Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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The excessive storage of iron in idiopathic haemochromatosis leads to severe organic lesion up to life-threatening conditions (cardiac insufficiency, portal decompensation). The symptoms melanodermia , diabetes mellitus and other endocrine failures, liver cirrhosis, cardiac insufficiency and arthropathy appear together or in various combinations. The diagnosis is ascertained by the proof of iron storage, the multiple organic affection and by familial accumulation of the various laboratory diagnostic possibilities are particularly to be emphasized the serum iron value together with the percetal transferrin saturation (as search test), serum ferritin, the desferrioxamine test, simple ferrokinetic investigations and the quantitative determination of iron in the liver in the bioptate . For family examinations, apart from the search test, a HLA typisation is reasonable, in order to estimate the risk of the disease (particularly of brothers and sisters). The therapy of choice are blood- lettings (0.5 l once to twice a week) up to obtaining a permanent easy iron deficiency anaemia. The maintenance therapy should be performed with monthly to quarterly blood- lettings . Only in cases exception a desferal treatment is indicated. Endocrine failures and cardiac disturbances need a particular therapy.
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PMID:[Idiopathic hemochromatosis--diagnosis and therapy]. 673 May 91

The effects of continuous ambulant (CAPD) and continuous cyclic peritoneal dialysis (CCPD) on a series of laboratory parameters in the blood and dialysate were assessed in two groups of nine juvenile diabetics each, suffering from terminal renal failure. The CCPD patients showed higher urea and creatinine levels in serum and, as a result of lower protein loss via the dialysate, also higher total protein and transferrin concentrations than the CAPD patients. The glucose absorption of the CCPD patients was about 50% lower than of the CAPD patients. Control of diabetes was equally successful with both procedures, the HbA1 values were less than 10%. The triglycerides were lowered by both CAPD and CCPD on the condition that the absorbed glucose amounts were included in the calculation of the dietary adjustment. Cholesterol and HDL-cholesterol remained unchanged. Thus CCPD appears to have advantages over CAPD, especially with respect to the lowering of the glucose absorption and the protein loss. The wider application of both methods will be, however, less influenced by the metabolic parameters than by other factors such as reduction of the risk of peritonitis.
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PMID:[Metabolic parameters of CAPD and CCPD in diabetics with terminal renal insufficiency]. 673 46

The nutritional status was assessed in 75 consecutive patients acutely admitted to a general medical ward. Weight-for-height, triceps skinfold thickness, arm muscle circumference, plasma albumin and serum transferrin were used as nutritional indicators. By combining abnormalities in two or more of these variables, we found obesity in 9% and undernutrition in 22% of the patients on admission. Energy deficiencies as well as acute and chronic protein undernutrition were observed. Age over 75 years, lack of own teeth and a reason for admission other than circulatory disorders or diabetes were tentatively identified as risk factors for undernutrition-some of them conceivably interdependent. Living conditions and regular medication seemed to be less important determinants in this group of patients. We conclude that undernutrition is prevalent among hospitalized medical patients in Sweden as in other industrialized countries. Patients with "hospital malnutrition" are partly recruited from a population of malnourished elderly people outside the hospital. Adequate nutritional support is an essential objective of hospital care in patients wih medical disorders.
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PMID:Nutritional status of medical patients on emergency admission to hospital. 681 16

The defect in host defense that makes the diabetic ketoacidotic (DKA) patient susceptible to mucormycosis has not been identified. Sera from 10 DKA patients and three normal volunteers were tested for their capacity to support the in vitro growth of a common etiologic agent of mucormycosis, Rhizopus oryzae. After equilibration with room air none of the normal or DKA sera, each of which was now extremely alkaline, supported growth of R. oryzae. When the sera were placed in a CO2 atmosphere that permitted simulation of the in vivo clinical pH (normal 7.40 and DKA 7.3-6.6), four of seven DKA sera supported profuse fungal growth. No growth occurred in normal serum. The three DKA sera that did not support fungal growth at pH less than or equal to 7.3 contained less iron (x = 13 micrograms/dl) than the four sera that supported profuse fungal growth (x = 69 micrograms/dl). Increasing the iron content of iron-poor DKA serum that did not support R. oryzae growth allowed profuse growth at acidotic conditions but not at pH greater than or equal to 7.4. Simulated acidotic conditions (pH 7.3-6.6) also decreased the iron-binding capacity of normal serum stepwise from 266 micrograms/dl to 0. Our data indicate that acidosis temporarily disrupts the capacity of transferrin to bind iron and suggest that this alteration abolishes an important host defense mechanism that permits growth of R. oryzae.
Diabetes 1982 Dec
PMID:A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. 681 46

To evaluate the roles of alcohol and genetic factors in hepatic iron overload, we studied prospectively 61 patients selected solely on the basis of increased stainable hepatic iron (grade 3 or 4). Independent comparisons were made between alcoholic (n = 20) and nonalcoholic (n = 41) patients, and between patients wih affected relatives (n = 25) and those without (n = 36). For the entire group, the mean value for mobilizable iron was 19.6 g and the prevalence of HLA-A3 was 69.6%, both findings compatible with genetic hemochromatosis. Subgroups were no different in clinical features (diabetes, pigmentation, cardiomyopathy, hypogonadism, or arthropaty), histologic findings (fat, inflammation, fibrosis), indexes of iron metabolism (serum iron, transferrin saturation, chelatable iron, and mobilizable iron stores), or frequency of HLA-A3 and HLA-B7. The only exception was that mean hepatic iron concentration was lower in alcoholic patients than in nonalcoholic patients (17,344 vs. 28,553 micrograms/g dry wt, p less than 0.001). Similarity between subgroups in almost all parameters examined is consistent with the hypothesis that heavy deposition of hepatic iron, as observed in our patients, is an indication of genetic hemochromatosis, regardless of alcohol consumption or the findings of affected relatives. The lower concentrations of hepatic iron in alcoholic patients, despite equal body stores in both groups, suggest that alcohol may alter the distribution of storage iron in genetic hemochromatosis.
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PMID:Hemochromatosis: genetic or alcohol-induced? 684 Apr 75

To evaluate the effect of improved metabolic control on kidney function, urinary excretion rate of beta-2-microglobulin, lysozyme, and gamma-glutamyltransferase were evaluated in nine poorly controlled, newly diagnosed diabetic patients before and during treatment. In six poorly controlled insulin-dependent nephropathic diabetic patients, besides the parameters cited above, urinary albumin excretion rate and IgG/transferrin clearance ratio were further investigated to estimate the permeability and the selectivity of glomerular barrier during conventional treatment and after improvement of the metabolic control by a glucose-controlled insulin infusion system (GCIIS). The improved glycemic control resulted in a significant reduction of urinary beta-2-microglobulin and lysozyme excretion in all diabetic patients. Significant decreases of urinary albumin excretion and of IgG/transferrin clearance ratio (indicating a more selective proteinuria) during strict metabolic control were also observed in nephropathic diabetic patients. The reduction of urinary beta-2-microglobulin and lysozyme excretion indicates that a tubular reabsorptive dysfunction, reversible with the amelioration of glycemic control, can be observed in poorly controlled, newly diagnosed and in insulin-dependent nephropathic diabetic patients during conventional treatment. In the latter patients, the permeability and the selectivity properties of glomerular barrier also improved during GCIIS.
Diabetes Care
PMID:Kidney function after improved metabolic control in newly diagnosed diabetes and in diabetic patients with nephropathy. 692 32

Monolayers of chicken embryo hepatocytes. cultured in chemically defined medium, retain the ability to synthesize a wide spectrum of plasma proteins for several days in the absence of added hormones. Addition of insulin to the medium elicited a biphasic stimulation of plasma protein synthesis: a rapid response of the synthesis of a limited number of plasma proteins (e.g., albumin and alpha 1-globulin "M"), then, after prolonged exposure to the hormone, the involvement of additional plasma proteins (e.g., fibrinogen and lipoproteins). Synthesis of transferrin and a few other plasma proteins was not affected by the presence of insulin. The degree of stimulation for the most response plasma proteins ranged between 2- to 4-fold during the early phase and 10- and even 30-fold during the late phase of the cells' response t insulin. Stimulated synthesis in the early phase was detected within 1 hr and was rapidly reversible. Plasma protein synthesis in culture was sensitive to concentrations of insulin below 0.35 nM, well within the physiological range. The delayed response was elicited only at higher hormone levels. Parallels between the control of synthesis of plasma proteins in this system and that observed in diabetic animals suggest that the embryonic chicken hepatocytes may be a useful model for studying liver function in diabetes as well as insulin action in general.
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PMID:Direct effect of insulin on the synthesis of specific plasma proteins: biphasic response of hepatocytes cultured in serum- and hormone-free medium. 703 64

With a view to studying the eventual alterations of protein metabolism, some serum protein fractions such as: immunoglobulins (IgG, IgA, IgM), transferrin and ceruloplasmin were determined in 100 diabetics (52 males, 48 females) in comparison with a control group of 26 healthy subjects. Significant differences were found between IgA and transferrin values both in diabetics and in controls. IgA tended to increase with the length of disease, whereas IgG, IgM and transferrin showed a contrary trend. IgA and transferrin values were higher in the patients with juvenile and young adult diabetes, as compared to maturity onset and senile diabetes. Other immunoglobulin and transferrin changes were related to sex, age, type of treatment, degree of stability, presence of chronic complications. No significant anomalies were found for ceruloplasmin. The results confirm the presence of serum protein alterations in diabetes mellitus, whose significance may be correlated with the clinical particularities of the disease.
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PMID:Study of some serum protein fractions in various clinical forms of diabetes mellitus. 723 48

The experience with chronic renal failure in two institutions, a tertiary care referral hospital with a high prevalence of diabetes mellitus and a Veterans Administration Hospital, was utilized to formulate guidelines for the nutritional assessment and therapy of chronic renal failure. For optimal nutritional support of patients with renal failure, it is important to characterize objectively nutritional deficiencies. Thus, dietary history, anthropometric measurements (weight/height ratio, arm muscle circumference, and triceps skinfold), and serum protein measurements (total protein, albumin, and transferrin, in particular) provide valuable data concerning the nutritional status of the patient. The serum urea nitrogen to serum creatinine ratio and urea nitrogen appearance are useful for selecting optimal protein intake. The serum urea nitrogen/creatinine ratio must be interpreted with respect to the factors which influence it; i.e., the urea clearance and the urea nitrogen appearance. The goal of nutritional therapy is the preservation of body cell mass and function, fluid, electrolyte, and acid-base homeostasis, mineral balances, and with early use of dialysis, the avoidance of uremic toxicity. Nutritional therapy, especially in patients with superimposed illnesses and associated anorexia, may be enhanced by the use of formula feedings, tube feedings, and, if necessary, total parenteral nutrition.
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PMID:Nutritional assessment and treatment of chronic renal failure. 739 79

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.
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PMID:Homozygosity for hemochromatosis: clinical manifestations. 743 83


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