Pancreatic fat in type 2 diabetes: Causal or coincidental?

Type 2 diabetes (T2D) is a multifactorial metabolic disorder affecting more than 450 million people across the globe. With the increasing prevalence of T2D and obesity, the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D. Over the past decade and a half, a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease. While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism, a few reports suggest a lack of such association. Pancreatic fat has also been linked with genetic risk of developing T2D, prediabetes, reduced insulin secretion, and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome. With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function, our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved. This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.     

Buccal spray insulin (Oralgen) for type 2 diabetes: what evidence?

INTRODUCTION: The achievement of a good glycemic control and, in particular, the management of postprandial hyperglycemia represent the most significant treatment target for the management of diabetes. Multiple daily insulin injections are often still required to gain the treatment goals. Since the noncompliance with injected insulin therapy causes a slowdown in the process of glycemic compensation, novel non-injectable insulin formulations have been developed. Oral spray insulin (Oralgen) is a tasteless liquid formulation that provides insulin absorption via buccal mucosa. AREAS COVERED: To elucidate the current status of Oralgen in type 2 diabetes patients, studies of pharmacodynamic and pharmacokinetic and clinical trials are reviewed. EXPERT OPINION: The 'psychological insulin resistance,' represented by the reluctance of both patients and health-care professionals to initiate insulin therapy, could be won by alternative routes of insulin administration, improving patients' compliance. In particular, Oralgen seems to be suitable to manage the postprandial hyperglycemia without hypoglycemic risk, although no comparative studies with rapid-acting insulin analogs and no randomized controlled trials in large cohort subjects with type 2 diabetes are available to date.     

Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

ObjectivesThe aim of study was to evaluate the relationship between serum cystatin C and insulin resistance (IR) in type 1 diabetic patients being the participants of Poznan Prospective Study.Design and methodsThe study was performed on 71 Caucasian patients (46 men); with type 1 diabetes, who were recruited into the Poznan Prospective Study, at the age of 39 ± 6.1 meanly, and treated with intensive insulin therapy since the onset of the disease. The follow-up period and diabetes duration were 15 ± 1.6 years. Insulin resistance (IR) was assessed by estimated glucose disposal rate (eGDR) calculation with cut-off point 7.5 mg/kg/min. Patients were divided into two groups, according to the presence or absence of IR.ResultsFrom among 71 patients, 31 patients (43.7%) presented decreased sensitive to insulin with eGDR below 7.5 mg/kg/min. Patients who had eGDR < 7.5 mg/kg/min (insulin resistant), compared with subjects with eGDR > 7.5 mg/kg/min (insulin sensitive), had higher level of serum cystatin C [0.59 (IQR:0.44–0.84) vs 0.46 (IQR:0.37–0.55) mg/L, p = 0.009]. A significant negative correlation between cystatin C and eGDR was revealed (Rs = − 0.39, p = 0.001). In regression model cystatin C was related to insulin resistance, adjusted for sex, BMI, eGFR and duration of diabetes [OR 0.03 (0.001–0.56), p = 0.01].ConclusionsHigher level of serum cystatin C is related to decreased insulin sensitivity in patients with type 1 diabetes. This relationship seems to have an important clinical implication.     

Dopexamine: immunomodulatory,hemodynamic, or both?

ICU patients are identified as targets for quality of care and patient safety improvement strategies. Critically ill patients are at high risk for complications due to the complex and invasive nature of critical care. Several reports in the literature describe initiatives aiming to zero the healthcare-associated infection rate. We discuss the results of a study assessing a systematic team approach with very aggressive interventions surrounding the Institute for Healthcare Improvement Central Line-associated Blood Stream Infection bundle, which obtained a successful reduction of the rates. In addition, we discuss why some healthcare-associated infections are not fully preventable and the different reasons for this, the identification of which would be a cornerstone of quality improvement and safety promotion initiatives in critically ill patients.     

Stalking: evil, illness, or both?

This article considers the definition and impact of stalking behaviours, and describes recent examples, as well as the characteristics and behaviours of stalkers. Current legal frameworks and their application are reviewed, including recent changes in the law. Management and treatment issues as well as attention to minimising a violent outcome and general ethical matters are discussed.     

Re-examining insulin compared to non-insulin therapies for type 2 diabetes: when in the disease trajectory is insulin preferable?

In patients with type 2 diabetes secondary to excess nutrients and energy balance, relative – not absolute – insulin deficiency plays a key role in disease development and progression. Although patients with type 2 diabetes who have features of insulin resistance would usually have hyperinsulinemia, insulin therapy remains recommended by guidelines particularly when patients fail to achieve glycemic goals. This approach does not prevent complications particularly macrovascular complications. This raises a controversial question regarding the benefit of using exogenous insulin for glycemic control in patients with type 2 diabetes who have features of insulin resistance. To address this concern, the authors performed a literature search looking for either randomized trials or meta-analyses directly comparing exogenous insulin to non-insulin therapy in the treatment of patients with type 2 diabetes. Our main outcomes of interest were effect on glycemic control and insulin resistance at various time points in the usual trajectory of type 2 diabetes. In trials investigating early short-term initiation of intensive insulin therapy, insulin therapy was beneficial in rapidly achieving glycemic control and reversing glucotoxicity. Following the initial 2 weeks to 3 months of adequate glycemic control in patients on intensive insulin therapy, there is little evidence that continuing insulin therapy provides greater glycemic control or improves insulin resistance beyond what can be achieved with other therapies. In conclusion, long-term insulin use appears neutral if not potentially harmful with respect to insulin resistance and cardiovascular outcomes. While this review has limitations and should be dealt cautiously, it raises questions regarding the benefit of insulin in patients with type 2 diabetes with features of insulin resistance. Further research is needed to confirm these findings.     

Exercise as ‘precision medicine’ for insulin resistance and its progression to type 2 diabetes: a research review

Type 2 diabetes and obesity epidemics are in effect in the United States and the two pathologies are linked. In accordance with the growing appreciation that ‘exercise is medicine,’ it is intuitive to suggest that exercise can play an important role in the prevention and/or treatment of these conditions. However, if exercise is to truly be considered as a viable alternative to conventional healthcare prevention/treatment strategies involving pharmaceuticals, it must be prescribed with similar scrutiny. Indeed, it seems reasonable to posit that the recent initiative calling for ‘precision medicine’ in the US standard healthcare system should also be applied in the exercise setting. In this narrative review, we consider a number of explanations that have been forwarded regarding the pathological progression to type 2 diabetes both with and without the concurrent influence of overweight/obesity. Our goal is to provide insight regarding exercise strategies that might be useful as ‘precision medicine’ to prevent/treat this disease. Although the etiology of type 2 diabetes is complex and cause/consequence characteristics of associated dysfunctions have been debated, it is well established that impaired insulin action plays a critical early role. Consequently, an exercise strategy to prevent/treat this disease should be geared toward improving insulin sensitivity both from an acute and chronic standpoint. However, research suggests that a chronic improvement in insulin sensitivity only manifests when weight loss accompanies an exercise intervention. This has resonance because ectopic fat accumulation appears to represent a central component of disease progression regardless of whether obesity is also part of the equation. The cause/consequence characteristics of the relationship between insulin resistance, pathological fat deposition and/or mobilsation, elevated and/or poorly-distributed lipid within myocytes and an impaired capacity to use lipid as fuel remains to be clarified as does the role of muscle mitochondria in the metabolic decline. Until these issues are resolved, a multidimensional exercise strategy (e.g., aerobic exercise at a range of intensities and resistance training for muscular hypertrophy) could provide the best alternative for prevention/treatment.     

Critical illness hyperglycemia: is failure of the beta-cell to meet extreme insulin demand indicative of dysfunction?

In the recent study by Preissig and Rigby in Critical Care, the authors argue that critical illness hyperglycemia in children with both respiratory failure and cardiovascular failure is due to a primary failure of the beta-cell. However, alternative explanations that the failure is secondary to an increase in insulin resistance leading to beta-cell exhaustion, or a negative impact of exogenous glucocorticoid therapy, may be equally likely.     

Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification?

A hallmark of type 2 diabetes is the reduction of pancreatic islet β cell mass through induction of apoptosis and lack of regeneration. In most patients, β cell dysfunction is associated with the presence of extracellular amyloid plaques adjacent to β cells and intracellular toxic oligomers that are comprised of islet amyloid polypeptide (IAPP). In this issue of the JCI, three independent research groups reveal that a functional autophagy system normally prevents the accumulation of toxic IAPP oligomers in human IAPP–expressing murine models. Furthermore, mice expressing human IAPP but deficient for β cell autophagy through genetic deletion of the autophagy initiator ATG7 developed β cell apoptosis and overt diabetes. Together, these studies indicate that autophagy protects β cells from the accumulation of toxic IAPP oligomers and suggest that enhancing autophagy may be a novel target for prevention of type 2 diabetes.