Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and diabetes mellitus are both common conditions which frequently co-exist. The calcium channel blockers are potentially diabetogenic since insulin secretion may be impaired by their use. The aim of this study was to determine whether nitrendipine, a second generation dihydropyridine derivative calcium antagonist, is capable of interfering with carbohydrate metabolism and insulin secretion in hypertensive diabetics at the doses commonly used in therapy. In a 12-week double blind placebo-controlled randomized clinical trial, the effects of nitrendipine (20 mg/day) on arterial blood pressure, glycaemic homeostasis and other metabolic parameters were evaluated in 30 patients with mild to moderate essential hypertension and type II diabetes mellitus. The results showed nitrendipine to be an effective antihypertensive agent which neither impaired the overall glucose homeostasis nor caused any other potentially harmful metabolic side effect. In conclusion, these data suggest that the calcium channel antagonist nitrendipine is a metabolically safe drug to use in the treatment of hypertension, especially in patients with diabetes mellitus.
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PMID:[Antihypertensive efficacy of nitrendipine and its effects on carbohydrate metabolism. A controlled clinical study versus placebo]. 194 44

Treatment of hypertension in patients with NIDDM should be administered with special attention not to increase insulin resistance nor to impair insulin secretion capacity. The coexisting risk for coronary artery disease and myocardial infarction should not be increased by undesired drug effects on the plasma lipoprotein profile. Late lesions of diabetes mellitus (nephropathy, neuropathy) have also to be taken into account. Consequently angiotensin converting enzyme inhibitors, if necessary combined with calcium channel blockers, should be administered first. If blood pressure is thus not sufficiently controlled, alpha-adrenergic blockers, vasodilating agents or sympatholytics may be added. Once insulin treatment is installed, or if required for other reasons (nephropathy, congestive heart failure, cardiac arrhythmia), also diuretics and beta-adrenergic blockers are indicated in antihypertensive treatment of diabetic patients.
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PMID:[Hypertension in type II diabetes mellitus]. 195 Mar 78

The pathophysiological connections between insulin resistance, hypertension and type 2 diabetes are discussed in this review article. Increased blood pressure levels are often found in type 2 diabetic patients long before the diabetes itself is diagnosed. By contrast, in type 1 diabetes hypertension is predominantly the consequence of diabetic glomerulopathy. Non-pharmacological strategies should be favoured in the treatment of hypertension in type 2 diabetic patients before specific pharmacological intervention is started. Antihypertensive treatment with beta-blocking agents and diuretics is criticized by many experts in the field of metabolic disorders, since these drugs induce a deterioration of glycaemic control and lipid metabolism in diabetic patients. Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking agents have no influence on metabolism, these drugs are recommended for the antihypertensive treatment of diabetic patients. Further studies should be undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective effect. Since most type 2 diabetic patients do not develop diabetic nephropathy, a possible nephroprotective effect of ACE inhibitors is only relevant to the antihypertensive treatment of type 1 diabetic patients.
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PMID:[Hypertension, insulin resistance and diabetes mellitus: pathophysiological interactions and therapeutic consequences]. 198 Jul 67

Hypertension combined with diabetes in the elderly is characterized by many important metabolic and cardiovascular changes, among which insulin resistance, hyperinsulinaemia and increased total peripheral resistance appear to be the most relevant. Non-insulin dependent diabetes mellitus is also characterized by insulin resistance and hyperinsulinaemia. Moreover, hyperinsulinaemia itself has been shown to increase total peripheral resistance. Hyperinsulinaemia thus seems to play a key role in the pathophysiology of hypertension in elderly diabetic subjects. Therefore elderly hypertensive diabetic patients should be treated with thiazide diuretics in low doses, calcium channel blockers and alpha-adrenergic blockers.
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PMID:Diabetes and hypertension in the elderly. 306 92

Doxazosin is a long-acting alpha 1-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in the treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM) and respiratory disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have reported an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha 1-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Doxazosin. An update of its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia. 753 94

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) are known to be elevated in patients on chronic hemodialysis. Since ET and ANP plasma levels are found to be raised in nonuremic diabetic versus nondiabetic subjects, we wanted to detect a possible difference in plasma levels of these hormones in diabetic versus nondiabetic patients who were on chronic renal replacement therapy. ET is a possible marker of increased vascular atherogenic activity. We measured plasma levels of ET and ANP pre- and posthemodialysis in 23 non-insulin-dependent (NIDDM) diabetic versus 23 nondiabetic patients who were matched according to age and time of day of hemodialysis, and who did not show clinical signs of overt cardiac decompensation. Mean plasma levels of ET and ANP did not differ in diabetic from nondiabetic patients, neither pre- nor postdialysis. In both patient groups, mean ET levels were twice the upper normal limit, did not change significantly pre- versus postdialysis, and did not correlate with blood pressure or with volume ultrafiltration during dialysis. Calcium channel blocker therapy was accompanied by a significant rise of ET pre- and postdialysis in nondiabetic patients but not in diabetic patients. In diabetic patients, ET plasma levels correlated positively with fructosamine levels as an indicator of short-term blood glucose control. Mean ANP plasma levels were about three times the upper normal limit and decreased significantly during dialysis, but this decrease correlated neither with volume ultrafiltration nor with blood pressure. In conclusion, we could not find a difference in plasma levels of ET and ANP for diabetic versus nondiabetic dialysis patients, but impaired short-term blood glucose control in diabetic and calcium channel blocker therapy in only nondiabetic dialysis patients showed concomitant increases in plasma ET levels and thus possibly different mechanisms of ET regulating pathways.
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PMID:Endothelin and atrial natriuretic peptide in non-insulin-dependent diabetic versus nondiabetic patients on chronic hemodialysis. 789 86

Calcium channels play an important role in insulin secretion from pancreatic beta cells, in which two different L-type voltage-dependent Ca2+ channels (VDCC), the beta cell/neuron type and the cardiac type are expressed. The former pre-dominant subtype gene (hCa CN4) consists of 49 exons spanning 120 kilo-bases. The promoter region of hCaCN4 is similar to that of housekeeping gene, which is extremely G+C rich and lacks a TATA-like sequence but has three possible binding regions for transcriptional factor Sp1. Changes of calcium channel mRNA in rat pancreatic islets after glucose infusion are introduced. It is important to investigate variations or mutations in the hCaCN4 gene, causing insufficient insulin secretion, leading to NIDDM.
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PMID:[The alpha 1 subunit of voltage-dependent calcium channel expressed in pancreatic beta cells]. 798 84

The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states.
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PMID:Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions. 820 15

Parathyroid hypertensive factor (PHF) in rats: PHF is an endogenous hypertensive substance which was originally associated with hypertension in spontaneously hypertensive rats (SHR). In this model, PHF was shown to act by increasing intracellular calcium levels in vascular smooth muscle and was linked with a characteristic pattern of abnormalities in overall calcium regulation. The action of PHF was blocked by calcium antagonists, suggesting that the effect of PHF was to increase extracellular calcium uptake. In SHR the parathyroid glands were shown to be the site of PHF secretion. This secretion was inhibited by an increase in dietary calcium. PHF was further shown to be unique to low-renin forms of hypertension, that is, those forms of hypertension characterized by abnormalities in calcium metabolism. PHF in humans: PHF was subsequently found in human low-renin salt-sensitive hypertension. As in SHR, calcium supplementation can lower PHF levels in humans. Similarly, there is circumstantial evidence for the parathyroid origin of PHF in humans. In human hypertensive patients, the presence of PHF has been shown to predict a favorable therapeutic response to calcium channel blockade. Recently, many of the abnormalities in calcium metabolism present in low-renin hypertension have also been described in other disease states. Notable among these diseases is non-insulin dependent diabetes mellitus. A survey of human non-insulin dependent diabetes mellitus has revealed that PHF was present in a disproportionate number of these patients independently of the blood pressure level. The significance of this latter finding needs to be explored, but PHF may prove to have relevance in diseases other than hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical aspects of parathyroid hypertensive factor. 820 59

Nicardipine is a second generation dihydropyridine calcium antagonist which selectively inhibits vascular smooth muscle contraction. In elderly patients, the drug has demonstrated clinical efficacy in the management of hypertension, angina pectoris and ischaemia-related cerebrovascular disease. In particular, nicardipine effectively controls blood pressure in elderly hypertensive patients with or without coexistent disease. In noncomparative trials, a regimen containing nicardipine has been associated with an improvement of symptoms in hypertensive patients with concurrent coronary artery, cerebrovascular or peripheral vascular disease, while in essentially 'healthy' elderly hypertensive patients, nicardipine monotherapy has resulted in improved indices of mobility and cognitive function. As yet, however, there is no evidence that nicardipine (and/or other calcium channel antagonists) decreases cardiovascular morbidity and mortality in elderly patients, as has been demonstrated for more established antihypertensive therapies, namely diuretics and/or beta-blockers. The pharmacokinetic properties of nicardipine in elderly hypertensive patients appear to be similar to those in younger patients. The main adverse events associated with nicardipine in the elderly are related to the vasodilator properties of the drug and include pedal oedema, headache and flushing. However, the drug does not exacerbate spontaneous postural hypotension in the elderly, nor does it adversely affect the coronary artery disease risk profile, even in patients with type II diabetes mellitus. In summary, widespread clinical experience in the elderly indicates that nicardipine monotherapy or a regimen containing nicardipine is useful for the treatment of hypertension, particularly in patients with coexistent coronary artery, cerebrovascular or peripheral vascular disease. Nicardipine monotherapy has also demonstrated efficacy in angina pectoris and shown promise in the management of ischaemia-related cerebrovascular diseases, notably subarachnoid haemorrhage.
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PMID:Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients. 847 49


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