Inflammatory mediators have an established role in inducing insulin resistance and promoting hyperglycemia. In turn, hyperglycemia has been argued to drive immune cell dysfunction as a result of mitochondrial dysfunction. Here, the authors review the evidence challenging this view. First, it is pointed out that inflammatory mediators are known to induce altered mitochondrial function. In this regard, critical care patients suffer both an elevated inflammatory tone as well as hyperglycemia, rendering it difficult to distinguish between the effects (...) of inflammation and hyperglycemia. Second, emerging evidence indicates that a decrease in mitochondrial respiration and an increase in reactive oxygen species (ROS) production are not necessarily manifestations of pathology, but adaptations taking shape as the mitochondria is abdicating its adenosine triphosphate (ATP)‐producing function (which is taken over by glycolysis) and instead becomes “retooled” for an immunological role. Collectively, these observations challenge the commonly held belief that acute hyperglycemia induces mitochondrial damage leading to immune cell dysfunction. (shrink)

Objective Diabetes is a global public health concern. Management of diabetes depends on successful implementation of strategies to alleviate decline in executive functions (EFs), a characteristic of diabetes progression. In this review, we describe recent research on the relationship between diabetes and EF, summarize the existing evidence, and put forward future research directions and applications. Methods Herein, we provide an overview of recent studies, to elucidate the relationship between DM and EF. We identified new screening objectives, management tools, and intervention (...) targets for diabetes management. We also discuss the implications for clinical practice. Results In both types 1 and 2 diabetes mellitus (DM), hyperglycemia substantially impairs EF in people of all age groups and ethnicities. Hypoglycemia can similarly impair EF. Interestingly, a decline in EF contributes to DM progression. Glucose dysregulation and EF decline exacerbate each other in a vicious cycle: poor blood glucose control, impaired EF, diabetes management task failure, then back to poor blood glucose control. Many pathophysiological indexes (e.g., obesity, metabolic index, inflammatory and immune factors), neuropsychological indexes (e.g., compliance, eating habits, physical exercise, sleep, and depression), and genetic factors are changed by this pathological interaction between DM and EF. These changes can provide insight into the pathophysiological mechanisms of diabetes-related EF decline. Conclusion Further studies, including large-scale prospective and randomized controlled trials, are needed to elucidate the mechanism of the interaction between diabetes and EF and to develop novel strategies for breaking this cycle. (shrink)

Type 2 diabetes mellitus (T2DM) is a multifaceted chronic condition characterized by insulin resistance and hyperglycemia. This review synthesizes evidence on the influence of lifestyle factors such as diet, physical activity, and stress on the development and progression of T2DM. It highlights the intricate relationship between obesity, insulin resistance, and β-cell dysfunction, with a particular focus on the role of psychological stress in exacerbating disease outcomes. Through the analysis of recent studies, the review explores how lifestyle interventions, including dietary (...) changes, exercise, and stress management, can improve glycemic control and reduce complications. This comprehensive review underscores the need for integrated, personalized management strategies in T2DM care, emphasizing the importance of addressing both physiological and psychological factors to optimize outcomes and prevent complications. (shrink)

The aetio-pathogenetic sequences and the physio-pathological patterns of diabetes, emphysema, cholera, circulatory shock and thrombosis have been analysed with respect to an evolutionary interpretation. The diseases, although reflecting alterations of processes that can always be described in physico-chemical language, occur only at the level of biological systems which reflects the decodification of genomic project: the teleonomic projects that have been developed during evolution. The concepts of evolutionary emergence and of downward causation have been used to discuss the relationship between the (...) molecular events responsible for the initiation of the disease, and the subsequent events responsible for the aetio-pathogenesis, for the systemic disarrangement and for the additional alterations of tissues and cells independent of the initial molecular events. In diabetes the systemic disarrangement, glycosuria and hyperglycemia, reflect the evolutionary emergence of the processes regulating carbohydrate metabolism, whereas the cardiovascular and neurological alterations are effects of the systemic disarrangement by a mechanism of downward causation. The complexity of the aetio-pathogenesis and of the physio-pathological patterns of diseases is due to the generation of information during the evolution of multi-hierarchical entities. The evolutionary epistemology approach is useful to explain the behaviour of complex systems. (shrink)

An embedded automaton is introduced to monitor the whole glycolysis process in pancreatic β-cell and it is a hybridization of both non-deterministic finite automaton and push-down automaton. The set of irreversible and reversible reactions in the glycolysis process are related to non-deterministic finite automaton and push-down automaton respectively. The embedded automaton is used to observe the glucose metabolism with the states of acceptance and rejection. The acceptance state of the embedded automaton depicts the normal level of glycolysis and insulin secretion. (...) The rejection state of this machine shows inhibition of glycolysis which obstructs the secretion of insulin. The subsequent low level of insulin leads to the high blood glucose level also known as hyperglycemia. In this study, the designed machine can be used to regulate the process of glycolysis through a group of regulatory glycolytic enzymes for the treatment of Diabetes mellitus at molecular level. (shrink)

Glycogen is synthesized and stored to maintain postprandial blood glucose homeostasis and to ensure an uninterrupted energy supply between meals. Although the regulation of glycogen turnover has been well studied, the effects of glycogen on aging and disease development have been largely unexplored. In Caenorhabditis elegans fed a high sugar diet, glycogen potentiates resistance to oxidants, but paradoxically, shortens lifespan. Depletion of glycogen by oxidants or inhibition of glycogen synthesis extends the lifespan of worms by an AMPK‐dependent mechanism. Thus, glycogen (...) is not merely an inert storage molecule, but also an active regulator of energy balance and aging. Its depletion by oxidants may be beneficial in the treatment of hyperglycemia and glycogen‐related diseases. (shrink)

Children diagnosed with type 1 diabetes mellitus (T1DM) are at risk for neurocognitive sequelae, including impaired attention functioning. The specific nature of the cognitive deficit varies; current literature underscores early age of diabetes diagnosis and increased disease duration as primary risk factors for this neurocognitive decline. Forty-three children with T1DM were evaluated for Attention Deficit/Hyperactivity Disorder (ADHD) symptomatology using the MOXO continuous performance test (MOXO-CPT) performed during a routine outpatient evaluation. The study cohort demonstrated a significant decline in all four (...) domains of attention functioning. The effect was most pronounced with early age at T1DM diagnosis, a longer disease duration and with poorer glycemic control (represented by higher HbA1c values). With increased disease duration (of 5 plus years), acute hyperglycemia was associated with inattention in the real-time setting. These findings highlight the need for routine screening of neurocognitive function in children with T1DM so that early intervention can be employed during this crucial period of cognitive development. (shrink)

Forecasting blood glucose values for patients can help prevent hypoglycemia and hyperglycemia events in advance. To this end, this study proposes an intelligent ensemble deep learning system to predict BG values in 15, 30, and 60 min prediction horizons based on historical BG values collected via continuous glucose monitoring devices as an endogenous factor and carbohydrate intake and insulin administration information as exogenous factors. Although there are numerous deep learning algorithms available, this study applied five algorithms, namely, recurrent neural (...) network, which is optimized for sequence data, and RNN-based algorithms, stacked LSTM, bidirectional LSTM, and gated recurrent unit). Then, a genetic algorithm was applied to the five prediction models to optimize their weights through ensemble techniques and to yield the final predicted BG values. The performance of the proposed model was compared to that of the autoregressive integrated moving average model as a baseline. The results show that the proposed model significantly outperforms the baseline in terms of the root mean square error and continuous glucose error grid analysis. For the valid 29 diabetic patients for the multivariate models, the RMSE was 11.08, 19.25, and 31.30 mg/DL for 15, 30, and 60 min PH, respectively. When the same data were applied to univariate models, the RMSE was 11.28, 19.99, and 33.13 mg/DL for 15, 30, and 60 min PH, respectively. Both the univariate and multivariate models showed a statistically significant difference compared with the baseline at a 5% statistical significance level. Instead of using a model with a single algorithm, applying a GA based on each output of a model with multiple algorithms was found to play a significant role in improving model performance. (shrink)