Characterizing Normal-use Temperature Conditions of Pumped Insulin

In this study, the temperature profiles of insulin pump reservoirs during normal wear conditions across multiple seasons were characterized. Thermocouples secured in reservoirs filled with insulin diluent were loaded in infusion pumps worn by volunteers. Reservoir and ambient environmental temperature data and activity levels were logged during the course of normal daily activities in February (winter), April (spring), and August (summer). Each seasonal data set comprised 7 to 14 days of wear from 3 to 5 volunteers. Reservoir temperature profiles were generally higher than ambient temperatures, likely due to heat transfer from the wearer when the pump was placed close to the body. Temperature conditions inside pump reservoirs fluctuated between 25°C and 37°C regardless of seasonal variations. The average reservoir temperature remained close to 30°C across all seasons, notably lower than used in previously published compatibility and stability protocols (37°C). Results from this study could be utilized to develop more accurate stability and compatibility testing procedures for new insulin formulations and/or delivery devices.     

Hydrogels for oral delivery of therapeutic proteins

In recent years there has been significant new interest in the development of transmucosal (mostly oral) pharmaceutical formulations for the delivery of therapeutic proteins. Emphasis has been given to the molecular design of new carriers for the delivery of insulin, calcitonin and various types of interferons for the treatment of diabetes, osteoporosis, multiple sclerosis and cancer. Most popular carriers include advanced designs of swollen hydrogels prepared from neutral or intelligent polymeric networks. In this review, the most successful of such systems are presented and their promise in the field described.     

Deciphering Brain Insulin Receptor and Insulin‐Like Growth Factor 1 Receptor Signalling

Insulin receptor (IR) and insulin‐like growth factor 1 receptor (IGF1R) are highly conserved receptor tyrosine kinases that share signalling proteins and are ubiquitously expressed in the brain. Central application of insulin or IGF1 exerts several similar physiological outcomes, varying in strength, whereas disruption of the corresponding receptors in the brain leads to remarkably different effects on brain size and physiology, thus highlighting the unique effects of the corresponding hormone receptors. Central insulin/IGF1 resistance impacts upon various levels of the IR/IGF1R signalling pathways and is a feature of the metabolic syndrome and neurodegenerative diseases such as Alzheimer's disease. The intricacy of brain insulin and IGF1 signalling represents a challenge for the identification of specific IR and IGF1R signalling differences in pathophysiological conditions. The present perspective sheds light on signalling differences and methodologies for specifically deciphering brain IR and IGF1R signalling.     

Cognitive dysfunction: An emerging concept of a new diabetic complication in the elderly

The incidence of type 2 diabetes mellitus (T2DM) has risen, and this trend is likely to continue. Recent advances suggest that T2DM is a risk factor for cognitive decline. We are now encountering novel complications of T2DM, namely cognitive dysfunction and dementia. Although the treatment strategy for diabetic patients with neurocognitive dysfunction has received a great deal of attention, the appropriate level of glycemic control for the prevention of the development and/or progression of cognitive decline in elderly diabetic patients remains to be elucidated. Another issue in diabetic treatment in patients with cognitive dysfunction is the selection of medicines. The best choice and combination of antidiabetic medications for the preservation of cognition should also be studied. Ample studies suggest that exercise helps to preserve cognitive function, although existing evidence does not necessarily indicate its effectiveness exclusively in diabetic patients. Exercise is a helpful non‐pharmacological therapy. Considering the progressive aging of the worldwide population, more research to investigate the best way to manage this population is important. Geriatr Gerontol Int 2012; ••: ••–•• .     

A Novel Hierarchal-Based Approach to Measure Insulin Sensitivity and Secretion in At-Risk Populations

Background:The pathogenesis of type 2 diabetes is characterized by insulin resistance and insulin secretory dysfunction. Few existing metabolic tests measure both characteristics, and no such tests are inexpensive enough to enable widespread use.Methods:A hierarchical approach uses 2 down-sampled tests in the dynamic insulin sensitivity and secretion test (DISST) family to first determine insulin sensitivity (SI) using 4 glucose measurements. Second the insulin secretion is determined for only participants with reduced SI using 3 C-peptide measurements from the original test. The hierarchical approach is assessed via its ability to classify 214 individual test responses of 71 females with an elevated risk of type 2 diabetes into 5 bins with equivalence to the fully sampled DISST.Results:Using an arbitrary SI cut-off, 102 test responses were reassayed for C-peptide and unique insulin secretion characteristics estimated. The hierarchical approach correctly classified 84.5% of the test responses and 94.4% of the responses of individuals with increased fasting glucose.Conclusions:The hierarchical approach is a low-cost methodology for measuring key characteristics of type 2 diabetes. Thus the approach could provide an economical approach to studying the pathogenesis of type 2 diabetes, or in early risk screening. As the higher cost test uses the same clinical protocol as the low-cost test, the cost of the additional information is limited to the assay cost of C-peptide, and no additional procedures or callbacks are required.     

Reactive oxygen and nitrogen species disturb Ca2+ oscillations in insulin-secreting MIN6 β-cells

Disturbances in pulsatile insulin secretion and Ca²⁺ oscillations in pancreatic β-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced β-cell function, and ROS/RNS target several Ca²⁺ pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca²⁺ oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca²⁺ oscillations in the MIN6 β-cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) inhibitor thapsigargin modifies the Ca²⁺ response to high concentrations of ROS/RNS. Further, thapsigargin produces effects that resemble those elicited by moderate ROS/RNS production. These results indicate that ROS/RNS interfere with endoplasmic reticulum Ca²⁺ handling. This idea is supported by theoretical studies using a mathematical model of Ca²⁺ handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion.     

IGF‐I concentrations are positively associated with carotid artery atherosclerosis in women

BACKGROUND. Alterations in the growth hormone (GH)/insulin‐like growth factor I (IGF‐I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF‐I levels.

AIMS. To investigate whether IGF‐I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery.

METHODS. Fasting plasma IGF‐I concentrations (n = 1008) were measured in a large population‐based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method.

RESULTS. Low IGF‐I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C‐reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF‐I concentrations were positively associated with the mean IMT of women (ß = 0.127, P = 0.009) whereas the association in men was weaker and negative (ß = ?0.088, P = 0.034). The 1169A allele was associated with low low‐density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women.

CONCLUSIONS. IGF‐I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF‐I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.     

糖尿病患者胰岛素泵强化治疗护理

目的：探讨采用胰岛素泵治疗糖尿病的有效护理方法。方法：对176例胰岛素泵治疗的糖尿病患者进行技术和心理等综合护理。结果：合理使用胰岛素泵,可有效控制患者血糖浓度,提高患者生活质量。结论：综合护理是胰岛素泵强化治疗的保障。