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)

A total of 78 Chinese patients with clinically uncomplicated non-insulin-dependent diabetes (NIDDM) who had plasma creatinine concentrations of < 150 mumol/l were studied. Antihypertensive treatment was discontinued for at least six weeks prior to measurements of routine biochemistry, proteinuria, plasma atrial natriuretic peptide (ANP) concentrations and components of the renin-angiotensin-aldosterone system (RAAS). BP was measured on three occasions during the six weeks period prior to these measurements. At the end of the six week period, a total of 33 patients had definite hypertension (supine BP > or = 160/95 mmHg). The hypertensive patients had significantly higher plasma sodium (mean +/- SD): 140.3 +/- 1.9 vs. 138.5 +/- 2.0 mmol/l, P < 0.001) and lower plasma potassium (3.8 +/- 0.5 vs. 4.2 +/- 0.5 mmol/l, P < 0.01) concentrations. These were associated with reduced plasma aldosterone (median (range): 297 (98-1145) vs. 448.5 (93-1330) pmol/l, P < 0.01) and renin concentrations (16.8 (7.4-71.8) vs. 23.5 (7.4-83.7) ng/l, P = 0.06). The hypertensive patients also had significantly higher plasma ANP concentrations (36.5 (20.5-125.1) vs. 23.2 (11.7-63.0) pg/ml, P < 0.001), serum angiotensin converting enzyme (ACE) activity (65 (26-140.9) vs. 47 (22-106) units/l, P < 0.001) and urinary albumin excretion (UAE) (35.4 (1.6-4800) vs. 7.8 (1.8-310.4) mg/day, P < 0.001). Glycaemic control and renal function were similar between the two groups. Mean arterial pressure (MAP) correlated positively with plasma ANP concentration (r = 0.53, P < 0.001) and serum ACE activity (r = 0.37, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide and renin-angiotensin-aldosterone system in non-insulin-dependent diabetes mellitus. 808 30

We investigated both sodium-lithium countertransport (Na-Li CT) and ouabain-sensitive sodium transport (Na pump) of erythrocytes in healthy subjects (group A), patients with non-insulin-dependent diabetes (NIDDM) without nephropathy (group B), patients in the proteinuric stage (group C), and those in the renal insufficiency stage (group D). Erythrocytes from all four groups had a similar initial water and ionic content and were loaded with similar degrees of Li and Na for efflux studies. There were no significant differences in erythrocyte Na-Li CT or Na pump among the four groups. However, the maximal rate of Na-Li CT was significantly higher in a group of subjects with essential hypertension when compared with groups A, B and C, consistent with the view that there is a genetic marker for essential hypertension. Ouabain-insensitive Na efflux (Na leak) of erythrocytes was found to be significantly higher in group D than in groups A or B. Also, a significant positive correlation existed between Na leak and urine protein levels of the subjects studied. Our results thus indicate that in contrast with insulin-dependent diabetic patients (IDDM) where an elevated Na-Li CT is observed, with diabetic nephropathy, Na-Li CT in NIDDM is apparently not associated with nephropathy; rather the ouabain-insensitive Na efflux appears to be correlated with the stages of nephropathy in NIDDM. The association suggests that the rate of ouabain-insensitive Na efflux may provide an index for assessing the degree of nephropathy in NIDDM patients.
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PMID:Abnormalities of sodium transport in non-insulin-dependent diabetes: association with renal disease. 810 99

A decrease in Na+,K(+)-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnormalities that characterize the neuropathic complications in different animal models of diabetes mellitus. The peripheral nerves from 17 patients with either type I or type II diabetes mellitus were studied to assess the importance of changes in Na+,K(+)-ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age- and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic subjects undergoing vascular or orthopedic surgery served as negative and positive controls, respectively. All specimens were processed blind. Ouabain-sensitive ATPase activity was measured by a modified spectrophotometric coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological patterns of surgical material. Morphometric analysis permitted calculation of fiber density in each nerve specimen and correlation of this figure with the relevant enzymatic activity. Na+,K(+)-ATPase activity was approximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both neuropathic conditions had significantly fewer fibers than those from normal individuals (diabetic -33%, and non-diabetic -22%), the decreases in Na+,K(+)-ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r2 = 0.096; P = 0.22). Taken together with data from experimental animal models, these results suggest that the reduction in Na+,K(+)-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an important factor in the pathogenesis and self-maintenance of human diabetic neuropathy.
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PMID:Decrease of nerve Na+,K(+)-ATPase activity in the pathogenesis of human diabetic neuropathy. 813 5

Association between insulin resistance and hypertension: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean young offspring and in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension as well as dyslipidemia, obesity and type 2 diabetes in a given subject. Pathogenetic mechanisms: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to dysbalance of vasoactive substances and/or raised cytosolic Ca2+) and/or a structural vasculopathy is a very important ultimate causative event. In the presumed mosaic of participating pressor mechanisms, distinct Na+ retention is almost obligatory with diabetes mellitus, while essential and particularly obesity-associated hypertension probably involves a tendency for sympathetic activation. Development of insulin resistance: Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or being overweight. Acute hyperinsulinemia on the one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, and it has been proposed that insulin resistance in certain transmembranous cation exchange systems may elevate cytosolic Ca2+. Nevertheless, whether insulin resistance and/or hyperinsulinemia itself contribute to the pathogenesis of hypertension is still unclear.
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PMID:Insulin resistance, hyperinsulinemia and hypertension. 815 79

Lithium is the best available marker of proximal tubular reabsorption of fluid. The first part of the present thesis reviews the background for the use of the lithium clearance (CLi) method. Micropuncture studies on proximal reabsorption of lithium, showed that CLi is a reasonably correct measure of end-proximal fluid delivery rate, even during osmotic diuresis. During severe salt restriction, distal reabsorption of lithium renders the CLi method inappropriate in animals, but this problem does probably not occur in humans. The major current issue is whether a quantitatively significant reabsorption of lithium occurs in the loop of Henle. Available evidence is in accord with the interpretation that it does not occur. The interpretation of results form CLi studies depends to a surprising degree on the investigators beliefs about renal physiology. In the evaluation of proximal tubular function, the relevant parameter is the absolute proximal reabsorption rate of fluid and sodium. In the evaluation of integrated distal tubular reabsorption of sodium, the relevant parameter is the fractional distal reabsorption rate of sodium. The fractional CLi does not give meaningful information, and calculated absolute distal reabsorption rate of sodium is inherently not suited to detect modest changes in distal reabsorption leading to large changes in sodium excretion. Results from the use of the CLi method in relation to diabetes are reviewed in the second section. Even in IDDM patients with early diabetic nephropathy, the proximal reabsorption rate is elevated, resulting in a normal CLi despite glomerular hyperfiltration. Overnight euglycemia did not change GFR in IDDM patients, but during maintained euglycemia, GFR was normalized. A few hours of hyperglycemia prevented the decline in GFR, whereas CLi was unchanged. Thus hyperglycemia produced changes in renal function similar to those observed previously, but the time-course of the effect of euglycemia on kidney function is delayed. Plasma levels of atrial natriuretic peptide, renin and glucagon were not importantly affected by plasma glucose. In NIDDM patients CLi was normal, despite slight hyperfiltration, although this observation must be confirmed in a study with larger sample size. Prompted by the clinical observation of a marked decline in the GFR induced by carbonic anhydrase inhibitors, we studied the renal effects of acetazolamide in a controlled study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus. 818 64

Systemic arterial hypertension is not merely a simple haemodynamic abnormality. It is as frequently as in 80% associated with metabolic deviations such as impaired glucose tolerance or NIDDM, obesity, hyperuricaemia, hyperlipoproteinaemia, rapid development of atherosclerosis. This cluster of different symptoms with higher BP readings is too frequent to be incidental. We speak therefore of hypertensive metabolic syndrome which is close to or identical with Reaven's syndrome X or familial dyslipidaemic hypertension. The common pathogenetic basis of the listed metabolic deviations and hypertension is probably genetic or acquired reduction of tissue sensitivity, in particular striated muscle sensitivity to the physiological action of insulin. The consequence of this insulin resistance and the effort to maintain euglycaemia is a compensating adaptational risk of plasma insulin. Hyperinsulinism in addition to an increased synthesis of triacylglycerols, VLDL and LDL lipoproteins can promote the rise of BP by a complex mechanism: it stimulates the activity of the sympathetic nervous system, it promotes sodium retention in the kidneys, it affects transmembrane transport mechanisms for electrolytes and an increase of intracellular sodium and calcium, it stimulates hypertrophy and remodelling of the vascular wall and hastens the development of atherosclerosis. Hyperinsulinaemia is also associated with resistance of hypertonic patients to antihypertensive treatment. Its reduction by non-pharmacological procedures (reduction of body weight, physical activity etc.) restore the effectiveness of antihypertensive drugs. Insulin resistance is most probably a genetically conditioned abnormality which has multiple phenotypic manifestations, depending how this congenital disposition is amplified or associated with other genetic abnormalties or external and internal factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The hypertensive metabolic syndrome]. 821 36

Insulin resistance has been recently distinguished as a syndrome associated with a clustering of metabolic disorders, including non-insulin dependent diabetes mellitus (NIDDM), obesity, hypertension, dyslipidemia and atherosclerosis. To date, it is thought that all of these disorders are the resulting consequences of primary insulin resistance. We propose that insulin resistance and the metabolic diseases mentioned can be caused by primary overactivity of the Na+/H+ exchange. This hypothesis has practical connotations for understanding the pathogenesis of the insulin resistance syndrome.
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PMID:Primary Na+/H+ exchanger dysfunction: a possible explanation for insulin resistance syndrome. 823 99

It is generally believed that the use of angiotensin-converting enzyme (ACE) inhibitors has no effect on the lipid profile. Our recent data show that in patients with proteinuric renal disease, serum levels of total cholesterol and lipoprotein(a) [Lp(a)] may be lowered during treatment with an ACE inhibitor, fosinopril sodium. During a 12-week randomized, placebo-controlled, double-blind study involving 26 patients with mild-to-moderate renal impairment, fosinopril administration was associated with significant decreases in both urinary protein excretion and serum total cholesterol levels, whereas placebo was not. During a 6-week washout phase, both parameters returned to baseline in fosinopril-treated patients and remained unchanged in placebo recipients. In addition, fosinopril-treated patients had a decrease in plasma levels of Lp(a), whereas this was not seen in placebo-treated patients. When data from a subset of 13 patients with proteinuric renal disease and hypertension were examined, a significant decrease in serum total cholesterol levels was observed; this decrease reversed after discontinuation of fosinopril. Analysis of the effect of fosinopril on plasma Lp(a) levels in a subset of patients who had type II diabetes mellitus and overt proteinuria revealed a significant decrease in plasma Lp(a) after administration of fosinopril. Moreover, fosinopril lowered plasma Lp(a) levels in blacks, whose pretreatment levels were higher than those of whites with comparable degrees of proteinuria and levels of serum total cholesterol. Thus, the reduction in serum Lp(a) levels may be related not only to amelioration of proteinuria, but also to another direct action of fosinopril on the metabolism of Lp(a).
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PMID:Metabolic effects of converting enzyme inhibitors: focus on the reduction of cholesterol and lipoprotein(a) by fosinopril. 828 81

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.
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PMID:[Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography]. 831 79

Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic-hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)--nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 +/- 13 vs. 185 +/- 15 mg/dl, mean +/- SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 +/- 3 vs. 18 +/- 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 +/- 4 mg/dl and 6 +/- 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes. 835 55


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