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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of type 2 diabetes mellitus is increasing world-wide, and is now one of the leading causes of end-stage renal disease in Western countries. Type 2 diabetes mellitus is also a major risk factor for cardiovascular events. Therefore, the early identification of patients at greatest risk, and the subsequent initiation of renal and cardiovascular protective treatments, are of the utmost importance. Microalbuminuria refers to a subclinical increase in urinary albumin excretion. By definition it corresponds to an albumin excretion rate of 20 to 200 microg/min (30 to 300 mg/day) or an albumin to creatinine ratio (mg/mmol) of 2.5 to 25 in males and 3.5 to 35 in females. Microalbuminuria is an important clinical finding because it is not only associated with an increased risk of progression to overt proteinuria (macroalbuminuria) and renal failure, but also cardiovascular events. In patients who progress to overt nephropathy, microalbuminuria usually precedes macroalbuminuria by an interval of 5 to 10 years. In patients with type 1 diabetes mellitus, blood pressure increases and renal function declines after the onset of macroalbuminuria. However, in patients with type 2 diabetes mellitus, hypertension and a decline in renal function may occur when albumin excretion is still in the microalbuminuric range. Large clinical trials have demonstrated that achieving tight glycemic (i.e. glycosylated hemoglobin < 7.0%) and blood pressure (i.e. < 130/85mm Hg) control retards the progression of renal disease. There is accumulating evidence to suggest that the use of antihypertensive agents which target the renin-angiotensin system (RAS) can slow the progression of renal disease and provide cardioprotection in patients with type 2 diabetes mellitus and microalbuminuria. Antihypertensive agents which target the RAS also appear to have advantages over and above reductions in systemic blood pressure. In summary, the annual screening of patients with type 2 diabetes mellitus for microalbuminuria, and the initiation of measures to retard the progression of renal and cardiovascular disease, are now considered part of routine clinical practice. In particular, the finding of microalbuminuria should provoke an intensified modification of the common risk factors for renal and cardiovascular disease, that is hyperglycemia, hypertension, dyslipidemia and smoking. Antihypertensive therapy in patients with microalbuminuria and type 2 diabetes mellitus should be initiated with angiotensin converting enzyme (ACE) inhibitors or angiotensin-II type 1 receptor antagonists.
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PMID:Treatment of microalbuminuria in patients with type 2 diabetes mellitus. 1579 9

Patients in whom nephropathy develops as a result of hypertension or diabetes mellitus are more likely to die of cardiovascular disease (CVD) than of kidney disease. An early sign of impending nephropathy is microalbuminuria, defined as urinary excretion of albumin at a rate of 28.8 mg/24 h to 288 mg/24 h. Microalbuminuria is a marker of endothelial dysfunction, vascular injury, and renal disease and CVD, and it is associated with increased risk for myocardial infarction. Oxidative stress and endothelial dysfunction are unifying factors mediated by the renin-angiotensin system in renal disease and CVD. Clinical trials show reduced cardiovascular risk and a reversal of microalbuminuria with the use of agents that affect the renin-angiotensin system: angiotensin-receptor blockers in patients with type 2 diabetes mellitus and nephropathy, or angiotensin-converting enzyme inhibitors in patients with type 1 diabetes mellitus.
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PMID:Slowing progression along the renal disease continuum. 1592 38

Recent studies have identified that first-line renoprotective agents that interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore the potential effects of these agents on the modulation of the receptor for AGE (RAGE). Bovine aortic endothelial cells that were exposed to the angiotensin-converting enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose demonstrated a significant increase in soluble RAGE (sRAGE) secreted into the medium. In streptozotocin-induced diabetic rats, ramipril treatment (ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked carboxymethyllysine and pentosidine, as well as circulating and renal AGE. Renal gene upregulation of total RAGE (all three splice variants) was observed in ACEi-treated animals. There was a specific increase in the gene expression of the splice variant C-truncated RAGE (sRAGE). There were also increases in sRAGE protein identified within renal cells with ACEi treatment, which showed AGE-binding ability. This was associated with decreases in renal full-length RAGE protein from ACEi-treated rats. Decreases in plasma soluble RAGE that were significantly increased by ACEi treatment were also identified in diabetic rats. Similarly, there was a significant increase in plasma sRAGE in patients who had type 1 diabetes and were treated with the ACEi perindopril. Complexes between sRAGE and carboxymethyllysine were identified in human and rodent diabetic plasma. It is postulated that ACE inhibition reduces the accumulation of AGE in diabetes partly by increasing the production and secretion of sRAGE into plasma.
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PMID:Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. 1597 94

Combination of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin II receptor blocker is advocated as a treatment option in diabetic patients with nephropathy and residual albuminuria while on antihypertensive therapy. Abrogation of albuminuria is a key treatment goal to prevent disease progression. The assumption is that albuminuria reduction is the result of more complete blockade of the renin angiotensin system; thus, the ACEI-angiotensin II receptor blocker combination would have a greater albuminuria-lowering effect than the combination of an ACEI with a calcium channel blocker such as amlodipine, which causes similar reductions in BP but does not affect the renin angiotensin system. Twenty-eight patients who had type 1 diabetes and known diabetic renal disease and had a persistently elevated albumin creatinine ratio (ACR) > 10 mg/mmol despite office BP recordings < or = 140/80 mmHg on maximal recommended dose of the ACEI lisinopril were studied. Patients were allocated to receive either candesartan (16 mg/d) or amlodipine (10 mg/d) in addition to preexisting ACEI inhibition and followed for 24 wk in a randomized, double-blind, parallel-group trial. By week 24, ACR fell by 56% with candesartan and 54% with amlodipine (P < 0.01 versus baseline for both) with no significant difference between groups. Mean arterial BP fell between 3 and 6 mmHg similarly in both groups. In neither group was a significant correlation found between the change in ACR and the change in BP. Candesartan and amlodipine lowered ACR and BP by a similar degree. The fall in ACR was disproportionate to the fall of systemic BP and independent of it. The mechanism of the reduction in albuminuria seen with these agents in combination with an ACEI remains to be elucidated.
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PMID:Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease. 1593 33

Atrial fibrillation (Af) is the most common disorder of cardiac rhythm and is responsible for substantial morbidity and mortality in the general population. A recent community-based observational study revealed that diabetes and hypertension were associated with the development of Af. Since there is no definite evidence to show that type 1 diabetes is at increased risk for the development of Af, insulin resistance rather than hyperglycemia per se could explain the link between diabetes and Af. Several clinical trials suggest that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of insulin resistance. Indeed, interruption of the RAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been shown to prevent the onset of diabetes in hypertensive patients. Further, several experimental and clinical studies showed the beneficial role for the inhibition of the RAS in preventing Af as well. However, to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af remains to be clarified. Recently, telmisartan, an ARB, was found to act as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma influences the gene expression involved in carbohydrate metabolism. In animal study, telmisartan administration caused a significant attenuation of weight gain and reduced glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet, compared with treatments of losartan, another type of ARB. Furthermore, recently, some clinical papers also reported the insulin-sensitizing effects of telmisartan in hypertensive patients. In this paper, we would like to propose the possible ways of clarifying to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af. (1) Does telmisartan reduce the development of Af in insulin resistant hypertensive patients? (2) When adjusted for blood pressure, is the effect of telmisartan superior to other ARBs? (3) Does this beneficial effect of telmisartan correlate to its insulin-sensitizing properties? Ongoing clinical trial (ONTARGET) has been designed the efficacy of telmisartan with an ACEI, ramipril, alone or in combination. This randomized, double-blind, multicenter international studies will provide further information whether telmisartan can improve insulin resistance and subsequently reduce the development of Af in high-risk hypertensive patients.
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PMID:Role of insulin-sensitizing property of telmisartan, a commercially available angiotensin II type 1 receptor blocker in preventing the development of atrial fibrillation. 1615 10

Nephropathy is the major life-threatening complication of type 1 diabetes. It is due to the adverse effects of glucose-induced preglomerular vasodilation on glomerular hemodynamics. Glomerulosclerosis is initiated early in the course of diabetic nephropathy by exacerbated expression of cytokines like tumor growth factor beta1. Not all type 1 diabetes patients are at risk of nephropathy, probably because some polymorphisms in the various factors involved in its pathogenesis can modulate the course of this disease from one individual to another. Blocking the course of nephropathy by blockers of the renin-angiotensin system relies on solid pathophysiological hypotheses and has proved to be efficacious for improving the prognosis of type 1 diabetes nephropathy.
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PMID:Nephropathy in type 1 diabetes. 1622

Diabetes mellitus and arterial hypertension are the leading causes of end-stage renal disease in industrialized countries. Although attention has focused on renal disease and insulin-dependent diabetes mellitus (type 1 diabetes), a silent epidemic of renal disease caused by type 2, noninsulin-dependent diabetes mellitus is rapidly developing. The course of renal function is heterogeneous in type 2 diabetic patients and reflects heterogeneous patterns of renal lesions. A subset of patients with microalbuminuria and proteinuria is characterized by the typical diabetic glomerulopathy usually observed in type 1 diabetic patients, with altered albumin excretion rate (AER), for example, glomerular basement membrane thickening and mesangial fractional volume expansion. These patients also have diabetic retinopathy and rapidly lose renal function despite tight blood pressure control. In contrast, a second subset of type 2 diabetic patients has normal or near-normal patterns of glomerular structure, despite abnormalities of AER comparable to those of the patients with diabetic glomerulopathy. Thus abnormalities of AER have a different renal prognostic value depending on the underlying renal structure. The patients with worse clinical prognosis and typical diabetic glomerulopathy also have diabetic retinopathy, whereas those with a better course of renal function quite often have no diabetic retinopathy. Several findings, albeit not unanimous, suggest that HbA1c levels above 7.5 to 8.0 % are closely associated with a rapid decay of renal function in type 2 diabetes. Tight blood pressure control plays a further important role in determining the progression of renal a damage in type 2 diabetes mellitus. Convincing evidence has been provided that drugs capable of inhibiting the renin-angiotensin hormonal system are quite effective in preventing and delaying the evolution of renal damage in both type 1 and 2 diabetes. Equally strong data support the view that other antihypertensive compounds such as beta-blockers and calcium antagonists also delay the progression of renal damage in diabetes mellitus. Whatever the drug used to treat hypertension, the majority of the authors conclude that blood pressure levels should be maintained below 130/85 mmHg in diabetic patients. While it is well established that uncontrolled diabetes underlies the development of diabetic nephropathy, newer evidence suggests that genetically determined susceptibility to hyperglycemia-caused glomerular injury is also necessary. More information on this issue will help to design new therapeutical approaches to treat hypertension and renal complications in type 2 diabetes.
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PMID:Hypertension and renal complications in type 2 diabetes. 1622 1

Diabetic nephropathy, the most common cause of end-stage renal disease in the United States, is also associated with increased cardiovascular mortality. The renin-angiotensin-aldosterone system (RAAS) plays a central role in the development and progression of kidney disease and cardiovascular disease. Randomized, controlled trials have demonstrated renoprotection with the use of angiotensin receptor blockers (ARBs) in type 2 and angiotensin-converting enzyme inhibitors (ACEIs) in type 1 diabetes. More recent studies have demonstrated similar cardiovascular benefits with the use of ARBs compared with ACEIs. The combination of the two classes of RAAS blockers has been investigated in large studies of patients with heart failure and after myocardial infarction, and a few small studies of patients with diabetic nephropathy. In this review, we summarized the results of the studies on the benefits of ARBs, ACEIs, and their combination in patients with diabetic nephropathy or cardiovascular diseases.
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PMID:The renin-angiotensin system and its blockade in diabetic renal and cardiovascular disease. 1652 75

Diabetes mellitus and arterial pulse pressure (PP) are two independent cardiovascular risk factors. This cross-sectional study investigated the influence of diabetes duration on PP in type 1 diabetic patients without any cardiovascular disease. PP was measured continuously during 3 minutes (active orthostatic test: 1 min standing--1 min squatting--1 min standing) using a fingertip plethysmograph (Finapres) in 159 type 1 diabetic patients aged 20-60 yrs. They were divided into 4 groups according to diabetes duration: (1) G1 : <10 yrs (n=39); G2: 11-20 yrs (n=45); G3: 21-30 yrs (n=57); and G4: >30 yrs (n=18). In order to separate the effects of age from the effects of diabetes duration, diabetic patients were compared to age- and sex-matched non diabetic controls. PP (expressed in mmHg; mean +/- SD) was higher in men than in women in both diabetic (58 +/- 15 vs. 50 +/- 14; p = 0.001) and non diabetic subjects (55 +/- 14 vs. 47 +/- 12; p = 0.001). Overall PP was higher in diabetic than in non diabetic individuals (54 +/- 15 vs. 50 +/- 13; p = 0.025). PP progressively increased according to diabetes duration: 47 +/- 16 vs. 51 +/- 13 vs. 59 +/- 14 vs. 62 +/- 12, from G1 to G4 respectively; p < 0.0001. Such an increase was not observed in age-matched non diabetic subjects: 50 +/- 11 vs. 52 +/- 12 vs. 49 +/- 14 vs. 52 +/- 18, from G1 to G4, respectively; NS. PP was higher in squatting than in standing position in non diabetic subjects (52 +/- 16 vs. 47 +/- 13; p < 0.0001) and even more in diabetic patients (59 +/- 17 vs. 50 +/- 14; p < 0.0001). Overall, PP difference between diabetic and non diabetic individuals was not significant in standing position (50 +/- 14 vs. 47 +/- 13; NS) although it became highly significant in squatting position (59 +/- 17 vs. 52 +/- 16; p = 0.0005). The squatting-standing difference in PP markedly increased with diabetes duration: 69 +/- 14 during squatting vs. 50 +/- 18 during standing in G4 compared to respectively 50 +/- 17 vs. 44 +/- 15 in G1 diabetic patients. Finally, PP was similar (NS) in diabetic patients with HbA1c < 8% (54 +/- 14) or > or =8% (55 +/- 16), with (57 +/- 17) or without (54 +/- 14) microalbuminuria, treated (56 +/- 14) or not (54 +/- 15) by inhibitors of the renin-angiotensin system. In conclusion, PP progressively increased with the duration of type 1 diabetes, independently of age. Such increase was more marked in squatting than in standing position. The role of such PP rise in the increased cardiovascular risk of patients with type 1 diabetes, although suspected in the recent EURODIAB Prospective Complications Study, deserves further investigation.
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PMID:[Arterial pulse pressure in relation to the duration of type 1 diabetes: a cross-sectional controlled study]. 1706 44

Type 2 diabetes (DM-2) has become a major global health problem that has been fueled mainly by increasing obesity and aging of the population. Most studies show that arterial stiffening occurs across all age groups in both type 1 diabetes and DM-2, and among those with impaired fasting glucose, impaired glucose tolerance, and the metabolic syndrome. Arterial stiffening in DM-2 results, in part, from the clustering of hyperglycemia, dyslipidemia and hypertension, all of which may promote insulin resistance, oxidative stress, endothelial dysfunction, and the formation of pro-inflammatory cytokines and advanced glycosylation end-products. Likewise, aging may increase arterial stiffening by altering the proportions of elastin and collagen in the aorta. The consequences of arterial stiffening are increased pulse pressure, hypertension, and a greater risk of cardiovascular disease. Treatment strategies to reduce or prevent arterial stiffening include pharmacologic agents that block the renin-angiotensin-aldosterone system, relax vascular smooth muscle, enhance release of nitric oxide from endothelial cells, and break glycosylation end-product cross-links, and fish oil supplementation.
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PMID:Diabetes and arterial stiffening. 1707 13


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