Basal Insulin Degludec and Glycemic Control Compared to Aspart Via Insulin Pump in Type 1 Diabetes (BIGLEAP): A Single-Center,Open-Label,Randomized, Crossover Trial

ObjectiveWe compared the efficacy of the second-generation basal insulin degludec (IDeg) to that of insulin aspart via pump using continuous glucose monitoring in patients with well-controlled type 1 diabetes.MethodsIn this 40-week, single-center, randomized, crossover-controlled trial, adults with well-controlled type 1 diabetes (hemoglobin A1C of <7.5% [<58 mmol/mol]) (N = 52) who were using an insulin pump and continuous glucose monitoring were randomized to 1 of 2 treatments for a 20-week period: a single daily injection of IDeg with bolus aspart via pump or a continuous subcutaneous insulin infusion (CSII) with aspart, followed by crossover to the other treatment. The primary endpoint was time in range (70-180 mg/dL) during the final 2 weeks of each treatment period.ResultsFifty-two patients were randomized and completed both treatment periods. The time in range for IDeg and CSII was 71.5% and 70.9%, respectively (P = .553). The time in level 1 hypoglycemia for the 24-hour period with IDeg and CSII was 2.19% and 1.75%, respectively (P = .065). The time in level 2 hypoglycemia for the 24-hour period with IDeg and CSII was 0.355% and 0.271%, respectively (P = .212), and the nocturnal period was 0.330% and 0.381%, respectively (P = .639). The mean standard deviation of blood glucose levels for the 24-hour period for IDeg and CSII was 52.4 mg/dL and 51.0 mg/dL, respectively (P = .294). The final hemoglobin A1C level for each treatment was 7.04% (53 mmol/mol) with IDeg, and 6.95% (52 mmol/mol) with CSII (P = .288). Adverse events were similar between treatments.ConclusionWe observed similar glycemic control between IDeg and insulin aspart via CSII for basal insulin coverage in patients with well-controlled type 1 diabetes.     

Mapping QTL in the porcine MHC region affecting fatness and growth traits in a Meishan/Large White composite population

A number of studies have mapped QTL regulating porcine fatness and growth traits to the region of the major histocompatibility complex (MHC) on porcine chromosome 7 using various experimental crosses. The QTL results from crosses using the Chinese Meishan (MS) (slow growing and fat) are particularly interesting because the MS alleles have been found to be associated with increased growth rate and reduced backfat depth. We investigated these QTL further in a composite population derived previously over eight generations by intercrossing Meishan and the European Large White breeds. Genotype information from 32 markers in a 15cM target region was used in linkage and association analyses. A two‐step variance component analysis identified QTL for three growth‐related traits, explaining 19 ～ 24% of the phenotypic variance with a confidence interval of 4 cM in the target region. SNP association analyses found that ss181128966 and ss181128924 within the QTL interval were strongly associated with the growth traits. Only weak signals for an effect on backfat depth were found in the association and linkage analyses, possibly because of past directional selection in the composite population.     

Malfunctioning of adipocytes in obesity is linked to quantitative surfaceome changes

Increased triglyceride accumulation in adipocytes caused by a misbalance between energy intake and energy consumption, results in increased adipocyte size, excess adipose tissue, increased body weight and ultimately, obesity. It is well established that enlarged adipocytes exhibit malfunctions that contribute to whole body insulin resistance, a key factor for the development of type 2 diabetes. However, the underlying molecular cause for dysfunctional adipocyte behavior and signaling is poorly understood. Since the adipocyte cell surface proteome, or surfaceome, represents the cellular signaling gateway to the microenvironment, we studied the contribution of this subproteome to adipocyte malfunctions in obesity. By using the chemoproteomic Cell Surface Capture (CSC) technology, we established surfaceome maps of primary adipocytes derived from different mouse models for metabolic disorders. Relative quantitative comparison between these surfaceome maps revealed a set of cell surface glycoproteins with modulated location-specific abundance levels. RNAi mediated targeting of a subset of the detected obesity modulated cell surface glycoproteins in an in vitro model system provided functional evidence for their role in adiponectin secretion and the lipolytic activity of adipocytes. Thus, we conclude that the identified cell surface glycoproteins which exhibit obesity induced abundance changes and impact adipocyte function at the same time contribute to adipocyte malfunction in obesity. The regulation of their concerted activities could improve adipocyte function in obesity.     

Inpatient Hyperglycemia and Transitions of Care: A Systematic Review

ObjectiveThe transition of diabetes care from home to hospital, within the hospital, and upon discharge is fraught with gaps that can adversely affect patient safety and length of stay. We aimed to highlight the variability in care during these transitions and point out areas where research is needed.MethodsA PubMed search was performed with a combination of search terms that pertained to diabetes, hyperglycemia, hospitalization, locations in the hospital, discharge to home or a nursing facility, and diabetes medications. Studies with at least 50 patients that were written in the English language were included.ResultsWith the exception of transitioning from intravenous insulin infusion to subcutaneous insulin and perhaps admission to the regular floors, few studies pointedly focused on transitions of care, leading us to extrapolate recommendations based on data from disparate areas of care in the hospital. There is evidence at every stage of care, starting from the entry into the hospital and ending with discharge home or to a facility, that patients benefit from having protocols in place guiding overall care.ConclusionPockets of care exist in hospitals where methods of effective diabetes management have been studied and implemented. However, there is no sustained continuum of care. Protocols and care teams that follow patients from one physical location to the other may result in improved clinical outcomes during and following a hospital stay.     

Regional Subcutaneous‐Fat Loss Induced by Caloric Restriction in Obese Women

Objective: With anthropometric models using skinfolds and circumferences, we studied changes in the percentage of subcutaneous fat in the total cross‐sectional area (SF%) at four body sites in obese women, before and after weight loss induced by 6 months of caloric restriction. Research Methods and Procedures: In 61 obese women [31 African Americans and 30 whites; ages, 24 to 68 years; body mass index (BMI), ≥28kg/m²], we measured SF% at the midpoint of the upper arm and thigh and the waistline and hipline, and we measured the percentage of total body fat by DXA before (Obs#1) and after (Obs#2) a 6‐month nonintervention control period and then after 6 months on a 1200 kcal/d diet (Obs#3). Results: The mean body weight and BMI increased (1.8 kg and 0.61 kg/m²; p = 0.0001), but there were no significant changes in any other body composition measurements from Obs#1 to Obs#2. The means of Obs#3 for weight and BMI decreased by 11%, and the percentage of total body fat decreased by 13% of Obs#2 mean values (p = 0.0001). The mean SF% at each site decreased 7.6% to 18.0% of the Obs#2 mean values (p < 0.001). The SF% decreases were greater at mid‐arm and mid‐thigh than in the cross‐sectional regions at the waistline and hipline (p = 0.05). There was no interaction between age or ethnicity (p > 0.2). Conclusions: In obese women, caloric restriction alone reduces anthropometrically measured subcutaneous fat proportionally more in peripheral than in central regions.     

Gender Differences in Changes in Subcutaneous and Intra-abdominal Fat during Weight Reduction: An Ultrasound Study

WIRTH, ALFRED, AND BERIT STEINMETZ. Gender differences in changes in subcutaneous and intra-abdominal fat during weight reduction: an ultrasound study. Obes Res. 1998;6:393–399. Objective : In weight-reducing programs, men usually display greater improvement in metabolic risk factors than women. This gender difference may be related to enhanced weight and fat loss due to a greater energy deficit in men. To clarify the relationship between changes in metabolic profile, body fat composition, and weight loss, both sexes were studied under a regimen in which similar amounts of weight were lost. Research Methods and Procedures : A cross-sectional study using anthropometric (body mass index and waist-to-hip ratio), impedance (bioelectrical impedance analysis) and ultrasound measurement methods (thickness of subcutaneous fat layers, intra-abdominal sagittal diameter) were conducted. The metabolic risk profile was determined by measuring lipids, lipoproteins, and blood pressure. The weight loss program lasted 15 weeks: 3 weeks under controlled conditions in the hospital and 12 weeks on an ambulatory basis. Patients were instructed to follow a mixed diet. Calorie intake was restricted to 1500 kcal/day for the men and 1200 kcal/day for the women. Thirty-two subjects with obesity (16 men and 16 women), with a mean body mass index of 35 kg/m²—matched with regard to age, height, and body weight—took part in the study. Results : As expected, weight loss was similar for both sexes (?13.4 kg vs. ?12.8 kg). Also, body fat mass changed to the same extent in absolute and relative terms. The waist-to-hip ratio was identical before and after treatment in both sexes. The men lost more visceral fat than the women. This result is based on changes in intra-abdominal diameter as well as abdominal subcutaneous fat in relation to waist circumference. Changes in abdominal diameter were paralleled by reductions in triglycerides and increases in high-density lipoprotein-cholesterol. Subcutaneous fat loss was more pronounced in women than in men. Discussion : Where absolute and relative reductions in body weight and body fat are similar, men mobilize more intraabdominal fat than women, whereas women lose more subcutaneous fat. The greater reduction in intra-abdominal fat seen in men is accompanied by a more pronounced improvement in the metabolic risk profile. Therefore, greater improvement of risk factors in men is not only related to a greater negative energy balance, as shown in most studies, but is also sex-specific.     

Steady state temperature distribution in dermal regions of an irregular tapered shaped human limb with variable eccentricity

The investigators in the past have developed some models of temperature distribution in the human limb assuming it as a regular circular or elliptical tapered cylinder. But in reality the limb is not of regular tapered cylindrical shape. The radius and eccentricity are not same throughout the limb. In view of above a model of temperature distribution in the irregular tapered elliptical shaped human limb is proposed for a three dimensional steady state case in this paper. The limb is assumed to be composed of multiple cylindrical substructures with variable radius and eccentricity. The mathematical model incorporates the effect of blood mass flow rate, metabolic activity and thermal conductivity. The outer surface is exposed to the environment and appropriate boundary conditions have been framed. The finite element method has been employed to obtain the solution. The temperature profiles have been computed in the dermal layers of a human limb and used to study the effect of shape, microstructure and biophysical parameters on temperature distribution in human limbs. The proposed model is one of the most realistic model as compared to conventional models as this can be effectively employed to every regular and nonregular structures of the body with variable radius and eccentricity to study the thermal behaviour.     

In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue

Cleanroom processing techniques have been used to mass-produce flexible, electroenzymatic glucose sensors designed for implantation in subcutaneous tissue. In vitro characterization studies have shown the sensor's performance to be acceptable. Initial in vivo studies were conducted with the sensor implanted in the subcutaneous tissue of rabbits. Sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation between glucose concentrations measured by the sensor and capillary finger sticks measured with a commercial analyzer.     

Tackling the human adipose tissue proteome to gain insight into obesity and related pathologies

Obesity is becoming an important public health problem given its strong association with insulin resistance and Type 2 diabetes. Previously considered an inert depot, fat is now regarded as a highly metabolically active tissue in many pathophysiological processes. In humans, the accumulation of omental rather than subcutaneous adipose tissue appears to be tightly linked to cardiovascular disease and other important comorbidities. Proteomics has emerged as a method for the large-scale study of proteins in biological samples, for instance, fluids, cells or tissues, which encompasses not only the identities of the proteins present, but also quantification and post-translational modification events. Human adipose tissue proteome analysis, still in its early stages, may help understand the molecular mechanisms of obesity and the role of omental fat in the pathogenesis of obesity-associated diseases. This review covers recent advances in human adipose tissue proteomics, focusing on the analysis of the omental and the subcutaneous fat.     

Lipohypertrophy and Insulin: An Old Dog That Needs New Tricks

ObjectiveTo review the current status of practical knowledge related to insulin-associated lipohypertrophy (LH) — an accumulation of fatty subcutaneous nodules commonly caused by repeated injections and/or infusions of insulin into the same site.MethodsReview of published literature with additional contributions from leading multidisciplinary experts with the emphasis on clinical aspects including pathophysiology, clinical and economic consequences, diagnosis, prevention and treatment.ResultsLH is the most common dermatologic complication of insulin therapy. Risk factors for the development of lipohypertrophy include repeated delivery of large amounts of insulin into the same location over time, repeated injection trauma to the skin and subcutaneous tissue, and multiple injections using the same needle. Subcutaneous insulin injection in skin areas with lipohypertrophy is associated with reduced pain; however, this problem can interfere with insulin absorption, thereby increasing the likelihood of glucose variability, hypo- and hyperglycemia when a site is changed. Modern visualization technology of the subcutaneous space with ultrasound can demonstrate lipohypertrophy early in the course of its development.ConclusionsThe physiological and psychological consequences of developing insulin lipohypertrophy can be prevented and treated with education focusing on insulin injection techniques.