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

Depletion of selected regulatory CD4+ T cell subsets induces the spontaneous onset of various immune or autoimmune disorders. It is not clear, however, whether a given subset, notably CD4+CD25+ regulatory T cells, protects from a wide spectrum of immune disorders, or whether specialized subsets of regulatory T cells control each given disease or group of diseases. We report here, using diabetes prone nonobese diabetic (NOD) mice, that depending on the regulatory T cells that are depleted, i.e., CD25+, CD62L+, or CD45RB(low), distinct immune diseases appear after transfer into NOD severe combined immunodeficiency (SCID) recipients. Thus, reconstitution of NOD SCID mice with CD25- T cells induces major gastritis and late-onset diabetes, but no or mild colitis. Reconstitution with CD62L- T cells induces fulminant diabetes with no colitis or gastritis. Reconstitution with CD45RB(high) T cells induces major colitis with wasting disease and no or very moderate gastritis and diabetes. Major differences among the three regulatory T cell subsets are also seen in vitro. The bulk of suppressor cells inhibiting the proliferation of CD4+CD25- T cells in coculture is concentrated within the CD25+ but not the CD62L+ or CD45RB(low) T cell subsets. Similarly, cytokine production patterns are significantly different for each regulatory T cell subset. Collectively, these data point to the diversity and organ selectivity of regulatory T cells controlling distinct autoimmune diseases whatever the underlying mechanisms.
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PMID:Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases. 1467 94

Passive elevations in glucocorticoids result in increased insulin and abdominal obesity with peripheral wasting, as observed in Cushing's syndrome, with little effect on chow intake. In the absence of insulin (streptozotocin-induced diabetes) diabetic rats markedly increase their chow intake in proportion to glucocorticoids. Given a choice of lard or chow, diabetic rats first eat lard, then reduce caloric intake to normal for 48 h before returning to hyperphagia on chow alone. We performed three experiments to determine the relationship of corticosterone and insulin to lard intake, chow intake, body weight, hormones, and fat depots. The results of these studies clarify the actions of both circulating glucocorticoids and insulin on caloric intake in adult male rats. Our experiments show that glucocorticoids provoke dose-related increases in total caloric intake that persist for days and weeks; the results also suggest that increasing insulin concentrations stimulated by glucocorticoids determine the amount of fat intake. Furthermore, we show that lard intake is associated with increasing insulin concentrations. Additionally, the results in adrenalectomized and adrenalectomized, streptozotocin-induced diabetic rats strongly suggest that it is a combination of corticosterone and insulin that increases abdominal fat depot weight. Independently of the hormonally manipulated rats, the results also show that intact rats voluntarily eat a considerable and stable proportion of their daily calories as lard when given a choice between lard and chow. These results suggest that some human obesities may result from elevated glucocorticoids and insulin increasing the proportional intake of high density calories.
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PMID:Interaction between corticosterone and insulin in obesity: regulation of lard intake and fat stores. 1496 93

Congenital adrenal hyperplasia (CAH) is caused by a defect in the biosynthesis of cortisol that results in maximal activity of the hypothalamic-pituitary adrenal axis with hyperplasia of the adrenals and hyperandrogenism due to the accumulation of androgen precursors. In the salt-wasting subtype of the disorder, which accounts for appr. 75 % of patients with classical CAH, patients are unable to synthesise sufficient amounts of aldosterone and are prone to life-threatening salt-losing crises, whereas the simple virilising form is predominantly characterized by clitoris hypertrophy and posterior labial fusion. In addition, a non-classical variant can be discerned which in most cases is diagnosed at the time of puberty or early adolescence when hirsutism and menstrual irregularities may occur. The vast majority of CAH patients have 21-hydroxylase deficiency (90 - 95 %). Less common forms, such as 11beta-hydroxylase deficiency, will not be discussed in this review. Unfortunately, a considerable number of CAH patients is lost to regular and competent follow-up once they move out of paediatric care. This is most probably the result of insufficient co-operation between paediatric and adult endocrinologists at the time of transition from adolescence to adulthood. Furthermore, there is a lack of clinical guidance regarding psychosexual development in these patients. In this overview we will focus on special aspects of CAH treatment in adolescence and adulthood, and report on our 10-year experience with a transfer system for endocrine patients from paediatric to internal medical care, known as the "Kieler Modell". For practical purposes, we here provide charts for follow-up of CAH patients that can be adapted for use in any endocrine outpatient clinic.
Exp Clin Endocrinol Diabetes 2004 Jul
PMID:Congenital adrenal hyperplasia - how to improve the transition from adolescence to adult life. 1523 19

To determine the prevalence and clinical characteristics of lipodystrophy in HIV-infected Thai patients, a cross-sectional study was performed on 278 HIV-infected patients at Bamrasnaradura Infectious Disease Institute. Laboratory data related to lipid and glucose metabolism were obtained from both patients who self reported fat maldistribution or diagnosed by a physician. The history of antiretroviral treatment and HIV infection were recorded. Prevalence of lipodystrophy found in the present study was 17%. Lipodystrophy was reported mostly on the face, buttock, legs, arms, and abdomen respectively. Two-thirds of these patients had mixed syndromes of fat accumulation and fat wasting and the others had only fat wasting. Ninety-three percent of lipodystrophic patients had at least 1 abnormality in either lipid or glucose metabolism. Eighty-eight percent had dyslipidemia, 21% had impaired glucose tolerance, 30% had insulin resistance and 27% had diabetes mellitus. Lipodystrophic patients have a high rate of lipid and glucose metabolism abnormalities which are the major risk factors for cardiovascular events.
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PMID:Prevalence of lipodystrophy in Thai-HIV infected patients. 1527 36

Cells contain limited and sequestered pools of Coenzyme A (CoA) that are essential for activating carboxylate metabolites. Some acyl-CoA esters have high metabolic and signalling impact, so control of CoA ester concentrations is important. This and transfer of the activated acyl moieties between cell compartments without wasting energy on futile cycles of hydrolysis and resynthesis is achieved through the carnitine system. The location, properties of and deficiencies in the carnitine acyltransferases are described in relation to their influence on the CoA pools in the cell and, hence, on metabolism. The protection of free CoA pools in disease states is achieved by excretion of acyl-carnitine so that carnitine supplementation is required where unwanted acyl groups build up, such as in some inherited disorders of fatty acid oxidation. Acetyl-carnitine improves cognition in the brain and propionyl-carnitine improves cardiac performance in heart disease and diabetes. The therapeutic effects of carnitine and its esters are discussed in relation to the integrative influence of the carnitine system across CoA pools. Recent evidence for sequestered pools of activated acetate for synthesis of malonyl-CoA, for the synthesis of polyunsaturated fatty acids and for the inhibition of carnitine palmitoyltransferase 1 to regulate fatty acid oxidation is reviewed.
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PMID:Carnitine acyltransferases and their influence on CoA pools in health and disease. 1536 37

We have developed a primary skeletal muscle cell culture model derived from normal prepubertal children to investigate the effects of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and tumour necrosis factor alpha (TNFalpha) on growth, differentiation and metabolism. Cells of myoblast lineage were characterized morphologically by desmin staining and differentiated successfully into multinucleated myotubes. Differentiation was confirmed biochemically by an increase in creatine kinase (CK) activity and IGFBP-3 secretion over time. IGF-I promoted whilst TNFalpha inhibited myoblast proliferation, differentiation and IGFBP-3 secretion. IGF-I partially rescued the cells from the inhibiting effects of TNFalpha. Compared to adult myoblast cultures, children's skeletal muscle cells demonstrated higher basal and day 7 CK activities, increased levels of IGFBP-3 secretion, diminished IGF-I/TNFalpha action and absence of the inhibitory effect of exogenous IGFBP-3 on differentiation. Additional studies demonstrated that TNFalpha increased basal glucose transport via GLUT1, nitric oxide synthase and p38MAPK-dependent mechanisms. These studies provide baseline data to study the interactivity effects of growth factors and cytokines on differentiation and metabolism in muscle in relation to important metabolic disorders such as obesity, type II diabetes or chronic wasting diseases.
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PMID:Isolation and validation of human prepubertal skeletal muscle cells: maturation and metabolic effects of IGF-I, IGFBP-3 and TNFalpha. 1608 85

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.
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PMID:Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. 1655 23

Good nutrition is key to a healthy lifestyle, regardless of whether one is living with HIV/AIDS. Optimal nutrition can help boost immune function, maximize the effectiveness of antiretroviral therapy, reduce the risk of chronic illnesses such as diabetes and cardiovascular disease, and contribute to a better overall quality of life. In the early years of the AIDS epidemic, many people with HIV were dealing with wasting and opportunistic infections (OIs) linked to unsafe food or water. While these problems are less common today in developed countries with widespread access to highly active antiretroviral therapy (HAART), many HIV positive people have traded these concerns for worries about body shape changes, elevated blood lipids, and other metabolic complications associated with antiretroviral therapy. Fortunately, maintaining a healthy diet can help address these problems. As HIV positive people live longer thanks to effective treatment, good nutrition can also help prevent problems (such as bone loss) associated with normal aging. But there is no single, optimal eating regimen appropriate for every person living with HIV/AIDS. Instead, HIV positive people should adopt a sensible balanced diet and consult an experienced nutrition specialist for individualized recommendations.
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PMID:Nutrition and HIV. 1661 Jan 16

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.
Exp Clin Endocrinol Diabetes 2006 Apr
PMID:Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1670 55

Until the early nineteenth century, diabetes mellitus was regarded as a disease of the kidney, in which there was an increase in the volume of urine and a wasting of the flesh. With the identification of glucose in blood and urine in the late eighteenth century, first it was re-framed as a disease of assimilation and only then became a metabolic disorder. Whilst these changing concepts were debated, it was noted in parallel that diabetics might show coagulable urine containing albumin, even before Bright and others had established this as a sign of kidney disease. Wilhelm Griesinger (1817-1868) was perhaps the first to suggest in 1859 that the diabetes might be causing the Bright's disease, with the latter as a 'complication'. During the next half-century the observation that as albuminuria appeared and increased, so glycosuria improved or might remit, with a parallel or subsequent evolution into uraemia. Glomerulosclerosis and arteriolosclerosis were described in occasional patients during the same period, but text-books of pathology ignored these observations. Thus it was only when diabetics began to survive longer using insulin treatment in the early 1920s that a diabetic nephropathy became widely recognized. After a few isolated descriptions which were ignored, the now famous paper of Paul Kimmelstiel and Clifford Wilson appeared in 1935 detailing nodular renal lesions in just 8 maturity-onset (48-68 year old) diabetics. They barely noted the association with diabetes however, and it was Arthur Allen in 1941 who clarified the association in 105 patients with diabetes, again all aged over 40. Despite the age of the patients in these early studies, diabetic nephropathy became thought of as a disease of young diabetics as a cohort of survivors of juvenile diabetes passed 15 years or more of disease and more than half developed nephropathy. In the 1950s the technique of renal biopsy was rapidly applied to the study of diabetics, and the early lesions defined using electron microscopy as well as optical methods. Then the role of diabetic nephropathy as a cause of renal failure changed: to begin with numbers of young insulin-requiring diabetics were small and infrequently referred for dialysis treatment or transplantation. Then in the 1970s and 1980s the proportion of such juvenile-onset diabetics developing renal failure gradually fell, but at the same time much larger numbers of older diabetics survived their vascular disease and required treatment for renal failure. World-wide, today diabetes accounts for 20-50% of patients entering established renal failure programs, and absolute numbers increase as greater longevity and western-style living has promoted an 'epidemic' of diabetes at all ages.
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PMID:The discovery of diabetic nephropathy: from small print to centre stage. 1687 18


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