Incorporating social determinants of health into the clinical management of type 2 diabetes

Type 2 diabetes (T2DM) is increasing in global and national prevalence. It is more common among people with poor social determinants of health (SDoH). Furthermore, SDoH are known to influence health related choice, and therefore the glycaemic management of people with T2DM. There is a growing body of evidence affirming an irrefutable relationship between SDoH and T2DM. Currently SDoH are considered at a population level, whereas T2DM is usually managed individually. Assessing and addressing SDoH related barriers, at an individual, clinical level may contribute to improved glycaemic management for people with T2DM. Developing an approach to assess SDoH related management barriers, and incorporating it into usual clinical care will allow insight into ‘nonclinical’ obstacles to self-management. Additionally, investigation into strategies to address the identified barriers will extend and contextualise this approach, and could broaden and augment current efforts to improve glycaemic management for people with T2DM. An exploratory, descriptive research design will facilitate the exploration of the most appropriate methods and strategies for incorporating SDoH into clinical practice. These approaches can then be trialled and evaluated to inform an evidence-based approach for this addition to the usual clinical care of people with T2DM. This presentation will describe a current research project that is investigating how SDoH can be incorporated into the clinical management of T2DM, and discuss the findings so far

Acute hypoglycemia impairs executive cognitive function in adults with and without type 1 diabetes

OBJECTIVE: Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. RESEARCH DESIGN AND METHODS: Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). RESULTS: Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. CONCLUSIONS: Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed

100 years on: The impact of the discovery of insulin on clinical outcomes

Throughout history, up to the early part of the 20th century, diabetes has been a devastating disorder, particularly when diagnosed in childhood when it was usually fatal. Consequently, the successful pancreatic extraction of insulin in 1921 was a miraculous, life-changing advance. In this review, the truly transformative effect that insulin has had on the lives of people with type 1 diabetes and on those with type 2 diabetes who are also dependent on insulin is described, from the time of its first successful use to the present day. We have highlighted in turn how each of the many facets of improvements over the last century, from advancements in the properties of insulin and its formulations to the evolution of different methods of delivery, have led to continued improvement in clinical outcomes, through the use of illustrative stories from history and from our own clinical experiences. This review concludes with a brief look at the current challenges and where the next century of technological innovation in insulin therapy may take us

Effects of Acute Insulin-Induced Hypoglycemia on Indices of Inflammation Putative mechanism for aggravating vascular disease in diabetes

OBJECTIVE: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry. RESULTS: In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P ≤ 0.02). Inflammation was triggered with CD40 expression increasing maximally at 24 h (3.13 ± 2.3% vs. 2.06 ± 1.0%) after hypoglycemia (P = 0.009). Both sCD40L and hsCRP (P = 0.02) increased with a nonsignificant rise in vWF and tPA, indicating a possible endothelial effect. A reduction in sCD40L, tPA, and P-selectin occurred during euglycemia (P = 0.03, P ≤ 0.006, and P = 0.006, respectively). In type 1 diabetes, both CD40 expression (5.54 ± 4.4% vs. 3.65 ± 1.8%; P = 0.006) and plasma sCD40L concentrations increased during hypoglycemia (peak 3.41 ± 3.2 vs. 2.85 ± 2.8 ng/ml; P = 0.03). Platelet-monocyte aggregation also increased significantly at 24 h after hypoglycemia (P = 0.03). A decline in vWF and P-selectin occurred during euglycemia (P ≤ 0.04). CONCLUSIONS: Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury

Metabolic and enzymatic changes associated with carbon mobilization, utilization and replenishment triggered in grain amaranth (Amaranthus cruentus) in response to partial defoliation by mechanical injury or insect herbivory

Background: Amaranthus cruentus and A. hypochondriacus are crop plants grown for grain production in subtropical countries. Recently, the generation of large-scale transcriptomic data opened the possibility to study representative genes of primary metabolism to gain a better understanding of the biochemical mechanisms underlying tolerance to defoliation in these species. A multi-level approach was followed involving gene expression analysis, enzyme activity and metabolite measurements. Results: Defoliation by insect herbivory (HD) or mechanical damage (MD) led to a rapid and transient reduction of non-structural carbohydrates (NSC) in all tissues examined. This correlated with a short-term induction of foliar sucrolytic activity, differential gene expression of a vacuolar invertase and its inhibitor, and induction of a sucrose transporter gene. Leaf starch in defoliated plants correlated negatively with amylolytic activity and expression of a β-amylase-1 gene and positively with a soluble starch synthase gene. Fatty-acid accumulation in roots coincided with a high expression of a phosphoenolpyruvate/phosphate transporter gene. In all tissues there was a long-term replenishment of most metabolite pools, which allowed damaged plants to maintain unaltered growth and grain yield. Promoter analysis of ADP-glucose pyrophosphorylase and vacuolar invertase genes indicated the presence of cis-regulatory elements that supported their responsiveness to defoliation. HD and MD had differential effects on transcripts, enzyme activities and metabolites. However, the correlation between transcript abundance and enzymatic activities was very limited. A better correlation was found between enzymes, metabolite levels and growth and reproductive parameters. Conclusions: It is concluded that a rapid reduction of NSC reserves in leaves, stems and roots followed by their long-term recovery underlies tolerance to defoliation in grain amaranth. This requires the coordinate action of genes/enzymes that are differentially affected by the way leaf damage is performed. Defoliation tolerance in grain is a complex process that can’t be fully explained at the transcriptomic level only

DAC-h3: A Proactive Robot Cognitive Architecture to Acquire and Express Knowledge About the World and the Self

This paper introduces a cognitive architecture for a humanoid robot to engage in a proactive, mixed-initiative exploration and manipulation of its environment, where the initiative can originate from both the human and the robot. The framework, based on a biologically-grounded theory of the brain and mind, integrates a reactive interaction engine, a number of state-of-the art perceptual and motor learning algorithms, as well as planning abilities and an autobiographical memory. The architecture as a whole drives the robot behavior to solve the symbol grounding problem, acquire language capabilities, execute goal-oriented behavior, and express a verbal narrative of its own experience in the world. We validate our approach in human-robot interaction experiments with the iCub humanoid robot, showing that the proposed cognitive architecture can be applied in real time within a realistic scenario and that it can be used with naive users

Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed

The motor theory of speech perception holds that we perceive the speech of another in terms of a motor representation of that speech. However, when we have learned to recognize a foreign accent, it seems plausible that recognition of a word rarely involves reconstruction of the speech gestures of the speaker rather than the listener. To better assess the motor theory and this observation, we proceed in three stages. Part 1 places the motor theory of speech perception in a larger framework based on our earlier models of the adaptive formation of mirror neurons for grasping, and for viewing extensions of that mirror system as part of a larger system for neuro-linguistic processing, augmented by the present consideration of recognizing speech in a novel accent. Part 2 then offers a novel computational model of how a listener comes to understand the speech of someone speaking the listener's native language with a foreign accent. The core tenet of the model is that the listener uses hypotheses about the word the speaker is currently uttering to update probabilities linking the sound produced by the speaker to phonemes in the native language repertoire of the listener. This, on average, improves the recognition of later words. This model is neutral regarding the nature of the representations it uses (motor vs. auditory). It serve as a reference point for the discussion in Part 3, which proposes a dual-stream neuro-linguistic architecture to revisits claims for and against the motor theory of speech perception and the relevance of mirror neurons, and extracts some implications for the reframing of the motor theory

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

Association Between Raised Inflammatory Markers and Cognitive Decline in Elderly People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE-To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes. RESEARCH DESIGN AND METHODS-A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing. RESULTS-Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, R,6 remained associated with three of the cognitive tests and with g. CONCLUSIONS-In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline. Diabetes 59:710-713, 201