Evaluation of the mean absolute glucose change as a measure of glycemic variability using continuous glucose monitoring data.

Background: The mean absolute glucose (MAG) change, originally developed to assess associations between glycemic variability (GV) and intensive care unit mortality, has not yet been validated. We used continuous glucose monitoring (CGM) datasets from patients with diabetes to assess the validity of MAG and to quantify associations with established measures of GV.

Subjects And Methods: Validation was based on retrospective analysis of 72-h CGM data collected during clinical studies involving 815 outpatients (48 with type 1 diabetes and 767 with type 2 diabetes).

Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs.

Aims/hypothesis: In non-diabetic people, insulin levels in the liver are two-fold higher than those in the systemic circulation. In contrast, patients with type 1 diabetes have similar hepatic and systemic insulin levels because insulin is administered peripherally. The aim of this study was to compare the effects of systemic (SI) and pre-portal (PI) insulin administration on energy, glucose and protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs.

Cell surface trafficking of Fas in NIT-1 cells and dissection of surface and total Fas expression.

The appearance of Fas receptor at the surface of pancreatic beta-cells affected by progressive insulitis strongly suggests that Fas-mediated beta-cell apoptosis plays an important role in the pathogenesis of type 1 diabetes. In support of this concept, the present study has shown that islet cells from NOD mice and the beta-cell line NIT-1 respond to the proinflammatory cytokines IL-1beta and IFN-gamma with Fas surface expression in a dose- and time-dependent manner. Moreover, the prevention of cytokine-induced surface Fas expression by actinomycin D, cycloheximide, and brefeldin A demonstrated that trafficking of Fas to the beta-cell surface requires RNA and protein synthesis and, in addition is critically dependent on intracellular protein transport.

Diabetes and hypertension in rodent models.

As shown by ourselves and others, animals models closely resembling human complex diseases like IDDM in BB/OK and hypertension in SHR/Mol rats can be used to dissect a complex disease into discrete genetic factors as has been done for hypertension in (BB/OK x SHR/Mol) cross hybrids. Discrete genetic factors, so-called QTLs, were detected on chromosomes 1, 10, 18, 20, and X. To gain additional information about the physiologic effect of the mapped blood pressure QTLs, genetically defined regions of the SHR rat were transferred onto the genetic background of diabetes-prone BB/OK rats.

Blood glucose lowering and glucagonostatic effects of glucagon-like peptide I in insulin-deprived diabetic dogs.

To establish potential effects of glucagon-like peptide I (GLP-I) on blood glucose control in insulin-deficient states, GLP-I [GLP-I(7-36) amide; 10 pmol x kg(-1) x min(-1)] was infused intravenously in six fasting, canine C-peptide-negative, chronically diabetic dogs for 8 h. Blood samples were saved for the analysis of hormones, metabolites, and turnover rates of glucose (6-(3)H-glucose), alanine (U-(14)C-alanine), and urea ((15)N(2)-urea) starting 22 h after the last subcutaneous dose of exogenous insulin. Circulating plasma GLP-I levels rose under infusion from 2.

Circadian variations in blood pressure and heart rate in diabetes prone and resistant rat strains compared with spontaneously hypertensive rats.

Circadian blood pressure (BP), heart rate (HR) and motor activity (MA) of nondiabetic (nd) and spontaneously diabetic (d) BB/OK rats were compared with that of spontaneously hypertensive rats (SHR). In addition a diabetes-resistant and non-hypertensive rat strain (LEW.1W) was monitored for the same parameters.

Identification of interleukin 1-induced apoptosis in rat islets using in situ specific labelling of fragmented DNA.

To study the ability of interleukin 1-beta (IL-1) to induce apoptosis in the endocrine pancreas, rat islets of Langerhans obtained from 14-day-old BB.1A rats were exposed to 25 U/ml IL-1 for 40 h. In order to prove the role of nitric oxide (NO) in this process islets were exposed either to 1 mmol/l N-nitro-L-arginine methylester (NAME) or to 25 mmol/l nicotinamide (NA) or to a combination of NA or NAME with IL-1.

Increased urea synthesis in insulin-dependent diabetic dogs maintained normoglycemic: effect of portal insulin administration and food protein content.

In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 2) to elucidate the impact of different food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic.

Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline.

The spontaneously diabetic BB rat is a well-established animal model of human insulin-dependent diabetes mellitus. Besides the lymphopenia gene (Iddm 1) and the MHC class-II genes of the RT1u haplotype (Iddm 2), at least one other non-MHC gene (Iddm 3) is considered essential for diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we analysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypically and genotypically.

Continuous in vivo monitoring in diabetes: the subcutaneous glucose concentration.

The most advanced glucose sensors are measuring amperometrically the hydrogen peroxide generated in a stoichiometric relation to the prevailing glucose concentration during glucose oxidase-mediated glucose oxidation. They proved useful in commercially available glucose analysers and in experimental subcutaneous (sc) monitoring. Here it is shown (a) that under steady state conditions the s.

Clinical usefulness of the glucose concentration in the subcutaneous tissue--properties and pitfalls of electrochemical biosensors.

Biosensors are miniaturized analytical tools which comprise a biological detection element providing specificity to the analyte, and a physical transducer which guarantees an output signal, e.g. an electric current the size of which is proportional to the concentration of the analyte.

Detection of autoantibodies to the 65-kD isoform of glutamate decarboxylase by radioimmunoassay.

Autoantibodies (AAb) to glutamate decarboxylase (GAD) occur with a high prevalence in sera of newly diagnosed type I (insulin-dependent) diabetic patients. The aim of this study was to establish a GAD-AAb radioimmunoassay using 125I-labelled GAD65 and to evaluate this assay in a cross-sectional study with newly diagnosed type I diabetic patients (diabetes duration < 6 weeks). Furthermore, subjects at high risk of developing type I diabetes and individuals suffering from other autoimmune diseases were examined in this assay.

KADIS: model-aided education in type I diabetes. Karlsburg Diabetes Management System.

Education and training in self-management of blood glucose control has become a permanent task for all people involved in the care of diabetic patients. Since this may be facilitated by applying state-of-the-art information technology, we have developed the decision support system KADIS (Karlsburg Diabetes Management System). It comprises computer-aided tools for (1) the evaluation (selection, aggregation, storage, statistics, graphics) of therapeutic data, e.

Glucose oxidase electrodes: effect of hydrogen peroxide on enzyme activity?

This paper presents a simple procedure to assess the amount of hydrogen peroxide arising in amperometric glucose oxidase sensors. At an external glucose concentration of 30 mmol/l, which represents the linear range of calibration, a hydrogen peroxide concentration of approximately 0.18 mmol/l is generated.

Primary health care of diabetic patients in a specialized outpatient setting: a DIABCARE-based analysis.

To assure health care quality requires a tool for establishing the feedback between parameters of patient management and related standards. To assess the current situation and to evaluate the DIABCARE system as a potential monitoring instrument, a retrospective study was performed in 85 randomly assigned insulin-treated patients (72% type 2) who were regularly attending the diabetes outpatient unit (total of 3,595 patients) in a township of approximately 90,000 inhabitants. 1,195 records of sequential medical visits during the years 1987 and 1990 were analyzed.

Model-based prediction of diabetes incidence in BB/OK rats.

In the BB/OK rat strain, the incidence of diabetes (in the context of animal diabetes defined as the percentage of animals developing diabetes up to the age of 200 days) is related to the sex distribution within litters and to the phenotype of the parents. On the basis of these observations, an algorithm was developed to predict the incidence of diabetes of an inbred generation as the percentage of diabetic animals of a given inbred generation. Thus, the incidence of diabetes was analysed in 25 inbred generations of our BB/OK colony according to sex ratio and the phenotype of parents, which is thought to be an important genetic factor for diabetes onset in the offspring.