Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Free and protein-bound serum sugars and serum lipids were analyzed in 65 adult diabetic patients, 10 age-matched controls, and 24 male medical students for correlation of carbohydrate changes with the extent of retinal, renal, and cardiovascular disease. In diabetic sera, both protein-bound sugars and free mannose, fucose, and hexosamine were significantly elevated; free galactose and inositol were elevated in some diabetic patients, and essentially undetectable in sera from controls. Serum triglycerides and pre-beta-lipoproteins were also elevated in diabetics, but alpha-lipoproteins decreased. Although no specific relationships were observed with the extent of retinal and renal disease, bivariate analyses by Pearson coefficients of correlation showed correlations between levels of serum-free mannose and systolic blood pressure, free hexosamine and duration of diabetes, and serum protein-bound fucose and age. Serum triglycerides and pre-beta-lipoprotein levels correlated with insulin therapy. These are preliminary leads of laboratory studies related to carbohydrate macromolecular changes which might aid in a better understanding of the cardiovascular complications associated with diabetes.
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PMID:Serum-free and protein-bound sugars and cardiovascular complications in diabetes mellitus. 124 17

Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.
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PMID:Low molecular weight proteins in children with renal disease. 128 25

Mild-to-moderate essential hypertension is the most common medical problem seen by physicians in Western populations, and pharmacologic antihypertensive therapy is now usually undertaken. Clinical trials have shown that lowering of elevated blood pressure using diuretics and beta-blockers reduces cardiovascular morbidity and mortality. Despite these benefits, the trials have provided no convincing evidence that the incidence of coronary artery disease or its complications is reduced: Treated hypertensive patients remain at increased cardiovascular risk compared with untreated normotensive subjects. Possible explanations for this disappointing outcome are that the drugs used may themselves have negative effects on serum lipids, glucose, and insulin resistance, thereby outweighing their antihypertensive benefits. An equally important role in this respect may be played by the diseases and therapies most commonly found in association with mild-to-moderate hypertension: hyperlipidemia, type II diabetes, coronary artery disease, left ventricular hypertrophy, cardiac arrhythmias, peripheral arterial disease, and nephropathy. Such conditions may be potent determinants of what constitutes the optimal first-line choice of antihypertensive therapy. Furthermore, the negative effects that antihypertensive drugs can have on quality-of-life factors may result in noncompliance and ineffective long-term treatment. Therefore, in a new therapeutic approach to the treatment of high blood pressure, it would be logical to base antihypertensive therapy on strategies that not only lower the blood pressure but that have beneficial impacts on hemodynamics, vascular and cardiac structure, metabolism, and quality-of-life issues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive therapy: new strategies beyond blood pressure control. 128 82

Calcium antagonists are of particular importance in the treatment of hypertension because they influence the free cytoplasmic calcium concentration and thereby many pressor mechanisms in the smooth muscle cell. A fall in the peripheral resistance is the main hemodynamic effect, and this is more marked with the second-generation calcium antagonists because they are more vasoselective than the first calcium-channel blockers. Particularly important is their lack of effect on lipid and glucose metabolism, as well as the absence of serious side effects. It has not yet been possible to confirm that the antiatherogenic effect found in some animal models also occurs in humans. Calcium antagonists are effective, safe, and well-tolerated antihypertensive agents that can be combined with all other antihypertensives with the exception of the combination of verapamil and a beta-blocker. They are easy to dose for individualized "stepped" therapy. They have a particular role in hypertensive patients with cardiac effects secondary to hypertension, coronary artery disease, obstructive bronchial diseases, diabetes, renal disease, and peripheral arterial occlusive disease.
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PMID:The role of calcium antagonists in the treatment of hypertension. 128 89

A progressive rise in arterial calcium content is the most characteristic age-associated alteration in the arterial wall and the decisive factor in arteriosclerotic degeneration. Experimental studies have demonstrated that calcium antagonists can prevent or retard the development of arterial calcinosis associated with vitamin D overload, hypertension or alloxan-induced diabetes. Although similar effects are more difficult to observe in humans, they have been demonstrated in patients with coronary artery disease and in patients with end-stage renal disease, which is characterised by an acceleration of the normal arterial aging process.
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PMID:Arterial calcinosis, chronic renal failure and calcium antagonism. 128 73

Diabetes mellitus can lead, along the years of its course, to chronic renal failure in a high proportion of cases. An early risk-indicator of later diabetic nephropathy is the presence of microalbuminuria, but it usually takes about fifteen to twenty years to appear. Before that, no clinical signs can disclose the underlying alterations of glomerular basement membrane that will eventually bring forth overt nephropathy. The usefulness of the altered excretion of isoenzymes of amylase as an early marker of the glomerular charge selectivity was tested in 202 juvenile onset insulin-dependent diabetics, compared with 51 normal subjects matched for age and sex. The diabetic patients studied showed increased excretion of salivary amylase into urine. The salivary to pancreatic amylase ratio of concentrations in urine was always below 1 in normal subjects, and was increased over 1 in 33.2% of diabetics, although microalbuminuria was present only in 26.2% of patients. The excretion of other proteins was within reference values in the majority of cases, indicating that the kidney was not seriously affected in those patients. Moreover, the altered salivary to pancreatic amylase ratio in urine was more prevalent than microalbuminuria (36.6% vs 18%) in the first decade of the evolution of the diabetes. These results indicate that the ratio of excretions of both isoamylases into urine is a more sensible and earlier marker of altered glomerular charge barrier for anionic proteins.
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PMID:Utility of filtration markers to monitor the quality of glomerular function. 128 36

Skiagram proved 35 cases of fibrocalculus pancreatic diabetes in order to analyse the clinical profile and its correlation with different descriptive epidemiological parameters were studied. Mean age was 25.17 +/- 7.85 years and male to female ratio was 6:1; 65.7% patients were poor (income < Rs 500 per month) and another 28.6% having average income (Rs 500 to Rs 1,000 per month); 74.3% came from rural areas having a family size of about > or = 7 members and sanitation was poor in all the cases. Mean body mass index was 15.93 +/- 3. Severe diabetes (ie, fasting blood sugar level > 251 mg%) and moderately severe diabetes (ie, fasting blood sugar level > 181 mg% but < 250 mg%) were noted in 51.4% and 11.4% cases respectively. Recurrent pain abdomen, infections, neuropathy, retinopathy, nephropathy and keto-acidosis were observed in 52.2%, 40.0%, 42.9%, 8.6%, 11.4% and 2.9% cases respectively. Mean soluble insulin requirement was 41.81 +/- 13.94 units. Four cases in whom pancreatic lithotomy was done, showed less insulin requirement and disappearance of pain. Parotid swelling, chronic diarrhoea and insulin resistance were not observed. Insulin requirement, epidemiological and biochemical parameters were similar to other young diabetics.
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PMID:Fibrocalculus pancreatic diabetes in western Orissa. 128 95

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520H columns at neutral pH (6.87) showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are reduced and oxidized form of HSA, respectively. We studied the conversion of HMA to HNA (mercapt-nonmercapt conversion) as an index of oxidative change of the tissues and organs in 28 normal subjects and in a total of 47 patients with non-insulin dependent diabetes mellitus (NIDDM). Mean (+/- SD) values of the HMA fraction of HSA, f(HMA), [HMA/(HMA + HNA)], was significantly lower in NIDDM patients than in normal subjects (0.63 +/- 0.067 vs 0.75 +/- 0.028, P < 0.001). It was lower in poorly controlled NIDDM patients (0.63 +/- 0.058, n = 20) than in well controlled NIDDM patients (0.67 +/- 0.032, n = 9) (P < 0.05). Plasma glucose values sampled on occasions including overnight fasting and postprandial ones (r = -0.441, n = 47, P < 0.01), but not plasma glucose values sampled on overnight fasting (r = -0.345, n = 29) or postprandial (r = -0.467, n = 18) conditions and HbA1c (r = -0.211, n = 34), negatively correlated with the f(HMA) values, indicating that mercapt-nonmercapt conversion may not be due to cumulative hyperglycemia over a month, but due to short-term alteration in blood glucose level. The presence or absence of diabetic complications including nephropathy, retinopathy and neuropathy did not affect the f(HMA) values. In conclusion, decreased f(HMA) values in the diabetic patients suggested the presence of a rapidly altered oxidative change of albumin due to hyperglycemia.
Diabetes Res Clin Pract 1992 Dec
PMID:Increased oxidized form of human serum albumin in patients with diabetes mellitus. 128 16

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

Since urinary guanidinoacetic acid (GAA) derives from the kidneys, its detection is suggested to be associated with renal disease. We have been making a practice of investigating renal GAA production in diabetic patients, using a citrulline/creatine loading test. We noted a marked increase in urinary GAA excretion in 1 patient. Since GAA-synthesis is hormonally regulated, we made a through investigation of endocrine function in this patient. She was a 58-year-old woman with a 15-year history of diabetes mellitus, proliferative diabetic retinopathy, and negative microalbuminuria. There was a high plasma GH level and urinary 17-KS analysis revealed an increase in the adrenal androgen-derived fractions. Based on the X-ray finding of ballooning of the sella turcica and the MRI data, empty sella syndrome was diagnosed. It was suggested that stimulated anabolic hormone release had accelerated renal nitrogen metabolism and induced aggravation of her retinopathy. The findings in this patient implied the involvement of hormones in the development of diabetic complications.
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PMID:[A diabetic patient with empty sella syndrome accompanied by stimulated guanidinoacetic acid metabolism]. 129 72


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