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

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

This study was performed to assess the possible involvement of humoral immunity in essential hypertension, independently of the presence of atherosclerotic disease, which in turn may be associated with immunologic changes. Sixty-five patients without demonstrated atherosclerotic disease were selected according to clinical and arteriographic criteria, including 23 hypertensive subjects (all pharmacologically treated) and 42 controls. Mean ages (58.7 +/- 8.3(1 S.D.) years in the controls and 57.7 +/- 7.9 years in the hypertensive subjects) and sex distribution were similar in the 2 groups. Of the main risk factors, atherosclerosis, smoking, diabetes, total cholesterol and HDL-cholesterol were equivalent, while triglycerides were higher in the hypertensive subjects than in the controls (142.6 +/- 52.7 vs. 112.6 +/- 67.7 mg/dl; p = 0.0065). In these subjects' sera the immunoglobulins IgG, IgA and IgM, and the third and fourth complement components (C3 and C4) were measured. Of these variables, only C3 was higher in the hypertensive subjects than in the controls (124.3 +/- 29.3 vs. 107.8 +/- 18.4 mg/dl; p = 0.0183). Furthermore, C3 was significantly correlated with triglycerides (tau = 0.3613; p < 0.0001), but the association with hypertension was confirmed only for C3, and not for triglycerides, by multiple logistic regression (p = 0.0142). The increase in serum C3 suggests the possible implication of humoral immunity in the pathogenesis or progression of essential hypertension.
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PMID:[Association of serum C3 and essential hypertension]. 129 20

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.
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PMID:Hyperinsulinemia, insulin resistance and essential hypertension. 130 12

There is evidence that the cytosolic free Ca2+, protein kinase C, and the Na(+)-H+ antiport cross-communicate with one another through positive and negative feedback mechanisms, thereby maintaining cellular Ca2+ and pH homeostasis. This triumvirate may play a role in the development of insulin resistance--a common characteristic of both essential hypertension and non-insulin-dependent diabetes mellitus. Circulating cells from patients with essential hypertension and non-insulin-dependent diabetes mellitus demonstrate elevated cytosolic free Ca2+, increased protein kinase C activity, or both, and these perturbations are associated with augmented activity of the Na(+)-H+ antiport. If present in other cells (e.g., striated muscle cells and adipocytes), these alterations could underlie insulin resistance in essential hypertension and non-insulin-dependent diabetes mellitus.
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PMID:The roles of cell Ca2+, protein kinase C and the Na(+)-H+ antiport in the development of hypertension and insulin resistance. 133 4

Insulin resistance is a frequently occurring abnormality. Although there can be insensitivity to any of insulin's actions, insulin resistance par excellence is a decreased insulin-mediated whole-body glucose disposal rate. A distinction is made between primary and secondary insulin resistance. Primary insulin resistance is of unknown origin, is only partially experimentally reproducible, and is essentially irreversible (spontaneously or by treatment). In addition, it is both pathway-specific (ie, glucose storage) and organ-specific (mostly skeletal muscle), and is compatible with a postreceptor defect in insulin action. Primary insulin resistance is found in a proportion (approximately 25%) of otherwise healthy people, in non-insulin-dependent diabetes mellitus, essential hypertension, and some forms of dyslipidemia. The idea of an insulin resistance syndrome derives from the striking pattern of overlap among these clinical conditions. Their tendency to cluster in the same individuals is evident from both cross-sectional and longitudinal observations. It is proposed that the insulin resistance syndrome is a large constellation of interrelated changes in metabolic, anthropometric, and hemodynamic variables centered around insulin resistance or hyperinsulinemia. There is a significant genetic component, a predisposing influence for non-insulin-dependent diabetes mellitus, hypertension, dyslipidemia, and possibly, a distinct atherogenic potential.
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PMID:The insulin resistance syndrome. 134 29

Although essential arterial hypertension is believed to have a strong genetic predisposition, the gene(s) responsible are unknown. The mechanisms underlying the regulation of blood pressure and experimental studies place the renin gene among the main candidate genes that need to be tested in humans. We tested the hypothesis of a linkage between the renin gene and essential hypertension using the affected sib pair method. Siblings (133 subjects, 52.1 +/- 10.9 years) from 57 families were selected for sustained hypertension (160.7 +/- 22.9/99.5 +/- 12.8 mmHg with 80% of patients under antihypertensive treatment), of early onset (40.7 +/- 12.0 years), in the absence of obesity, diabetes mellitus, and secondary hypertension. Eight renin haplotypes were generated from three diallelic renin restriction fragment length polymorphisms (RFLPs) (TaqI, HinfI, HindIII) located throughout the renin gene. The allelic concordance between the sib pairs was analyzed by identity by state relationships for 98 sib pairs (41 for 41 couples, 39 for 13 trios, 18 for 3 quartets). Allelic frequencies in the 57 hypertensive probands were similar to those observed among 102 hypertensive subjects studied previously. Six of eight possible haplotypes were observed, the informativity of the marker corresponded to 70% of heterozygosity. Allelic concordance for all sib pairs according to sibship size was not significantly different from that expected under the hypothesis of no linkage (t = 0.52, P = 0.15) reflecting only a small excess of renin alleles shared by the hypertensive sibs (1.44 +/- 0.6 vs 1.36 +/- 0.6). Likewise the linkage hypothesis was unsupported by weighted estimates to correct for possible bias due to large sibship size. Thus, the sib pair analysis suggests that the renin gene does not have a frequent role in the pathogenesis of essential hypertension; further more powerful linkage studies or other approaches will be needed to detect contributions at the renin locus to the heritability of essential hypertension.
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PMID:Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. 134 86

The safety and tolerability of carvedilol, a new antihypertensive agent with the combined pharmacological activities of beta-blockade and vasodilation, and of nifedipine were investigated in patients with essential hypertension and non-insulin-dependent (type II) diabetes mellitus. Twenty patients were openly randomized to receive 25 mg carvedilol once daily (five men and five women; mean age, 63 years) or 10 mg nifedipine t.i.d. (three men and seven women; mean age, 64 years) for a period of 4 weeks. Baseline mean sitting blood pressures were 168/98 and 169/95 mm Hg in the carvedilol and nifedipine groups, respectively. Baseline mean areas under the curve (AUC) of the intravenous glucose tolerance test (IVGTT) for the carvedilol and nifedipine groups were 6,136 +/- 1,195 and 6,287 +/- 1,228 mg/dl/min, respectively. Demographic and efficacy variables were not statistically different between treatment groups. After 4 weeks of therapy, mean sitting blood pressure was significantly (p less than 0.02) reduced to 144/91 mm Hg in the carvedilol group and to 149/87 mm Hg in the nifedipine group. Week 4 IVGTT AUC values of 5,735 +/- 1,464 mg/dl/min in the carvedilol group and 5,988 +/- 993 mg/dl/min in the nifedipine group, representing mean reductions of 6.14% and 3.17%, respectively, were not statistically different from baseline. Both treatments were well tolerated. No patient experienced adverse events in the carvedilol treatment group, whereas two patients in the nifedipine group reported episodes of headache (one patient) and palpitations (one patient); each episode was mild in severity and considered to be related to study medication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the effects of carvedilol and nifedipine in patients with essential hypertension and non-insulin-dependent diabetes mellitus. 137 56

Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.
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PMID:Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders. 138 18

Hypertension and diabetes mellitus are strongly associated conditions from epidemiologic, genetic, and pathophysiologic points of view. The prevalence of hypertension is high in patients with diabetes, and, conversely, many patients with essential hypertension are glucose intolerant. Proteinuria appears in 40-50% of patients with insulin-dependent diabetes mellitus and 20-30% of patients with non-insulin-dependent diabetes mellitus. Progressive renal failure occurs in 30-40 and 3-8% of patients, respectively, hypertension being a leading factor in its rate of progression. In various animal experiments, ACE inhibitors are able to prevent proteinuria and glomerular sclerosis, presumably by lowering transglomerular capillary pressure. In the diabetic human, ACE inhibitors are powerful antihypertensive drugs, devoid of metabolic side effects. Clinical studies indicate that ACE inhibitors reduce proteinuria and possibly slow the rate of decline in renal function. Such an effect is not observed with beta-blockers. Large-scale studies are needed to confirm this very important hypothesis.
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PMID:Angiotensin-converting enzyme inhibition and diabetic nephropathy. 138 63

We have investigated the cellular basis for the clinical and epidemiologic linkage of hypertension, left ventricular hypertrophy (LVH), obesity, and non-insulin-dependent diabetes mellitus (NIDDM) and have studied cytosolic free calcium and free magnesium levels in these syndromes. Specifically, intracellular free calcium is elevated and free magnesium is deficient in hypertension, and both are related (directly and inversely, respectively) to the ambient level of blood pressure, to LV mass index (and thus to the degree of cardiac hypertrophy), and to the hyperinsulinemia and insulin resistance of essential hypertension. Dynamically, the ability of dietary salt loading to elevate blood pressure corresponds to its ability to elevate cytosolic free calcium and reciprocally to suppress free magnesium levels. Conversely, the ability of calcium channel blockade to reverse salt-induced hypertension is related to its ability to prevent these transmembrane ionic effects. Higher steady-state free calcium or lower free magnesium, or both, are also observed in clinical states linked to hypertension, such as obesity and NIDDM. Oral glucose loading in normal subjects itself elevates free calcium and suppresses free magnesium levels, as does hyperglycemia in vitro. These data suggest an ionic hypothesis of cardiovascular and metabolic disease, in which a generalized defect in cell ion handling is present in all tissues, resulting in higher steady-state free calcium and lower free magnesium levels. In pancreatic beta cells, this would produce hyperinsulinemia; in fat and skeletal muscle, cause peripheral insulin resistance; and in renal tissue, increase proximal sodium resorption and increase urinary calcium excretion--all features of essential hypertension. In vascular smooth muscle, high cytosolic free calcium would increase smooth muscle tone and cause vasoconstriction, and in heart muscle, independent of blood pressure, would increase contractility and predispose to LVH. Therefore, what may appear clinically to be the separate syndromes of hypertension, obesity, and NIDDM may pathophysiologically be different manifestations of the same underlying cellular defect, thus explaining their frequent clinical coexistence. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion-specific agents, such as calcium channel blocking drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent excess morbidity and mortality of the concurrent cardiac, vascular, and metabolic aspects of the hypertensive state.
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PMID:Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. 138 62


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