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

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

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

An Antiretroviral/Zinc Combination Gel Provides 24 Hours of Complete Protection against Vaginal SHIV Infection in Macaques

Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc acetate and micromolar doses of the novel non-nucleoside reverse transcriptase inhibitor MIV-150 for up to 24 h after repeated gel application.Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 µM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h.A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Effect of a LoBAG₃₀ diet on protein metabolism in men with type 2 diabetes. A Randomized Controlled Trial

<p>Abstract</p> <p>Background</p> <p>We previously reported that a weight-maintenance diet with a carbohydrate:protein:fat ratio of 30:30:40%, ingested for 5 weeks, improved blood glucose control in subjects with untreated type 2 diabetes. In this study we also determined that insulin and insulin-like growth factor-I (IGF-I) were increased. In this report we provide further information. Specifically, 24-hour total and individual amino acids, glucagon and cortisol data are provided. In addition, we determined whether these multiple effectors resulted in a positive nitrogen balance and an increase in fat-free mass. Insulin and IGF-I should stimulate protein accumulation. An increase in amino acids, particularly branched chain amino acids, should facilitate this, whereas glucagon and cortisol could have adverse effects in this regard.</p> <p>Methods</p> <p>Eight men with untreated type 2 diabetes were studied. A randomized crossover design was used. Data were obtained before and after 5 weeks on a control diet (55% carbohydrate:15% protein:30% fat) and on a 30% carbohydrate:30% protein:40% fat diet. Nitrogen balance and body composition were determined at the beginning and end of each dietary intervention.</p> <p>Results</p> <p>As expected, the mean 24-hour total amino acid area response was higher after ingesting the 30:30:40 diet. However, the increase was only statistically significant for the branched chain amino acids, and phenylalanine and tyrosine. The 24-hour cortisol profile was unchanged. Glucagon was increased. Nitrogen balance was positive. Body weight was stable. Body composition and computed tomography data indicate no change in the fat-free mass.</p> <p>Conclusion</p> <p>This high protein, low carbohydrate diet induced a metabolic milieu which strongly favors a positive protein balance, and a positive balance was present. However, an increase in lean (protein) mass was not documented. Whether such a diet in people with type 2 diabetes is useful in preventing or delaying the loss of total lean body mass and/or sarcopenia associated with aging remains to be determined.</p