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Type 2 diabetes (T2D) is a multifaceted metabolic disorder associated with distinctive pathophysiological disturbances. One of the pathophysiological risk factors observed in T2D is dysregulation of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Both hormones stimulate insulin secretion by acting postprandially on pancreatic β-cell receptors. Oral glucose administration stimulates increased insulin secretion in comparison with isoglycemic intravenous glucose administration, a phenomenon known as the incretin effect. While the evidence for incretin defects in individuals with T2D is growing, the etiology behind this attenuated incretin effect in T2D is not clearly understood. Given their central role in T2D pathophysiology, incretins are promising targets for T2D therapeutics. The present review synthesizes the recent attempts to explain the biological importance of incretin hormones and explore potential pharmacological approaches that target the incretins.

The concept of metabolically unhealthy vs. healthy obese (MUO vs. MHO) was expanded to non-obese individuals as obesity-related comorbidities exist in a subgroup of metabolically unhealthy vs. healthy normal-weight (MUNW vs. MHNW) . It is unclear if MUNW differs from MHO with respect to cardiometabolic health. Here, we applied a widely accepted definition of metabolic health (JAMA 20285: 2486) and examined differences in cardiometabolic risk factors among 4 subgroups of Korean adults (N=7,594) . Individuals with NW vs. obesity (BMI ≥25 kg/m2) were categorized as either MU or MH if those met one or more of the following criteria: triglyceride ≥150 mg/dl; fasting glucose ≥100 mg/dl; HDL Disclosure M.Seo: None. W.Cho: None. J.Rosenberg: None. L.White: None. J.Kim: n/a.

There is currently a lack of consensus as to what defines exercise and resistance training in the cancer setting and whether current studies comply with exercise guidelines. This study aimed to quantify the available research studies using resistance training exercise interventions in the breast cancer setting for future clinical trial utilization. We systemically reviewed all available resistance exercise studies during and after breast cancer treatment in an attempt to quantify to the prescribed dose and whether regimens aligned with general exercise guidelines to improve functional mobility, body composition, and metabolic function. They were then compared with recommendations set forth by the national committees that create evidence-based exercise guidelines. Fifty studies met the initial criteria, with 35 meeting analysis criteria for evaluation. Fifteen studies evaluated an exercise regimen during cancer treatment, and 20 evaluated a regimen after treatment. The average adherence rates were 84% for all studies. Only 23 studies listed specific exercises used within the protocol. Most exercise regimens relied on open chain movements and machine exercises. Around half of studies met criteria to achieve hypertrophy, and 66% met American College of Sports Medicine exercise guidelines for cancer patients. A minority of breast cancer studies implementing a resistance training exercise regimen prescribed a regimen or specific dose that follows general exercise guidelines. This study highlights a potential deficiency in exercise programs designed for patients with breast cancer, and these findings should be considered in future study design.

Incretin hormones have recently been considered an important pathophysiological factor for T2D in adults and youth due to their role in augmenting insulin secretion (Michaliszyn et al., 2014). It is recognized that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are glucose-dependent hormones released from the gut that stimulate insulin release from pancreatic β-cells (Muscelli et al., 2006). Thus, the insulin response to oral glucose is significantly greater than the intravenous (IV) glucose administration response; this is known as the incretin effect (Michaliszyn et al., 2014). To date, adults with T2D demonstrate a remarkable decrease in the incretin effect (Nauck et al., 1986), whereas there is lack of evidence in pediatric populations. The incretin effect is also associated with β-cell glucose sensitivity (βCGS), attesting incretins as a high-promising target for T2D treatment (Michaliszyn et al., 2014). Utilizing GLP-1 receptor agonists can be advantageous as a therapeutic option for both adults and youth (Tamborlane et al., 2019; Vanderheiden et al., 2016; Yeow et al., 2017). While metformin and insulin were the sole treatment options for Y-T2D prior to FDA approval (in 2019) for the use of GLP-1 agonists, a recent RISE (Restoring Insulin Secretion) clinical trial reported disappointing results that both metformin alone and insulin glargine for three months followed by metformin for nine months were not effective in restoring/preserving β-cell function in youth with prediabetes and T2D (RISE Consortium & RISE Consortium Investigators, 2019). On the contrary, the role of GLP-1 and the efficacy of the GLP-1 receptors in T2D signifies a strong target for potential treatment. Additional clinical trials are warranted to see if monotherapy of GLP-1 agonist vs. combined (metformin + liraglutide) therapy is effective to reserve Y-T2D to prediabetes and/or normal state. More importantly, future research should focus on disease prevention rather than treatment to avoid aggressive complications and metabolic degradations of Y-T2D (RISE Consortium & RISE Consortium Investigators, 2019). Altogether, it would be germane to investigate whether lifestyle changes (diet, physical activity, exercise medicine) can improve the incretin effect in conjunction with glycemic control in youth.

The variation in parameters for childhood metabolic syndrome (MetS) has hindered the development of a consensus for the diagnostic criteria in this group. Despite these inconsistencies, it is accepted that exercise can ameliorate the deleterious effects of MetS. However, direct comparison between aerobic versus resistance exercise on MetS symptomology in adolescents is lacking.Aim of this review was to discuss controversies associated with current MetS operation definitions in adolescents and present a review summarizing longitudinal studies relevant to the influence of aerobic and resistance training on children with MetS.Reviews of PubMed and Web of Science were conducted to identify literature focusing on the influence of aerobic and resistance training on children with MetS. Selected manuscripts featured longitudinal research only.A universally accepted definition of MetS for the pediatric population has yet to be established. As such, consensus regarding diagnostic criteria for MetS among children is lacking despite the presence of various descriptions in the literature. Though studies support the importance of aerobic and resistance exercise to combat comorbidities associated with MetS, longitudinal studies investigating the benefits of each exercise type among adolescents are limited and inconsistent.An improved understanding of the impact of aerobic and resistance training on children with MetS is clinically relevant because it may facilitate more appropriate exercise recommendations for children with MetS. Additional large cohort studies are warranted to determine optimal exercise type.

High glucose concentrations acutely provoke endothelial cell oxidative stress and are suggested to trigger diabetes-related macro- and microvascular injury in humans. Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may each independently alter vascular function and obscure the effect of acute hyperglycaemia per se. Surprisingly, no studies have examined the acute effects of intravenous glucose-induced hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations. In this randomized study of healthy young adults, we compared macrovascular (i.e. brachial artery flow-mediated dilatation, carotid-femoral pulse wave velocity and post-ischaemic brachial artery flow velocity) and microvascular (heart and skeletal muscle perfusion by contrast-enhanced ultrasound) functional responses to euglycaemia and hyperglycaemia. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute intravenous glucose-induced hyperglycaemia enhanced brachial artery flow-mediated dilatation (P = 0.004), increased skeletal muscle microvascular blood volume and flow (P = 0.001), and expanded cardiac muscle microvascular blood volume (P = 0.014). No measure of vascular function changed during octreotide-maintained euglycaemia. Our findings suggest that unlike meal-provoked acute hyperglycaemia, 4 h of intravenous glucose-induced hyperglycaemia enhances brachial artery flow-mediated dilatation, provokes cardiac and skeletal muscle microvascular function, and does not impair aortic stiffness. Previous findings of acute large artery vascular dysfunction during oral glucose or mixed meal ingestion may be due to differences in study populations and meal-induced humoral or neural factors beyond hyperglycaemia per se. (ClinicalTrials.gov number NCT03520569.)

In obese non-diabetic youth, glucose response curve (GRC) and 1-hr glucose concentration during an oral glucose tolerance test (OGTT) represent novel biomarkers for T2D risk. Obese youth with monophasic- vs. biphasic-GRC and 1-hr glucose concentration of ≥155 (Above155) vs.