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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When aiming at preventing IDDM in man, knowledge of the molecular mechanisms leading to beta cell destruction may facilitate identification of new possible intervention modalities. A model of IDDM pathogenesis in man suggests that cytokines, and IL-1 in particular, are of major importance in the initial events (Nerup et al 1994) (Fig. 1). In vitro rat experiments demonstrated that rhIL-1 beta inhibits beta cell function and induces beta cell death both in isolated islets of Langerhans and in the isolated perfused pancreatic gland. With the long term goal of identifying new modalities capable of preventing IDDM in man, the aim af this review was to investigate the effects of rhIL-1 beta on beta-cell function and viability in normal rats. This review discussed 1) the pharmacokinetics of IL-1 beta in rats as the basis for choice of route of administration and dose of rhIL-1 beta, 2) the effects and molecular mechanisms of IL-1 beta on temperature and food intake used as control parameters for successful injection of rhIL-1 beta in rats, 3) the effects of one or more injection of IL-1 beta on rat beta cell function, 4) the molecular mechanisms leading to IL-1 beta induced beta cell inhibition in vivo, and some possible intervention modalities based on the molecular mechanisms, 5) the effects of IL-1 beta on spontaneous diabetes mellitus in DP BB rats, and 6) the effects and molecular mechanisms of IL-1 beta induced inhibition of thyroid epithelial cell function and aggravated thyroiditis in DP BB rats, compared to the effects of IL-1 beta on rat beta cell function. Finally, this review discussed the effects of IL-1 beta on human beta cells in vitro, and the clinical relevance of these experiments, with special reference to a clinical trial with the aim of preventing IDDM in man. The pharmacokinetic studies suggested that IL-1 beta is distributed according to a two-compartment model with a first-order elimination. Interleukin-1 beta reached all the investigated organs in the rats, was accumulated in kidneys and was excreted in the urine. The data suggested that IL-1 beta also accumulated in the islets of Langerhans. After injection of 4.0 micrograms/kg pathophysiologically relevant concentrations of rhIL-1 beta were reached and intact rhIL-1 beta persisted for up to 5 hrs in plasma. Peripheral injections of IL-1 beta dose-dependently induced fever and anorexia in rats, probably via induction of PGE2 in the brain or in peripheral tissues thereafter passing the blood-brain barrier. Nitric oxide produced by cNOS seems to be a molecular mediator of IL-1 beta induced fever but not of anorexia. Fever and anorexia are well described effects of IL-1 beta in rats, and are as such usefull control parameters of the absorption and biological activity of IL-1 beta after peripheral injection. Injections of rhIL-1 beta to normal, non-diabetes prone rats induced initial beta cell stimulation followed by inhibition, in accordance with in vitro data. Furthermore, induction of peripheral insulin resistance coincided with beta cell inhibition after one daily injection for 5 days, leading to a transient diabetes mellitus-like state, characterized by hyperglycemia and hypoinsulinemia. At this time point, electron-microscopy did not demonstrate beta cell destruction. However, IL-1 beta induced intercellularly edema and microvillous processes on the beta cells, which might be early evidence of apoptosis. The diabetes mellitus-like state was not aggravated if the daily injections were continued beyond 5 days. Daily injections of rhIL-1 beta for 2 to 4 weeks induced formation of blocking IL-1 beta-antibodies in normal rats. Hence, injections exceeding 2 weeks should only be performed using species homologous IL-1 beta. The molecular mechanism of IL-1 beta induced beta cell inhibition in rats in vivo as in vitro, are likely to involve binding of IL-1 beta to the IL-1RtI, since the IL-1RtII is considered to be a decoy receptor. (ABSTRACT TRUNCATED)
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PMID:Interleukin-1 beta induced transient diabetes mellitus in rats. A model of the initial events in the pathogenesis of insulin-dependent diabetes mellitus? 958 1

To determine the eating habits of patients with anorexia nervosa, we compared a group of 21 anorectic girls satisfying DSM-III-R criteria (A: 19 +/- 6.6 years; 14.2 +/- 2 kg/m2) with 30 control girls (C: 19.8 +/- 3.3 years; 20.9 +/- 4.4 kg/m2). A standardised form listing 226 food items was used to assess their food preferences. For each food category except vegetables and fish, the medium rate of positive appreciation was lower in group A than in group C. However, a positive correlation was found between the two groups (except for dairy and diet products), showing no major distortion of taste in group A. Anorectic girls generally discarded the sweetest fruit and the fattest meats, but sometimes chose to eat high-calorie food, possibly because of its supposed nutritional value. Their dislike for so-called "light" products was also apparent. Moreover, no regressive tendency to childish choices was found in their eating habits. It is concluded that group A displayed a narrowed food field, but without distortions of taste.
Diabetes Metab 1998 Jun
PMID:[Food preferences in anorectic girls at the beginning of therapy]. 969 62

Weaning is the cause of much concern among first-time mothers. A milk-only diet is advised until 3-4 months of age. Health professionals should ensure the baby receives a sufficient and balanced diet during the weaning period, to meet the needs for energy and growth. Breast milk or infant formula should continue up to the age of at least one year. The weaning period is a good time to educate parents in good nutrition. A wide variety of foods should be the aim in child nutrition, but each different type needs to be started separately during weaning. Care is needed to ensure vegetarian babies receive enough proteins, vitamins and minerals (especially iron). Failure to thrive has a multitude of causes, and treatment must be that of the cause. Strictly vegan children who eat no dairy products will need added synthetic vitamin B12. Failure to thrive may be due to physical problems (eg choanal atresia), infection, vomiting, diarrhoea, anorexia, parental ignorance or poverty. Other causes include coeliac disease, cow's milk protein allergy, cystic fibrosis, severe eczema or asthma, or diabetes.
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PMID:Common feeding problems in babies and children: 2. 981 53

In a woman aged 80 years arriving in the Emergency Room with progressive malaise, anorexia and somnolence, a large resistance was found in the lower abdomen, which proved to be due to cystitis emphysematosa. The patient was known to suffer from non-insulin dependent diabetes mellitus. Imaging revealed a large accumulation of gas in the urinary bladder, which was treated successfully with catheterization and antibiotics. Cystitis emphysematosa is a rare condition, characterized by collection of gas in the bladder and bladder wall and brought about by gas-forming micro-organisms that decompose glucose. In patients with diabetes mellitus optimal regulation of the blood glucose levels, with a view to preventing glycosuria, is a condition of speedy recovery. Although cases with a fatal outcome have been reported, the prognosis in general is favourable.
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PMID:[A diabetic patient with cystitis emphysematosa]. 986 38

Within a 6-year period from January 1991 to December 1996, 249 patients of salmonellosis admitted to Kaohsiung Medical College Hospital were enrolled for clinical and microbiological analysis. The number of patients increased by year from 1991 (14 patients) to 1996 (79 patients), especially in the case of nontyphoid salmonellosis. There were 57 different serotypes isolated during these period. Salmonella typhimurium was the most common clinical serotype of human origin in southern Taiwan, followed by S. choleraesuis, S. schwanzengrund, and S. derby. Fever (81.1%), diarrhea (68.9%), and anorexia (44.6%) were the most common manifestations of human salmonellosis. Relative bradycardia was a more important feature in S. typhi group (100%) than nontyphoid salmonellosis. Leukocytosis, especially lymphocytosis, was found especially in nontyphoid, but not in typhoid salmonellosis. Elevated liver function tests were found in the most severe patients, such as S. choleraesuis and S. typhi infections. Malignancy (8.8%), especially hematological malignancy (5.2%), gastrointestinal diseases (8.8%), and diabetes mellitus (6.4%) were the common underlying diseases. Case fatality rate of human salmonellosis was 8% (20/249), especially high in S. choleraesuis group. The severity of underlying diseases may be the major cause in S. choleraesuis group. There was no fatal case with typhoid fever. Very high resistance rate to commonly used antimicrobial agents in nontyphoid Salmonella was noted in southern Taiwan with overall rates of resistance to ampicillin, 67.9%, chloramphenicol, 66.7%, and TMP/SMZ, 42.2%. The emergence of ciprofloxacin-resistant and multiresistant strains was also a major therapeutic problem in this study.
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PMID:Epidemiological study of human salmonellosis during 1991-1996 in southern Taiwan. 1022 36

The adipocyte hormone leptin reduces food intake in normal animals. During uncontrolled type 1 diabetes, plasma leptin levels fall, whereas food intake increases. To test the hypothesis that low leptin levels contribute to diabetic hyperphagia, we investigated the effect on food intake of replacement of leptin at basal plasma concentrations for 7 days in Long-Evans rats with uncontrolled diabetes induced by streptozotocin (STZ). One group of STZ diabetic rats received saline (STZ + Sal) (n = 11), while the other group (STZ + Lep) (n = 15) received a subcutaneous infusion of recombinant rat leptin (100 microg x kg(-1) x day(-1)) via osmotic minipumps. A nondiabetic control group (Con) (n = 11) received saline only. In the STZ + Sal group, plasma leptin levels decreased by 75% (P < 0.05) from 2.4+/-0.5 on the day before STZ/citrate buffer vehicle (Veh) injection (day 0) to 0.6+/-0.2 ng/ml on day 7. In contrast, plasma leptin levels on days 3-7 were comparable to pretreatment values in both the STZ + Lep group (day 0: 2.6+/-0.4 vs. day 7: 2.5+/-0.3 ng/ml, NS) and the Con group (day 0: 3.8+/-0.4 vs. day 7: 2.9+/-1.0 ng/ml, NS). In the STZ + Sal group, daily food intake increased gradually to values 43% above basal by day 7 (day 0: 24+/-2 to day 7: 33+/-3 g, P < 0.05), whereas food intake did not increase in either the STZ + Lep group (day 0: 24+/-1 vs. day 7: 21+/-2 g, NS), or the Con group (day 0: 23+/-1 vs. day 7: 23+/-2 g). Plasma glucose levels exceeded nondiabetic control values (7.7+/-0.2 mmol/l) in both diabetic groups, but were lower in the STZ + Lep group (17.2+/-1.8 mmol/l) than in the STZ + Sal group (24.3+/-1.1 mmol/l, P < 0.05). To determine if sensitivity to leptin-induced anorexia was affected by STZ treatment, a second experiment was performed in which the effect of intracerebroventricular leptin injection (at doses of 0.35, 1.0, or 3.5 microg) on food intake was measured 10 days after STZ or Veh treatment. Leptin suppressed both 4- and 24-h food intake in the two groups to an equal extent at every dose (by 15, 22, and 35%, respectively). These findings support the hypothesis that the effect of uncontrolled diabetes to lower leptin levels contributes to diabetic hyperphagia and that this effect is not due to altered leptin sensitivity.
Diabetes 1999 Jun
PMID:Low plasma leptin levels contribute to diabetic hyperphagia in rats. 1034 16

TNF-alpha (so-called cachectin), IL-1 and 6 are important regulating agents in the homeostasis of energy in the organism, as among others they control processes of apoptosis and thus also the volume of adipose and muscular tissues. They are produced not only in immunocompetent cells but also in adipocytes and muscle cells. The cytokine system is then activated not only in tumours and infections but elevated values were found also in obesity, NIDDM, in myocardial infarction and in advanced decompensated cardiac patients. By acting on phosphorylation of IRS-1 and PI-3 kinase TNF-alpha promotes significantly insulin resistance, causes deterioration of diabetes, as well as elevated body temperature, sleepiness and anorexia. In a group of 65 patients, mostly with android obesity, in hyperleptinaemic and insulin resistant probands with coronarographically confirmed microvascular angina pectoris (n = 22) or IHD, mostly after a myocardial infarction (n = 43) with one or more significant stenoses on the epicardial coronary arteries in half the patients positive or elevated TNF-alpha was found and in 28% also IL-6. This increase did not correlate however with BMI, the percentage of body fat, IRI and C peptide levels nor with cortisol and leptin levels. Insulin resistant subjects had more frequently elevated homocysteine and Lp(a) values which are further two independent risk factors of atherothrombogenesis. Hyperhomocysteinaemia can be favourably influenced by vitamin fortification of the diet or by administration of folate and pyridoxine (1 tablet per day) involving negligible financial costs.
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PMID:[Relation between cytokines (TNF-alpha, IL-1 and 6) and homocysteine in android obesity and the phenomenon of insulin resistance syndromes]. 1042 20

The diagnosis of pancreatic cancer usually depends upon symptoms; consequently it is late when there is no chance for cure. At this point, pain, anorexia, early satiety, sleep problems and weight loss are present. Back pain also may be prominent, which predicts unresectability and shortened survival after resection. However, earlier recognition of symptoms of pancreatic cancer might improve early detection of the cancer. For example, 25% of patients have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis and 15% of patients may seek medical attention more than 6 months prior to diagnosis. These symptoms erroneously may be attributed to problems such as irritable syndrome. Symptoms, however, may be less common. For example a quarter of patients with pancreatic cancer may have no pain at diagnosis, and half, particularly those with pancreatic head tumors, may have little pain compared with patients with body-tail tumors. However, if the tumor is suspected because of predisposing conditions, earlier diagnosis may be possible. These conditions include diseases such as chronic pancreatitis, intraductal papillary mucinous tumor (IPMT), and recent onset of diabetes mellitus, particularly if the diabetes occurs during or beyond the sixth decade. In addition inherited syndromes also are associated with an increased risk of pancreatic cancer including familial pancreatic cancer, hereditary pancreatitis, familial adenomatous polyposis syndrome (FAP) and familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nevus syndrome). Of these conditions, recent onset of diabetes may be the best clue and should be included in a clinical profile of patients prior to the onset of symptoms to identify a high-risk group to apply screening strategies for detection of early disease. Contrary to a clinical aphorism that pancreatic cancer patients are elderly, lean and recently may have developed diabetes, we found that patients who develop pancreatic cancer are overweight prior to onset of symptoms compared to controls (body mass index, 28 vs 25). Forty percent had the diagnosis of diabetes made at the time of diagnosis of pancreatic cancer and more patients with a resectable tumor had diabetes (58%) compared to patients with locally unresectable or metastatic disease (37%). Perhaps, screening overweight persons who have new-onset diabetes may lead to a diagnosis of asymptomatic, early, resectable pancreatic cancer.
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PMID:Pancreatic cancer: clinical presentation, pitfalls and early clues. 1043 7

A 84-year-old woman presented with chronic febrile illness and anorexia from June 1998. She was diagnosed as pulmonary tuberculosis and was admitted to our hospital in August 1998. Her sputum smear was Gaffky 2, and the type of chest radiograph was b III 3. By family contact examination in August 1998, chest radiological examinations of her husband, a 86-year-old man, showed consolidation in middle lobe, right pleural effusion and two calcified mediastinal lymphnodes. He was diagnosed as pulmonary tuberculosis complicated with pleurisy. He had poor controlled diabetes mellitus. Tubercle bacilli isolated from their sputa showed the same pattern in restriction fragment length polymorphism analysis. Pulmonary tuberculosis of the husband was considered to be caused by exogenous reinfection.
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PMID:[A case of elderly patient with pulmonary tuberculosis considered to be caused by exogenous reinfection]. 1056 32

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 +/- 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 +/- 1.0 to 22.9 +/- 1.3 kg; P < 0.01), truncal fat mass (11.5 +/- 0.7 to 13. 2 +/- 0.9 kg; P < 0.001), and serum leptin levels (20.1 +/- 3.8 to 35.6 +/- 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 +/- 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 +/- 4.2 to 42.7 +/- 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 +/- 8.4 to 19.2 +/- 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.
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PMID:Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. 1086 87


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