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The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy.Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study.Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period.Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Objective Due to the growing diabetes pandemic, the number of colonoscopies performed in patients with diabetes is steadily rising. However, recommendations on adjustments of anti-hyperglycaemic agents (AHG) during bowel preparation for colonoscopy are limited. Methods A total of nine articles were revealed on a PubMed search using the search terms “diabetes” and “colonoscopy”, “sigmoidoscopy”, “endoscopy”, “endoscopic intervention”, “endoscopic invasive diagnostics”, “endoscopic surgery”, or “diabetes care in the hospital” and manual screening of the references of the articles reporting on AHG adjustment during bowel preparation. Results Regular glucose measurements and the opportunity to contact the diabetes team were commonly advised. Recommendations also agreed that all oral AHG and short-acting insulin should be omitted when patients are on clear fluids. Recent studies suggest discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors even three days before the colonoscopy. In contrast, recommendations differed regarding adjustment of basal insulin depending on diabetes type and time point in relation to the intervention. Conclusions While discontinuation of oral AHG and short-acting insulin during bowel preparation for colonoscopy is generally accepted, recommendations on the adaptation of basal insulin follow different approaches.

Diabetes is an increasingly common disease that poses an immense challenge to public health. Hyperglycemia is also a common complication in clinical patients in the intensive care unit, increasing the rate of infection and mortality. The accurate and real-time prediction of blood glucose concentrations after each short-acting insulin injection has great clinical significance and is the basis of all intelligent blood glucose control systems. Most previous prediction methods require long-term continuous blood glucose records from specific patients to train the prediction models, resulting in these methods not being used in clinical practice. In this study, we construct 13 deep neural networks with different architectures to atomically predict blood glucose concentrations after arbitrary independent insulin injections without requiring continuous historical records of any patient. Using our proposed models, the best root mean square error of the prediction results reaches 15.82 mg/dL, and 99.5% of the predictions are clinically acceptable, which is more accurate than previously proposed blood glucose prediction methods. Through the re-validation of the models, we demonstrate the clinical practicability and universal accuracy of our proposed prediction method.

To assess the efficacy and safety of ultra-rapid insulin analogues used with continuous subcutaneous insulin infusion systems (CSII) in adults with type 1 diabetes (T1DM).We searched MEDLINE and Cochrane Library up to May 2022 for randomized controlled trials comparing ultra-rapid with rapid-acting insulin analogues (RAIAs) used with CSII. We performed random effects meta-analyses for % of 24-h time in range of 70-180 mg/dl (TIR), time in hypoglycaemia (70 mg/dl) and hyperglycaemia (180 mg/dl), 1- and 2-hour post-prandial glucose [PPG] increment after a meal test, HbA1c and average insulin dose at endpoint, unplanned infusion set changes and severe hypoglycaemia.Nine studies (1,156 participants) were included. Ultra-rapid insulins were superior to RAIAs on TIR (mean difference [MD] 1.1 %, 95 % CI 0.11-2.11), time spent in hypoglycaemia (MD -0.47 %, 95 % CI -0.63 to -30), and 1- and 2-hour PPG (MD -12.20 mg/dl, 95 % CI -19.85 to -4.54 and MD -17.61 mg/dl, 95 % CI -28.55 to -6.66, respectively). Ultra-rapid insulins increased odds of unplanned infusion set changes (odds ratio 1.60, 95 % CI 1.26-2.03).Ultra-rapid acting insulins provided better PPG control compared to RAIAs but their use might result in more infusion set changes.

OBJECTIVE: To investigate the current status of the availability and affordability of specific essential medicines and diagnostics for diabetes in Africa. METHODS: Systematic review and meta-analysis. Studies conducted in Africa that reported any information on the availability and affordability of short-acting, intermediate-acting, and premixed insulin, glibenclamide, metformin, blood glucose, glycated haemoglobin or HbA1c, and lipid profile tests were included. Random-effect model meta-analysis and descriptive statistics were performed to determine the pooled availability and affordability, respectively. RESULTS: A total of 21 studies were included. The pooled availability of each drug was as follows: short-acting insulin 33.5% (95% CI: 17.8% - 49.2%, I2 =95.02%), intermediate-acting insulin 23.1% (95% CI: 6.3% - 39.9%, I2 =91.6%), premixed insulin 49.4% (95% CI: 24.9% - 73.9%, I2 =90.57%), glibenclamide 55.9% (95% CI: 43.8% - 68.0%, I2 =96.7%), and metformin 47.0% (95% CI: 34.6% - 59.4, I2 =97.54%). Regarding diagnostic tests, for glucometers the pooled availability was 49.5% (95% CI: 37.9% - 61.1%, I2 =97.43%), for HbA1c 24.6% (95% CI: 3.1% - 46.1%, I2 =91.64), and for lipid profile tests 35.7% (95% CI: 19.4% - 51.9%, I2 =83.77%). The median (IQR) affordability in days' wages was 7 (4.7-7.5) for short-acting insulin, 4.4 (3.9-4.9) for intermediate-acting insulin, 7.1 (5.8-16.7) for premixed insulin, 0.7 (0.7-0.7) for glibenclamide, and 2.1 (1.8-2.8) for metformin. CONCLUSION: The availability of the five essential medicines and three diagnostic tests for diabetes in Africa is suboptimal. The relatively high cost of insulin, HbA1c, and lipid profile tests is a significant barrier to optimal diabetes care. Pragmatic country-specific strategies are urgently needed to address these inequities in access and cost.

ObjectiveUltra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog® and Lyumjev® formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model.MethodsWe employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy.ResultsThrough experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step.ConclusionsThis study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future.HighlightsHexamer dissociation is not the absorption rate-limiting step for insulin lisproLyumjev excipients enhance insulin microvascular absorption and diffusionVascular endothelial transit determines the overall absorption for insulin lisprInsulin diffusion studied for the first time at the injection site of live animalsIn vivo imaging is a powerful tool to study injection site dynamics

Human insulin and its synthetic analogs are considered as life-saving drugs for people suffering from diabetes mellitus. Next to the therapeutic use, scientific and non-scientific literature (e.g. bodybuilding forums; antidoping intelligence and investigation reports) indicate that these prohibited substances are used as performance enhancing agents. In the present report, the development and validation of a sensitive analytical strategy is described for the urinary detection of three rapid-acting insulin analogs (Lispro, Aspart, Glulisine). The method is based on sample purification by the combination of ultrafiltration and immunoaffinity purification and subsequent analysis by nano-flow liquid chromatography coupled to high resolution mass spectrometry. Next to the results on different validation parameters (LOD: 10 pg/mL; recovery: 25-48%; matrix effect: -3-(-8) %), data on urinary elimination times, which were obtained in the frame of an administration study with the participation of healthy volunteers, are presented. The determined detection windows (~9 hours) are expected to help to evaluate current routine analytical methods and aim to aid doping authorities to set appropriate target windows for efficient testing.

Despite several molecular and technological advances in insulin therapy and insulin delivery, global evidence highlights inadequate glycemic control in populations with type 1 diabetes (T1D) and type 2 diabetes (T2D). In this review, we discuss the importance of more precise dosing of insulin as one of the approaches to improve glycemic control while reducing hypoglycemic events. This report is based on the expert opinion of authors and literature search of articles relevant to the past and present insulin delivery devices in diabetes management, especially half-unit insulin pens. We describe the various factors that facilitate better glycemic control, focusing on the impact of appropriate insulin delivery device selection on diabetes management. Precision dosing of insulin is a lesser-studied factor that contributes toward better glycemic control. Insulin pens have consistently outperformed syringes as delivery devices due to their greater accuracy and precision of dosing, ease-of-use, and patient preference. These advantages make them better suited to administer insulin in hypoglycemia-prone insulin-sensitive people with T1D, particularly younger children and geriatric patients. Half-unit insulin pens further extend this benefit by delivering half-unit doses of insulin accurately. They may contribute to better management of diabetes by allowing flexible dosing for mealtimes and physical activities even in erratic diet situations or illnesses by offering corrective doses in small increments. They are ideal delivery devices for insulin-sensitive people with T1D who require greater accuracy and precision in insulin delivery to achieve more stringent glycemic control.

Aims/hypothesis We analysed data obtained from the electronic patient records of inpatients with diabetes admitted to a large university hospital to understand the prevalence and distribution of inpatient hypoglycaemia. Methods The study was conducted using electronic patient record data from Oxford University Hospitals NHS Foundation Trust. The dataset contains hospital admission data for patients coded for diabetes. We used the recently agreed definition for a level 1 hypoglycaemia episode as any blood glucose measurement Results We analysed data obtained from 17,658 inpatients with diabetes (1696 with type 1 diabetes, 14,006 with type 2 diabetes, and 1956 with other forms of diabetes; 9277 men; mean ± SD age, 66 ± 18 years) who underwent 32,758 hospital admissions between July 2014 and August 2018. The incidence of level 1 hypoglycaemia was 21.5% and the incidence of level 2 hypoglycaemia was 9.6%. Recurrent level 1 and level 2 hypoglycaemia occurred, respectively, in 51% and 39% of hospital admissions in people with type 2 diabetes with at least one hypoglycaemic episode, and in 55% and 45% in those with type 1 diabetes. The incidence of level 2 hypoglycaemia in people with type 2 diabetes, when corrected for the number of people who remained in hospital, remained constant for the first 100 h at approximately 0.15 events per h per admission. With regards to the hypoglycaemia distribution during the day, after correcting for the number of blood glucose tests per h, there were two clear spikes in the rate of hypoglycaemia approximately 3 h after lunch and after dinner. The highest rate of hypoglycaemia per glucose test was seen between 01:00 hours and 05:00 hours. Medication had a significant impact on the incidence of level 2 hypoglycaemia, ranging from 1.5% in people with type 2 diabetes on metformin alone to 33% in people treated with a combination of rapid-acting insulin analogue, long-acting insulin analogue and i.v.-administered insulin. Conclusions/interpretation Retrospective analysis of data from electronic patient records enables clinicians to gain a greater understanding of the incidence and distribution of inpatient hypoglycaemia. This information should be used to drive evidence-based improvements in the glycaemic control of inpatients through targeted medication adjustment for specific populations at high risk of hypoglycaemia.

BackgroundWe aim to evaluate the impact of prepregnancy overweight on treatment modalities of Gestational Diabetes Mellitus (GDM). We assessed the association of increased pregravid Body Mass Index (BMI) with dosing of basal and rapid acting insulin as well as pregnancy outcome.MethodsWe included 509 gestational diabetic women (normal weight: 200, overweight: 157, obese: 152), attending the pregnancy outpatient clinic at the Department of Obstetrics and Gynecology, Medical University of Vienna, in this retrospective study. We used a prospectively compiled database to assess patient characteristics, treatment approaches – particularly maximum doses of basal and rapid acting insulin or metformin – and pregnancy outcome.ResultsIncreased BMI was associated with the need of glucose lowering medication (odds ratio (OR): 1.08 for the increase of 1 kg/m² BMI, 95%CI 1.05–1.11, pConclusionsTreatment modalities and outcome in GDM pregnancies are closely related to the extent of maternal BMI. Patients with obesity required glucose lowering medication more often and were at higher risk of adverse pregnancy outcomes. It is crucial to further explore the underlying pathophysiologic mechanisms to optimize clinical management and individual treatment approaches.

International audience; Objectives: In the management of diabetic patients on insulin therapy, adherence to medication is a key element for avoiding chronic complications. The purpose of this study was to evaluate diabetic patients' ability to translate glycemic results into an appropriate insulin dose and thus, adherence to insulins.Methods: This was an observational, retrospective, monocentric pilot study. Diabetic patients on insulin therapy being followed at the metabolic and endocrine diseases department were divided into two groups depending on their mode of glycemic control at home: capillary glycemia (Notebook group) or interstitial glycemia using the FreeStyle Libre® flash system (FSL group). Adherence was assessed based on the rate of compliance in adapting insulin doses to the prescribed protocols (depending on type of insulin, glycemic targets, and patients' characteristics) by a pharmacy resident and a senior diabetologist. Good adherence was defined as a minimum rate of 80% of conforming insulin injections for each patient.Results: A total of 50 patients were included, 35 in the Notebook group and 15 in the FSL group. Two-thirds of patients were non-adherent to insulin. Dose adjustment errors mainly concerned rapid-acting insulin with 51.1% of non- conformities, 10.0% of which were due to underdosing in the Notebook group and 21.7% to overdosing in the FSL group. Hyperglycemia was predominant in both populations with a median time in range of 19.0% in the FSL group and well below recommendations (>70%).Conclusions: Despite the use of increasingly efficient, easy-to-use devices in diabetes monitoring, insulin non-adherence and glycemic imbalance are unresolved major issues. Diabetic patients require reinforced medical follow-up for optimal insulin management.

Guidelines discourage sliding scale insulin (SSI) use after the first week of a nursing home (NH) admission. We sought to determine the prevalence of SSI and identify factors associated with stopping SSI or transitioning to another short-acting insulin regimen.In an observational study from October 1, 2013, to June 30, 2017 of non-hospice Veterans Affairs NH residents with type 2 diabetes and an NH admission over 1 week, we compared the weekly prevalence of SSI versus two other short-acting insulin regimens - fixed dose insulin (FDI) or correction dose insulin (CDI, defined as variable SSI given alongside fixed doses of insulin) - from week 2 to week 12 of admission. Among those on SSI in week 2, we examined factors associated with stopping SSI or transitioning to other regimens by week 5. Factors included demographics (e.g., age, sex, race/ethnicity), frailty-related factors (e.g., comorbidities, cognitive impairment, functional impairment), and diabetes-related factors (e.g., HbA1c, long-acting insulin use, hyperglycemia, and hypoglycemia).In week 2, 21% of our cohort was on SSI, 8% was on FDI, and 7% was on CDI. SSI was the most common regimen in frail subgroups (e.g., 18% of our cohort with moderate-severe cognitive impairment was on SSI vs 5% on FDI and 4% on CDI). SSI prevalence decreased steadily from 21% to 16% at week 12 (p for linear trend0.001), mostly through stopping SSI. Diabetes-related factors (e.g., hyperglycemia) were more strongly associated with continuing SSI or transitioning to a non-SSI short-acting insulin regimen than frailty-related factors.SSI is the most common method of administering short-acting insulin in NH residents. More research needs to be done to explore why sliding scale use persists weeks after NH admission and explore how we can replace this practice with safer, more effective, and less burdensome regimens.

AIMS The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D. MATERIALS AND METHODS This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups. RESULTS Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group. CONCLUSIONS For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

Glycemic control through titration of insulin dosing remains the mainstay of diabetes mellitus treatment. Insulin therapy is generally divided into dosing with long- and short-acting insulin, where long-acting insulin provides basal coverage and short-acting insulin supports glycemic excursions associated with eating. The dosing of short-acting insulin often involves several steps for the user including blood glucose measurement and integration of potential carbohydrate loads to inform safe and appropriate dosing. The significant burden placed on the user for blood glucose measurement and effective carbohydrate counting can manifest in substantial effects on adherence. Through the application of computer vision, we have developed a smartphone-based system that is able to detect the carbohydrate load of food by simply taking a single image of the food and converting that information into a required insulin dose by incorporating a blood glucose measurement. Moreover, we report the development of comprehensive all-in-one insulin delivery systems that streamline all operations that peripheral devices require for safe insulin administration, which in turn significantly reduces the complexity and time required for titration of insulin. The development of an autonomous system that supports maximum ease and accuracy of insulin dosing will transform our ability to more effectively support patients with diabetes.

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.