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)

Protein alteration resulting from a nonenzymatic reaction between ambient glucose and primary amino groups on proteins to form glycated residues called Amadori products is termed the Maillard reaction. By dehydration and fragmentation reactions, Amadori products are transformed to stable covalent adducts called advanced glycosylation end products (AGEs). In diabetes, accelerated synthesis and tissue deposition of AGEs is proposed as a contributing mechanism in the pathogenesis of clinical complications. Uremia in diabetes is associated with both a high serum level of AGEs and accelerated macro- and microvasculopathy. Diabetic uremic patients accumulate advanced glycosylated end products in "toxic" amounts that are not decreased to normal by hemodialysis or peritoneal dialysis but fall sharply to within the normal range within 8 h of restoration of half-normal glomerular filtration by renal transplantation. It follows that the higher mortality of hemodialysis-treated diabetic patients compared with those given a renal transplant may relate, in part, to persistent AGE toxicity. Pharmacologic prevention of AGE formation is an attractive means of preempting diabetic microvascular complications because it bypasses the necessity of having to attain euglycemia, an often unattainable goal. Pimagidine (aminoguanidine) interferes with nonenzymatic glycosylation and reduces measured AGE levels leading to its investigation as a potential treatment. The mechanism by which pimagidine prevents renal, eye, nerve, and other microvascular complications in animal models of diabetes is under investigation. Separate multicenter clinical trials of pimagidine in type 1 and type 2 diabetes, where proteinuria is attributable to diabetic nephropathy, are in progress. The effect of treatment on the amount of proteinuria, progression of renal insufficiency, and the course of retinopathy will be monitored.
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PMID:Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. 1009 2

Transient neonatal diabetes mellitus (TNDM) is a rare condition which presents with intrauterine growth retardation, dehydration, and failure to thrive. The condition spontaneously resolves before 1 year of age but predisposes patients to type 2 diabetes later in life. We have previously shown that, in some cases, TNDM is associated with paternal uniparental disomy (UPD) of chromosome 6 and suggested that an imprinted gene responsible for TNDM lies within a region of chromosome 6q. By analysing three families, two with duplications (family A and patient C) and one with several affected subjects with normal karyotypes (family B), we have further defined the TNDM critical region. In patient A, polymorphic microsatellite repeat analysis identified a duplicated region of chromosome 6, flanked by markers D6S472 and D6S311. This region was identified on the Sanger Centre's chromosome 6 radiation hybrid map (http://www.sanger.ac.uk/HGP/Chr6) and spanned approximately 60 cR3000. Using markers within the region, 418 unique P1 derived artificial chromosomes (PACs) have been isolated and used to localise the distal breakpoints of the two duplications. Linkage analysis of the familial case with a normal karyotype identified a recombination within the critical region. This recombination has been identified on the radiation hybrid map and defines the proximal end of the region of interest. We therefore propose that an imprinted gene for TNDM lies within an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q24.1-q24.3 between markers D6S1699 and D6S1010.
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PMID:Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q. 1020 43

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.
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PMID:Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth. 1079 84

Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene 7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an AlCl(3)-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of 7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield. Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide, followed by saponification, completed a five-step synthesis of 1 in 33% yield. FeCl(3)-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with chloromethylterephthalate 14 afforded ketone 15 in 81% yield. Saponification of 15 and reaction with 50% aqueous NH(2)OH in AcOH afforded a 9:1 mixture of cis and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield. The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach to the synthesis of this class of compounds.
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PMID:Synthesis of novel retinoid X receptor-selective retinoids. 1151 Dec 51

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.
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PMID:Attenuation of vasopressin-induced antidiuresis in poorly controlled type 2 diabetes. 1529 31

Although people age at different rates, changes to the composition of the human body are a hallmark of aging. As a result of such changes, disease can present differently in a person over 65 years old than it would in a younger adult or child. This article identifies the critical indicators of underlying conditions, including changes in mental status, loss of function, decrease in appetite, dehydration, falls, pain, dizziness, and incontinence. It also describes the presentation of diseases common to older adults, including depression, infection, cardiac disease, gastrointestinal disorders, thyroid disease, and type 2 diabetes.
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PMID:Presentation of illness in older adults. 1549 36

Hyperglycemic hyperosmolar nonketotic syndrome, a life-threatening complication commonly associated with uncontrolled type 2 diabetes mellitus in adults, is characterized by severe hyperglycemia, a marked increase in serum osmolality, and clinical evidence of dehydration without the accumulation of beta-hydroxybutyric or acetoacetic ketoacids. There is a variable alteration in sensorium. The syndrome has been rarely reported in children with leukemia undergoing induction therapy. The authors' aim is to sensitize physicians to this life-threatening illness, which can be treated effectively if diagnosed early.
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PMID:Hyperglycemic hyperosmolar nonketotic syndrome in a child with acute lymphoblastic leukemia undergoing induction chemotherapy: case report. 1583

Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. With the dramatic increase in the prevalence of type 2 diabetes and the aging population, this condition may be encountered more frequently by family physicians in the future. Although the precipitating causes are numerous, underlying infections are the most common. Other causes include certain medications, non-compliance, undiagnosed diabetes, substance abuse, and coexisting disease. Physical findings of hyperosmolar hyperglycemic state include those associated with profound dehydration and various neurologic symptoms such as coma. The first step of treatment involves careful monitoring of the patient and laboratory values. Vigorous correction of dehydration with the use of normal saline is critical, requiring an average of 9 L in 48 hours. After urine output has been established, potassium replacement should begin. Once fluid replacement has been initiated, insulin should be given as an initial bolus of 0.15 U per kg intravenously, followed by a drip of 0.1 U per kg per hour until the blood glucose level falls to between 250 and 300 mg per dL. Identification and treatment of the underlying and precipitating causes are necessary. It is important to monitor the patient for complications such as vascular occlusions (e.g., mesenteric artery occlusion, myocardial infarction, low-flow syndrome, and disseminated intravascular coagulopathy) and rhabdomyolysis. Finally, physicians should focus on preventing future episodes using patient education and instruction in self-monitoring.
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PMID:Hyperosmolar hyperglycemic state. 1588 46

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed till recently. Now it is being diagnosed with increasing frequency in obese children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go up, given global increase in incidence of childhood obesity, increased insulin resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality and dehydration without accumulation of beta -hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by the ability of the pancreas to secrete small amount of insulin. Prolonged phase of osmotic diuresis leads to severe depletion of body water, which excees that of sodium, resulting in hypertonic dehydration. These children, usually obese adolescents with T2 DM, present with signs of severe dehydration and depressed mental status but continue to have increased rather than decreased urine output and are at increased risk of developing rhabdomyolysis and malignant hyperthermia. Emergency treatment is directed at restoration of the intravascular volume, followed by correction of deficits of fluid and electrolyte (Na+, K+, Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough search for conditions that may lead to this metabolic decompensation and their treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic stabilization initially, followed by 0.45% saline with insulin infusion at the rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of insulin infusion once the blood glucose is 250 to 300 mg/dl is generally recommended. However, evidence-based guidelines about composition and tonicity of fluids and electrolyte solutions for early resuscitation and rehydration, the rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of HHNS in children are awaited. Careful monitoring of glucose levels and ensuring adequate hydration in patients 'at risk' of HHNS, including those receiving medications that interfere with the secretion or effectiveness of insulin should decrease the risk of HHNS.
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PMID:Hyperglycemic hyperosmolar nonketotic syndrome. 1644 62

ALTHOUGH PEOPLE AGE at different rates, changes to the composition of the human body are a hallmark of aging. As a result of such changes, disease can present differently in a person over 65 years old than it would in a younger adult or child. THIS ARTICLE IDENTIFIES the critical indicators of underlying conditions, including changes in mental status, loss of function, decrease in appetite, dehydration, falls, pain, dizziness, and incontinence. It also describes the presentation of diseases common to older adults, including depression, infection, cardiac disease, gastrointestinal disorders, thyroid disease, and type 2 diabetes.
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PMID:Presentation of illness in older adults. If you think you know what you're looking for, think again. 1654 57


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