Aims
To establish whether the risk of hypoglycaemia is greater with 2 consecutive days of very‐low‐calorie diet compared with 2 non‐consecutive days of very‐low‐calorie diet in people with Type 2 ...diabetes.
Methods
This was a non‐blinded randomized parallel group interventional trial of intermittent fasting in adults. The participants had a BMI of 30–45 kg/m2, Type 2 diabetes treated with metformin and/or hypoglycaemic medications and an HbA1c concentration of 50–86 mmol/mol (6.7–10%). The participants followed a 2092–2510‐kJ diet on 2 days per week for 12 weeks. A total of 41 participants were randomized 1:1 to consecutive (n=19) or non‐consecutive (n=22) day fasts, of whom 37 (n=18 and n=19, respectively) were included in the final analysis. The primary outcome was difference in the rate of hypoglycaemia between the two study arms. Secondary outcomes included change in diet, quality of life, weight, lipid, glucose and HbA1c levels, and liver function.
Results
The mean hypoglycaemia rate was 1.4 events over 12 weeks. Fasting increased the rate of hypoglycaemia despite medication reduction (RR 2.05, 95% CI 1.17 to 3.52). There was no difference between fasting on consecutive days and fasting on non‐consecutive days (RR 1.54, 95% CI 0.35 to 6.11). Improvements in weight, HbA1c, fasting glucose and quality of life were experienced by participants in both arms.
Conclusions
In individuals with Type 2 diabetes on hypoglycaemic medications, fasting of any type increased the rate of hypoglycaemia. With education and medication reduction, fewer than expected hypoglycaemic events occurred. Although it was not possible to determine whether fasting on consecutive days increased the risk of hypoglycaemia, an acceptable rate was observed in both arms.
What's new?
The benefits of a very‐low‐calorie diet on glucose homeostasis are now well recognized, and there is a great public awareness of very‐low‐calorie diets. Intermittent ‘5:2’ diets, 2 days of very‐low‐calorie diet per week with ad libitum intake on the other 5 days, have popular appeal but implementation in people with diabetes can be daunting in view of the risk of hypoglycaemia caused by changing requirements for medication with weight loss.
This is the first study of intermittent fasting‐related hypoglycaemia comparing consecutive‐day and non‐consecutive‐day fasting regimens
We describe a novel medication adjustment protocol for individuals with Type 2 diabetes on hypoglycaemic medication after an intermittent fast.
In individuals with Type 2 diabetes on hypoglycaemic medication, intermittent fasting with weekly supervision, hypoglycaemia education and structured medication reduction, resulted in an increased risk of hypoglycaemia on fasting days but a low overall risk of hypoglycaemia. Our protocol can be adopted for future studies on the tolerability and efficacy of intermittent fasting in this population.
Reward and novelty are potent learning signals that critically rely on dopaminergic midbrain responses. Recent findings suggest that although reward and novelty are likely to interact, both functions ...may be subserved by distinct neuronal clusters. We used high-resolution functional magnetic resonance imaging (fMRI) to isolate neural responses to reward and novelty within the human substantia nigra/ventral tegmental area (SN/VTA) complex to investigate the spatial delineation and integration of reward- and novelty-related activity clusters. We demonstrate that distinct clusters within the caudal portion of the medial SN/VTA and the lateral portion of the right SN are predominantly modulated by the anticipation of reward, while a more rostral part of the medial SN/VTA was exclusively modulated by novelty. In addition, the caudal medial SN/VTA cluster embodied an interaction between novelty and reward where novelty selectively increased reward-anticipation responses. This interaction, in turn, was paralleled by differences in the functional-connectivity patterns of these SN/VTA regions. Specifically, novel as compared to familiar reward-predictive stimuli increased the functional connectivity of the medial SN/VTA with mesolimbic regions, including the nucleus accumbens and the hippocampus, as well as with the primary visual cortex. This functional correlation may highlight how afferents of the medial SN/VTA provide integrative information about novelty and reward, or, alternatively, how medial SN/VTA activity may modulate memory processes for novel events associated with rewards.
► High-resolution fMRI delineates responses to novelty and reward in the human SN/VTA. ► Novelty increases reward-anticipation responses in the caudal medial SN/VTA. ► This novelty-related augmentation increases mesolimbic functional connectivity. ► The study highlights the midbrain's integrative role in human behavior and memory.
Update of the Healthy Eating Index: HEI-2010 Guenther, Patricia M., PhD, RD; Casavale, Kellie O., PhD, RD; Reedy, Jill, PhD, RD ...
Journal of the Academy of Nutrition and Dietetics,
04/2013, Letnik:
113, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract The Healthy Eating Index (HEI) is a measure of diet quality in terms of conformance with federal dietary guidance. Publication of the 2010 Dietary Guidelines for Americans prompted an ...interagency working group to update the HEI. The HEI-2010 retains several features of the 2005 version: (a) it has 12 components, many unchanged, including nine adequacy and three moderation components; (b) it uses a density approach to set standards, eg, per 1,000 calories or as a percentage of calories; and (c) it employs least-restrictive standards; ie, those that are easiest to achieve among recommendations that vary by energy level, sex, and/or age. Changes to the index include: (a) the Greens and Beans component replaces Dark Green and Orange Vegetables and Legumes; (b) Seafood and Plant Proteins has been added to capture specific choices from the protein group; (c) Fatty Acids, a ratio of polyunsaturated and monounsaturated to saturated fatty acids, replaces Oils and Saturated Fat to acknowledge the recommendation to replace saturated fat with monounsaturated and polyunsaturated fatty acids; and (d) a moderation component, Refined Grains, replaces the adequacy component, Total Grains, to assess overconsumption. The HEI-2010 captures the key recommendations of the 2010 Dietary Guidelines and, like earlier versions, will be used to assess the diet quality of the US population and subpopulations, evaluate interventions, research dietary patterns, and evaluate various aspects of the food environment.
Successful behavior requires a finely-tuned interplay of initiating and inhibiting motor programs to react effectively to constantly changing environmental demands. One particularly useful paradigm ...for investigating inhibitory motor control is the Stop-signal task, where already-initiated responses to Go-stimuli are to be inhibited upon the rapid subsequent presentation of a Stop-stimulus (yielding successful and unsuccessful Stop-trials). Despite the extensive use of this paradigm in functional neuroimaging, there is no consensus on which functional comparison to use to characterize response-inhibition-related brain activity. Here, we utilize conjunction analyses of successful and unsuccessful Stop-trials that are each contrasted against a reference condition. This conjunction approach identifies processes common to both Stop-trial types while excluding processes specific to either, thereby capitalizing on the presence of some response-inhibition-related activity in both conditions. Using this approach on fMRI data from human subjects, we identify a network of brain structures that was linked to both types of Stop-trials, including lateral-inferior frontal and medial frontal cortical areas and the caudate nucleus. In addition, comparisons with a reference condition matched for visual stimulation identified additional activity in the right inferior parietal cortex that may play a role in enhancing the processing of the Stop-stimuli. Finally, differences in stopping efficacy across subjects were associated with variations in activity in the left anterior insula. However, this region was also associated with general task accuracy (which furthermore correlated directly with stopping efficacy), suggesting that it might actually reflect a more general mechanism of performance control that supports response inhibition in a relatively nonspecific way.
Reward has been shown to promote human performance in multiple task domains. However, an important debate has developed about the uniqueness of reward-related neural signatures associated with such ...facilitation, as similar neural patterns can be triggered by increased attentional focus independent of reward. Here, we used functional magnetic resonance imaging to directly investigate the neural commonalities and interactions between the anticipation of both reward and task difficulty, by independently manipulating these factors in a cued-attention paradigm. In preparation for the target stimulus, both factors increased activity within the midbrain, dorsal striatum, and fronto-parietal areas, while inducing deactivations in default-mode regions. Additionally, reward engaged the ventral striatum, posterior cingulate, and occipital cortex, while difficulty engaged medial and dorsolateral frontal regions. Importantly, a network comprising the midbrain, caudate nucleus, thalamus, and anterior midcingulate cortex exhibited an interaction between reward and difficulty, presumably reflecting additional resource recruitment for demanding tasks with profitable outcome. This notion was consistent with a negative correlation between cue-related midbrain activity and difficulty-induced performance detriments in reward-predictive trials. Together, the data demonstrate that expected value and attentional demands are integrated in cortico-striatal-thalamic circuits in coordination with the dopaminergic midbrain to flexibly modulate resource allocation for an effective pursuit of behavioral goals.
Nonvolatile RAM using resistance contrast in phase-change materials or phase-change RAM (PCRAM) is a promising technology for future storage-class memory. However, such a technology can succeed only ...if it can scale smaller in size, given the increasingly tiny memory cells that are projected for future technology nodes (i.e., generations). We first discuss the critical aspects that may affect the scaling of PCRAM, including materials properties, power consumption during programming and read operations, thermal cross-talk between memory cells, and failure mechanisms. We then discuss experiments that directly address the scaling properties of the phase-change materials themselves, including studies of phase transitions in both nanoparticles and ultrathin films as a function of particle size and film thickness. This work in materials directly motivated the successful creation of a series of prototype PCRAM devices, which have been fabricated and tested at phase-change material cross-sections with extremely small dimensions as low as 3 nm × 20 nm. These device measurements provide a clear demonstration of the excellent scaling potential offered by this technology, and they are also consistent with the scaling behavior predicted by extensive device simulations. Finally, we discuss issues of device integration and cell design, manufacturability, and reliability. PUBLICATION ABSTRACT
Performance in a behavioral task can be facilitated by associating stimulus properties with reward. In contrast, conflicting information is known to impede task performance. Here we investigated how ...reward associations influence the within-trial processing of conflicting information using a color-naming Stroop task in which a subset of ink colors (task-relevant dimension) was associated with monetary incentives. We found that color-naming performance was enhanced on trials with
potential-reward versus those without. Moreover, in
potential-reward trials, typical conflict-induced performance decrements were attenuated if the incongruent word (task-irrelevant dimension) was unrelated to reward. In contrast, incongruent words that were semantically related to reward-predicting ink colors interfered with performance in
potential-reward trials and even more so in no-reward trials, despite the semantic meaning being entirely task-irrelevant. These observations imply that the prospect of reward enhances the processing of task-relevant stimulus information, whereas incongruent
reward-related information in a task-irrelevant dimension can impede task performance.
Intermittent fasting (IF) is a dietary intervention that has been investigated as an alternative weight-loss diet due to conventional approaches having poor long-term adherence. However, the ...macronutrient and micronutrient intake and composition of IF diets have been overlooked. The primary aim of this study was to describe the macronutrient and micronutrient intake of individuals following the 5:2 intermittent fasting diet (IF 5:2).
Thirty eight overweight and obese participants were included from two previous studies of IF 5:2. The participants selected included 27 males and 11 females, with and without Type 2 Diabetes. The dietary intervention, IF 5:2, consisted of two days per week fasting, either consecutive or non-consecutive, and five days per week of habitual intake. Prospectively completed 4-day estimated food records were used to assess macronutrient and micronutrient intake at baseline and week six. The 4-day records were weighted to give a mean daily intake during IF 5:2.
During IF 5:2 the median (25th, 75th quartile) daily macronutrient composition was 22 (19, 24)% from protein, 33 (29, 37)% from fat and 39 (36, 43)% from carbohydrates. The intake (g/d) of carbohydrates and fibre decreased significantly from baseline to week six (p < 0.001) as well as on fasting days compared to non-fasting days (p < 0.001). The intake of calcium, zinc, magnesium and potassium were lower than recommended guidelines. Sodium intake exceeded the suggested daily target. On fasting days, the percent of total energy from protein significantly increased from 21% to 25% (p = 0.02). Despite intake being unrestricted on non-fasting days the energy intake decreased by week six when compared with baseline.
The composition of IF 5:2 was a high protein, moderate fat, low carbohydrate diet with a low fibre intake. Some micronutrients have lower than recommended intake. However, overall IF 5:2 is a safe acceptable weight-loss diet strategy.
Prone positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory ...distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptp
) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptp
, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning.
In forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEP
), (B) the lowest static elastance of the respiratory system (PEEP
), and (C) targeting a positive Ptp
(PEEP
). The primary endpoint was to analyze whether Ptp
differed significantly according to PEEP titration strategy during supine and prone positioning.
Ptp
increased progressively with prone positioning compared with supine positioning as well as with PEEP
and PEEP
compared with PEEP
(positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEP
and PEEP
(positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEP
and PEEP
compared with PEEP
, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions.
Prone positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEP
) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS.
German Clinical Trials Register ( DRKS00017449 ). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449.
The formation of amyloid-containing spherulite-like structures has been observed in some instances of amyloid diseases, as well as in amyloid fibril-containing solutions in vitro. In this article we ...describe the structure and kinetics of bovine insulin amyloid fibril spherulites formed in the presence and absence of different salts and at different salt concentrations. The general spherulite structure consists of radially oriented amyloid fibrils, as shown by optical microscopy and environmental scanning electron microscopy. In the center of each spherulite, a “core” of less regularly oriented material is observed, whose size decreases when the spherulites are formed in the presence of increasing concentrations of NaCl. Similarly, amyloid fibrils form faster in the presence of NaCl than in its absence. A smaller enhancement of the rate of formation with salt concentration is observed for spherulites. These data suggest that both amyloid fibril formation and random aggregation occur concurrently under the conditions tested. Changes in their relative rates result in the different-sized cores observed in the spherulites. This mechanism can be likened to that leading to the formation of spherulites of polyethylene, in agreement with observations that polypeptide chains under partially denaturing conditions can exhibit behavior not dissimilar to that of synthetic polymers.
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