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

Researchers studying type 2 diabetes are optimistic that they are closing in on the elusive causes of the world's most prevalent metabolic disorder--although no one is willing to bet the bank on it. Using both biochemical and genetic approaches, diabetes researchers have identified multiple intracellular signaling pathways that appear to lie at the heart of this condition, which affects some 250 million people worldwide and is the leading cause of blindness, kidney failure, and amputation among adults. And in the process, they have thrown out much of the dogma of the past 10 years.
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PMID:Biomedicine. New insights into type 2 diabetes. 1092 26

One of the most important tasks of clinical and experimental nephrology is to identify the risk factors of progression of renal failure. A major renal risk factor which has not been sufficiently acknowledged despite increasing evidence is cigarette smoking. Diabetologists were the first to recognize the adverse effects of smoking on the kidney: both in type 1 and in type 2 diabetes smoking (i) increases the risk of development of nephropathy and (ii) nearly doubles the rate of progression to end-stage renal failure. Until recently it was not known whether smoking also increases the risk to progress to end-stage renal failure in patients with primary renal disease. A retrospective multicenter European case-control study showed that smoking is an independent risk factor for end-stage renal failure in patients with inflammatory and noninflammatory renal disease, i.e. IgA glomerulonephritis and polycystic kidney disease. The pathogenesis of the smoking-related renal damage is largely unknown. The intermittent increase in blood pressure during smoking seems to play a major role in causing renal damage, but further potential pathomechanisms are presumably also operative. Smoking as a renal risk factor is of great interest to diabetologists as well as nephrologists, but unfortunately so far this information has had little impact on patient management. The present article reviews the current knowledge about the renal risks of smoking and discusses the potential mechanisms of smoking-mediated renal injury.
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PMID:Smoking--a renal risk factor. 1097 Nov 49

The development of microalbuminuria in individuals with type 2 diabetes mellitus is associated with a 10-fold increase in the risk of progression to overt nephropathy and eventual end-stage renal failure. The present study reports long-term (up to 8 yr) follow-up of 43 Pima Indians with type 2 diabetes detected on screening to have microalbuminuria. The natural history of albuminuria in these individuals included progression to overt proteinuria (urinary albumin excretion > or = 300 mg/d) in half of the participants by 7 yr of follow-up. The size selectivity of the glomerular barrier was also investigated using dextran sieving and pore theory. Whereas a comparison group of macroalbuminuric Pima Indians had an excess of large pores that served as a macromolecular "shunt," individuals with microalbuminuria had a shunt size no different from long-term diabetic, normoalbuminuric control subjects. An abrupt transition from little or no relationship to a highly significant and positive relationship between increasing albuminuria and shunt size occurred at an albumin-to-creatinine ratio of approximately 3000 mg/g. Shunt size in macroalbuminuric individuals correlated with the extent of foot process broadening. Podocyte foot processes in microalbuminuric participants were not different from those in control subjects. In conclusion, although microalbuminuria in type 2 diabetic Pima Indians often heralds progressive glomerular injury, it is not the result of defects in the size permselectivity of the glomerular barrier but rather of changes in either glomerular charge selectivity or tubular handling of filtered proteins or of a combination of these two factors.
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PMID:Glomerular permselectivity at the onset of nephropathy in type 2 diabetes mellitus. 1105 86

Diabetic nephropathy is the most common single cause of end-stage renal failure (ESRF) in the Western world, recorded as the cause of renal failure in up to 40% to 45% of those entering renal replacement therapy (RRT) programs. However, marked differences exist between countries; the percentage of patients entering RRT in Norway because of diabetic nephropathy is 10% of the incident RRT population. The percentage in the United States is approximately 40%; therefore, the purpose of the present study was to compare data from Norway with data from the United States in an attempt to detect factors that might explain some of the differences. To make the comparisons as valid as possible, an attempt has been made to focus on populations of similar genetic make-up. The incidence of type 1 diabetes is a little higher in Norway than in the United States, whereas the prevalence of type 2 diabetes may be twice as high in the United States as in Norway; marked differences in the prevalence of obesity is probably a significant causative factor. There seems to be no striking difference in the prevalence of microalbuminuria in people with diabetes in the two populations, whereas there are insufficient data to compare the prevalence of overt proteinuria. The incidence of patients with a diagnosis of diabetic nephropathy as the cause of ESRF entering RRT in the two study populations showed marked differences; the incidence for 1997 was 8.9/million population in Norway and 113/million population in the United States. The proportion of type 2 diabetes was 46% in Norway and 64% in the US (1997). It is unlikely that the marked difference in incidence of RRT can be explained by differences in type 2 diabetes prevalence alone. The populations may not be directly comparable, and differences in the size of study populations and in the choice of renal diagnosis in patients with diabetes as a comorbid factor at the beginning of RRT may introduce uncertainties. Further, data on other factors--such as incidence of death before RRT is indicated, quality of care, and health care delivery, expressed as degree of blood pressure and metabolic control--were not available. Differences in acceptance of diabetes patients into RRT programs are not believed to contribute significantly. Norway is seeing a development toward increasing body weight and a change toward a more sedentary lifestyle, together with an increasing prevalence of type 2 diabetes earlier in life than has previously been the case. An increase in diabetic nephropathy and need for RRT because of type 2 diabetes must therefore be expected in Norway. To understand differences and to best design preventive programs, further comparative studies of the two populations seem warranted.
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PMID:Diabetic nephropathy and end-stage renal failure: the Norwegian story. 1117 23

Cardiovascular risk is increased in patients with diabetic nephropathy. The aim of this study was to examine the relative impacts of albuminuria and renal failure, the two important features of diabetic nephropathy, on potentially atherogenic lipoprotein changes in this condition. The subjects were 160 non-diabetic healthy controls and a total of 200 type 2 diabetes patients with various degrees of nephropathy. The diabetic patients were divided into four groups by urinary albumin/creatinine ratio (U-ACR) and serum creatinine (S-Cr) levels: DM-1 (U-ACR< 30 mg/g, N=85), DM-2 (U-ACR=30-300 mg/g, N=48), DM-3 (U-ACR > 300 mg/g, N=29) and DM-4 (S-Cr>177 micromol/l or 2.0mg/dl, N=38). Lipids in very low (VLDL), intermediate (IDL), low (LDL), and high density (HDL) lipoproteins were measured following ultracentrifugation. VLDL-cholesterol (VLDL-C) was elevated (by 73-100%) in diabetic patients and it did not differ among the stages of nephropathy. IDL-C was higher as the nephropathy stage was advanced, and the elevation was significant in the DM-3 (by 75%) and DM-4 (by 131%) groups. LDL-C was not elevated in diabetic patients and was not different among the stages of nephropathy. Reduction of HDL-C was significant in DM-1, DM-2 and DM-3 (by 12-16%) and it was more exaggerated in DM-4 (by 35%). Multiple regression analyses indicated that elevated S-Cr, but not U-ACR, was an independent factor associated with raised IDL-C and lowered HDL-C in diabetic patients. These results indicate that diabetic patients with nephropathy show multiple lipoprotein changes, and that renal failure has greater impact than albuminuria on abnormalities in IDL and HDL. These lipoprotein alterations may contribute to an increased cardiovascular risk in diabetic nephropathy, especially in diabetic renal failure.
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PMID:Atherogenic lipoprotein changes in diabetic nephropathy. 1139 40

In developed countries diabetics patients are the most numerous group with renal replacement therapy (USA 34%). The main and diagnostically irreplaceable criterion of incipient diabetic nephropathy is microalbuminuria which is usually associated with hypertension and poor glycaemic compensation. With advancing microalbuminuria progresses diabetic retinopathy and neuropathy. The increased transcapillary albumin escape rate and changes of some haemocoagulation factors in diabetics patients with microalbuminuria indicate that endothelial dysfunction is involved. In type 1 diabetes microalbuminuria is an indicator of increased mortality in which participate in particular cardiovascular diseases and to a minor extent renal failure. In type 2 diabetes microalbuminuria is an independent risk of generalized vascular disease. Microalbuminuria is also in non-diabetic subjects with hypertension associated with abnormalities such as impaired glucose tolerance and insulin resistance, an unflavourable lipidogram and altered diurnal blood pressure rhythm. The results of a coronarographic investigation revealed that the risk of severe coronary artery disease is more than double in subjects with microalbuminuria. Hypertension and hypercholesterolaemia are causal risk factors of cardiovascular diseases and concurrent microalbuminuria implies a higher expression of already existing microvascular damage in hormonal and metabolic disorders with an atherogenic potential.
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PMID:[Microalbuminuria--a risk factor for diabetic nephropathy and cardiovascular disease]. 1139 74

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

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
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PMID:Hypertension and diabetes: the scope of the problem. 1146 14

Renal involvement is one of the major microvascular complications of both type 1 and type 2 diabetes mellitus. Diabetic nephropathy is the major cause of end-stage renal failure in most Western nations and is associated with increased morbidity and mortality as compared to other causes of renal disease. The pathogenesis of renal involvement in diabetes is presumed to be the result of the interplay of metabolic and hemodynamic factors. Significant advances in the prevention and treatment of progression of diabetic nephropathy have been achieved with intensive glycemic control and the treatment of elevated blood pressure. Patients with diabetes should thus be screened regularly for the appearance of any of the risk factors for renal or other complications and treated intensively according to established guidelines for control of hyperglycemia and hypertension. Ancillary therapeutic measures include treatment of hyperlipidemia, low-protein diet, and the cessation of smoking.
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PMID:Diabetic nephropathy. 1147 36

Metformin is an oral hypoglycemic agent belonging to the class of biguanides that are commonly used in the treatment of type II diabetes mellitus. Lactic acidosis is a rare but severe adverse reaction that occurs primarily in patients with contraindications such as renal failure. The case of a 71-year-old woman with type II diabetes, in whom severe metformin-associated lactic acidosis was precipitated by acute renal failure in the absence of pre-existing chronic renal failure or other absolute contraindications to biguanide use, is presented. Aggressive correction of the acidosis and prolonged dialysis resulted in a favourable outcome despite severe acidosis. The present case report shows that metformin-associated lactic acidosis can occur in patients without pre-existing renal insufficiency. Metformin should be temporarily stopped when acute renal failure occurs or is anticipated.
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PMID:Metformin-associated lactic acidosis in a low risk patient. 1149 39


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