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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of genetic investigations in diabetes one can describe in aspect of their role in the pathogenesis of type 1 and type 2 as well as in pathogenesis of chronic complications and gene therapy of diabetes. There is not only one gene responsible for type 1 diabetes. Similarly there are many gene-candidates in type 2 diabetes. Only in 6 types of MODY the genes responsible for beta-cell dysfunction were described. In diabetic complications some role e.g. in retinopathy may be played by genes of growth factors, heparan sulfate synthesis as well as genes of adrenergic receptor beta 3. In diabetic nephropathy the genes of renin synthesis, converting enzyme, aldose reductase or angiotensin receptor can be of importance. It should be emphasized that identification of human genome and genes responsible for diabetes can contribute to introduction of gene therapy in diabetes.
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PMID:[The role of genetic studies in finding the etiopathogenesis of diabetes mellitus]. 1129 31

The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria) study is to assess the effect of a dual blockade of the renin-angiotensin system--using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure and microalbuminuria. The study included 200 patients randomized to receive candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the same monotherapy or a combination treatment. Main outcomes are the reduction of microalbuminuria and blood pressure. All three of the treatments are effective, but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in reducing microalbuminuria, systolic and diastolic blood pressure. No comparison is made between this "new" association and the more frequently used biotherapy (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular practice is still to be determined.
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PMID:[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy]. 1129 48

CS-866 is a new angiotensin II receptor blocker that has demonstrated effectiveness for lowering blood pressure in animal models of hypertension. Given the proposed involvement of the renin-angiotensin system in diabetic nephropathy and atherosclerosis, we have tested CS-866 in animal models of these conditions. The renal protective properties of CS-866 were examined in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes that develops progressive hyperglycemia, glomerulosclerosis, and proteinuria. Treatment of ZDF rats with CS-866 in the diet for 19 weeks resulted in a dose-dependent reduction in urinary protein excretion compared with vehicle-treated control rats, which was independent of changes in blood pressure and glycemic state. The antiatherosclerotic properties of CS-866 were tested in 2 animal models. In the first study, cynomolgus monkeys were fed a high-cholesterol diet for 6 months while receiving CS-866 or vehicle. At the end of this period, CS-866-treated animals had 64% less plaque area in the aorta than controls. CS-866 was also tested in the Watanabe heritable hyperlipidemic (WHHL) rabbit model of atherosclerosis. WHHL rabbits were treated for 32 weeks with CS-866 (1 mg/kg), pravastatin (50 mg/kg), a combination of the 2 drugs, or vehicle. CS-866 had no effect on plasma cholesterol levels and reduced blood pressures minimally. Pravastatin alone reduced serum cholesterol but had no effect on blood pressure or lesion area. In contrast, treatment with CS-866 resulted in a 40% reduction in lesion area compared with vehicle-treated control when given alone and a 50% reduction in combination with pravastatin. On the basis of results from animal models, CS-866 may be a useful treatment for diabetic nephropathy and atherosclerosis.
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PMID:New pharmacologic aspects of CS-866, the newest angiotensin II receptor antagonist. 1133 66

Diabetes-related cardiovascular disease remains the leading cause of death in patients with type 2 diabetes. Hypertension is common among diabetics and has the same pathogenetic mechanisms as insulin resistance, in which the activated renin-angiotensin system contributes to the emerging high blood pressure and hyperglycemia. Hyperglycemia is one of the triggering factors for vascular dysfunction and clotting abnormalities and, therefore, for accelerated atherosclerosis in diabetes. Glycated hemoglobin levels, as a reflection of the degree of glycemia, are strongly associated with the risk of cardiovascular disease in diabetics and in the general population. Tight glycemic control, the treatment of dyslipidemia and raised blood pressure, in addition to the use of antiplatelet therapy, all powerfully reduce the risks associated with diabetes. Furthermore, angiotensin-converting enzyme inhibitors might offer additional cardioprotection to diabetics above that provided by blood pressure reduction.
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PMID:Diabetes mellitus and diabetes-associated vascular disease. 1139 48

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.
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PMID:Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy. 1140

Aging in Westernized industrialized societies is associated with an increasing prevalence of hypertension, type II diabetes mellitus, renal disease, and atherosclerotic vascular disease. This increase in the chronic disease processes in industrialized societies is related, in part, to increasing obesity, reduced physical activity, medications such as nonsteroidal anti-inflammatory agents, and other environmental influences. Hypertension in the elderly is characterized by high peripheral vascular resistance, reduced baroreflex sensitivity, a low renin state with reduced cardiac output/increased hypertrophy, reduced intravascular volume, and an increased propensity to salt-sensitivity. Initial antihypertensive therapy in the elderly patient should be based on attempts to affect hygienic measures such as weight reduction, decreased salt and fat intake, and a careful aerobic exercise program. The initial antihypertensive drugs of choice are low doses of diuretics, which have been shown to reduce cardiovascular mortality in the elderly. Low doses of diuretics do not substantively affect carbohydrate and lipid metabolism. Lipid abnormalities in the elderly should generally be treated in a similar fashion to those in the middle-aged individual. Compliance with medical therapy in the elderly patient has been demonstrated to be relatively good.
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PMID:Treatment of Elderly Hypertensive Patients With Diabetes, Renal Disease, and Coronary Heart Disease. 1141 94

Blood pressure reduction is the most significant factor in delaying onset and progression of renal disease. Blockade of the renin-angiotensin system (RAS) using angiotensin-converting enzyme inhibitors (ACEIs) delays renal disease progression. More recently, agents that block the RAS by preventing angiotensin II from binding to its subtype 1 receptor (ARBs) have been developed in an effort to prevent deleterious consequences of pathologic levels of angiotensin II and to reduce the adverse effects of RAS blockade associated with ACEIs. Human studies with a variety of ARBs have clearly demonstrated the antihypertensive and antiproteinuric efficacy of these agents in patients with progressive renal diseases. Moreover, the effects of ARBs are similar or identical to those of ACEIs. Ongoing long-term clinical trials are designed to determine whether ARBs also preserve renal function similar to ACEIs. Specifically, the role of ARBs in patients with hypertension and type 2 diabetes is being evaluated in 3 large trials, including Appropriate Blood Pressure Control in Diabetes-Part 2 With Valsartan, the Losartan Renal Protection Study, and the Irbesartan Diabetic Nephropathy Trial. Definitive evidence of the long-term protective effects of ARBs in chronic progressive renal disease is expected from these important studies.
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PMID:Angiotensin II subtype 1 receptor blockers and renal function. 1142 96

The renin-angiotensin system is important in the control of hemodynamic status and pathogenesis of macrovascular disease, which is a major cause of morbidity and mortality in patients with type 2 diabetes with nephropathy. Serum angiotensin-converting enzyme (ACE) and angiotensinogen (Atg) levels are related to their respective gene polymorphisms. Seventy patients with type 2 diabetes with overt nephropathy (serum creatinine >/= 1.5 mg/dL) were studied. Serum ACE activity was measured by the spectrophotometric method. ACE deletion/insertion (D/I) and Atg M235T genotypes were determined by polymerase chain reaction. Patients with and without macroangiopathy were compared. Those with macroangiopathy had increased ACE activity (median, 60.9 U/L; range, 37.9 to 100 U/L versus without macroangiopathy, 47.9 U/L; range, 11.2 to 84.5 U/L; P = 0.01) and prevalence of ACE DD/DI genotypes (DD/DI:II: with macroangiopathy, 61%:39% versus without macroangiopathy, 34%:66%; P = 0.03). Multivariate analysis using age; sex; duration of diabetes; glycemic, blood pressure, and lipid level control; serum creatinine level; and presence of the ACE D allele showed that presence of the D allele (P = 0.03; odds ratio, 1.8; confidence interval, 1.1 to 3.1) and serum creatinine level (P = 0.0007) were independent risk factors for macroangiopathy. Association of the D allele became insignificant after serum ACE activity was included in the analysis in which only serum ACE activity (P = 0.004) and serum creatinine level (P = 0.01) were independent risk factors. Neither Atg M235T nor its synergistic effect with the ACE D allele showed an association with macroangiopathy. In conclusion, the ACE D allele is associated with macroangiopathy in Chinese patients with type 2 diabetes with nephropathy. The association is dependent on its effect on serum ACE activity, which is an independent risk factor for the development of macroangiopathy.
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PMID:Contribution of gene polymorphisms in the renin-angiotensin system to macroangiopathy in patients with diabetic nephropathy. 1143 Nov 75

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.
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PMID:Pathogenesis of diabetic nephropathy. 1146 May 89

Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of < 130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT(1) receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease. (c)2001 Le Jacq Communications, Inc.
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PMID:Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists. 1149 50


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