Anna R. Kahkoska

ISPAD Clinical Practice Consensus Guidelines 2018 Definition, epidemiology and classification of diabetes in children and adolescents

Diagnostic criteria for all types of diabetes in children and adolescents are based on laboratory measurement of plasma glucose levels (BGL) and the presence or absence of symptoms (E). Finger prick BGL testing should not be used to diagnose diabetes (E). A marked elevation of the BGL confirms the diagnosis of diabetes, including a random plasma glucose concentration ≥11.1 mmol/L (200 mg/dl) or fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) in the presence of overt symptoms. This article is protected by copyright. All rights reserved.

Bioresponsive transcutaneous patches

Transdermal drug delivery systems that utilize transcutaneous patches of arrayed microneedles have attracted increasing interest in medical practice as an alternative method to hypodermic injection. Over the past ten years, research has focused on leveraging physiological signals associated with diseases or skin-specific tissues to create bioresponsive patches that release drug directly in response to an internally-generated stimulus. This review surveys the recent advances in the development and use of bioresponsive transcutaneous patches for on-demand smart and precise drug delivery, exploiting different physiological signals including pH, serum glucose levels, and enzyme activity. The clinical potential of these devices, including challenges and opportunities, is also discussed.

Insulin-Responsive Glucagon Delivery for Prevention of Hypoglycemia

Hypoglycemia, the state of abnormally low blood glucose level, is an acute complication of insulin and sulfonylurea therapy in diabetes management. Frequent insulin dosing and boluses during daily diabetes care leads to an increased risk of dangerously low glucose levels, which can cause behavioral and cognitive disturbance, seizure, coma, and even death. This study reports an insulin-responsive glucagon delivery method based on a microneedle (MN)-array patch for the prevention of hypoglycemia. The controlled release of glucagon is achieved in response to elevated insulin concentration by taking advantage of the specific interaction between insulin aptamer and target insulin. Integrating a painless MN-array patch, it is demonstrated that this insulin-triggered glucagon delivery device is able to prevent hypoglycemia following a high-dose insulin injection in a chemically induced type 1 diabetic mouse model.

Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps

Purpose of ReviewThis review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.Recent FindingsWeight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited.SummaryThere is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

Polymeric microneedles for transdermal protein delivery

&NA; The intrinsic properties of therapeutic proteins generally present a major impediment for transdermal delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal protein delivery. The clinical potential and future translation of MNs are also discussed. Graphical abstract Figure. No caption available.

Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework

As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will ‘close the loop’ between blood glucose monitoring and automated insulin delivery and may transform day‐to‐day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed‐loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed‐loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed‐loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non‐restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed‐loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long‐term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management.

Bioresponsive Microneedles with a Sheath Structure for H2O2 and pH Cascade-Triggered Insulin Delivery

Self-regulating glucose-responsive insulin delivery systems have great potential to improve clinical outcomes and quality of life among patients with diabetes. Herein, an H2 O2 -labile and positively charged amphiphilic diblock copolymer is synthesized, which is subsequently used to form nano-sized complex micelles (NCs) with insulin and glucose oxidase of pH-tunable negative charges. Both NCs are loaded into the crosslinked core of a microneedle array patch for transcutaneous delivery. The microneedle core is additionally coated with a thin sheath structure embedding H2 O2 -scavenging enzyme to mitigate the injury of H2 O2 toward normal tissues. The resulting microneedle patch can release insulin with rapid responsiveness under hyperglycemic conditions owing to an oxidative and acidic environment because of glucose oxidation, and can therefore effectively regulate blood glucose levels within a normal range on a chemically induced type 1 diabetic mouse model with enhanced biocompatibility.

Core–Shell Microneedle Gel for Self-Regulated Insulin Delivery

A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

Photoacoustic Drug Delivery

Photoacoustic (PA) technology holds great potential in clinical translation as a new non-invasive bioimaging modality. In contrast to conventional optical imaging, PA imaging (PAI) enables higher resolution imaging with deeper imaging depth. Besides applications for diagnosis, PA has also been extended to theranostic applications. The guidance of PAI facilitates remotely controlled drug delivery. This review focuses on the recent development of PAI-mediated drug delivery systems. We provide an overview of the design of different PAI agents for drug delivery. The challenges and further opportunities regarding PA therapy are also discussed.

Association of Race and Ethnicity With Glycemic Control and Hemoglobin A1c Levels in Youth With Type 1 Diabetes

Key Points Question Is there evidence for racial/ethnic health inequity with respect to longitudinal patterns of glycemic control among youth with type 1 diabetes? Findings In a longitudinal cohort study of 1313 youths (aged <20 years) with type 1 diabetes, patients with black race or Hispanic ethnicity were at higher risk of being in the highest and most rapidly increasing hemoglobin A1c trajectory group over 9 years after diabetes diagnosis when compared with non-Hispanic white patients. These associations persisted only among male patients and those with diagnosis at age 9 years or younger. Meaning There is health inequity with regard to glycemic control, particularly among young nonwhite male patients and nonwhite youth diagnosed earlier in life.