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)

The syndrome of insulin resistance comprises the following H-phenomena: 1. Hyperinsulinism compensating the inborn postreceptor insulin resistance, 2. Hyperglycaemia-non-insulin-dependent diabetes mellitus, 3. Hyperlipoproteinaemia with android obesity, 4. Hypertension, 5. Hirsutism with the syndrome of polycystic ovaries as a manifestation of a hyperandrogenic situation in the female organism. Molecular syndromes of this syndrome of insulin resistance are obscure. They are the subject of intensive studies because H-phenomena are an aggregation of the main risk factors of atherogenesis. Recently attention is focused also on amylin--a 37 amino acid peptide with a 50% homologous amino acid sequence with a calcitonin-gene--related peptide (CGRP), which is the product of a gene made up of three introns on the 12th chromosome. Amylin acts in the beta-cells of the pancreas as a co-secretion of insulin. If in excess, it is deposited in the form of an amyloid in the beta-cells. In the early stage of NIDDM it alters the physiological response of the beta-cell to glycaemic stimuli and food, in later stages of the disease, after accumulation, it causes apoptosis of the beta-cell and reduces thus the secretory capacity of the Langerhans islets. It is excreted in the urine and thus, if the glomerular filtration is reduced, it cumulates in the blood stream and thus enhances insulin resistance already in the early stages of chronic renal insufficiency, or in diabetic nephropathy. In type II diabetes similarly as insulin levels also amylin levels are elevated, while in type I diabetes with early autoimmune destruction of the beta-cells the insulin and amylin levels are reduced or even zero. Amylin reduces in the muscle, probably by inhibition of glycogen synthase, the insulin stimulated non-oxidative utilization of glucose into muscle glycogen and conversely by stimulation of phosphorylase it stimulates glycogenolysis and thus also lactate production and gluconeogenesis in the liver which all are anti-insulin effects which intensify the insulin resistance of the main target tissues. Amylin, similarly as CGRP or calcitonin, reduces Ca blood levels and has a vasodilatating effect; it reduces the BP but in different minimal and maximal doses and by a different mechanism and via special receptors because the link of amylin to calcitonin receptors is 100 times lower and does not produce a rise of cAMP in the target cell. The effect on the enhancement of insulin resistance in muscle was proved also by direct measurements using an hyperinsulinaemic euglycaemic clamp. After prolongation of the clamp to more than two hours the effect on insulin resistance disappeared, although the hypocalcinaemic effect persisted. Amylin is able by its biological action to modify the secretion as well as the effectiveness of insulin to pathological values. These two characteristics are typical for impaired glucose tolerance in type II diabetes. Studies are under way to find out whether the effect of amylin is involved directly also in the pathogenesis of the other H-phenomena or only via accentuation of hyperinsulinism. In any case amylin is a new link the role of which in the pathogenesis of NIDDM and the syndrome of insulin resistance awaits evaluation. Due to its effect on gastric evacuation it participates also in the postprandial glycaemic control in particular in type I diabetes where it it begins to be used in therapy. Perhaps it will be possible to administer it in these patients along with insulin to improve diabetes compensation.
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PMID:[Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome]. 896 27

Several strategies are available to delay progression of renal disease and the development of associated co-morbidities. Hypertension is a strong independent risk factor for end-stage renal disease (ESRD) and there is consensus that blood pressure (BP) management is an important aspect of care in patients with chronic renal insufficiency (CRI). Clinical studies have shown that angiotensin-converting enzyme (ACE) inhibitors have renoprotective properties, independent of their antihypertensive effects, which can delay the onset of ESRD. Studies have also shown that intensive therapy of both type 1 and type 2 diabetes patients, to give near normal blood glucose concentrations, can reduce the incidence of progressive clinical proteinuria and may, therefore, protect against ESRD. Additionally, data are emerging that treatment of renal anaemia with epoetin can reduce mortality and delay the onset of dialysis in CRI patients, but these encouraging results need to be confirmed in large prospective studies. In conclusion, control of BP and hyperglycaemia, as well as use of ACE inhibitors and anaemia treatment, all have potential in delaying the progression of CRI or improving patient outcomes. If benefit is proven in future studies, these strategies will be most effective if implemented early in the course of CRI.
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PMID:The rationale for early management of chronic renal insufficiency. 1159 Feb 58

The prevalence of hypertension in patients with chronic renal insufficiency is high. In the stage of renal insufficiency it is 60% and in conservatively terminal renal failure it is as high as 90%. After the initiation of dialyzation treatment it declines temporarily, it is higher during chronic haemodialysis (50-80%) and lower in continuous ambulatory peritoneal dialysis (30%). After transplantation it is recorded in 70-80% recipients of a renal graft. Among the causes of renal hypertension in subjects with conservatively treated chronic renal insufficiency at present secondary renal impairment is increasing--in type 2 diabetes and also renal vascular affection due to atherosclerotic changes and essential arterial hypertension. Approximately 30% of patients where chronic dialyzation treatment is started, come "from the street". In the pathogenesis of renal hypertension sodium retention is involved with volume expansion and an impaired ratio of the formation of vasoactive (vasopressor and vasodepressor) substances. In chronic renal failure the volume component of hypertension predominates markedly. The causes of the development of hypertension after renal transplantation are multifactorial and are most closely associated with immunosuppressive treatment and graft rejection. Pharmacological treatment of renal hypertension prefers inhibitors of the angiotensin converting enzyme (possibly angiotensin II antagonists) because of their concurrent renoprotective action. In the stage of renal insufficiency they call for reduced doses and combination with other antihypertensive agents. The objective of treatment is to achieve a blood pressure < 130/80 mm Hg. In chronic dialyzation treatment the main therapeutic provision in hypertension is adjustment of the volume of extracellular fluid by regime provisions and effective haemoelimination treatment. Calcium blockers are useful in particular in the treatment of hypertension in haemodialyzed subjects and in hypertension after renal transplantation.
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PMID:[Hypertension and chronic renal insufficiency--chronic kidney failure]. 1290 74

In the nineties of the 20th century diabetic nephropathy has become the leading cause of regular dialysis treatment (RDT) in developed countries. In particular type 2 diabetics are involved. A similar trend can be observed also in the Czech Republic which holds in this respect the first place among countries of the former eastern block (33% patients with RDT) suffer from diabetes. The cause of the increase of patients with diabetic nephropathy and renal failure caused by diabetes is not only the rising prevalence and incidence of type 2 diabetes in the population but in particular the better care provided to patients with type 2 diabetes which enables them to survive macro- and microvascular complications incl. diabetic nephropathy. It is estimated that diabetic nephropathy affects 4-8% patients attending diabetic clinics. With regard to the increasing number of diabetics in RDT, moreover associated with their high polymorbidity, this is a serious medical and economic problem. The main factors which influence in the diabetic patients the risk of development of diabetic nephropathy are long-term control of glycaemia, genetic (ethnic) factors, age and sex. The decisive factor influencing in patients with diabetic nephropathy the progression of chronic renal insufficiency is control of the blood pressure. Including diabetics in RDT is not associated only with medical problems but also with socio-economic issues. The quality of life of diabetics is much lower and the survival of diabetics treated within the framework of RDT is still almost half as compared with the survival of non-diabetic patients. Decision on the selection of the dialysis method is not easy. Medical differences are well defined but should not be considered absolute. It is important to consider also which method is preferred by the patient. Optimally the decision is taken during the period of dispensarization. Both dialyzation methods have comparable results and survival although for diabetics under 50 years of age a more favourable prognosis of peritoneal dialysis is reported. However, the risk of "failure of the method" is in general higher in peritoneal dialysis.
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PMID:[Diabetes mellitus and chronic renal insufficiency]. 1290 75

The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known diabetes duration >or=10 years (control subjects). The genotypic distribution of the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/- 10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4 vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl), HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.
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PMID:The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. 1463 65

Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important factors in the pathogenesis of type 2 diabetes and have a promising therapeutic potential. Alterations of their secretion, in vivo degradation, and elimination in patients with chronic renal insufficiency (CRI) have not yet been characterized. Ten patients with CRI (aged 47 +/- 15 years, BMI 24.5 +/- 2.2 kg/m(2), and serum creatinine 2.18 +/- 0.86 mg/dl) and 10 matched healthy control subjects (aged 44 +/- 12 years, BMI 24.9 +/- 3.4 kg/m(2), and serum creatinine 0.89 +/- 0.10 mg/dl) were included. On separate occasions, an oral glucose tolerance test (75 g), an intravenous infusion of GLP-1 (0.5 pmol. kg(-1). min(-1) over 30 min), and an intravenous infusion of GIP (1.0 pmol. kg(-1). min(-1) over 30 min) were performed. Venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1 (total and intact), and GIP (total and intact; specific immunoassays). Plasma levels of GIP (3-42) and GLP-1 (9-36 amide) were calculated. Statistics were performed using repeated-measures and one-way ANOVA. After the oral glucose load, plasma concentrations of intact GLP-1 and intact GIP reached similar levels in both groups (P = 0.31 and P = 0.87, respectively). The concentrations of GIP (3-42) and GLP-1 (9-36 amide) were significantly higher in the patients than in the control subjects (P = 0.0021 and P = 0.027, respectively). During and after the exogenous infusion, GLP-1 (9-36 amide) and GIP (3-42) reached higher plasma concentrations in the CRI patients than in the control subjects (P < 0.001 and P = 0.0033, respectively), whereas the plasma levels of intact GLP-1 and GIP were not different between the groups (P = 0.29 and P = 0.27, respectively). Plasma half-lives were 3.4 +/- 0.6 and 2.3 +/- 0.4 min for intact GLP-1 (P = 0.13) and 5.3 +/- 0.8 and 3.3 +/- 0.4 min for the GLP-1 metabolite (P = 0.029) for CRI patients vs. healthy control subjects, respectively. Plasma half-lives of intact GIP were 6.9 +/- 1.4 and 5.0 +/- 1.2 min (P = 0.31) and 38.1 +/- 6.0 and 22.4 +/- 3.0 min for the GIP metabolite (P = 0.032) for CRI patients vs. healthy control subjects, respectively. Insulin concentrations tended to be lower in the patients during all experiments, whereas C-peptide levels tended to be elevated. These data underline the importance of the kidneys for the final elimination of GIP and GLP-1. The initial dipeptidyl peptidase IV-mediated degradation of both hormones is almost unaffected by impairments in renal function. Delayed elimination of GLP-1 and GIP in renal insufficiency may influence the pharmacokinetics and pharmacodynamics of dipeptidyl peptidase IV-resistant incretin derivatives to be used for the treatment of patients with type 2 diabetes.
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PMID:Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. 1498 49

Hepatitis C virus (HCV) infection is often associated with kidney diseases such as membranoproliferative glomerulonephritis (MPGN), with and without cryoglobulinemia, membranous glomerulonephritis (MGN) or glomerulosclerosis (FSGN). The aim of our study was to determine the frequency of HCV with or without hypertransaminasemia in patients with chronic nephropathy in the predialytic phase. We tested 340 subjects with chronic renal insufficiency (CRI) from our hospital's nephrology outpatient clinic for anti-HCV antibodies. In positive subjects we tested for HCV RNA by PCR method, monitoring, for at least 4 months, common biohumoral parameters including transaminases (AST, ALT). Of the 340 subjects, 46 (13.5%) were positive for HCV RNA, and 8 of these (17%) showed constant alteration of transaminases. HBsAg was found in 8 of the total study population (2.3%), and none of these showed altered transaminases. Type II diabetes mellitus was found in 26% (12/46) of the HCV-RNA positive patients, and in only 12.5% (37/294) of the negative ones. The kidney diseases we found in the 46 HCV-RNA positive patients were: diabetic nephropathy in 11 (23.9%), MPGN in 7 (15.2%), MPGN + cryoglobulinemia in 2 (4.3%), interstitial nephropathy in 4 (8.7%), IgA mesangial GN in 3 (6.5%), hypertensive nephropathy in 2 (4.3%), focal and segmental GN in 1 (2.2%), urologic disease in 4 (8.7%), other (hematological, genetic, iatrogenic) in 3 (6.6%), unknown in 9 (19.6%). Our data show that the most frequent kidney diseases associated with HCV infection were diabetic related nephropathy and MPGN with and without cryoglobulinemia. HCV infection had a positive association with diabetes. It is interesting to note that in this study population the hepatitis C concomitant to kidney disease was unusually mild: only 4 of the 46 subjects (9%) showed clinical, biohumoral and ultrasound evidence of cirrhosis.
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PMID:Hepatitis C and kidney disease. 1793 31

The epidemiology of diabetic nephropathy (DN) should be approached from two angles: a) incidence of diabetic nephropathy in patients with diabetes, and b) epidemiology of chronic renal failure (CHRF) in diabetic patients. According to data from different sources, DN affects, in all its stages, about one third of patients irrespective of the type of diabetes they suffer from, with the peak rate of incidence after 15 years of duration of the illness. It is estimated that the rate of DN prevalence is 4-8% of patients monitored in diabetes centres. In addition, a significant portion of diabetics, especially the type 2 diabetic patients, are affected by the non-diabetic type nephropathy of primarily atherosclerotic etiology. Currently, DN is the principal cause of CHRF in advanced industrial countries (Western Europe, USA,Japan). A similar trend has been recorded in the Czech Republic which has one of the highest incidences of DN among the former Eastern Block countries. Most affected patients are type 2 diabetes patients. The cause of the above increase is the growing prevalence and incidence of type 2 diabetes, and, primarily, better care for type 2 diabetes patients who live long enough to develop severe macro and microvascular complications including DN. The principal factors influencing the risk of a diabetic patient developing DN are long-term monitoring ofglycaemia, control of hypertension, genetic (ethnic) factors, age and sex. Metabolic control has an effect on the risk of diabetic nephropathy developing in type 1 and 2 diabetes, yet it is blood pressure control which is critical for the progression of chronic renal insufficiency in DN patients. In view of the high number of diabetic patients with CHRF which, in addition, associates with their high polymorbidity and extensive demands put on medical and nursing care which is not directly associated with CHRF therapy, we have to do with a serious medical and economic problem.
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PMID:[Epidemiology of diabetic nephropathy]. 1863 Jun 34

Metformin-associated lactic acidosis is a very rare but critical condition. It is seen in patients with type 2 diabetes mellitus who take metformin and attempt suicide with a metformin overdose. Here, we report a 43-year-old woman with type 2 diabetes mellitus and chronic renal insufficiency who developed hypoglycemia, hypothermia, tachycardia and lactic acidosis after a suicide attempt with a metformin overdose. She was successfully treated by continuous venovenous hemofiltration, and adequate hemodynamic and ventilatory support. Although metformin does not usually cause hypoglycemia when administered as monotherapy, hypoglycemia can occur in a condition coexistent with lactic acidosis secondary to metformin overdose. Metformin intoxication should be suspected when patients present with high anion gap metabolic acidosis after attempting suicide by ingesting drugs, particularly when comorbidities such as renal failure are present. Early diagnosis and rapid correction of the metabolic acidosis using hemodialysis or hemofiltration, together with concomitant cardiovascular support, and maintenance of blood glucose and core body temperature, provide the possibility of a positive outcome.
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PMID:Successful treatment of severe lactic acidosis caused by a suicide attempt with a metformin overdose. 1932 13

The study included 20 patients aged 61-86 (mean 73.1 +/- 3.1) years with stage II hypertensive disease, type 2 diabetes and nephropathy with signs of grade I chronic renal insufficiency (CRI). The major parameters measured were AP, HR, laboratory characteristics of carbohydrate metabolism and renal function. Prestarium given at a dose of 4 mg BID had not only antihypertensive but also negative chronotropic effect, decreased energy consumption by myocardium, and normalized daily AP profile (24 hr AP monitoring). Adequate control of diabetes ensured close-to-normal carbohydrate metabolism. Prestarium therapy did not cause further aggravation of renal insufficiency in patients with grade I CRI, nor did it alter creatinine and urea levels.
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PMID:[Use of prestarium (perindopril) in patients with polymorbidity syndrome (AH, DM, nephropathy)]. 2001 55


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