Current Diabetes Reviews - Current Issue

Cell culture plays a crucial role in addressing fundamental research questions, particularly in studying insulin resistance (IR) mechanisms. Multiple in vitro models are utilized for this purpose, but their technical distinctions and relevance to in vivo conditions remain unclear. This study aims to assess the effectiveness of existing in vitro models in inducing IR and their ability to replicate in vivo IR conditions.

The role of 3-phosphoinositide-dependent kinase 1 (PDK1) has been well-documented in the development of diabetes. This review offers a thorough examination of its composition and associated routes, specifically focusing on insulin signaling and glucose processing. By examining the precise connection between PDK1 and diabetes, various strategies specifically targeting PDK1 were also investigated. Additionally, recent discoveries from mouse models were compiled where PDK1 was knocked out in certain tissues, which demonstrated encouraging outcomes for focused treatments despite the absence of any currently approved clinical PDK1 activators. Moreover, the dual nature of PDK1 activation was discussed, encompassing both anti-diabetic and pro-oncogenic effects. Hence, the development of a PDK1 modifier is of utmost importance, as it can activate anti-diabetic pathways while inhibiting pro-oncogenic pathways, thus aiding in the treatment of diabetes. In general, PDK1 presents a noteworthy opportunity for future therapeutic strategies in the treatment of diabetes.

Dementia is the primary cause of disability and dependence among the elderly population worldwide. The population living with dementia is anticipated to double in the next 17 years. Recent studies show the fact that compared to people without diabetes, people with Type 2 Diabetes (T2D) have about a 60% increased chance of developing dementia. In addition to cholinergic function being downregulated, improper insulin signalling also has a negative impact on synaptic plasticity and neuronal survival. Type 2 diabetes and dementia share various similar pathophysiological components. The ageing of the population and the ensuing rise in dementia prevalence are both results of ongoing medical advancements. It is possible that restoring insulin signaling could be a helpful therapy against dementia, as it is linked to both diminished cognitive function and the development of dementia, including AD. This review article comprehensively focused on scientific literature to analyze the relationship of Dementia with diabetes, recent experimental studies, and insight into incretin-based drug therapy for diabetes-related dementia.

Several epidemiological studies have appreciated the impact of “duration” and “level” of hyperglycemia on the initiation and development of chronic complications of diabetes. However, glycemic profiles could not fully explain the presence/absence and severity of diabetic complications. Genetic issues and concepts of “hyperglycemic memory” have been introduced as additional influential factors involved in the pathobiology of late complications of diabetes. In the extended phase of significant diabetes randomized, controlled clinical trials, including DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control at the early time around the diabetes onset could maintain its protective or detrimental impact throughout the following diabetes course.

There is no reliable indication of the mechanism by which the transient exposure to a given glucose concentration level could evoke a consistent cellular response at target tissues at the molecular levels. Some biological phenomena, such as the production and the concentration of advanced glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C (PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways, may be accountable for the development of hyperglycemic memory. This work summarizes evidence from previous experiments that may substantiate the hyperglycemic memory soundness by its justification in molecular terms.

In light of the escalating global concern surrounding diabetes mellitus, contemporary medical practices predominantly hinge on pharmaceutical interventions, accompanied by inherent side effects and enduring limitations. This investigation accentuates a discernible research void regarding the amalgamation of Ayurvedic principles an age-old traditional medical system with prevalent approaches to diabetes management. Despite Ayurveda's promising potential in furnishing a comprehensive and personalized strategy for diabetes treatment, the imperative for further research and collaboration between Ayurvedic practitioners and contemporary healthcare professionals becomes evident.

Existing scholarly works underscore the potential advantages of Ayurveda in delivering holistic diabetes care, encompassing not only glycemic control but also fostering overall well-being. Nevertheless, a closer examination reveals specific limitations, challenges, and gaps in current research, necessitating targeted efforts to enable a more exhaustive exploration of Ayurvedic interventions within diabetes management. This comprehensive review scrutinizes Ayurvedic recommendations pertaining to dietary practices, lifestyle adjustments, and herbal therapeutics, shedding light on their plausible efficacy. It serves as a clarion call for heightened research endeavors, aiming to bridge existing gaps and carve a pathway toward an integrated, patient-centric paradigm in diabetes care. In summary, as diabetes prevalence continues to rise globally, the study underscores the limitations of current pharmaceutical-centric approaches and highlights the need for extensive research and collaboration to unlock the full potential of Ayurvedic principles in providing a more holistic and personalized framework for diabetes management. The review navigates through Ayurvedic recommendations, emphasizing the urgency for intensified research efforts to fill existing gaps and pave the way for a seamlessly integrated, patient-focused approach to diabetes care.

Cardiovascular complications are a primary focus in the clinical management of type 2 diabetes, as they are the leading causes of disability and mortality in individuals with diabetes. Insulin resistance and endothelial dysfunction commonly coexist in diabetic patients. An increasing body of research indicates a reciprocal and interconnected association between endothelial function and insulin resistance. Insulin resistance can manifest in two distinct forms: endothelial and metabolic, with the former predominantly affecting vascular endothelial cells and the latter primarily impacting peripheral cells. The understanding of endothelial insulin resistance is crucial in comprehending the pathophysiology of cardiovascular complications in type 2 diabetes. Hence, the objective of this study is to examine the correlations, interplays, and molecular pathways linking endothelial insulin resistance and metabolic insulin resistance, with the aim of offering novel insights and scholarly resources for the prevention and management of diabetic vascular complications.