Home About us Contact
|
Home About us Contact | ||
|
|
||
Secondary Failure (secondary + failure)
Selected AbstractsBeta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetesDIABETIC MEDICINE, Issue 7 2001M. J Taverna Abstract Background and aims Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. Materials and methods HOMA was measured in 84 Type 2 diabetic patients aged 58 ± sd 6 years, with diabetes duration 11 ± 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide ,,15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). Results Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 ± 6% vs. 76 ± 7%, normal values 59,161%) were comparable in the two groups. HbA1c was higher (10.0 ± 0.2% vs. 8.3 ± 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 ± 2% vs. 43 ± 6%, normal values 70,150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA1c >,8%, duration of diabetes ,,10 years, HbA1c combined with diabetes duration, insulin sensitivity ,,40%, insulin secretion ,,20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). Conclusions (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584,588 (2001) [source] Human liver-derived cells stably modified for regulated proinsulin secretion function as bioimplants in vivoTHE JOURNAL OF GENE MEDICINE, Issue 4 2002Xiang Chen Abstract Background Insulin deficiency is currently treated with pharmacological insulin secretagogues, insulin injections or islet transplants. Secondary failure of pharmacological agents is common; insulin injections often fail to achieve euglycemic control; and islet transplants are rare. Non-, cells capable of regulated insulin secretion in vivo could be a functional cure for diabetes. Hepatocytes are good candidates, being naturally glucose-responsive, protein-secreting cells, while the liver is positioned to receive direct nutrient signals that regulate insulin production. Methods Human liver-derived Chang cells were modified with a plasmid construct in which a bifunctional promoter comprising carbohydrate response elements and the human metallothionein IIA promoter controlled human proinsulin cDNA expression. Secretory responses of stable cell clones were characterized in vitro and in vivo by proinsulin radioimmunoassay. Results Transfected Chang cells secreted 5,8,pmol proinsulin/106 cells per 24,h in continuous passage for at least a year in response to 5,25,mM glucose and 10,90,µM zinc in vitro. Glucose and zinc synergistically increased proinsulin production by up to 30-fold. Non-glucose secretagogues were also active. Glucose transporter 2 (GLUT2) and glucokinase cDNA co-transfection enhanced glucose responsiveness. Intraperitoneally implanted Chang cells secreted proinsulin in scid and Balb/c mice. Serum proinsulin levels were further increased 1.3-fold (p<0.05) after glucose and 1.4- to 1.6-fold (p<0.005) after zinc administration in vivo. Conclusions These results are the first to demonstrate stable proinsulin production in a human liver-derived cell line with activity in vitro and in vivo and provide a basis for engineering hepatocytes as in vivo bioimplants for future diabetes treatment. Copyright © 2002 John Wiley & Sons, Ltd. [source] Mouse diaphragm assay for detection of antibodies against botulinum toxin type BMOVEMENT DISORDERS, Issue 12 2005Dirk Dressler MD Abstract With the advent of a commercial preparation of botulinum toxin type B (BT-B) for treatment of cervical dystonia detection of antibodies against BT-B (BT-B-AB) becomes necessary. For this purpose, we carried out a mouse diaphragm assay (MDA) by continuous measurement of the twitch force of a mouse hemidiaphragm preparation elicited by electric stimulation of its phrenic nerve. After exposing the preparation to BT-B 3 ng/ml the time to half-maximal twitch force reduction (paralysis time [PT]) was 69 ± 4 min (n = 25). Addition of sera from patients with antibodies against BT-A produced a PT of 68 ± 5 min (n = 24), whereas addition of sera from controls with antibodies against tetanus toxoid produced a PT of 67 ± 6 min (n = 30). When defined amounts of BT-B-AB were added to the MDA, PT was prolonged. This prolongation was correlated closely to the amount of BT-B-AB added, thus producing a calibration curve. The threshold for BT-B-AB detection was 0.4 mU/ml. When sera from 7 patients (4 women, 3 men; age 50.6 ± 14.2 years) with cervical dystonia (Toronto Western Spasmodic Torticollis Rating Scale score, 18.9 ± 2.9) and complete secondary failure of BT-B therapy (NeuroBloc; Elan Pharmaceuticals, Shannon, Ireland; 12,229 ± 2,601 MU/injection series, 1.86 ± 0.69 injection series before complete secondary therapy failure; 100.4 ± 15.8 days between injection series with normal therapeutic effect) were tested, BT-B-AB titers of more than 10 mU/ml were found in all of them. The MDA can be used to measure neutralizing BT-B-AB titers quantitatively and with adequate sensitivity and specificity. Further studies are necessary to understand the role of intermediate BT-B-AB titers in partial BT-B therapy failure. © 2005 Movement Disorder Society [source] Combination treatment of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitusPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2004AN Dixon MRCP (UK) Clinical Research FellowArticle first published online: 7 DEC 200 Abstract The recently published guidelines from the National Institute for Clinical Excellence (NICE) on the management of blood glucose in type 2 diabetes and the NICE guidelines on the use of the long-acting insulin analogue, glargine, have brought to the fore the use of combination therapy of insulin with oral hypoglycaemic agents (OHAs). The NICE guidelines recommend that when a patient with type 2 diabetes is failing to achieve satisfactory glycaemic control with OHAs alone, insulin should be initiated in combination with OHAs. However, evidence for this approach is less than robust and combination treatment of OHAs with insulin remains a controversial area. This article presents the evidence for different insulin regimens in patients who have secondary failure to OHAs, including combination therapy with basal insulin. The evidence and potential drawbacks of such regimens are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||