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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to determine if continuous subcutaneous insulin infusion (CSII) could improve control, diminish episodes of diabetic ketoacidosis (DKA), decrease number of hospitalizations and save health care expenditure in children and adolescents with long-standing poorly controlled diabetes mellitus. A retrospective analysis was done of six patients with type 1 diabetes for 1-8 years, of whom 4 were non-adherent to the diabetic regimen (ages 12-16.5 years) and 2 of whom had brittle diabetes (ages 8.5 and 10 years). These patients were non-randomly placed on the MiniMed (Sylmar, CA) CSII system. The year prior to CSII was compared with the year during pump use. Glycoslyated hemoglobin (HbA1c), spot urinary microalbumin, total cholesterol, insulin dose, growth velocity, number of convulsions and hypoglycemic events, number of episodes of DKA, number of hospitalizations and total inpatient costs were compared for the 2 years. The year prior to CSII, mean HbA1c was 9.02% (S.D. = 0.86%), mean number of hospitalizations was 5.2/patient (S.D. = 4.6), mean number of hospital days was 20.8/patient (S.D. = 14.7) and mean cost was $29330/patient (S.D. = $22804). During 1 year of CSII, mean number of hospital days decreased to 5 days/patient (S.D. = 0.8, P = 0.016), mean number of hospitalizations (including DKA and pump initiation) decreased to 1.7/patient (S.D. = 0.7, P = 0.31), mean inpatient costs decreased to $12762/patient (S.D. = $5.950, P = 0.047). HbA1c, urinary microalbumin, cholesterol, insulin dose and growth velocity did not change in a statistically significant manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous subcutaneous insulin infusion (CSII) in children and adolescents with chronic poorly controlled type 1 diabetes mellitus. 755 2

Acarbose represents a new pharmacological approach to achieving the metabolic benefits of a slower carbohydrate absorption in diabetes, by acting as a potent, competitive inhibitor of intestinal alpha-glucosidases. Acarbose molecules attach to the carbohydrate binding sites of alpha-glucosidases, with an affinity constant that is much higher than that of the normal substrate. Because of the reversible nature of the inhibitor-enzyme interaction, the conversion of oligosaccharides to monosaccharides is only delayed rather than completely blocked. Acarbose has the structural features of a tetrasaccharide and does not cross the enterocytes after ingestion. Thus, its pharmacokinetic properties are well suited to the pharmacological action directed exclusively towards the intestinal glucosidases. The most important clinical consequence of the delayed carbohydrate digestion caused by acarbose is the attenuation of postprandial increases in blood glucose levels. Other effects have also been described: a decreased beta-pancreatic response to meals, and influences on gut hormone secretion and plasma lipid levels. Gastrointestinal discomfort is frequently reported as an adverse effect of acarbose administration, but incidence usually decreases with time. The suitability of acarbose for improving glucose homeostasis as an adjunct to dietary control or to administration of sulphonylureas or insulin has been extensively studied in patients both with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Acarbose can be used as first-line therapy in patients with type 2 diabetes which is poorly controlled by diet alone. Moreover, the lack of bodyweight gain or hypoglycaemic effects reported during acarbose treatment may be advantageous for obese or elderly patients. Finally, the reduction in fluctuations of glucose levels throughout the day may help to control type 1 diabetes in patients with 'brittle diabetes'. Long term prospective studies are still needed to confirm these indications and the usefulness of acarbose in conditions other than diabetes, notably reactive hypoglycaemia and dumping syndrome.
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PMID:Pharmacokinetic-pharmacodynamic relationships of Acarbose. 890 94

The polyglandular autoimmune syndromes (PGA) are well known and are distinguished into type I, type II and type III. PGAI, also called APECED (autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy), is an autosomal recessive disorder, appearing in childhood and typically characterized by hypoparathyroidism (unusual in PGAII and PGAIII) and adrenal insufficiency. In APECED, autoimmune destruction of the pancreatic beta cells with development of insulin-dependent type 1 diabetes is possible, but less frequent than in the other PGAs, especially PGAII. The pathogenesis of this unique autoimmune disease is unknown. No HLA association seems to exist and genetic studies have assigned the autosomal APECED locus to chromosome 21. The case of a 28-years-old female suggesting the diagnosis of APECED, is presented, characterized by psycho-somatic abnormal development, teeth alterations, post-puberal gonadal failure with dystrophic hypoplasia of external genitalia, previous vaginal candidiasis, a slowly developing juvenile brittle diabetes. Intestinal malabsorption induced by Giardia lamblia occurred (probably resulting, like candidiasis, from immunological anergy). A strong familiarity linked to female sex was noticed (the mother, a sister, the little nice and some maternal female cousins being affected) while the father and a brother were healthy. Diabetes seems to be characterized by early onset and severe complications. In this patient no organo-specific antibodies were detected and the only immunologic disorder was a small decrease of CD3 and CD4/CD8 ratio, both CD4 and CD8 being at the lower normal range. This patient (and her female maternal relatives) needs a long-term follow-up in order to evaluate the function of endocrine glands and to initiate early treatment for hormonal deficits, as well as to detect the non-endocrine components of disease.
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PMID:[A rare case of juvenile diabetes mellitus associated with APECED (autoimmune poly-endocrinopathy, candidiasis and ectodermal dystrophy) with strong X-linked familial inheritance]. 930 48

Insulin dependent diabetes mellitus is one of the most common metabolic diseases and affects 150,000 persons in France. To achieve good metabolic control requires a strict daily management of the treatment by the patients themselves. Lack of active involvement can have direct consequences which underlines the importance of a good adherence to the treatment. About 50% of the patients do not obtain adequate metabolic control. The major problem of insulin treatment consists in the repeated occurrence of severe hypoglycemias which may be accompanied by an alteration of the perception of hypoglycaemic signs. On the other hand, when the risk of severe hypoglycaemia is removed, glycosylated haemoglobin levels rise. Permanent hyperglycaemia leads to numerous somatical complications. An extremely dramatic combination of these two types of metabolic unbalance is represented by the brittle diabetes characterised by very frequent and extreme oscillations between hypo and hyperglycaemia. This raises the question of the influence of psychopathological factors on metabolic control and the possibility of improving metabolic control by acting on these factors. Epidemiological studies in diabetic patients have established higher prevalence rates of psychiatric disorders, in particular mood and anxiety disorders. The current prevalence rate of depression was found to be homogeneous in the literature about 11% and life time prevalence rates of major depressive disorders vary between 24% and 29%. The symptom profile of depression in diabetic patients is similar to that in depressed non diabetic psychiatric patients and it has been shown that highly sensitive psychiatric diagnosis of depression can be made among diabetic patients. There is no specific personality pattern in diabetic patients. There seems to be a relationship between metabolic control as defined by glycosylated haemoglobin and psychiatric disorders. Indeed, high levels of glycosylated haemoglobin are found in patients with psychiatric disorders. There seems to be some evidence of an association between blood glucose levels and actual emotional states. Nothing is known about the specificity of the link between psychiatric disorders and insulin-dependent diabetes mellitus. No study has evaluated if the relationship between psychiatric disorders and insulin-dependent diabetes mellitus is due to the disease itself or to the chronic feature of diabetes.
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PMID:[Insulin-dependent diabetes and psychiatric pathology: general clinical and epidemiologic review]. 945 27

Instability of glycemic levels is "normal" in type 1 diabetes, with different levels of severity, up to the restrictive definition of brittle diabetes (repeated ketoacidosis and/or severe hypoglycemias). Quantification of glycemic instability, in terms of intraday variability and day-to-day reproducibility, is advisable. Standard deviation of blood glucose, though a simple index does not discriminate between slow and brutal variations. Repartition of blood glucose values also only indicates dispersion. M values compares the patient values to an ideal blood glucose level, emphasizing the role of low values. The MAGE index measures the amplitude of the largest glucose excursions, thus evaluating appropriately glycemic variability. The Low Blood Glucose Index (LBGI) is a new index of variability emphasising (as the M value) the low glycemias. Each glycemia is given a value from O (if >=110 mg/dl) to 100 (if 20 mg/dl). It thus integrates the frequency and severity of hypoglycemias. According to its authors the LBGI would be the best indicator of severe hypoglycemias. The Mean of Daily Differences (MODD) evaluates the day-to-day reproducibility of blood glucose values. All the above indexes could easily be incorporated in the programmes of large memory glucose meters.
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PMID:[How to measure glycemic instability?]. 1080 31

A Canadian research team recently reported a series of 7 consecutive patients with type 1 brittle diabetes who could achieve sustained excellent metabolic control in the absence of insulin therapy after successful islet transplantation. This exceptional success, which contrasts with previous less favourable results, is probably due to the transplantation of a higher number of islets of good quality and to the use of a new glucocorticoid-free immunosuppressive regimen. These remarkable results which provide proof of the principle that islet transplantation can be reproducibly successful, at least for one year, may raise new hope in patients with type 1 diabetes. However, the problem of supply and demand of islets is huge and will require a careful, and probably difficult, selection of the best candidates to benefit from this new therapeutic approach.
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PMID:[Clinical study of the month. Prolonged insulin independence after transplantation of islets of Langerhans in a patient with type 1 diabetes: achievement of a dream?]. 1105 79

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.
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PMID:Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. 1128 33

Disordered gastric motility occurs frequently in diabetes mellitus. Gastric emptying time is abnormal in about 50% of diabetic patients and delayed emptying time is known as an important cause for brittle diabetes in type 1 diabetes. We compared the rise in blood glucose after a standardized meal (oatmeal test) as a noninvasive screening test for diabetic gastropathy with the noninvasive measurement of gastric emptying time with ultrasound in type 1 and type 2 diabetic patients. The test result was considered pathological if the rise of blood glucose after an initial steady state did not reach 20 mg/dl in the first 20 min after the meal (prolonged blood glucose latency). We found a sensitivity of 90% (58.7-99.8) and a specificity of 100% (71.5-100) for the oatmeal test in type 1 diabetes in the gastropathy screening. In type 2 diabetes we found a sensitivity of 13% (1.5-38.3) and a specificity of 78% (60-90.7) (95% CI). In conclusion, the oatmeal test seemed to be a good, noninvasive screening test in diabetic gastropathy in type 1 diabetes, but has no diagnostic value in type 2 diabetes. The causes for such a difference may be due to a different postprandial blood glucose regulation in type 2 diabetes compared to the beta-cell-depleted type 1 diabetes.
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PMID:Postprandial blood glucose latency after oatmeal is a valid screening test for diabetic gastropathy in type 1 diabetes, but not in type 2 diabetes. 1133 Apr 3

Transplantation of islets of Langerhans in patients with type 1 diabetes allows for improved metabolic control and insulin independence. The need for chronic immunosuppression limits this procedure to selected patients with brittle diabetes. Definition of therapeutic strategies allowing permanent engraftment without the need for chronic immunosuppression could overcome such limitations. We tested the effect of the use of protoporphyrins (CoPP and FePP), powerful inducers of the cytoprotective protein heme-oxygenase 1 (HO-1), on allogeneic islet graft survival. Chemically induced diabetic C57BL/6 mice received DBA/2 islets. Treatment consisted in peritransplant administration of CoPP or saline. Islets were either cultured in the presence of FePP or vehicle before implant. Short-course administration of CoPP led to long-term islet allograft survival in a sizable proportion of recipients. Long-term graft-bearing animals rejected third-party islets while accepting a second set donor-specific graft permanently, without additional treatment. Preconditioning of islets with FePP by itself led to improved graft survival in untreated recipients, and provided additional advantage in CoPP-treated recipients, resulting in an increased proportion of long-term surviving grafts. Preconditioning of the graft with protoporphyrins prior to implant resulted in reduction of class II expression. Administration of protoporphyrins to the recipients of allogeneic islets also resulted in transient powerful immunosuppression with reduced lymphocyte proliferative responses, increased proportion of regulatory cells (CD4+CD25+), decreased mononuclear cell infiltrating the graft, paralleled by a systemic upregulation of HO-1 expression. All these mechanisms may have contributed to the induction of donor-specific hyporesponsiveness in a proportion of the protoporphyrin-treated animals.
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PMID:Prolonged allogeneic islet graft survival by protoporphyrins. 1588 18

A 75-year-old man with type 1 diabetes and history of insulin therapy for previous 3 years using only human recombinant ones was suffering from unstable glycemic control. He had a high level of total insulin and a high titer of insulin antibodies (IA) (bound/total ratio: 89.8%). Low affinity constant (k(1): 0.0312 x 10(8) M(-1)) and high binding capacity (b(1): 51.8 x 10(-8) M) of IA in the patient detected by the Scatchard analysis were not compatible with those of IA associated with exogenous insulin injections in the diabetic patients, but compatible with those of the insulin autoantibodies found in patients with insulin autoimmune syndrome (IAS), although he had DRB1*0405, which may have protection against IAS development. The glucose infusion rate during hyperinsulinemic euglycemic clamp was 2.84 mg/kg/min, suggesting a high level of insulin resistance. Steroid pulse therapy (1000 mg for 3 days) aimed at reducing the possible effect of the IA on his insulin resistance and glycemic instability successfully decreased IA titer (from 89.8 to 58.3%), lowered its binding capacity (51.8-9.8 x 10(-8) M), increased glucose infusion rate (from 2.84 to 5.55 mg/kg/min) and improved glycemic control (HbA(1c): from 10.0 to 7.4%) with reduced blood glucose excursion. In conclusion, the alteration in insulin pharmacokinetics induced by IA seemed to be the cause of the brittle diabetes of the present case. Steroid treatment might be useful for the improvement of glycamic control in such patients with high IA levels and unstable blood glucose.
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PMID:A case of slowly progressive type 1 diabetes with unstable glycemic control caused by unusual insulin antibody and successfully treated with steroid therapy. 1643 34


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