Soluble Insulin Research Articles

Cytoplasmic soluble Lispro insulin production in Escherichia coli, product yield optimization and physiochemical characterization

Lispro is an insulin analog with an accelerated action profile suitable for post-prandial injections and glycemic control in diabetes. Insulin production in Escherichia coli leads to inclusion body formation due to its reducing inner environment. This conventional platform requires refolding procedures with relatively low recovery resulting in product loss and increased production time. We introduced a novel approach for high yield cytoplasmic soluble expression of Lispro insulin in E. coli. Presence of the SUMO fusion tag and being expressed in SHuffle T7 improved the solubility of Lispro precursor to10 mg/L. Product yield increased to approximately 5-fold after the optimization procedure. The scalability of the optimized condition was confirmed in a fed-batch fermentor that resulted in high cell density and high yield soluble expression (540 mg/L). 25 mg/L bioactive Lispro insulin was generated and purified. The final product was identical to the commercial analog based on physiochemical characterization analyses.

The mediating role of vascular inflammation in traffic-related air pollution associated changes in insulin resistance in healthy adults.

The precise pathophysiologic pathway linking traffic-related air pollution (TRAP) to diabetes mellitus is not well elucidated. We aimed to investigate whether activation of vascular inflammation can be a mechanistic linkage between ambient TRAP and insulin resistance. Study outcomes were determined by assessing a series of circulating biomarkers indicative of insulin resistance and vascular inflammation among 73 healthy adults who underwent repeated clinical visits in Beijing, China, 2014-2016. Concomitantly, concentrations of ambient TRAP indices, including particulate matter in diameter <2.5μm (PM2.5), particles in size fractions of 5-560nm, black carbon, carbon monoxide, nitrogen dioxide, and oxides of nitrogen, were continuously monitored. Participants experienced extremely high levels of TRAP exposures, with mean (standard deviation) PM2.5 concentrations of 91.8 (48.3) μg/m3, throughout the study. We found that interquartile range increases in exposure to moving average concentrations of various TRAP indices at prior up to 7 days were associated with significant elevations of 8.9-49.6% in insulin levels. Higher pollutant levels were also related to worsening metrics of insulin resistance (soluble insulin receptor ectodomain, adipokines, and homeostasis model assessment of insulin resistance) and heightened vascular inflammatory responses, particularly disruptions of the receptor activator of nuclear factor κB ligand/osteoprotegerin system balance and elevations of monocyte/macrophage and T cell activation markers. Mediation analyses showed that activation of vascular inflammation could explain up to 66% of the alterations in metrics of insulin resistance attributable to air pollution. Our results suggest that ambient traffic pollution exposure was capable of promoting insulin resistance possibly via generating vascular inflammation.

Maxillary necrosis by Mucormycosis: A Case Report

A 50-year-old woman with type 2 diabetes was referred to the hospital with a 4-week history of a facial redness that proceeded to significant midface ulceration and bilateral vision loss. Her nasal bridge was completely collapsed, she had naso-palatal ulceration with black eschars on the mucosa, and her fasting blood sugar was significantly increased. Her blood sugar was controlled with soluble insulin through sliding scale, and surgical debridement was performed, which revealed fungal hyphae on histo-pathological assessment. Ketoconazole, an antifungal drug, was commenced immediately. She progressed slowly but steadily after that and her wound became clear with fresh granulation tissue. Keywords: Mucormycosis, Uncontrolled diabetic mellitus

Serum Biomarkers and Classification and Regression Trees Can Discriminate Symptomatic from Asymptomatic Carotid Artery Disease Patients

ObjectiveTo assess biomarkers between symptomatic and asymptomatic patients, and to construct a classification and regression tree (CART) algorithm for their discrimination.Patients and Methods136 patients were enrolled. They were symptomatic (high risk) (N = 82, stenosis degree ≥ 50%, proven to be responsible for ischemic stroke the last six months) and asymptomatic (low risk) (N = 54, stenosis degree ≤ 50%). Levels of fibrinogen, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), soluble intercellular adhesion molecule (SiCAM), soluble vascular cell adhesion molecule (SvCAM), adiponectin and insulin were measured on a Luminex 3D platform and their differences were evaluated; subsequently, a CART model was created and evaluated.ResultsAll measured biomarkers, except adiponectin, had significantly higher levels in symptomatic patients. The constructed CART prognostic model had 97.6% discrimination accuracy on symptomatic patients and 79.6% on asymptomatic, while the overall accuracy was 90.4%. Moreover, the population was split into training and test sets for CART validation.ConclusionSignificant differences were found in the biomarkers between symptomatic and asymptomatic patients. The CART model proved to be a simple decision-making algorithm linked with risk probabilities and provided evidence to identify and, therefore, treat patients being at high risk for cardiovascular disease.

100 years of insulin-enormous gratitude for my extra 65 years!

My name is Peter Davies, and with this year being the one hundredth anniversary of insulin, it is a tremendous honour to be invited to write this account of my life with Diabetes.

Ongoing efforts to improve the management of patients with diabetes in Bangladesh and the implications

ABSTRACT Background Prevalence rates of patients with diabetes are growing across countries, and Bangladesh is no exception. Associated costs are also increasing, driven by costs associated with the complications of diabetes including hypoglycemia. Long-acting insulin analogues were developed to reduce hypoglycemia as well as improve patient comfort and adherence. However, they have been appreciably more expensive, reducing their affordability and use. Biosimilars offer a way forward. Consequently, there is a need to document current prescribing and dispensing rates for long-acting insulin analogues across Bangladesh, including current prices and differences, as a result of affordability and other issues. Methods Mixed method approach including surveying prescribing practices in hospitals coupled with dispensing practices and prices among community pharmacies and drug stores across Bangladesh. This method was adopted since public hospitals only dispense insulins such as soluble insulins free-of-charge until funds run out and all long-acting insulin analogues have to be purchased from community stores. Results There has been growing prescribing and dispensing of long-acting insulins in Bangladesh in recent years, now accounting for over 80% of all insulins dispensed in a minority of stores. This increase has been helped by growing prescribing and dispensing of biosimilar insulin glargine at lower costs than the originator, with this trend likely to continue with envisaged growth in the number of patients. Consequently, Bangladesh can serve as an exemplar to other low- and middle-income countries struggling to fund long-acting insulin analogues for their patients. Conclusions It was encouraging to see continued growth in the prescribing and dispensing of long-acting insulin analogues in Bangladesh via the increasing availability of biosimilars. This is likely to continue benefitting all key stakeholder groups.

Decision support system for predicting metabolic risks in patients with comorbid non-alcoholic fatty liver disease and gallstone disease after cholecystectomy

183 patients with non-alcoholic fatty liver disease (NAFLD) were included into the case control study. Objective. Development a medical decision support system to improve the prediction of metabolic risks in persons with comorbid NAFLD and gallstone disease (GD) after cholecystectomy. Materials and methods. The main group was represented by patients with NAFLD and GD (n = 88), of which 53 patients underwent cholecystectomy. The comparison group was represented by patients with NAFLD without GD (n = 95). A standard laboratory and instrumental examinations were performed, including elastometry to assess of the stage of liver fibrosis and assessment of the level of hormones leptin, its soluble receptor, adiponectin and insulin. Results. Patients suffering from GD and NAFLD had a symptom of dyspepsia and general weakness. High prevalence of type 2 diabetes (rs = 0.164; р ≤ 0.01) and сoronary heart disease (25.00 % versus 9.47 % in the comparison group; р ≤ 0.01), high level of LDL and GGT (rs = 0.228, р ≤ 0.01 and rs = 0.298, р ≤ 0.01) were found in patients with GD after cholecystectomy. The phenomenon of insulin and leptin resistance, high levels of adiponectin were detected in patients suffering from NAFLD and GD. Hyperleptinemia was observed in NAFLD patients with GD after cholecystectomy (H = 5.812, p ≤ 0.05, rs = 0.313, p ≤ 0.05). Cholecystectomy in patients suffering from GD and NAFLD was associated with the formation of progressive stages of liver fibrosis (rs = 0.366; р ≤ 0.01). Conclusion. We have developed a decision support system to assess of the possibility of cholecystectomy in patients with NAFLD and GD according to the level metabolic risk of cardiovascular diseases and NAFLD progression.

KAPOSI SARCOMA COEXISTING WITH NEW ONSET DIABETES MELLITUS IN A 42-YEAR-OLD KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT

Background: Renal allograft recipients develop several complications such as infections and neoplasms. New onset diabetes mellitus is a common transplant complication but rarely coexist with Kaposi sarcoma. Case report: We report the case of a 42-year-old banker who presented with polyuria, polydipsia, polyphagia, weight loss and dark spots in the lower limbs 8 months after he had received a live-related kidney transplant in India. He is not a known diabetic and had no family history of diabetes mellitus. His post-transplant immunosuppressive drugs included Myfortic® (mycophenolate), tacrolimus and prednisolone. At presentation he was wasted, dehydrated and afebrile, with multiple hyperpigmented nodules and plaques in both his lower limbs. Random blood glucose was 38mmol/l, had 2+ glucosuria and no ketones. Biopsy of skin lesions showed features of Kaposi sarcoma. A diagnosis of post-transplant diabetes mellitus and Kaposi sarcoma was made. His treatment included soluble insulin and antibiotics. Tacrolimus was changed to sirolimus and mycophenolate was reduced to 360mg twice daily. Conclusion: Coexistence of diabetes mellitus and karposi sarcoma occurs rarely among kidney transplant recipients. Evaluation of transplant recipient who developed diabetes for malignancies such as karposi sarcoma will improve patient and graft survival.

386-P: Acute Hypoglycemia Does Not Alter Serum Levels of Amyloid-Related Proteins Associated with Dementia

Objective: Hypoglycemia is a common complication of tighter glucose control regimens in type 2 diabetes (T2D) and may increase the risk of dementia, Alzheimer’s disease being the most common form. We measured amyloid-related proteins during induced hypoglycemia in a cohort of subjects with and without T2D, hypothesizing that these protein levels would be further elevated during hypoglycemia in T2D subjects. Methods: A prospective, parallel study was conducted in individuals with T2D (n=23) and controls (n=22). Hypoglycaemia (&amp;lt;2.2mmol/l: &amp;lt;40mg/dl) was achieved by intravenous infusion of soluble insulin. Blood samples were collected at baseline and at 0, 30, 60, 120, 240 minutes and 24 hours following hypoglycaemia and proteomic (Somalogic) analysis of four amyloid-related proteins (Amyloid P component [APCS], Amyloid precursor protein [APP], Pappalysin [PAPPA] and Serum amyloid A1 [SAA1]) at baseline, at hypoglycemia and at 24-hours post-clamp was undertaken. Results: No changes from baseline in serum levels of the four amyloid-related proteins were seen in subjects with or without T2D, either at the time of hypoglycemia or at 24-hours post-clamp. Conclusions: Induced hypoglycemia is not associated with a significant increase in serum levels of amyloid-related proteins. Thus, no clear mechanistic link based on serum proteins between T2D-related hypoglycemic episodes and Alzheimer’s disease emerged from this study, although it is important to consider that protein levels in the cerebrospinal fluid may differ. Disclosure A. Moin: None. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. S. Atkin: None. A.E. Butler: None.

Visible-Light-Activated High-Density Materials for Controlled in Vivo Insulin Release.

In this work, we describe the synthesis, characterization, and ultimate in vivo assessment of second-generation insulin photoactivated depot (PAD) materials. These are the first to use visible light to stimulate insulin release and have an in vivo performance that is 28-fold improved relative to first-generation materials. This improvement is due to two major factors linked to the utilized chemistry: (1) we have incorporated the coumarin photocleavable group, which increases the photorelease wavelength into the visible range, enhancing tissue penetration of the light; (2) phototoggling of insulin solubility is produced by linking three insulin molecules to a central bridge via light cleaved groups, and not by bonding to a large polymer. The resulting trimer is, therefore, highly dense (87% insulin dry w/w) but retains the insolubility required of the approach. Only after irradiation with visible light is native, soluble insulin is released from the dermal depot. This high density increases the amount and ease of insulin release, as the density of photolytic groups is 10-20-fold higher than in polymer-based first-generation materials. We have synthesized new azide-terminated coumarin linkers that we react with the amine groups of insulin. Using mass spectrometry methods, we identify the sites of reaction and purify individual isomers, which we demonstrate have in vitro photolysis rates that are within a factor of 2 of each other. We then reacted these terminal azide groups with a tridentate strained alkyne linker. We show that the resulting insulin trimer is highly insoluble, but can be milled into injectable particles that release insulin only in response to light from a 406 nm light source. Finally, we demonstrate that these materials have a significantly improved in vivo performance, releasing 28-fold more insulin on a per energy basis than first-generation materials.

El receptor soluble de insulina y el síndrome metabólico.

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e. metabolic syndrome. Electrophoresis of the rats' plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Release of Soluble Insulin Receptor From Neurons by Cerebrospinal Fluid From Patients With Neurocognitive Dysfunction and HIV Infection.

Previously, we found that high levels of soluble insulin receptor (sIR) in the cerebrospinal fluid (CSF) of an HIV-infected women cohort were associated with the presence and severity of HIV-associated neurocognitive disorders (HAND). In this study we investigated if CSF from this population, HIV-1 Tat, and selected cytokines induces sIR secretion from human neuronal cells. Twenty-three (23) HIV-seropositive women stratified by cognitive status and five HIV- seronegative women were evaluated. Soluble IR levels were measured in the extracellular medium of neuronal cells (SH-SY5Y) that were exposed (for 24 h) to the CSF of patients. The levels of sIR, HIV-1 Tat, and cytokine levels (IL-2, IL4, IL-6, IFNγ, TNFα, and IL-10) were quantified in the CSF of participants by ELISA and flow cytometry. Neuronal secretion of sIR was measured after exposure (24 h) to HIV-1 Tat (0.5–250 nM), or specific cytokines. The effects of TNFα and HIV-1 Tat on sIR secretion were also evaluated in the presence of R7050 (TNFα antagonist; 10 nM). Neurons exposed to the CSF of HIV-infected women had higher sIR levels according to the severity of neurocognitive impairment of the participant. Increased CSF sIR levels were associated with the presence and severity of HAND and were positively correlated with CSF HIV-1 Tat levels in HIV-infected women with cognitive impairment. CSF levels of IL-2, IFNγ, and TNFα were significantly increased with HAND. However, only TNFα (5 pg/mL) and HIV-1 Tat (100 nM) induced a significant increase in neuronal sIR secretion after 24 h exposure, an effect that was antagonized when each were combined with R7050. Our data suggests that TNFα and HIV-1 Tat from the CSF of HIV-infected women may regulate the secretion of sIR from neuronal cells and that the effect of HIV-1 Tat on sIR secretion may depend on TNFα receptor activation.

Soluble Antigen Arrays for Selective Desensitization of Insulin-Reactive B Cells.

Autoimmune diseases are believed to be highly dependent on loss of immune tolerance to self-antigens. Currently, no treatments have been successful clinically in inducing autoantigen-specific tolerance, including efforts to utilize antigen-specific immunotherapy (ASIT) to selectively correct the aberrant autoimmunity. Soluble antigen arrays (SAgAs) represent a novel autoantigen delivery system composed of a linear polymer, hyaluronic acid (HA), displaying multiple copies of conjugated autoantigen. We have previously reported thatsoluble antigen arraysdisplaying proteolipidpeptide (SAgAPLP) induced tolerance tothis specific multiple sclerosis (MS) autoantigen. Utilizing SAgA technology, we have developed a new ASIT as a possible type 1 diabetes (T1D) therapeutic by conjugating human insulin to HA, known as soluble antigen array insulin (SAgAIns). Three types were synthesized, low valency lvSAgAIns (2 insulins per HA), medium valency mvSAgAIns (4 insulins per HA), and, high valency hvSAgAIns (9 insulins per HA), to determine if valency differentially modulates the ex vivo activity of insulin-binding B cells (IBCs). Extensive biophysical characterization was performed for the SAgA molecules. SAgAIns molecules were successfully used to affect the biologic activity of IBCs by inducing desensitization of the B cell antigen receptors (BCR). SAgAIns bound specifically to insulin-reactive B cells without blocking epitopes recognized by antibodies against the Fc regions of membrane immunoglobulin or CD79 transducer components of the BCR. Preincubation of IBCs (125Tg) with SAgAIns, but not HA alone, rendered the IBCs refractory to restimulation. SAgAIns induced a decrease in BCR expression and IP3R-mediated intracellular calcium release. Surprisingly, SAgAIns binding to BCR on the surface of IBCs induced the observed effects at both high and low SAgAIns valency. Future studies aim to test the effects of SAgAIns on disease progression in the VH125.NOD mouse model of T1D.

Total, insoluble, and soluble dietary fiber intake and insulin resistance and blood pressure in adolescents.

Background/Objectives:To evaluate sex and race differences in fiber intakes, which are understudied in adolescents, and to investigate whether low insoluble and soluble fiber intakes would be associated with higher risk for insulin resistance and blood pressure (BP).Subjects/Methods:A total of 754 black and white adolescents, 14 to 18 years old (49.2% blacks; 50.3% female) were previously recruited in Augusta, Georgia, the US between 2001 to 2005. Diet was assessed with four to seven independent 24-hour dietary recalls.Results:The average daily consumption of total, insoluble, and soluble fiber were 10.9, 6.7, and 4.0g, respectively. Only two adolescents met their daily fiber intake recommendation. Adjusted multiple linear regressions revealed that increasing dietary fiber intake from current averages to recommendation levels (12g to 38g in the male and 9.9g to 25g in the female), were associated with predicted decreases of 5.4 and 3.0 mg/dL fasting glucose, 7.0 and 5.0 mg/dL fasting insulin, 1.6 and 1.1 HOMA-IR, 6.3 and 3.7 mmHg SBP, and 5.2 and 3.0 mmHg DBP in the males and females, respectively (all p < 0.05). Furthermore, both insoluble and soluble fiber intakes were inversely associated with fasting insulin and HOMA-IR (p <0.05); whereas only soluble fiber intake was found to be associated with BP (p <0.05).Conclusions:Fiber consumption in adolescents is far below daily-recommended levels across all sex and race groups. Lower fiber intake of all types is associated with higher insulin level. Fiber Intake at recommendation levels may be associated with significant cardiometabolic benefits.

Dynamic, Bioresponsive Hydrogels via Changes in DNA Aptamer Conformation.

DNA aptamers are integrated into synthetic hydrogel networks with the aim of creating hydrogels that undergo volume changes when exposed to target molecules. Specifically, single-stranded DNA aptamers in cDNA-bound, extended state are incorporated into hydrogel networks as cross-links, so that the nanoscale conformational change of DNA aptamers upon binding to target molecules will induce macroscopic volume decreases of hydrogels. Hydrogels incorporating adenosine triphosphate (ATP)-binding aptamers undergo controllable volume decreases of up to 40.3±4.6% when exposed to ATP, depending on the concentration of DNA aptamers incorporated in the hydrogel network, temperature, and target molecule concentration. Importantly, this approach can be generalized to aptamer sequences with distinct binding targets, as demonstrated here that hydrogels incorporating an insulin-binding aptamer undergo volume changes in response to soluble insulin. This work provides an example of bioinspired hydrogels that undergo macroscopic volume changes that stem from conformational shifts in resident DNA-based cross-links.

Intraoperative blood glucose level changes between obese and non-obese non-diabetic patients undergoing general anaesthesia for creniotomy surgeries

Background: Surgery causes a considerable metabolic stress in the non-diabetic and more so in a diabetic subject. In non-diabetic subjects the stress response is more in obese population than in non-obese due to the presence of insulin resistance. The severity of surgery as well as the type of anesthesia influences the magnitude of the counter regulatory response The study was undertaken to observe the effect of stress of surgery in obese and non-obese non-diabetic patients undergoing craniotomy under general anesthesia. Methods: A Prospective randomized parallel group study was done on a total of 100 patients. They were divided into two groups non-obese patients and obese patients comprising of 50 patients in each group depending on their BMI. If at any time intraoperative CBG was found to be more than or equal to 150mg/dL calculated dose of human soluble insulin was given as intravenous bolus equal to the amount of CBG/100 units. Results: 36% patients in obese population developed at least one episode of hyperglycemia (CBG ≥150 mg/dL) but only 20% in non-obese population did so. Insulin consumption was significantly higher in obese population than in non-obese population to maintain normoglycemia. The relative risk of becoming hyperglycemic in obese compared to non-obese is 1.80 (95% CI 0.92 to 3.51) Conclusion: We conclude that stress induced hyperglycemic response in patients undergoing craniotomy surgery under general anaesthesia is common in non-diabetic obese non-obese population.

Knowledge, attitude and practice of Sudanese individuals with type 2 diabetes about medication used in treatment of diabetes, hypertension and dyslipidaemia: a matter of debate or matter of concern?

Background: Diabetes is a chronic disease requires lifelong integrated treatment that includes lifestyle modifications and use of diabetes medication. The aim of this study was to establish knowledge, attitude and practice of Sudanese individuals with type 2 diabetes toward their medication. Methods: This was a cross-sectional study that recruited 383 individuals with type 2 diabetes attend Jabir Abu Eliz Diabetes Canter. They aged between 18–65 years old. Individuals with type 2 diabetes are selected randomly and invited to complete the questionnaire, while Individuals with type1 diabetes, gestational diabetes and those aged less than 18 years old were excluded from this study. Results: 76.5% of the interviewed patients had a valid health insurance, especially with 44% have diabetes for more than 10 years. Hypertension was one of the commonest co-morbidities (58%). Importantly 73% of the patients didn’t purchase all their prescribed medications (medicine not available, no medical insurance and expensive medication). The common medication used in treatment of diabetes is metformin (46%). Glibenclamide accounted for (16%), glimepiride for (10%), glipizide for (0.3%) and pioglitazone for (1.3%).The most common antihypertensive medication used are angiotensin converting enzyme inhibitor (27%), angiotensin receptor blocker (24%) and calcium channel blocker (24%). 17% of the study population were receiving statins and 84% in low dose aspirin. Almost one third (31.7%) of interviewed patients were on insulin. Approximately 72% of these patients were using mixed insulin, 21% using soluble insulin and 3% used more than one type of insulin at the same time. Two-third of this population usually takes the insulin dose by themselves and (34%) of this group rotated injection site routinely in comparison with (66%) who stick to one site. In Sudan room temperature rarely drops to under 30 °C which necessitated refrigeration of insulin. Majority of the patients (81%) confirmed the storage of insulin vials in the refrigerator. Conclusions: More than two third of Sudanese individuals did not bought all medications used in treatment of diabetes and co-morbidities. Metformin and sulfonylureas were widely used in treatment of diabetes. Hypertension is well treated but lipid lowering medication was used by almost less than one fifth of the individual with type 2 diabetes. Intensive education is needed to increase knowledge of individuals about diabetes in order to enhance attitude and practice. This education can be achieved in part by both community and clinical pharmacists.

The Study on the Clinical Efficacy of Insulin Degludec/Insulin Aspart (IDegAsp)

Aim: Insulin degludec and aspart (IDegAsp) is the first soluble insulin preparation to combine two different types of insulin analogs in one pen. However, there are few reports describing the long-term use of IDegAsp in clinical practice. Method: 140 outpatients received IDegAsp during the period between Feb 2016 and Dec 2017 and were retrospectively analyzed for HbA1c, body weight, and units of insulin used (mean follow-up period, 8.2 months). Also, a questionnaire survey was conducted 3 months after the introduction of IDegAsp, to assess patient satisfaction (Q1, device usability; Q2, glycemic control; Q3, frequency of hypoglycemia; Q4, formulation not requiring suspension procedure). The subjects were 69 men and 71 women with a mean age of 64 years, HbA1c of 8.8 %, and body weight of 59.0 kg. Treatment before IDegAsp introduction included no previous insulin therapy (group A) in 46 patients, once daily injection of long-acting insulin in 28 patients, twice daily injection of premixed insulin in 20 patients, once daily injection of premixed insulin in 13 patients, and intensive insulin therapy in 33 patients. Results: The changes in HbA1c after the introduction of IDegAsp in the subjects overall were 8.1% (1 month [M]), and 7.3% (6 M), showing significant improvement as compared with the values before introduction. The body weights were 57.5 kg (1 M), and 57.6 kg (6 M), showing no significant changes. The changes in HbA1c, according to prior treatment, were 10.3% (0 M), 8.7% (1 M), and 7.0% (6 M) in group A, with each value showing significant improvement as compared with the baseline. In the patient survey on the use of IDegAsp, the percentages of patients responding "very good" or "good" to Q1, Q2, Q3, and Q4 were 31%, 85%, 91%, and 43%, respectively. Discussion: The introduction of IDegAsp consistently improved glucose metabolism. Also, the patient questionnaire showed mostly favorable results with use of IDegAsp. We plan to conduct a further study and report the results including a detailed assessment of each group. Disclosure M. Kusama: None.

Premeal Low-Fat Yogurt Consumption Reduces Postprandial Inflammation and Markers of Endotoxin Exposure in Healthy Premenopausal Women in a Randomized Controlled Trial

BackgroundMetabolic endotoxemia is associated with obesity and contributes to postprandial inflammation.ObjectiveWe aimed to determine if low-fat yogurt consumption prevents postprandial inflammation and dysmetabolism in healthy women by inhibiting biomarkers of metabolic endotoxemia.MethodsPremenopausal women defined as obese and nonobese [body mass index (BMI, in kg/m2) 30–40 and 18.5–27, respectively, n = 120] were randomly assigned to consume 339 g of low-fat yogurt (YN, yogurt nonobese; YO, yogurt obese) or 324 g of soy pudding (CN, control nonobese; CO, control obese) for 9 wk (n = 30/group). The intervention foods each supplied 330 kcal with 3 g fat, 66 g carbohydrate, and 4–6 g protein. At weeks 0 and 9, participants ingested 226 g of yogurt or 216 g of soy pudding before a meal providing 56–60 g fat, 82 g carbohydrate, and 28–30 g protein. Plasma soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), LPS activity, interleukin-6 (IL-6), glucose, triglyceride, and insulin were measured hourly for 4 h to assess differences in postprandial responses between groups by 2-factor ANOVA.ResultsPremeal yogurt consumption prevented the postprandial decrease in sCD14 net incremental area under the curve (net iAUC) by 72% in obese individuals at week 0 (P = 0.0323). YN and YO had ≥40% lower net iAUC of LBP-to-sCD14 ratio and plasma IL-6 concentration than CN and CO, respectively (P < 0.05). CO had postprandial hyperglycemia which was not evident in YO; in contrast YN had 57% less postprandial hypoglycemia than did CN (P-interaction = 0.0013). After 9 wk of yogurt consumption, ΔAUC of LBP-to-sCD14 ratios of YO and YN were less than half of those of the control groups (P = 0.0093).ConclusionYogurt consumption improved postprandial metabolism and biomarkers of metabolic endotoxemia in healthy premenopausal women. Premeal yogurt consumption is a feasible strategy to inhibit postprandial dysmetabolism and thus may reduce cardiometabolic risk. This trial was registered at clinicaltrials.gov as NCT01686204.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.