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Biomedical subjects

J F Yale

Publications and source records attributed to J F Yale.

At least 19 recordsLinked to original sources

The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin. A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The thiazolidinediones are a new class of antidiabetes medication that enhances the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients for whom insulin is the usual therapeutic alternative for improved glycemic control. OBJECTIVE: To determine the effects of troglitazone on hemoglobin A(1c) level in patients treated with maximum tolerated doses of sulfonylurea and metformin who have hemoglobin A(1c) levels of at least 0.085 (8.5%). This trial was completed before troglitazone was taken off the U.S. market. DESIGN: Randomized, double-blind, placebo-controlled trial, followed by an open-label extension during which all patients received troglitazone. SETTING: 16 outpatient clinics in Canada. PATIENTS: 200 patients (mean age, 59 years) with type 2 diabetes mellitus and hemoglobin A(1c) levels at least 0.085 (8.5%) (mean hemoglobin A(1c) level, 0.097 [9.7%] and mean fasting plasma glucose level, 12.9 mmol/L [233 mg/dL]) while receiving maximum doses of sulfonylurea and metformin. MEASUREMENTS: Levels of hemoglobin A(1c), fasting plasma glucose, total insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. RESULTS: Troglitazone, 400 mg/d, when added to sulfonylurea and metformin, significantly decreased hemoglobin A(1c) level by 0.014 +/- 0.002 (95% CI, 0.0167 to 0.0109; P < 0.001) (1.4% +/- 0.2% [CI, 1.67% to 1.09%]) and insulin by 19 +/- 4 pmol/L (CI, 30 to 10 pmol/L; P < 0.001). At 6 months, 43% of troglitazone-treated patients achieved hemoglobin A(1c) levels of 0.08 (8%) or lower compared with 6% of placebo recipients. Efficacy was maintained at 12 months. CONCLUSIONS: The thiazolidinedione troglitazone, at a dosage of 400 mg/d, is effective when used in combination with sulfonylurea and metformin. Thiazolidinediones may therefore offer an effective alternative to insulin for patients treated with sulfonylurea and metformin who do not achieve adequate glycemic control.

Blood Glucose↗

Teaching subjects with type 2 diabetes how to incorporate sugar choices into their daily meal plan promotes dietary compliance and does not deteriorate metabolic profile.

OBJECTIVE: To determine whether teaching free-living subjects with type 2 diabetes how to incorporate added sugars or sweets into their daily meal plan results in a greater consumption of calories (fat or sugar) and deteriorates their glycemic or lipid profiles but improves their perceived quality of life. RESEARCH DESIGN AND METHODS: In an 8-month randomized controlled trial, 48 free-living subjects with type 2 diabetes were taught either a conventional (C) meal plan (no concentrated sweets) or one permitting as much as 10% of total energy as added sugars or sweets (S). Mean individual nutrient intake was determined using the average of six 24-h telephone recalls per 4 months. Metabolic control and quality of life were evaluated every 2 months. Quality of life was assessed using the Medical Outcome Survey and the Diabetes Quality of Life questionnaire. RESULTS: The S group did not consume more calories (fat or sugar) and in fact ate significantly less carbohydrate (-15 vs. 10 g) and less starch (-7 vs. 8 g) and had a tendency to eat fewer calories (-77 vs. 81 kcal) than the C group. Weight remained stable, and there was no evidence that consuming more sugar worsened metabolic profile or improved their perceived quality of life. CONCLUSIONS: Giving individuals with type 2 diabetes the freedom to include sugar in their daily meal plan had no negative impact on dietary habits or metabolic control. Health professionals can be reassured and encouraged to teach the new "sugar guidelines," because doing so may result in a more conscientious carbohydrate consumption.

Adult↗

Improved postprandial glycemic control with Humalog Mix75/25 after a standard test meal in patients with type 2 diabetes mellitus.

OBJECTIVE: This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog Mix75/25, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus. BACKGROUND: Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues. METHODS: This randomized, multicenter, double-blind, crossover study monitored patients' postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp(ex)), maximum glucose excursion (Gex(max)), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex4) were calculated. RESULTS: Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9+/-2.2 mmol/L [160.2+/-39.6 mg/dL]; 70/30: 8.6+/-1.9 mmol/L [154+/-34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp(ex) (3.35+/-2.28 vs 4.13+/-2.26 mmol/L), Gex(max) (4.51+/-1.88 vs 5.19+/-1.98 mmol/L), and AUCex4 (8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L) compared with 70/30. CONCLUSIONS: In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Adult↗

Optimizing insulin delivery: assessment of three strategies in intensive diabetes management.

OBJECTIVE: To compare three intensive management strategies with respect to metabolic control (glycated haemoglobin, preprandial blood glucose, lipid profile, body weight, hypoglycaemic episodes) and psycho-social adaptation (quality of life, self-efficacy, stress and perceived complexity). RESEARCH DESIGN AND METHODS: Fifteen adults with type 1 diabetes completed this 1-year, randomized, prospective, cross-over study. The three treatment strategies were categorized according to flexibility with insulin self-adjustments as follows: Simplified (SIMP) = meal plan based on food exchanges with no self-adjustments of insulin for food, exercise and stress; Qualitative (QUAL) = meal plan based on food exchanges with qualitative adjustment of insulin for food, exercise and stress; Quantitative (QUANT) = meal plan using carbohydrate counting with quantitative adjustment of insulin for food and qualitative adjustment for exercise and stress. All three strategies allowed for adjustments of insulin for preprandial blood glucose and the option of adjusting diet for exercise. All subjects followed each strategy for 3.5 months. Subjects kept detailed log sheets where they recorded preprandial blood glucose, insulin dosages, food intake, activity and stress level at least four times/day. The psycho-social aspects were determined with validated questionnaires that were completed before and after each strategy. RESULTS: There were no statistically significant differences in metabolic control, quality of life and self-efficacy between the three strategies. The mean (+/- s.e.) for HbA1 levels (normal < 8.5%) were: Baseline: 10.9+/-0.06 and End of SIMP = 9.7+/-0.03; QUAL = 9.5+/-0.04; QUANT = 10.2+/-0.04. Body weight and serum lipid levels did not change significantly. The frequency of severe hypoglycaemic episodes for the entire study was 20 episodes/100 patient-years. Perceived complexity of treatment strategy increased (p < 0.0001) from SIMP to QUANT (least to most flexible). Although the majority of subjects (n = 11) were following a strategy similar to SIMP prior to entering the study, 12 subjects chose to continue with QUAL, three with QUANT and none with SIMP at the end of the study. CONCLUSIONS: These results indicate that a strategy that allows for flexibility of self-adjustments of insulin and is not very complex (such as QUAL) may be the strategy of choice for intensive management programmes.

Adult↗

Effect of acarbose on insulin sensitivity in elderly patients with diabetes.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.

Acarbose↗

Humalog Mix25 offers better mealtime glycemic control in patients with type 1 or type 2 diabetes.

To compare the postprandial glucodynamics of Humalog Mix25, (Humalog Mix75/25 in the US; Mix25), to human insulin 30/70 (Humulin 70/30 in the US; 30/70) in patients with type 1 or type 2 diabetes. Ninety-three patients with type 1 diabetes and 84 patients with type 2 diabetes were evaluated in two separate but identical protocols using a randomized, multicenter, double-blind, crossover design. Patients consumed test meals 5 minutes after equal doses of Mix25 or 30/70. Plasma glucose was measured at baseline and 15 minute intervals for 4 hours after the meal. Two-hour postprandial glucose (2pp), 2-hour glucose excursion (2pp(ex) ), glucose versus time area under the curve 0 to 4 hours (AUC(0-4) ) and glucose excursion area under the curve 0 to 2 and 0 to 4 hours (AUCex(0-2), AUCex(0-4) ) were calculated. For the combined patient population, Mix25 resulted in significantly lower 2pp (12.45 +/- 3.59 vs. 13.47 +/- 3.62 mmol/L; p <0.001), AUC(0-4) (44.45 +/- 12.20 vs. 47.25 +/- 11.97 mmol x h/L; p <0.001), and glucose excursion parameters: 2pp(ex) (3.20 +/- 2.72 vs. 4.40 +/- 2.81 mmol/L; p <0.001), AUCex(0-2) (5.45 +/- 3.15 vs 6.60 +/- 3.13 mmol x h/L; p <0.001), and AUCex(0-4) (7.57 +/- 8.37 vs. 11.02 +/- 8.47 mmol x h/L; p <0.001) compared to 30/70. Further analysis of the treatment by type of diabetes indicated that Mix25 provided nearly identical glucose excursion responses in type 1 and type 2 diabetes up to 2 hours after the test meal, in contrast to 30/70. Pre-meal injection of Mix25 resulted in lower postprandial blood glucose levels compared to 30/70. The postprandial blood glucose response following Mix25 was similar in patients with either type 1 or type 2 diabetes.

Adult↗

Prevention of type 2 diabetes.

The importance of type 2 diabetes is due to its high prevalence, the difficulties in achieving optimal glucose control (financial, time, quality of life) and the high frequency of chronic microvascular and macrovascular complications that add very significantly to the morbidity, mortality and overall cost of the disease. Numerous risk factors have been identified that predict the future onset of type 2 diabetes in individuals and an early stage of the disease (impaired glucose tolerance) can often be identified. Insulin resistance is central to the pathogenesis and is initially compensated by an increased insulin secretion. Over time, insulin secretion progressively fails and diabetes appears. Several approaches have been proposed for the prevention of diabetes. Lifestyle changes (nutritional therapy and physical activity) have been shown to reduce the frequency of diabetes in small studies and are being assessed in the NIH-funded Diabetes Prevention Trial. Metformin, which reduces insulin resistance and hyperinsulinaemia, is being assessed in this same trial. Acarbose, which has been shown to reduce post-prandial insulin secretion and improve insulin resistance, is being assessed in the STOP-NIDDM trial. The ACE inhibitor ramipril has been shown in the HOPE study to reduce the appearance of diabetes by one third when given to patients with vascular disorders and this class of agents has been shown to improve insulin resistance. Another very promising approach is the use of thiazolidinediones (rosiglitazone, pioglitazone) to improve the insulin resistance and possibly preserve the beta cells by reducing the need for increased insulin secretion. These lifestyle changes and medications have been shown to be safe in the treatment of type 2 diabetes. There is a high probability that one of these approaches will be effective in delaying or preventing type 2 diabetes, and prevention may become a clinical reality in the near future.

Diabetes Mellitus, Type 2↗

Conceptual knowledge and decision strategies in relation to hypercholesterolemia and coronary heart disease.

This paper reports on a study that examines physicians' understanding of concepts and decision making in problems pertaining to hypercholesterolemia and coronary heart disease (CHD). The study was carried out in two phases: (1) a simulated clinical interview in which two clinical problems were presented and (2) a session in which subjects responded to a series of questions. The questions were related to the analysis of risk factors, diagnostic criteria (DC) for determining elevated lipid values, and differential diagnosis for lipid disorders. The subjects included 12 family practitioners who were randomly selected from a continuing medical education program at McGill University. The results indicate that all subjects exhibited gaps in their understanding of domain concepts. In particular, most physicians demonstrated a lack of knowledge concerning the primary genetic disorders that contribute to CHD, as well as deficiencies in understanding the secondary causes of hypercholesterolemia. The majority of subjects tended to overestimate the lipid value intervals for determining patients at high risk. Physicians had no difficulty diagnosing the first patient problem of familial hypercholesterolemia, but failed to identify the problem of elevated lipids secondary to hypothyroidism. We observed a dissociation between subjects' conceptual understanding and their application of knowledge in solving patient problems. The implications of this work are discussed in terms of the cognitive dimensions of technologies for supporting learning and evidence-based decision making.

Adult↗

A controlled evaluation of a national continuing medical education programme designed to improve family physicians' implementation of diabetes-specific clinical practice guidelines.

AIMS: New approaches to continuing medical education will facilitate the implementation of clinical practice guidelines. This study assessed the short and long-term impact of a 7-h, small group workshop on family physicians' attitude, knowledge and self-reported practice patterns regarding diabetes mellitus. METHODS: One hundred and seventy-seven of 1807 family physicians who participated in this nationwide workshop, and 113 non-participant controls completed two validated questionnaires. Participants completed one questionnaire before the workshop and a second equivalent questionnaire 1 month later. Non-participant controls also completed the two questionnaires 1 month apart. Between 8 and 24 months later, these individuals were mailed the same questionnaire they completed on the first occasion; 143 participants and 50 controls returned this third questionnaire. RESULTS: Participants were more likely to be female (P = 0.03), not certified in family practice (P = 0.02), in a smaller centre (P = 0.0005), recent medical graduates (P = 0.001) and seeing fewer patients per month (P = 0.01) than controls. Compared to controls, participants had improved their attitude (P<0.0001), knowledge (P = 0.04) and self-reported practice patterns (P<0.002) regarding diabetes after 1 month but not after 1 year. CONCLUSIONS: An interactive, small group, diabetes continuing education programme effectively disseminates practice guidelines to family physicians. The impact of such a programme declines after 1 year.

Canada↗

1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association.

OBJECTIVE: To revise and expand the 1992 edition of the clinical practice guidelines for the management of diabetes in Canada incorporating recent advances in diagnosis and outpatient management of diabetes mellitus and to identify and assess the evidence supporting these recommendations. OPTIONS: All aspects of ambulatory diabetes care, including organization, responsibilities, classification, diagnosis, management of metabolic disorders, and methods for screening, prevention and treatment of complications in all forms of diabetes were reviewed, revised as required and expressed as a set of recommendations. OUTCOMES: Reclassification of types of diabetes based on pathogenesis; increased sensitivity of diagnostic criteria; recommendations for screening for diabetes; improved delivery of care; recommendations for tighter metabolic control; and optimal methods for screening, prevention and treatment of complications of diabetes. EVIDENCE: All recommendations were developed using a justifiable and reproducible process involving an explicit method for the citation and evaluation of the supporting evidence. VALUES: All recommendations were reviewed by an expert committee that included people with diabetes, family physicians, dietitians, nurses, diabetologists, as well as other subspecialists and methodologists from across Canada. BENEFITS, HARM AND COSTS: More aggressive screening strategies and more sensitive testing and diagnostic procedures will allow earlier detection and management of diabetes. Cost-effectiveness analyses suggest that this will lead to savings in health care costs relating to diabetes care by reducing the incidence of complications of diabetes. Similarly, tighter metabolic control in most people with diabetes, through intensive diabetes management, seeks to reduce the incidence of complications and, hence, their associated social and economic burdens. RECOMMENDATIONS: This document contains numerous detailed recommendations pertaining to all aspects of ambulatory diabetes care, ranging from service delivery to prevention and treatment of diabetes-related complications. The terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" should be replaced by the terms "type 1" and "type 2" diabetes. Testing for diabetes using fasting plasma glucose (FPG) level should be performed every 3 years in those over 45 years of age. More frequent or earlier testing should be considered for people with additional specific risk factors for diabetes. The FPG level at which diabetes is diagnosed should be reduced from 7.8 to 7.0 mmol/L to improve the sensitivity of the main diagnostic criterion and reduce the number of missed diagnoses. Depending on the type of diabetes and the therapy required to achieve euglycemia, people with diabetes should generally strive for close metabolic control to achieve optimal glucose levels. This entails receiving appropriate diabetes education through a diabetes health care team, diligent self-monitoring of blood glucose, attention to lifestyle and adjustments in diet and physical activity, and the appropriate and stepwise use of oral agents and insulin therapies needed to maintain glycemic control. Also highlighted is the need for appropriate surveillance programs for complications and management options. VALIDATION: All recommendations were graded according to the strength of the evidence and consensus of all relevant stakeholders. Collateral efforts of the American Diabetes Association and the World Health Organization and the input of international experts were also considered throughout the revision process.

Canada↗

In vivo insulin mimetic effects of pV compounds: role for tissue targeting in determining potency.

Peroxovanadium (pV) compounds activate the insulin receptor kinase in hepatocytes and inhibit the dephosphorylation of insulin receptors in hepatic endosomes with highly correlated potencies (Posner, B. I., R. Faure, J. W. Burgess, A. P. Bevan, D. Lachance, G. Zhang-Sun, J. B. Ng, D. A. Hall, B. S. Lum, and A. Shaver J. Biol. Chem. 269: 4596-4604, 1994). After intravenous administration, K2[VO(O2)2(picolinato)].2H2O [bpV(pic)], VO(O2) (picolinato) (H2O)2 [mpV(pic)], K[VO(O2)2(picolinato)].3H2O [bpV(phen)], and K[VO(O2)2(4,7-dimethyl-1,10-phenanthroline)].1/2H2O [bpV(Me2phen)] produced 50% of their maximal hypoglycemic effect at doses of 0.04, 0.04, 0.32, and 0.65 mumol/100 g body wt, respectively. In contrast, their potencies as inhibitors of dephosphorylation were bpV(pic) = bpV(phen) > mpV(pic) = bpV(Me2phen). bpV(pic) stimulated [14C]glucose incorporation into rat diaphragm glycogen in vivo, and its effect was dose dependent, synergistic with insulin, and evident in other skeletal muscles. In contrast, bpV(phen) displayed no effect on glycogen synthesis in skeletal muscle. mpV(pic) stimulated and bpV(Me2phen) had no effect on glycogen synthesis in the diaphragm. bpV(pic) augmented rat diaphragm insulin receptor kinase 2.2-fold with a time-integrated response 70% that of insulin. In contrast, the effect of bpV(phen) was delayed and much reduced. Thus, the in vivo potencies of pV compounds reflect differing capacities to act on skeletal muscle. The ancillary ligand within the pV complex may target one tissue in preference to another.

Animals↗

Hypoglycemic effects of peroxovanadium compounds in Sprague-Dawley and diabetic BB rats.

Highly purified peroxovanadium (pV) compounds, each containing an oxo ligand, one or two peroxo anions, and an ancillary ligand in the inner coordination sphere of vanadium, were shown to decrease plasma glucose markedly in both normal Sprague-Dawley and insulin-deprived diabetic BB rats. Maximal decreases in plasma glucose were at 60-100 min after intravenous, intraperitoneal, or subcutaneous administration. Synergism between these compounds and insulin was observed. Whereas parenterally administered orthovanadate or vanadyl sulfate did not induce hypoglycemia before inducing acute mortality, pV compounds effected hypoglycemia at doses much lower than those inducing acute mortality. When administered subcutaneously over a period of 3 days to insulin-deprived diabetic BB rats, pV compounds, but not vanadate, caused a significant decrease in plasma glucose concentrations and prevented the appearance of ketosis in these animals. Thus, pV compounds are the first agents other than insulin that acutely and markedly reduce plasma glucose in hypoinsulinemic diabetic BB rats.

Animals↗

Predictive value of lymphocyte antibodies for the appearance of diabetes in BB rats.

Lymphocyte antibodies have been described in autoimmune disorders, including insulin-dependent diabetes mellitus (IDDM). We have developed a quantitative method to measure autoantibodies directed against T-lymphocytes, based on two-color fluorescence labeling of Wistar mononuclear cells and analysis of fluorescence by flow cytometry. The lymphocyte antibody levels were determined retrospectively in the serum of 73 BB and 18 Wistar rats. We demonstrated the binding of the lymphocyte autoantibodies of both CD4+ and CD8+ T-cells. Lymphocyte antibodies were present in 90% of the BB rats at diabetes onset, compared with 11% of the Wistar rats. At 75 days of age, 83% of the BB rats, which later became diabetic, were positive for the lymphocyte antibodies, compared with 15% of their littermates who maintained a normal glucose tolerance. In all cases, the antibodies were of the immunoglobulin M isotype. We conclude that lymphocyte antibodies are present before diabetes onset and, using this method, that their presence can predict the development of diabetes with a sensitivity of 83% and a specificity of 85% in BB rats.

Animals↗

Protection of islets of Langerhans from antibodies by microencapsulation with alginate-poly-L-lysine membranes.

Microencapsulation of islets has been proposed to prevent their immune destruction following transplantation. An indirect immunofluorescence technique has been developed and used to study the permeability of the alginate-poly-L-lysine microcapsules to antibodies. Wistar rat islets were incubated with the R2D6 monoclonal mouse IgM antibody against rat islets, microencapsulated, and incubated with fluorescein-labeled goat IgG antibodies against mouse IgG and IgM. For the negative controls, the first antibody was omitted or both antibodies were omitted. The positive controls included islets incubated with both antibodies before they were encapsulated. Our study demonstrated that the alginate-poly-L-lysine membranes are not permeable to IgG when poly-L-lysine of molecular weights ranging from 21,000 to 390,000 are used. This simple immunofluorescence technique demonstrated the nonpermeability of the microcapsules to IgG, and could be useful for the initial evaluation of new types of membranes.

Alginates↗

Prevention of adoptive transfer in BB rats by prophylactic insulin treatment.

Prophylactic insulin can prevent diabetes in the BB rat. We evaluated its use to prevent adoptive transfer of diabetes by activated splenocytes. ConA-activated spleen cells from acutely diabetic BB rats were divided into two equal aliquots and injected intravenously in paired diabetes-prone BB rat littermates. At the time of cell injection, subcutaneous insulin injections (15 U.kg-1.day-1) were started in one of each pair (n = 21) of littermates, and the control littermates (n = 21) were injected with saline. The incidence of diabetes, observed 35 days after cell injection, was 95% in control rats compared with 29% in insulin-treated rats (P less than 0.05). To confirm the absence of diabetes, insulin was stopped in all nondiabetic insulin-treated rats at 63 days of age. An OGTT was performed at 65 days of age: 4 rats were glucose intolerant. All rats received comparable numbers of ConA-activated splenocytes. At the time the rats were killed, 3 insulin-treated rats had a completely normal morphology and a normal glucose tolerance. All control rats had insulitis whether they were diabetic or not. No significant difference in any mononuclear subset was observed in relation to insulin treatment. We conclude that prophylactic insulin can prevent adoptive transfer of diabetes in the BB rat without inducing changes in the mononuclear cell subsets.

Animals↗