Further decrease in glycated hemoglobin following ingestion of a LoBAG30 diet for 10 weeks compared to 5 weeks in people with untreated type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>We previously determined that a weight-maintenance, non-ketogenic diet containing 30% carbohydrate (CHO), 30% protein, 40% fat, (30:30:40) (LoBAG₃₀) decreased glycated hemoglobin (%tGHb) from 10.8 to 9.1% over a 5 week period in subjects with untreated type 2 diabetes. Both the fasting glucose and postprandial glucose area were decreased. Our objective in the present 10-week study was to determine: 1) whether the above results could be maintained, or even improved (suggesting a metabolic adaptation) and 2) whether the subjects would accept the diet for this longer time period. In addition, protein balance, and a number of other blood and urine constituents were quantified at 5 and at 10 weeks on the LoBAG₃₀diet to address metabolic adaptation.</p> <p>Methods</p> <p>Eight men with untreated type 2 diabetes were studied over a 10-week period. Blood was drawn and urine was collected over a 24 hour period at the beginning of the study with subjects ingesting a standard diet of 55% CHO, 15% protein, 30% fat, and at the end of 5 and 10 weeks following ingestion of a LoBAG₃₀diet.</p> <p>Results</p> <p>Body weight was stable. Fasting glucose decreased by 19% at week 5 and 28% at week 10; 24-h total glucose area decreased by 27% at week 5 and 35% at week 10 compared to baseline. Insulin did not change. Mean %tGHb decreased by 13% at week 5, 25% at week 10, and was still decreasing linearly, indicating that a metabolic adaptation occurred. Serum NEFA, AAN, uric acid, urea, albumin, prealbumin, TSH, Total T₃, free T₄, B₁₂, folate, homocysteine, creatinine, growth hormone and renin did not differ between weeks 5 and 10. IGF-1 increased modestly. Urinary glucose decreased; urinary pH and calcium were similar.</p> <p>Conclusions</p> <p>A LoBAG₃₀diet resulted in continued improvement in glycemic control. This improvement occurred without significant weight loss, with unchanged insulin and glucagon profiles, and without deterioration in serum lipids, blood pressure or kidney function. Extending the duration of time on a LoBAG₃₀diet from 5 to 10 weeks had little or no further effect on the hormones and metabolites measured, i.e. a metabolic equilibrium was established.</p

Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition

BACKGROUND: Over the past several years our research group has taken a systematic, comprehensive approach to determining the effects on body function (hormonal and non-hormonal) of varying the amounts and types of proteins, carbohydrates and fats in the diet. We have been particularly interested in the dietary management of type 2 diabetes. Our objective has been to develop a diet for people with type 2 diabetes that does not require weight loss, oral agents, or insulin, but that still controls the blood glucose concentration. Our overall goal is to enable the person with type 2 diabetes to control their blood glucose by adjustment in the composition rather than the amount of food in their diet. METHODS: This paper is a brief summary and review of our recent diet-related research, and the rationale used in the development of diets that potentially are useful in the treatment of diabetes. RESULTS: We determined that, of the carbohydrates present in the diet, absorbed glucose is largely responsible for the food-induced increase in blood glucose concentration. We also determined that dietary protein increases insulin secretion and lowers blood glucose. Fat does not significantly affect blood glucose, but can affect insulin secretion and modify the absorption of carbohydrates. Based on these data, we tested the efficacy of diets with various protein:carbohydrate:fat ratios for 5 weeks on blood glucose control in people with untreated type 2 diabetes. The results were compared to those obtained in the same subjects after 5 weeks on a control diet with a protein:carbohydrate:fat ratio of 15:55:30. A 30:40:30 ratio diet resulted in a moderate but significant decrease in 24-hour integrated glucose area and % total glycohemoglobin (%tGHb). A 30:20:50 ratio diet resulted in a 38% decrease in 24-hour glucose area, a reduction in fasting glucose to near normal and a decrease in %tGHb from 9.8% to 7.6%. The response to a 30:30:40 ratio diet was similar. CONCLUSION: Altering the diet composition could be a patient-empowering method of improving the hyperglycemia of type 2 diabetes without weight loss or pharmacologic intervention

Bayesian parameter estimation in the oral minimal model of glucose dynamics from non-fasting conditions using a new function of glucose appearance

Background and objective The oral minimal model (OMM) of glucose dynamics is a prominent method for assessing postprandial glucose metabolism. The model yields estimates of insulin sensitivity and the meal-related appearance of glucose from insulin and glucose data after an oral glucose challenge. Despite its success, the OMM approach has several weaknesses that this paper addresses. Methods A novel procedure introducing three methodological adaptations to the OMM approach is proposed. These are: (1) the use of a fully Bayesian and efficient method for parameter estimation, (2) the model identification from non-fasting conditions using a generalised model formulation and (3) the introduction of a novel function to represent the meal-related glucose appearance based on two superimposed components utilising a modified structure of the log-normal distribution. The proposed modelling procedure is applied to glucose and insulin data from subjects with normal glucose tolerance consuming three consecutive meals in intervals of four hours. Results It is shown that the glucose effectiveness parameter of the OMM is, contrary to previous results, structurally globally identifiable. In comparison to results from existing studies that use the conventional identification procedure, the proposed approach yields an equivalent level of model fit and a similar precision of insulin sensitivity estimates. Furthermore, the new procedure shows no deterioration of model fit when data from non-fasting conditions are used. In comparison to the conventional, piecewise linear function of glucose appearance, the novel log-normally based function provides an improved model fit in the first 30 min of the response and thus a more realistic estimation of glucose appearance during this period. The identification procedure is implemented in freely accesible MATLAB and Python software packages. Conclusions We propose an improved and freely available method for the identification of the OMM which could become the future standardard for the oral minimal modelling method of glucose dynamics

A glucose-only model to extract physiological information from postprandial glucose profiles in subjects with normal glucose tolerance

Background: Current mathematical models of postprandial glucose metabolism in people with normal and impaired glucose tolerance rely on insulin measurements and are therefore not applicable in clinical practice. This research aims to develop a model that only requires glucose data for parameter estimation while also providing useful information on insulin sensitivity, insulin dynamics and the meal-related glucose appearance (GA). Methods: The proposed glucose-only model (GOM) is based on the oral minimal model (OMM) of glucose dynamics and substitutes the insulin dynamics with a novel function dependant on glucose levels and GA. A Bayesian method and glucose data from 22 subjects with normal glucose tolerance are utilised for parameter estimation. To validate the results of the GOM, a comparison to the results of the OMM, obtained by using glucose and insulin data from the same subjects is carried out. Results: The proposed GOM describes the glucose dynamics with comparable precision to the OMM with an RMSE of 5.1 ± 2.3 mg/dL and 5.3 ± 2.4 mg/dL, respectively and contains a parameter that is significantly correlated to the insulin sensitivity estimated by the OMM (r = 0.7) Furthermore, the dynamic properties of the time profiles of GA and insulin dynamics inferred by the GOM show high similarity to the corresponding results of the OMM. Conclusions: The proposed GOM can be used to extract useful physiological information on glucose metabolism in subjects with normal glucose tolerance. The model can be further developed for clinical applications to patients with impaired glucose tolerance under the use of continuous glucose monitoring data

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

CyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

CyBorD DARA as induction is well tolerated and induces deep responses when used in conjunction with ASCT for MM.Mechanism of action studies indicate that CyBorD DARA enhances macrophage activation, which may play a role in its clinical efficacy. Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The Problem of Pantheism in John Scotus Eruigena

Abstract not availabl