1/192. Insulin-mediated pseudoacromegaly in a patient with severe insulin resistance: association of defective insulin-stimulated glucose transport with impaired phosphatidylinositol 3-kinase activity in fibroblasts.The purpose of this study was to clinically and biochemically describe an insulin resistant patient with insulin-mediated pseudoacromegaly and in addition, to examine the molecular cause responsible for the defective insulin-stimulated glucose transport in cultured fibroblasts derived from the patient. The patient was a 64 year old female with severe insulin resistant diabetes mellitus, requiring up to 200 U insulin per day, associated with typical acromegaloid characteristics including increased hand and foot size, macroglossia and development of coarse facial features. Pituitary magnetic resonance imaging as well as multiple GH and IGF-1 measurements were normal. In cultured fibroblasts derived from the patient, (i) insulin-stimulated glucose transport, (ii) the subcellular distribution of GLUT1 glucose transporters, (iii) insulin-stimulated IRS-1-immunoprecipitable phosphatidylinositol (PI) 3-kinase activity, as well as (iv) protein expression of the small GTP-binding protein Rab4 was determined. The results indicate, that insulin's ability to stimulate glucose transport is defective in the patients fibroblasts although the GLUT1 content in the plasma membrane was increased by 34% when compared to control cells. Furthermore, the IRS-1 dependent activation of PI 3-kinase was reduced by 39.6% after incubation with 10 nM insulin for 5 min. Interestingly, immunodetection of the small GTP-binding protein Rab4, which is believed to be involved in the regulation of glucose transporter vesicle targeting to the plasma membrane, revealed a marked reduction of the expression of Rab4 protein in a total membrane fraction by 57.4%. In conclusion, in fibroblasts of a patient with clinical and biochemical evidence of pseudoacromegaly, the defective insulin-stimulated glucose transport was associated with impaired insulin-stimulated PI 3-kinase activity, which may contribute to the severe insulin resistant state of this patient.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
2/192. insulin resistance in patients with depression and its changes in the clinical course of depression: a report on three cases using the minimal model analysis.It has been reported that depression and diabetes mellitus often occur together, and insulin resistance has been observed in patients with depression. For further understanding of the relationship of depression to insulin resistance, three patients with depression were given the oral glucose tolerance test (OGTT) and the frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis before and after antidepressant treatment. Depressive patients showed decreased glucose tolerance, enhanced insulin secretion, and diminished insulin sensitively during OGTT and FSIGT. These abnormalities were resolved after their recovery from depression without changes in body weight or diet.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
3/192. Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency.Raised plasma triglycerides (TGs) and nonesterified fatty acid (NEFA) concentrations are thought to play a role in the pathogenesis of insulin-resistant diabetes. We report on two sisters with extreme hypertriglyceridemia and overt diabetes, in whom surgical normalization of TGs cured the diabetes. In all of the family members (parents, two affected sisters, ages 18 and 15 years, and an 11-year-old unaffected sister), we measured oral glucose tolerance, insulin sensitivity (by the euglycemic-hyperinsulinemic clamp technique), substrate oxidation (indirect calorimetry), endogenous glucose production (by the [6,6-2H2]glucose technique), and postheparin plasma lipoprotein lipase (LPL) activity. In addition, GC-clamped polymerase chain reaction-amplified dna from the promoter region and the 10 coding LPL gene exons were screened for nucleotide substitution. Two silent mutations were found in the father's exon 4 (Glu118 Glu) and in the mother's exon 8 (Thr361 Thr), while a nonsense mutation (Ser447 Ter) was detected in the mother's exon 9. Mutations in exons 4 and 8 were inherited by the two affected girls. At 1-2 years after the appearance of hyperchylomicronemia, both sisters developed hyperglycemia with severe insulin resistance. Because medical therapy (including high-dose insulin) failed to reduce plasma TGs or control glycemia, lipid malabsorption was surgically induced by a modified biliopancreatic diversion. Within 3 weeks of surgery, plasma TGs and NEFA and cholesterol levels were drastically lowered. Concurrently, fasting plasma glucose levels fell from 17 to 5 mmol/l (with no therapy), while insulin-stimulated glucose uptake, oxidation, and storage were all markedly improved. Throughout the observation period, plasma TG levels were closely correlated with both plasma glucose and insulin concentrations, as measured during the oral glucose tolerance test. These cases provide evidence that insulin-resistant diabetes can be caused by extremely high levels of TGs.- - - - - - - - - - ranking = 8keywords = diabetes (Clic here for more details about this article) |
4/192. A case of acromegaly accompanied by adrenal preclinical Cushing's syndrome.We encountered a 58-year-old woman with acromegaly accompanied by a cortisol-secreting adrenal tumor without clinical features of hypercortisolism. The simultaneous occurrence of these two endocrinopathies in one individual is extremely rare. She was diagnosed as having diabetes mellitus 8 years ago. Afterwards, in spite of insulin therapy, her hyperglycemia could not be well controlled. Her acromegaly and preclinical Cushing's syndrome were histopathologically proven to be due to a pituitary adenoma and an adrenocortical adenoma, respectively. Successful treatment for these endocrinopathies resulted in greatly improved blood sugar control because of a reduction in insulin resistance. In this case of preclinical Cushing's syndrome, replacement therapy with glucocorticoid was able to be discontinued at only 8 weeks after adrenalectomy, so that the period of necessary replacement was much shorter than that for overt Cushing's syndrome. This is the first report describing insulin resistance before and after treatment in a case of acromegaly accompanied by adrenal preclinical Cushing's syndrome.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
5/192. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34.Congenital generalized lipodystrophy (CGL, Berardinelli-Seip syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid x receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
6/192. Migratory ichthyosiform dermatosis with type 2 diabetes mellitus and insulin resistance.BACKGROUND: In addition to the well-defined hereditary primary ichthyoses, many sporadic or less well-defined keratinization disorders with or without systemic manifestations have been reported. Herein we describe ichthyosiform dermatosis associated with type 2 diabetes mellitus. OBSERVATIONS: The patients were members of a large Arab family with heavy consanguinity. Eighteen members were affected with a variously severe scaly disorder. They showed migratory polycyclic keratotic scaly plaques evolving into diffuse generalized scaling or complete remission. acanthosis nigricans-like lesions were also noted, and there was an association with type 2 diabetes mellitus. A scarcity of intercorneocyte lamellae and reduction in lamellar body contents were observed. CONCLUSIONS: We could not find a report of a similar dermatosis. Furthermore, an association between ichthyosis and diabetes has not been documented. Therefore, we believe that this may constitute a new entity.- - - - - - - - - - ranking = 7keywords = diabetes (Clic here for more details about this article) |
7/192. Improvement in severe insulin resistance with frequent injections of lispro insulin.Extreme insulin resistance is common in obese african americans with type 2 diabetes. This case report describes an obese African-American woman who was treated with subcutaneous injections of lispro insulin every 2 hours with resultant decrease of mean daily blood glucose from 264.7 mg/dL to 111 mg/dL and in insulin requirement from 479 U/24 hours to 60 U/24 hours. This case demonstrates that extreme insulin resistance is reversible in the short term.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
8/192. alternative splicing of exon 17 and a missense mutation in exon 20 of the insulin receptor gene in two brothers with a novel syndrome of insulin resistance (congenital fiber-type disproportion myopathy).The insulin receptor (IR) in two brothers with a rare syndrome of congenital muscle fiber type disproportion myopathy (CFTDM) associated with diabetes and severe insulin resistance was studied. By direct sequencing of Epstein-Barr virus-transformed lymphocytes both patients were found to be compound heterozygotes for mutations in the IR gene. The maternal allele was alternatively spliced in exon 17 due to a point mutation in the -1 donor splice site of the exon. The abnormal skipping of exon 17 shifts the amino acid reading frame and leads to a truncated IR, missing the entire tyrosine kinase domain. In the correct spliced variant, the point mutation is silent and results in a normally translated IR. The paternal allele carries a missense mutation in the tyrosine kinase domain. All three cDNA variants were present in the lymphocytes of the patients. Purified IR from 293 cells overexpressing either of the two mutated receptors lacked basal or stimulated IR beta-subunit autophosphorylation. A third brother who inherited both normal alleles has an normal muscle phenotype and insulin sensitivity, suggesting a direct linkage of these IR mutations with the CFTDM phenotype.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
9/192. Non-specific viral infections as possible synchronising events of the manifestation of type 1 diabetes.Four cases of simultaneous manifestation of Type 1 diabetes in two members of the same household are reported. In all cases, a flu-like infection preceded diabetes onset. Surprisingly, despite simultaneous development of insulin dependency, insulin requirements were strikingly different at 3 months in all cases. These observations suggest that increased insulin resistance during infection may cause insulin deficiency in individuals with widely varying residual beta cell activity.- - - - - - - - - - ranking = 6keywords = diabetes (Clic here for more details about this article) |
10/192. insulin resistance and acanthosis nigricans. Report of a case with antibodies to insulin receptors.A 64-year-old black man presented with the syndrome of acanthosis nigricans and insulin-resistant diabetes mellitus requiring up to 3000 units of insulin per day. The patient's plasma contained circulating antibodies to insulin receptors thought to be responsible for the insulin resistance. The marked insulin resistance, the manifestations of acanthosis nigricans, the evidence of immunologic dysfunction by the absence of expected circulating antibodies to insulin, and the demonstration of circulating antibodies to insulin receptors put this patient in Kahn's category B of insulin resistance and acanthosis nigricans. There was no evidence of malignancy, lipodystrophy, or endocrine abnormality. The occurrence of acanthosis nigricans with insulin resistance due to binding of cell membrane insulin receptors by antibodies has been reported exclusively in women. This case report is the first description of a male patient with the syndrome of insulin resistance and acanthosis nigricans and focuses attention on features that might mislead one to suspect other causes of insulin resistance.- - - - - - - - - - ranking = 1keywords = diabetes (Clic here for more details about this article) |
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