Background Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year. Methods Seven consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization. Results All seven patients quickly attained sustained insulin independence after transplantation of a mean (±SD) islet mass of 11,547±1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from tw...

https://www.nejm.org/doi/pdf/10.1056/NEJM200007273430401

Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen

Evolution and ecology of influenza A viruses.

If the host population is taken to be a dynamic variable (rather than constant, as conventionally assumed), a wider understanding of the population biology of infectious diseases emerges. In this first part of a two-part article, mathematical models are developed, shown to fit data from laboratory experiments, and used to explore the evolutionary relations among transmission parameters. In the second part of the article, to be published in next week's issue, the models are extended to include indirectly transmitted infections, and the general implications for infectious diseases are considered.

Population biology of infectious diseases: Part II

ContextGlycemic disorders, one of the main risk factors for cardiovascular disease, are associated with activation of oxidative stress.ObjectiveTo assess the respective contributions of sustained chronic hyperglycemia and of acute glucose fluctuations to oxidative stress in type 2 diabetes.Design, Setting, and ParticipantsCase-control study of 21 patients with type 2 diabetes (studied 2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in Montpellier, France.Main Outcome MeasuresOxidative stress, estimated from 24-hour urinary excretion rates of free 8-iso prostaglandin F2α (8-iso PGF2α). Assessment of glucose fluctuations was obtained from continuous glucose monitoring system data by calculating the mean amplitude of glycemic excursions (MAGE). Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose level above preprandial values (mean postprandial incremental area under the curve [AUCpp]). Long-term exposure to glucose was estimated from hemoglobin A1c, from fasting glucose levels, and from mean glucose concentrations over a 24-hour period.ResultsMean (SD) urinary 8-iso PGF2α excretion rates were higher in the 21 patients with diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg of creatinine). In univariate analysis, only MAGE (r = 0.86; P<.001) and AUCpp (r = 0.55; P = .009) showed significant correlations with urinary 8-iso PGF2α excretion rates. Relationships between 8-iso PGF2α excretion rates and either MAGE or AUCpp remained significant after adjustment for the other markers of diabetic control in multiple linear regression analysis (multiple R2 = 0.72 for the model including MAGE and multiple R2 = 0.41 for the model including AUCpp). Standardized regression coefficients were 0.830 (P<.001) for MAGE and 0.700 (P = .003) for AUCpp.ConclusionsGlucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.

https://jamanetwork.com/journals/jama/articlepdf/202670/JPC60001.pdf

Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.

Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures. Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options. Here we use a large-scale epidemic simulation to examine intervention options should initial containment of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2-3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40-50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics.

/pdf/strategies-for-mitigating-an-influenza-pandemic-455cgwlemi.pdf

Strategies for mitigating an influenza pandemic

Model studies of blood-glucose regulation

A complete description of the response of man to large doses of glucose involves the use of more than sixteen rate constants, each varying from one person to the next. It is demonstrated here that the response of blood-glucose concentration (G) as a function of time (t) can be represented adequately by an equation involving only four constants in the equation: G=G0+A e−αt sin ωt. The values of these four constants are defined by the four measurements usually made in an ordinary glucose-tolerance test. The natural frequency ω0=r(ω2 + α2) is shown to represent the product of the rate constants for insulin production due to added glucose and for glucose utilization due to insulin action. On the basis of measurements on over 750 persons, it is suggested that the value of ω0 can be used to distinguish normal from diabetic persons more closely than any other parameter.

https://iopscience.iop.org/article/10.1088/0031-9155/9/2/307/pdf

A Mathematical Model of the Glucose-tolerance test

A glucose oxidase-peroxidase method for continuous automated monitoring of blood glucose has been developed. The response is linear over the range 0-800 mg/100 ml. Sensitivity can be maintained for 24 hr or longer and can be restored by rinsing the analytic system with sulfuric acid to permit studies of longer than 48 hr in duration. A precision of ± 1% can be maintained between rinses for samples containing 100-600 mg of glucose per 100 ml. This method is satisfactorily specific for glucose: The response with other sugars is less than 1% of the response obtained with the same concentration of glucose. Ascorbic acid causes no significant inhibition of the response to glucose. The inhibition by uric acid has been reduced fifty-fold compared to that in other methods. Transit through the sampling catheter and analytic system requires 15 min. Timed from the first detectable response to a change in concentration, 25% of total response is achieved in 30 sec and 90% in 80 sec. Fifty percent of an oscillation with a half-period of 45 sec can be detected; no oscillations this short were observed in records of human blood glucose. Applicability and feasibility of this method have been demonstrated in over 2000 hr of repeated blood glucose recordings in 12 diabetic and 6 normal subjects.

Glucose Oxidase Method for Continuous Automated Blood Glucose Determination

Continuous blood glucose analysis in ambulatory fed subjects. I. General methodology.

Tests of a mathematical model of the blood-glucose regulatory system.

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