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

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

Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants

Publisher Copyright: © 2022Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.Peer reviewe

Distortion of the Local Magnetic Field Appears to Neither Disrupt Nocturnal Navigation nor Cue Shelter Recognition in the Amblypygid \u3ci\u3eParaphrynus laevifrons\u3c/i\u3e

Many arthropods are known to be sensitive to the geomagnetic field and exploit the field to solve spatial problems. The polarity of the geomagnetic field is used, for instance, as an orientation cue by leafcutter ants as they travel on engineered trails in a rainforest and by Drosophila larvae as they move short distances in search of food. A ubiquitous orientation cue like the geomagnetic field may be especially useful in complex, cluttered environments like rainforests, where the reliability of celestial cues used to navigate in more open environments may be poor. The neotropical amblypygid Paraphrynus laevifrons is a nocturnal arachnid that wanders nightly in the vicinity of its shelter and occasionally travels 30 m or more in the rainforest understory before it returns to its shelter. Here, we conducted a field experiment to determine whether navigation by P. laevifrons is guided by the ambient magnetic field and a complementary laboratory experiment to assess whether a magnetic anomaly could be used to pinpoint the entrance of a shelter. In the field experiment, subjects were fitted with a radio transmitter and a small, powerful magnet or a similar-sized brass disk and displaced 10 m from their shelter. The return rate of magnet-fitted subjects was similar to that of brass-fitted subjects and to that of subjects in an earlier study fitted with only a radio transmitter. In the laboratory experiment, we trained P. laevifrons with a protocol under which the amblypygid Phrynus marginemaculatus rapidly learns—in 1–14 trials over two daily sessions—to associate an olfactory stimulus with access to a shelter. The conditioned stimulus here was a magnetic anomaly characterized by a high total field intensity and a 180° reversal of the polarity of the ambient magnetic field. The magnetic anomaly–shelter contingency was not learned in 50 trials conducted over 10 daily sessions. These results imply prima facie that P. laevifrons does not rely on a magnetic compass to locate or recognize a shelter and, perhaps, that the magnetic field cannot be detected, but alternative explanations are discussed

Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q)

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire. METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean &plusmn; sd age 48&plusmn;10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean &plusmn; sd age 44&plusmn;16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire. RESULTS: Iterative design resulted in 33 items eliciting answers on awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting \u27impaired awareness\u27, \u27symptom level\u27 and \u27symptom frequency\u27. Convergent validity was indicated by strong correlations between the impaired awareness subscale and existing measures of awareness: (Gold: rs =0.75, P&lt;0.01; Clarke: rs =0.76, P&lt;0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P&lt;0.01) and HbA1c (rs =-0.05, non-significant). The impaired awareness subscale and other items discriminated between those with impaired and intact awareness (Gold score). The impaired awareness subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep. CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent, divergent and known groups validity. The impaired awareness subscale and other items contribute significantly to models explaining recall of severe and nocturnal hypoglycaemia. Prospective validation, including determination of a threshold to identify impaired awareness, is now warranted.<br /

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