicity with false discovery rate (FDR) correction. In PEAR blacks, a KCNJ1 SNP was associated with increased FG during HCTZ treatment (beta=8.47, P(FDR)=0.009). KCNJ1 SNPs and haplotypes were associated with NOD risk in all INVEST race/ethnic groups (strongest association: odds ratio 2.14 (1.31-3.53), P(FDR)=0.03). Our findings support that KCNJ1 variation is associated with HCTZ-induced dysglycemia and NOD.
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PMID:Association of KCNJ1 variation with change in fasting glucose and new onset diabetes during HCTZ treatment. 2290 31

Thiazide (hydrochlorothiazide,...) and thiazide-like (chlortalidone, indapamide,...) diuretics are widely used to treat hypertensive patients. There is growing evidence that these diuretics are not interchangeable and that it might be preferable to choose a thiazide-like diuretic whenever the use of a diuretic is considered. This is in order to prevent optimally the development of cardiovascular complications and the occurrence of metabolic side effects, in particular diabetes.
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PMID:[Are all diuretics equal for the treatment of hypertensive patients?]. 2302 82

Hypertension treatment regimens used by African American adults in the Jackson Heart Study were evaluated at the first two clinical examinations (2415 treated hypertensive persons at examination I [exam I], 2000-2004; 2577 at examination II [exam II], 2005-2008). Blood pressure (BP) was below 140/90 mm Hg for 66% and 70% of treated participants at exam I and exam II, respectively. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure treatment targets were met for 56% and 61% at exam I and exam II, respectively. Persons with diabetes or chronic kidney disease were less likely to have BP at target, as were men compared with women. Thiazide diuretics were the most commonly used antihypertensive medication, and persons taking a thiazide were more likely to have their BP controlled than persons not taking them; thiazides were used significantly less among men than women. Although calcium channel blockers are often considered to be effective monotherapy for African Americans, persons using calcium channel blocker monotherapy were significantly less likely to be at target BP than persons using thiazide monotherapy.
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PMID:Treatment of hypertension among African Americans: the Jackson Heart Study. 2373 Sep 82

Heart failure (HF) is an epidemic associated with significant morbidity and mortality, affecting over 5 million people in the United States and 1-2% of the population worldwide. Observational studies have suggested that a healthy lifestyle can reduce HF risk. Although no clinical trials have targeted the prevention of HF as a primary endpoint, many have evaluated outcomes associated with the development of symptomatic disease (i.e., progression to HF, HF hospitalization or death) as secondary endpoints. Blood pressure treatment represents the most effective strategy in preventing heart failure; each 5 mm Hg decrease in systolic blood pressures reduces the risk of HF development by 24%. Thiazide diuretics appear to be the most efficacious agents in patients with hypertension. Angiotensin converting enzyme inhibitors and angiotensin-II receptor blockers are first line agents for patients with chronic atherosclerosis, diabetes, or chronic kidney disease. Beta blockers appear less effective as single agents and cardioselective agents are preferred. Calcium channel blockers, specifically non-dihydropyridines, should be avoided and alpha blockers should not be used to reduce HF risk.
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PMID:Stage A: can heart failure be prevented? 2425 57

Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.
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PMID:Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes. 2459 94

We concluded in 2004 that the first-choice treatment for hypertension in adults was single-agent therapy with the thiazide diuretic chlortalidone or, when this drug is not available, the thiazide diuretic hydrochlorothiazide. As of early 2014, does evidence challenge this choice in adults without diabetes or cardiovascular or renal disease? To answer this question, we reviewed the available evidence, using the standard Prescrire methodology. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/100 mmHg or 160/90 mmHg, with some uncertainty over which diastolic threshold should be used. Apart from certain diuretic-based combinations, the use of combinations of antihypertensive drugs as first-line therapy has not been evaluated in terms of the complications of hypertension. A number of systematic reviews with meta-analyses of data on tens of thousands of patients have compared the main classes of antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevented about 2 to 3 deaths and 2 strokes per 100 patients treated for 4 to 5 years. Several systematic reviews concluded that neither calcium-channel blockers, ACE inhibitors nor beta-blockers are more effective than thiazide diuretics in reducing mortality or the incidence of stroke. The efficacy of the thiazide diuretic chlortalidone is supported by the highest-level evidence, from three comparative clinical trials versus placebo, an ACE inhibitor, or a calcium-channel blocker, in more than 50 000 patients. In one of these trials, chlortalidone was superior to the ACE inhibitor lisinoprilin preventing stroke. It was also superior to the calcium-channel blocker amlodipine in preventing heart failure. The effect of hydrochlorothiazide, combined with amiloride or triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, a beta-blocker, or a calcium-channel blocker. Hydrochlorothiazide appeared more effective than the beta-blocker atenolol in reducing the incidence of coronary events. The addition of a potassium-sparing diuretic (amiloride or triamterene) to first-line hydrochlorothiazide therapy has not been demonstrated to provide clinical benefit. The evaluation of indapamide, another thiazide diuretic, is less convincing. Since no head-to-head trials have been conducted, there is no evidence that it is more effective than chlortalidone or hydrochlorothiazide. None of the antihypertensive drugs appears to have a better overall adverse effect profile than the others. Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As of early 2014, the first-choice treatment for hypertension in nondiabetic adults without cardiovascular or renal disease should be chlortalidone. If chlortalidone is not available, it appears reasonable to choose another thiazide diuretic, hydrochlorothiazide, possibly combined with amiloride or triamterene. When a diuretic cannot be used, it is better to choose an ACE inhibitor: captopril, lisinopril or ramipril.
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PMID:Treating essential hypertension. The first choice is usually a thiazide diuretic. 2532 25

Hypertension is the most common chronic condition treated by family physicians. Elevated blood pressure is associated with an increased risk of heart failure, myocardial infarction, cerebrovascular disease, and death. Treatment of hypertension reduces the risk of these events. Several lifestyle modifications are associated with improvements in blood pressure, including the Dietary Approaches to Stop Hypertension diet, sodium restriction, regular exercise, and moderate weight loss. There is strong evidence that reducing diastolic blood pressure to less than 90 mm Hg is beneficial in adults older than 30 years. Although there is good evidence to support reducing systolic blood pressure to less than 150 mm Hg in adults older than 60 years, the evidence in younger adults is insufficient to recommend a specific goal. Black patients with chronic kidney disease who are treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to a blood pressure of less than 140/90 mm Hg experience slower declines in glomerular filtration rates than patients treated with other medications. A blood pressure goal of less than 140/90 mm Hg is recommended in patients with chronic kidney disease and in those with diabetes mellitus. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers are the preferred medications in nonblack patients; thiazide diuretics and calcium channel blockers are preferred in black patients.
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PMID:Common questions about the initial management of hypertension. 2582 79


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