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Background: In the onset 5 trial, fast-acting insulin aspart (faster aspart) was noninferior to insulin aspart (IAsp) for change from baseline glycated hemoglobin at 16 weeks, when used in continuous subcutaneous insulin infusion by participants with type 1 diabetes. The aim of this post hoc analysis was to investigate whether infusion set wear-time was associated with changes in sensor glucose, measured using continuous glucose monitoring (CGM). Materials and Methods: This was a post hoc analysis of onset 5 data. Mean infusion set wear-time and duration of CGM-wearing period were assessed. Mean CGM sensor glucose 24 h before and 24 h after were used to calculate the before–after difference (CGM sensor glucose drift). Results: Mean infusion set wear-time was 2.9 and 3.0 days in the faster aspart and IAsp arms, respectively. At 16 weeks, the average duration of the CGM wearing period was 13.7 and 13.8 days, respectively. Mean CGM sensor glucose before versus after an infusion set change, at week 16, was 10.14 versus 9.39 mmol/L with faster aspart and 9.48 versus 9.47 mmol/L with IAsp. The estimated treatment difference in CGM sensor glucose drift at 16 weeks for faster aspart versus IAsp was +0.72 mmol/L (95% confidence interval: 0.48–0.96, P

Introduction We investigated the safety of, and glucose control by, the insulin-only configuration of the iLet® bionic pancreas delivering fast-acting insulin aspart (faster aspart), using the same insulin-dosing algorithm but different time to maximal serum drug concentration (tmax) settings, in adults with type 1 diabetes. Methods We performed a single-center, single-blinded, crossover (two 7-day treatment periods) escalation trial over three sequential cohorts. Participants from each cohort were randomized to a default tmax setting (t65 [tmax = 65 min]) followed by a non-default tmax setting (t50 [tmax = 50 min; cohort 1], t40 [tmax = 40 min; cohort 2], t30 [tmax = 30 min; cohort 3]), or vice versa, all with faster aspart. Each cohort randomized eight new participants if escalation-stopping criteria were not met in the previous cohort. Results Overall, 24 participants were randomized into three cohorts. Two participants discontinued treatment, one due to reported ‘low blood glucose’ during the first treatment period of cohort 3 (t30). Mean time in low sensor glucose ( 70% for all cohorts, except the default tmax setting in cohort 1. No severe hypoglycemic episodes were reported. Furthermore, there were no clinically significant differences in adverse events between the groups. Conclusion There were no safety concerns with faster aspart in the iLet at non-default tmax settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default tmax settings. Trial Registration ClinicalTrials.gov, NCT03816761. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01087-x., Plain Language Summary One way to give insulin is to use an insulin delivery system. The iLet® is a new type of insulin delivery system that works together with a continuous sugar monitoring tool (CGM). The CGM shows the blood sugar level in the body throughout the day. Based on this, the iLet automatically gives the insulin that is needed to control the blood sugar. Fast-acting insulin aspart (faster aspart) is a type of insulin that doctors can prescribe for use with insulin pens and insulin pumps. The researchers wanted to test the safety of faster aspart when given to people at different delivery settings in the iLet. Twenty-four men and women with type 1 diabetes from the USA took part. The different insulin delivery settings were the standard setting (tmax65 = 65 min) and new settings (tmax50 = 50 min; tmax40 = 40 min; tmax30 = 30 min). The shorter the tmax setting, the faster the insulin was assumed to be absorbed into the body by the iLet. People had good blood sugar control with faster aspart delivered using the iLet. The time with low blood sugar (i.e., < 54 mg/dl) was low for both the standard setting and the new settings. The average blood sugar was lower with the shorter, non-standard tmax settings. No people had serious side effects. No severe hypoglycemic episodes were reported. In this study, researchers found that it was safe to use faster aspart with the different settings in the iLet. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01087-x.

Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 ( P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment ( P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.

In type 2 diabetes (T2D), injections with long-acting insulin can become necessary to regulate blood glucose and avoid long-term complications. However, finding a safe and effective insulin dose, a process known as titration, is both challenging and time demanding. In this paper, we propose a new method for safe and rapid identification of a personalized insulin dose with long-acting insulin through short-term use of fast-acting insulin in an artificial pancreas (AP). To illustrate this novel concept, we simulate our method by modelling the glucose response to fast-and long-acting insulin in people with T2D. We apply a simple control-algorithm for the AP to adjust the insulin infusion rate during fasting periods. In this case-study, we simulate an insulin naive T2D patient on AP treatment for one week, gradually adjusting the insulin infusion rate. After one week, we convert the insulin infusion rate, unit-to-unit, to a daily injection of long-acting insulin. We compare our method to titration with the standard of care 2-0-2 algorithm. Our simulations indicate that we can reduce the titration period from five weeks to a single week, whilst easing the burden on the patient.

This study aimed to confirm the efficacy and safety of mealtime and post-meal fast-acting insulin aspart versus insulin aspart, both with basal insulin degludec, in Japanese patients with type 1 diabetes. This was a subgroup analysis of onset 8, a randomized multicenter, treat-to-target trial of mealtime fast-acting insulin aspart (subgroup n = 73), mealtime insulin aspart (n = 83), or open-label post-meal fast-acting insulin aspart (n = 89), all for 26 weeks. Change from baseline in HbA1c was considered the primary endpoint. After 26 weeks, the estimated treatment difference (ETD, 95% CI) for change from baseline in HbA1c between mealtime fast-acting insulin aspart or post-meal fast-acting insulin aspart vs. insulin aspart was 0.01% (-0.16;0.19) and 0.10% (-0.07;0.27), respectively. Following a standardized meal test, ETD for change from baseline in postprandial glucose (PPG) increment at 1 hour was -16.91 mg/dL (-32.15;-1.68) for mealtime fast-acting insulin aspart and 40.16 mg/dL (25.46;54.87) for post-meal fast-acting insulin aspart, both versus insulin aspart. Mean self-measured blood glucose 1-hour PPG increments also showed a trend towards improved PPG control with mealtime fast-acting insulin aspart versus insulin aspart. Rates of overall hypoglycemia (35.56, 37.72 and 38.75 per patient-year of exposure with mealtime fast-acting insulin aspart, post-meal fast-acting insulin aspart and insulin aspart, respectively) and meal-related hypoglycemia were similar between treatment arms. Consistent with findings of onset 8, this analysis confirmed mealtime and post-meal fast-acting insulin aspart provided effective HbA1c and PPG control versus insulin aspart, with similar safety profiles, in Japanese adults with type 1 diabetes.

OBJECTIVE To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes. RESEARCH DESIGN AND METHODS After a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to RESULTS At week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference −0.17% [95% CI −0.30; −0.03], −1.82 mmol/mol [−3.28; −0.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose–confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp. CONCLUSIONS In children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA1c control compared with IAsp.

Introduction Insulin dosing based on carbohydrate counting is the gold standard for improving glycaemic control in type 1 diabetes (T1D). This post hoc analysis aimed to explore the efficacy and safety of fast-acting insulin aspart (faster aspart) according to bolus dose adjustment method in people with T1D. Methods Post hoc analysis of two 26-week, treat-to-target, randomised trials investigating treatment with double-blind mealtime faster aspart, insulin aspart (IAsp), or open-label post-meal faster aspart (onset 1, n = 1143; onset 8, n = 1025). Participants with previous experience continued carbohydrate counting (onset 1, n = 669 [58.5%]; onset 8, n = 428 [41.8%]), while remaining participants used a bolus algorithm. Results In onset 1, HbA1c reduction was statistically significantly in favour of mealtime faster aspart versus IAsp with carbohydrate counting (estimated treatment difference [ETD 95% CI] − 0.19% [− 0.30; − 0.09]; − 2.08 mmol/mol [− 3.23; − 0.93]). In onset 8, there was no statistically significant difference in HbA1c reduction with either dose adjustment method, although a trend towards improved HbA1c was observed for mealtime faster aspart with carbohydrate counting (ETD − 0.14% [− 0.28; 0.003]; − 1.53 mmol/mol [− 3.10; 0.04]). In both trials, bolus insulin doses and overall rates of severe or blood glucose-confirmed hypoglycaemia were similar between treatments across dose adjustment methods. Conclusion For people with T1D using carbohydrate counting, mealtime faster aspart may offer improved glycaemic control versus IAsp, with similar insulin dose and weight gain and no increased risk of hypoglycaemia. Trial Registration ClinicalTrials.gov: NCT01831765 (onset 1) and NCT02500706 (onset 8). Funding Novo Nordisk. Electronic supplementary material The online version of this article (10.1007/s13300-019-0608-4) contains supplementary material, which is available to authorized users.

The aim of this post-hoc subgroup analysis, which was based on data from the treat-to-target, 26-week, onset 7 trial, was to confirm the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both in combination with basal insulin degludec, in children and adolescents from Japan with type 1 diabetes (T1D). Of the onset 7 trial population (1 to18 years; N = 777), 66 participants from Japan (65 Asian and one non-Asian) were randomized to mealtime faster aspart (n = 24), post-meal faster aspart (n = 19), or IAsp (n = 23). Data for the subgroup from Japan were analysed descriptively. Change from baseline in hemoglobin A1c 26 weeks after randomization was 0.23%, 0.74%, and 0.39%, for mealtime faster aspart, post-meal faster aspart, and IAsp respectively. Change from baseline in 1-h post-prandial glucose increment (based on 8-point self-measured blood glucose profiles) showed numerical differences in favor of mealtime faster aspart versus IAsp at breakfast (-30.70 vs. -2.88 mg/dL) and over all meals (-18.21 vs. -5.55 mg/dL). There were no clinically relevant numerical differences between treatment arms in the overall rate of severe or blood glucose-confirmed hypoglycemia. At week 26, mean total insulin dose was 1.119 U/kg/day for mealtime faster aspart, 1.049 U/kg/day for post-meal faster aspart, and 1.037 U/kg/day for IAsp. In conclusion, in children and adolescents with T1D from Japan, mealtime and post-meal faster aspart with insulin degludec was efficacious in controlling glycemia without additional safety concerns versus IAsp.

Background: Although guidelines advocate similar continuous glucose monitoring (CGM) targets for insulin-treated persons with type 1 diabetes (T1D) and type 2 diabetes (T2D), it is unclear how thes...

Aims: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). Methods: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. Results: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c 40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. Conclusions: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Aim To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections. Materials and Methods We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements. Results Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire. Conclusion The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines. Funding Agencies|NU Hospital Group, Trollhattan, Sweden; Dexcom, Inc.; Swedish government (Avtalet om Lakareutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]); NU Hospital Group, Uddevalla, Sweden

OBJECTIVE According to recent guidelines, individuals with type 1 diabetes should spend RESEARCH DESIGN AND METHODS In the GOLD randomized crossover trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomized to continuous glucose monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycemia and various mean glucose and HbA1c levels. RESULTS Time spent in hypoglycemia ( CONCLUSIONS Reaching current targets for time in hypoglycemia while at the same time reaching HbA1c targets is challenging for patients with type 1 diabetes treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment if they are to have a chance to approach hypoglycemia targets.

Medtronic has developed a virtual patient simulator for modeling and predicting insulin therapy outcomes for people with type 1 diabetes (T1D). An enhanced simulator was created to estimate outcomes when using the MiniMedSixty-seven participants' PK profiles were generated per type of insulin (Total of 134 PK profiles). 7,485 virtual patients' PK measurements was matched with one of the 67 NovoLog® PK Tmax values. These 7,485 virtual patients were then simulated using the Medtronic MiniMed™ 670G algorithm following an in-silico protocol of 90 days: 14 days in open loop (Manual Mode) followed by 76 days in closed loop (Auto Mode). Simulation study was repeated with each NovoLog® PK profile being replaced by its corresponding Fiasp® PK profile in the same virtual patient. To validate our in-silico analysis, we compared the results of "actual" 19 "real life" patients from a clinical study RESULTS: Simulated overall and postprandial glycemic outcomes improved in all age groups with Fiasp®. The percentage of time in the euglycemic range increased by about ~2.2% with Fiasp®, in all age groups (p 0.01). The percentage of time spent at70 mg/dL was reduced by about ~0.6% with insulin Fiasp® (p 0.01) and the mean glucose was reduced by about 1.3 mg/dL (p 0.01), excluding those age7 years. The simulated mean postprandial SG was reduced by ~5 mg/dL, a significant difference for all age groups. A clinical study results showed similar improvements with MiniMedThe simulation studies indicate that using Fiasp® in place of NovoLog® with the MiniMed

Objective: According to recent guidelines, individuals with type 1 diabetes should spend less than 4.0% per day with glucose levels Research methods: In the GOLD randomised cross-over trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomised to Continuous Glucose Monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycaemia and various mean glucose and HbA1c levels. Results: Time spent in hypoglycaemia ( Conclusions: Reaching current targets for time in hypoglycaemia and at the same time HbA1c targets is challenging for type 1 diabetes patients treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycaemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment to have a chance to approach hypoglycaemia targets.

The impact of baseline HbA1c on the efficacy and safety of fast-acting insulin aspart (FA) was assessed in a post-hoc analysis of a 16-week, treat-to-target trial in adults with type 2 diabetes (T2D) not optimally controlled with a basal-bolus regimen (onset 9). Participants (n=1091) were randomized to FA or insulin aspart (IAsp), each with insulin degludec with or without metformin. In this analysis, participants were separated by baseline HbA1c ( Change from baseline in HbA1c was similar between treatments in the FA provides effective overall glycemic control with improved PPG control vs. IAsp in adults with T2D. For individuals with HbA1c Disclosure E. Franek: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Bioton, Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim, Novo Nordisk. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. Ó. Thórisdóttir: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Rathor: Employee; Self; Novo Nordisk. L. Rose: None. A. Soto Gonzalez: Advisory Panel; Self; Novartis, Novo Nordisk. Consultant; Self; Mundipharma International, Novartis, Novo Nordisk. Speaker’s Bureau; Self; Eli Lilly and Company, Janssen/Mundipharma, Novartis, Novo Nordisk, Sanofi. R.J. Silver: Advisory Panel; Self; Medtronic, Novo Nordisk. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. W. Lane: Research Support; Self; AstraZeneca, Gilead, Mylan, Sanofi, Tolerion, vTv. Other Relationship; Self; Dexcom, Insulet, Novo Nordisk. Funding Novo Nordisk

A previous post-hoc analysis of the 26-week onset 2 trial indicated that with insulin glargine the effect of fast-acting insulin aspart (FA) vs. insulin aspart (IAsp) on PPG increment (meal test) was larger for subjects on high bolus insulin doses in bolus-naïve adults with T2D (duration ≥6 mo). This post-hoc analysis of the 16-week onset 9 trial aimed to confirm this and explore efficacy and safety of FA vs. IAsp, both with insulin degludec, in bolus-experienced adults with T2D (duration ≥10 yrs) by insulin requirement. Participants were divided by meal test bolus dose at baseline: ≤10 U (n=303), 10-20 U (n=518) or >20 U (n=270). Baseline characteristics were similar across subgroups; except for BMI and daily insulin dose, which increased with meal test dose (Table). Change from baseline in HbA1c 16 weeks post randomization was similar for FA vs. IAsp across subgroups. There was a trend in favor of FA vs. IAsp for change from baseline in PPG increments (meal test), but treatment differences did not depend on subgroup. There was a trend towards lower rates of severe or blood glucose-confirmed hypoglycemia with higher insulin doses at meal test, with a benefit for FA vs. IAsp in the >20 U subgroup. Treatment difference (FA vs. IAsp) in change from baseline in PPG increments was unaffected by bolus insulin dose; however hypoglycemia risk may be lower with FA vs. IAsp in adults with long-standing T2D and high bolus insulin requirements. Disclosure W. Lane: Research Support; Self; AstraZeneca, Gilead, Mylan, Sanofi, Tolerion, vTv. Other Relationship; Self; Dexcom, Insulet, Novo Nordisk. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. Ó. Thórisdóttir: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. E. Jódar: Other Relationship; Self; Elli Lilly & Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. A. Oviedo: None. N. Rathor: Employee; Self; Novo Nordisk. P. Senior: Research Support; Self; Allergan, Novo Nordisk. G. Sesti: Advisory Panel; Self; Servier, Mylan, Novo Nordisk, Boehringer Ingelheim, Lilly, AstraZeneca, MSD, Sanofi, Amgem, Novartis, GSK. Speaker’s Bureau; Self; Novo Nordisk, Servier, MSD, Boehringer Ingelheim, Lilly, AstraZeneca, L-Nutra, Theras, Sanofi, Mundipharma, Omikron, Novartis. E. Franek: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Bioton, Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim, Novo Nordisk. Funding Novo Nordisk

We examined automated glycemic control with the insulin-only configuration of the iLet® bionic pancreas using faster aspart (Fiasp), comparing non-default tmax settings of the iLet® to a default tmax setting in a two-period, random-order cross-over design within each of three cohorts with eight different participants. Each participant was randomized to use the default tmax setting (t65 minutes) followed by the non-default tmax setting (t50, t40, or t30 minutes in cohorts 1, 2, and 3, respectively), or vice versa, for one week each. The group mean CGM glucose (CGMG) was significantly lower (two-sided p-value 0.05). Using an autoregressive time series model, we determined the intra-individual statistical significance of differences in mean CGMG and time Disclosure L.E. Castellanos: None. H. Zheng: None. C.A. Balliro: None. J. Sherwood: None. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.

This survey aimed to explore real-world physician experiences and treatment satisfaction with fast-acting insulin aspart (faster aspart) in clinical practice across Europe and Canada. An online web-based survey was used for physicians treating people with type 1 or type 2 diabetes. General practitioners and specialists, with experience using faster aspart, were interviewed. A total of 191 physicians participated in the survey. Most of their patients (68% of those with T1D and 63% of those with T2D) were previously treated with another mealtime insulin before switching to faster aspart. At the time of initiating faster aspart, nearly half of patients had an HbA1c level between 7.5% (59 mmol/mol) and 8.5% (69 mmol/mol). The main prescription drivers for faster aspart, versus other mealtime insulins, were faster onset of action, improved postprandial glucose (PPG) control, and dosing flexibility. Most physicians were more satisfied with faster aspart than other mealtime insulins regarding at-meal (66%) and post-meal (71%) dosing flexibility, improved PPG levels (66%), and onset of action (61%). Main reasons for not prescribing faster aspart included a good response to current treatment (76%) or patient reluctance to switch (57%). Overall, 12% of patients discontinued faster aspart, for reasons including concerns of hypoglycemia (17%), poor adherence (17%), and level of patient co-pay (17%). More than half of physicians had fewer concerns regarding postprandial hyperglycemia, and were more confident in their patients reaching their HbA1c target with faster aspart than with other mealtime insulins. The findings of this survey are based heavily on physicians’ experiences, and could therefore be subject to recall bias. Reported physician and patient experiences of using faster aspart have been positive, and better PPG control and increased dosing flexibility are expected to improve glycemic management.

OBJECTIVE According to recent guidelines, individuals with type 1 diabetes should spend

BACKGROUND Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS Children and adolescents (aged 1 to

Introduction Medtronic has developed a virtual patient simulator for modeling and predicting insulin therapy outcomes for people with type 1 diabetes (T1D). An enhanced simulator was created to estimate outcomes when using the MiniMedTM 670G system with standard NovoLog® (EU: NovoRapid, US: NovoLog) versus Fiasp ® by using clinical data. Methods Sixty-seven participants' PK profiles were generated per type of insulin (Total of 134 PK profiles). 7,485 virtual patients' PK measurements was matched with one of the 67 NovoLog® PK Tmax values. These 7,485 virtual patients were then simulated using the Medtronic MiniMed™ 670G algorithm following an in-silico protocol of 90 days: 14 days in open loop (Manual Mode) followed by 76 days in closed loop (Auto Mode). Simulation study was repeated with each NovoLog® PK profile being replaced by its corresponding Fiasp® PK profile in the same virtual patient. To validate our in-silico analysis, we compared the results of “actual” 19 “real life” patients from a clinical study Results Simulated overall and postprandial glycemic outcomes improved in all age groups with Fiasp®. The percentage of time in the euglycemic range increased by about ~2.2% with Fiasp®, in all age groups (p Conclusions The simulation studies indicate that using Fiasp® in place of NovoLog® with the MiniMedTM 670G system will significantly improve the time spent in the healthy, euglycemic range and reduce exposure to hyperglycemia and hypoglycemia in most patients.

Introduction The effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified. Methods Analyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants. Results The mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group. Conclusion For type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population. Trial Registration ClinicalTrials.gov, number (EudraCT nr: 2012-001941-42). Funding Novo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal’s Rapid Service Fee. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-00692-1) contains supplementary material, which is available to authorized users.

Macrostresses and microstresses coexist in ceramics, but are difficult to distinguish. In this work, these two types of residual stresses were separated by comparing the stress levels on the mechanically and argon beam polished surfaces of Al2O3–15 vol%SiC particulate reinforced composites. Stresses were measured using the shift of a Raman peak of β-SiC, the shift of a luminescence line of α-Al2O3 and a self-consistent approach. The critical grain size of SiC, over which will result in the crack formation in Al2O3 matrix, was calculated to be 13.5–26.4 μm. New microcracking did not form in Al2O3 grains during progressive mechanical polishing.

Introduction The majority of elderly patients (≥ 65 years of age) with type 2 diabetes mellitus (T2DM) will eventually require insulin therapy, but they are particularly vulnerable to hypoglycemia and challenging to treat. Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart administered in a single injection, either once or twice daily with main meals. Methods A combined analysis of the phase 3 BOOST INTENSIFY PREMIX I (NCT01009580) and BOOST INTENSIFY ALL (NCT01059812) trials has previously reported lower rates of hypoglycemia during the maintenance period in patients with T2DM treated with IDegAsp twice daily (BID) versus biphasic insulin aspart 30 (BIAsp 30) BID. This post hoc analysis examined the safety and efficacy of IDegAsp versus BIAsp 30 in elderly patients from the global population of these two trials, and also from the Japanese cohort of BOOST INTENSIFY ALL. Results Change in HbA1c was similar for IDegAsp versus BIAsp 30 (p > 0.5). Compared with BIAsp 30, IDegAsp resulted in significant reductions in fasting plasma glucose (p

Aim To compare the performance of HbA1c with established glucose criteria during an oral glucose tolerance test (OGTT) and to assess HbA1c as a screening test for undiagnosed diabetes and pre-diabetes after gestational diabetes mellitus (GDM). Methods Glucose homeostasis was re-evaluated 1–5 years after delivery in 140 women with previous GDM, by means of OGTT and simultaneous HbA1c measurement. Glucose tolerance was defined according to World Health Organisation criteria. HbA1c ≥6.5% (≥48 mmol/mol) was used for diabetes diagnosis and HbA1c ≥5.7% (≥39 mmol/mol) to define abnormal glucose homeostasis. Results HbA1c had low sensitivity (14.3%) and high specificity (99.1%) in diabetes diagnosis. Sensitivity and specificity of HbA1c to detect abnormal glucose tolerance were 29.5% and 95.2%, respectively. The consistency in classifying abnormal glucose tolerance between HbA1c and OGTT criteria was 59% (κ = 0.227) and the area under the receiver operating characteristic curve was 0.708. The combined use of HbA1c and fasting glucose criteria showed similar performance to that of fasting glucose criteria alone. The latter identified 63% of the women with pre-diabetes or diabetes in the study cohort. However, by lowering the cut-point of HbA1c to ≥5.0% (≥31 mmol/mol), an additional proportion (27%) with isolated post-glucose load hyperglycaemia was identified. Conclusion Proposed thresholds of HbA1c had low diagnostic sensitivity. Combined with a fasting glucose test, the performance was no better than with using a fasting glucose test alone. Combining a fasting glucose test with a lower HbA1c cut-point may be an alternative approach for selection of women for an OGTT., Highlights • We compare the performance of HbA1c with established glucose criteria during an oral glucose tolerance test (OGTT). • We also assess HbA1c as a screening test for undiagnosed diabetes and pre-diabetes after gestational diabetes mellitus. • Proposed thresholds of HbA1c had low diagnostic sensitivity relative to OGTT. • Combining HbA1c with a fasting glucose test the performance was no better than using a fasting glucose test alone. • Combining a fasting glucose test with a lower HbA1c cut-point may be an option for selection of women for an OGTT.

Multicenter long-term studies of predictors for the effectiveness of continuous subcutaneous insulin infusion (CSII) in clinical practice are lacking. We hypothesized that there are substantially greater reductions in hemoglobin A1c (HbA1c) in patients with poor glycemic control and that other predictors may also exist.We used data from 10 outpatient diabetic clinics in Sweden and studied CSII treatment over 5 years. Patients with HbA1c values available ≤ 6 months before starting CSII and at 5 years were included (n = 272, 82% of CSII patients) along with 2,437 contemporaneous controls on multiple daily insulin injections (MDI). Baseline variables evaluated were age, sex, diabetes duration, insulin dose, body mass index (BMI), HbA1c at baseline, and outpatient clinical care unit.At 5 years, significantly greater reductions in HbA1c by CSII compared with MDI were found for patients with higher baseline HbA1c (P = 0.032) and lower baseline BMI (P = 0.013). For baseline HbA1c levels of 7.0%, 8.0%, and 9.0% and a BMI of 25 kg/m(2), the reduction in HbA1c level by CSII was 0.08% (difference not significant), 0.16% (95% confidence interval, 0.03-0.29%), and 0.25% (95% confidence interval, 0.11-0.39%), respectively. Corresponding analyses for the change in HbA1c level from start to 1 and 2 years revealed a significant interaction of insulin pump therapy only with baseline HbA1c levels (P0.001 and P = 0.030, respectively). The interaction term between outpatient clinical care unit and CSII treatment was statistically significant for some care units, with some care units demonstrating a benefit from CSII and others demonstrating a detriment.Patients with high HbA1c levels have a greater probability of improved HbA1c after initiating pump therapy, but effects remain relatively modest even for patients with poor control. Factors predicting successful insulin pump use need further study.

Aims To compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. Methods In this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin ± oral antidiabetic drugs for ≥90 days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8–20 weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30–50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose Results During the treatment period, IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: −0.54 mmol/L [−1.02; −0.07]95% CI, p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. Conclusions IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.

We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes. We monitored 174 women with gestational diabetes by performing oral glucose tolerance tests during pregnancy as well as 1, 2 and 5 years postpartum. Women who developed impaired fasting glucose, impaired glucose tolerance or diabetes were compared with women who remained normoglycaemic at 5 years. Insulinogenic index, disposition index and HOMA-beta cell index were used to assess beta cell function; insulin resistance was estimated by HOMA index of insulin resistance. At 5 years postpartum, 30% of the women had developed diabetes and 51% some form of abnormal glucose tolerance. Women who developed diabetes had higher fasting glucose and HbA(1c) during pregnancy than those who remained normoglycaemic. They also had lower HOMA-beta cell index, insulinogenic index and disposition index than the normoglycaemic women. HbA(1c) and fasting glucose during pregnancy as well as the number of previous pregnancies and family history of diabetes were independent predictors of postpartum diabetes. HbA(1c) a parts per thousand yen4.7% (Swedish Mono S) or a parts per thousand yen5.7% (National Glycohemoglobin Standardization Program) and fasting blood glucose a parts per thousand yen5.2 mmol/l were associated with a four- to sixfold increased risk. Among women with gestational diabetes mellitus, those at risk of future diabetes can be identified by HbA(1c) and fasting glucose values in the upper normal range during pregnancy. A family history of diabetes and previous pregnancies further increase this risk.

Introduction Non-diabetic ketoacidosis is a rare condition which can be caused by starvation. Lack of glucose can force the body into ketogenesis causing a metabolic acidosis. As previously reported in the literature, ketoacidosis might, on rare occasions, be caused by a diet with low carbohydrate content. However, to the best of our knowledge this is the first reported case in the literature of ketoacidosis, in a non-diabetic patient, associated with a combination of low carbohydrate, high fat diet and lactation. Case presentation A healthy non-diabetic, 32-year old white woman started a low carbohydrate, high fat diet when she was breastfeeding her son of 10 months of age. After 10 days she was admitted to our hospital with nausea and vomiting and a serum pH of 7.20 and base excess of −19. Clinical signs and blood samples were compatible with ketoacidosis. She was given fluids intravenously and insulin. No anamnestic or clinical signs of diabetes were found. She recovered quickly and was discharged 3 days later. Conclusions Ketogenic diets like low carbohydrate, high fat may induce ketoacidosis. Lactation might further aggravate the condition and can perhaps even be the trigger into ketoacidosis. Health services should be aware of the risks associated with ketogenic diets, and be able to recognize this serious condition when it is presented.

Study question What are the effects of liraglutide, an incretin based treatment, on glycaemic control in people with type 2 diabetes treated with multiple daily insulin injections? Methods The study was a randomised, double blind, placebo controlled trial with a parallel group design carried out at 13 hospital based outpatient clinics and one primary care unit in Sweden. Patients were considered eligible for inclusion if they had type 2 diabetes and inadequate glycaemic control (HbA1c concentrations ≥58 mmol/mol (7.5%) and ≤102 mmol/mol (11.5%)), a body mass index of 27.5-45 kg/m2, and required multiple daily insulin injections. Overall, 124 participants were randomised 1:1 to subcutaneous liraglutide or placebo by minimisation allocation. The main outcome measure was change in HbA1c level from baseline to week 24. Study answer and limitations Liraglutide was associated with a significant reduction of 16.9 mmol/mol (1.5%) in HbA1c versus 4.6 mmol/mol (0.4%) for placebo, difference −12.3 mmol/mol (95% confidence interval −15.8 to −8.8 mmol/mol; −1.13%, −1.45 to −0.81 mmol/mol). Body weight was significantly reduced in participants in the liraglutide compared with placebo group (3.8 v 0.0 kg, difference −3.8, −4.9 to −2.8 kg), and total daily insulin doses were significantly reduced, by 18.1 units and 2.3 units (difference −15.8, −23.1 to −8.5 units). Reductions in mean and standard deviation of glucose levels estimated by masked continuous glucose monitoring were significantly greater in the liraglutide group than placebo group (−1.9 and −0.5 mmol/L). Neither group experienced severe hypoglycaemic events nor were there any significant differences in symptomatic or asymptomatic non-severe hypoglycaemia (

Aim: Guidelines for the treatment of type 1 diabetes generally recommend quarterly or more frequent Haemoglobin A1c (HbA1c) assessment in patients with inadequate glycaemic control. The purpose of the current study was to evaluate to what extent these guidelines are followed in clinical practice in Sweden. Method: We studied 5989 patients with type 1 diabetes from 10 outpatient diabetes clinics in Sweden from 1 January 2005 to 31 December 2009. Data on HbA1c measurement frequency were obtained from the Diab-Base electronic medical records database, where HbA1c measurements are recorded together with other patient characteristics, including treatment and other general risk factors for diabetic complications. The frequency of HbA1c measurements was obtained for all patients by calendar year, care unit, and during time periods where glucose was classified as well controlled (HbA1c7% was performed within 4 months. The probability of a subsequent assessment in the 4 months following an HbA1c value>7.0% increase in patients treated with continuous subcutaneous insulin infusion (CSII), OR=1.57 (1.46-1.69). Differences were also noted by care unit, age, gender, glycaemic control, calendar year, and weight and diabetes duration. Conclusion: In patients with type 1 diabetes, HbA1c is measured less frequently in clinical practice in Sweden than guidelines recommend, although patients with CSII and treated in certain care units receive more frequent assessments.

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has suggested new diagnostic criteria for gestational diabetes mellitus. Many centers in Europe still use the World Health Organization (WHO) criteria. In southern Sweden we use the 2-h threshold of the European Association for the Study of Diabetes criteria based on universal screening with a 75-g oral glucose tolerance test. We have retrospectively scrutinized oral glucose tolerance tests in a subset of 174 women included in a previous study, diagnosed with gestational diabetes mellitus 1996-1999. A complete repeat oral glucose tolerance test was performed directly after diagnosis in 120 women. When applying the current Swedish criteria, and the IADPSG and the WHO criteria to the material, gestational diabetes mellitus was confirmed in 67% (80/120), 84% (101/120), and 80% (96/120), respectively. Hence, 26% (101/80) more women were identified by the IADPSG criteria and 20% (96/80) more women by the WHO criteria, compared with the criteria presently in use.

The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1-2 years after delivery in 456 women with previous GDM (362 European, 94 non-European; including 41 Arab and 43 Asian women) and 133 control women. Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to quantify insulin secretion. Women developing diabetes after GDM were characterized by increased HOMA-IR [p = 0.010, adjusted for body mass index (BMI)], whereas the disposition index was decreased in all women with previous GDM irrespective of glucose tolerance, most pronounced in the presence of diabetes (BMI-adjusted p = 1 × 10(-5)). Non-European origin was associated with increased HOMA-IR (p = 0.001 vs. European), strengthened by adjustment for BMI in Asian women (p = 0.046 vs. p = 0.016), but eradicated among Arab women (p = 0.004 vs. p = 0.65). Non-European women exhibited an increased frequency of diabetes after GDM (17 % vs. European 4 %, p = 2 × 10(-5)). In addition to BMI, non-European and Asian origin was associated with the development of diabetes after GDM in a multivariate logistic regression analysis, whereas Arab origin was not. Our results highlight the importance of preventive measures to ensure a healthy lifestyle in women with GDM, particularly in high-risk ethnic groups.

Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p = 0.00016 after adjustment for age and ethnicity). Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

C and SiO2 of different types were mixed and heat-treated (1410° to 1550°C), according to a standardized temperature program, in flowing N2 at different pressures. It was found that a starting material combination of C (115 m2/g) and SiO2 (50 m2/g) yielded pure Si3N4 after about 2 h at 1550°C and 1.3 MPa. By adjustment of the pressure in the range 2 to 6 MPa, irreversible evaporation of SiO(g) as well as formation of nonequilibrium phases was suppressed, and the amounts of residual C and O in the sample were controlled. Even a small amount of CO in the N2 was observed to retard the nitridation. Possible explanations are discussed, based on thermodynamic calculations on the Si-O-N-C system.

C and SiO2 of different types were mixed and heat-treated (1410° to 1550°C), according to a standardized temperature program, in flowing N2 at different pressures. It was found that a starting material combination of C (115 m2/g) and SiO2 (50 m2/g) yielded pure Si3N4 after about 2 h at 1550°C and 1.3 MPa. By adjustment of the pressure in the range 2 to 6 MPa, irreversible evaporation of SiO(g) as well as formation of nonequilibrium phases was suppressed, and the amounts of residual C and O in the sample were controlled. Even a small amount of CO in the N2 was observed to retard the nitridation. Possible explanations are discussed, based on thermodynamic calculations on the Si-O-N-C system.

With the purpose of elucidating gas-phase reaction routes to Si3N4 within a C–SiO2 powder mixture, pieces of carbon and silica have been heat-treated at different temperatures and pressures in the range 1550–1710 °C, 0.5–6.0 MPa. The experiments were performed in gas autoclaves and with a controlled gas flow of N2 or N2–CO mixture through the sample container.Whether or not Si3N4 would form from the gas phase at specific T, p and CO content can be approximately predicted from thermodynamic calculations, based on a simple model including N2(g), SiO(g) and oxygen. The same model was found to be useful in predicting Si3N4 formation and growth in SiC powder heated in an N2–CO gas mixture. The nitridation rate in a fine-grained SiC powder, determined as a function of T and p, was found to increase with increasing p(N2) and p(SiO) but to decrease with increased oxygen activity. A tentative kinetic expression including these concentration variables has been formulated.

OBJECTIVE—To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—We studied mutations in MODY1–4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS—There was no increase in type 1 diabetes–associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1α gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS—MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.

Phase relations in the Si-C-O-N system were studied by subjecting mixtures of carbon and silica (C/SiO2= 2 to 3) to high temperatures (up to 2000 K) and elevated nitrogen pressures (0.5 to 2.0 MPa) in a gas autoclave. The condensed-phase assemblages obtained at different temperatures, pressures, and N/Si ratios are reported and compared with thermodynamic calculations. Values of ΔGfo(Si2ON2) consistent with the experimental data are -397 kJ/mol at 1780 K and -369 kJ/mol at 1890 K. The influence on the synthesis of seeding the starting material is discussed.