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This study presents a portable, low-cost, point-of-care (POC) system for the simultaneous detection of blood glucose and hematocrit. The system consists of a disposable origami microfluidic paper-based analytical device (μPAD) for plasma separation, filtration, and reaction functions and a 3D-printed cassette for hematocrit and blood glucose detection using a smartphone. The origami μPAD is patterned using a cost-effective label printing technique instead of the conventional wax printing method. The 3D-printed cassette incorporates an array of LED lights, which mitigates the effects of intensity variations in the ambient light and hence improves the accuracy of the blood glucose and hematocrit concentration measurements. The hematocrit concentration is determined quantitatively by measuring the distance of plasma wicking along the upper layer of the origami μPAD, which is pretreated with sodium chloride and Tween 20 to induce dehydration and aggregation of the red blood cells. The filtered plasma also penetrates to the lower layer of the origami μPAD, where it reacts with embedded colorimetric assay reagents to produce a yellowish-brown complex. A color image of the reaction complex is captured using a smartphone inserted into the 3D-printed cassette. The image is analyzed using self-written RGB software to quantify the blood glucose concentration. The calibration results indicate that the proposed detection platform provides an accurate assessment of the blood glucose level over the range of 45-630 mg/dL (R 2 = 0.9958). The practical feasibility of the proposed platform is demonstrated by measuring the blood glucose and hematocrit concentrations in 13 human whole blood samples. Taking the measurements obtained from commercial glucose and hematocrit meters as a benchmark, the proposed system has a differential of no more than 6.4% for blood glucose detection and 9.1% for hematocrit detection. Overall, the results confirm that the proposed μPAD is a promising solution for cost-effective and reliable POC health monitoring.

In low-resource settings, dermatologists may not have the preferred tools needed to evaluate a patient or perform a procedure. Commonplace affordable supplies can be substituted when needed. We describe the use of a blood glucose testing lancet and a paper clip for milia extraction.

A ternary hierarchical hybrid Ni@Co x S y /poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@Co x S y /PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@Co x S y /PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@Co x S y /PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 μM ~ 2.0 mM) with high sensitivity (1546.32 μA cm -2  mM -1 ), a rapid response time (5 s), an ultralow detection limit (0.094 μM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

While there are data regarding the glycaemic index (GI) and glycaemic load (GL) of many foods in the literature, the values for packaged vegan analogue foods have not been previously published, although processed vegan foods usually contain more carbohydrates than their animal-based counterparts. This study was carried out to determine the GI and GL values of a selection of packaged vegan foods popular in Türkiye. To determine the GI and GL of test foods, 12 healthy volunteer females participated in the study. Participants randomly consumed test and reference foods (glucose and white bread) on each trial day, and capillary blood glucose was measured at baseline, 15, 30, 45, 60, 90 and 120 mins in duplicate. The GIs of vegan schnitzel, vegan chickpea burger, vegan mince pita, vegan chocolate, vegan snack bar and vegan cheese were 26.1 ± 19.61 (low), 27.1 ± 17.21 (low), 65.1 ± 28.60 (moderate), 42.7 ± 22.32 (low), 63.6 ± 45.86 (moderate), 36.4 ± 16.85 (low), respectively, according to the glucose reference, and were 28.2 ± 16.17 (low), 34.7 ± 18.26 (low), 81.2 ± 31.96 (high), 48.8 ± 12.87 (low), 82.0 ± 54.05 (high), 46.7 ± 28.66 (low), respectively, according to the white bread reference. GLs were 3.5 ± 2.66 (low), 8.6 ± 5.46 (low), 26.6 ± 11.67 (high), 6.1 ± 3.19 (low), 14.2 ± 10.28 (moderate), 5.7 ± 2.63 (low), respectively, according to the glucose reference, and were 3.8 ± 2.19 (low), 11.0 ± 5.80 (moderate), 33.1 ± 13.04 (high), 7.0 ± 1.84 (low), 18.4 ± 12.12 (moderate), 7.3 ± 4.47 (low), respectively, according to the white bread reference. The data from this study provide preliminary data for the GIs and GLs of packaged and processed vegan foods and show that the GIs and GLs of meat and cheese vegan analogues, while still low or moderate, tend to be higher than their animal-based counterparts which have lower or no glycaemic responses. Further research on the GIs and GLs of more vegan foods is needed., (© 2024 British Nutrition Foundation.)

Objectives: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance., Materials and Methods: High-risk individuals with a CDKN2A/p16 germline pathogenic variant participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve was computed., Results: In total, 220 HRIs were included between 2000 and 2019. Median age was 61 (interquartile range. 53-71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (odds ratio, 1.21; 95% confidence interval, 0.39-3.78) and 4 of 5 PDAC cases seemed to have NOD within 3 months before diagnosis. Furthermore, NOD did not differentiate between HRIs with and without PDAC (area under the curve, 0.54; 95% confidence interval, 0.46-0.61)., Conclusions: In this study, we found no added value for longitudinal glucose monitoring in CDKN2A pathogenic variant carriers participating in an imaging-based pancreatic cancer surveillance program., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

We study the effect of economic conditions early in life on the occurrence of type-2 diabetes in adulthood using contextual economic indicators and within-sibling pair variation. We use data from Lifelines: a longitudinal cohort study and biobank including 51,270 siblings born in the Netherlands from 1950 onward. Sibling fixed-effects account for selective fertility. To identify type-2 diabetes we use biomarkers on the hemoglobin A1c concentration and fasting glucose in the blood. We find that adverse economic conditions around birth increase the probability of type-2 diabetes later in life both in males and in females. Inference based on self-reported diabetes leads to biased results, incorrectly suggesting the absence of an effect. The same applies to inference that does not account for selective fertility., (© 2024 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Purpose: The diagnosis of insulinoma can be challenging, requiring documentation of hypoglycaemia associated with non-suppressed insulin and C-peptide, often achieved during a prolonged 72 h fast performed in inpatient setting. Our goal is to predict weather a shorter outpatient fasting test initiated overnight and prolonged up until 24 h could be a sensitive method for diagnosing insulinoma., Methods: We conducted a retrospective monocentric study on subjects admitted to our Unit of Endocrinology from 2019 to 2022 for clinical suspicion of insulinoma and underwent the short fasting test. A comparison between the short test group and the group of subjects who underwent the standard prolonged fasting test (from 2003 to 2018) has also been performed. The short fasting test was initiated by the patient overnight at home and proceeded the following day in outpatient setting (Day Hospital). As in the standard protocol, symptoms and capillary blood glucose (CBG) were strictly monitored. Venous blood was drawn for glycaemia, insulin and C-peptide at admission and at established intervals, in case of symptoms of hypoglycaemia or if CBG ≤ 45 mg/dl, when the fast would be suspended., Results: The final sample consisted of 37 patients, with mean age of 44.5 ± 12.6 years (17-74). Short and standard tests were performed in 15 and 22 subjects, respectively. Diagnostic values for insulinoma were observed in 12 patients: in 5/15 who underwent the short fasting test, in 6/22 who underwent the prolonged test and in 1 patient who was initially negative on the short test and subsequently showed diagnostic values during the prolonged test. The diagnosis of insulinoma was achieved in 11/12 cases within 24 h of the beginning of the fast (91.7%)., Conclusions: A short fasting test could be a valid, sensitive and reliable first-line workup in diagnosing insulinoma., (© 2024. The Author(s).)

The volume of interstitial fluid (ISF) in the human body is three times that of blood. Yet, collecting diagnostically useful ISF is more challenging than collecting blood because the extraction of dermal ISF disrupts the delicate balance of pressure between ISF, blood and lymph, and because the triggered local inflammation further skews the concentrations of many analytes in the extracted fluid. In this Perspective, we overview the most meaningful differences in the make-up of ISF and blood, and discuss why ISF cannot be viewed generally as a diagnostically useful proxy for blood. We also argue that continuous sensing of small-molecule analytes in dermal ISF via rapid assays compatible with nanolitre sample volumes or via miniaturized sensors inserted into the dermis can offer clinically advantageous utility, particularly for the monitoring of therapeutic drugs and of the status of the immune system., (© 2023. Springer Nature Limited.)

Previous studies on the effect of Brassica vegetables on blood glucose and lipid profile have reported inconclusive findings. Due to the high prevalence of glucose and lipid metabolism disorders and their importance as predictors of chronic diseases, the present meta-analysis was performed to clarify the effect of Brassica vegetables on blood glucose and lipid profile. A systematic search of the databases of PubMed, Scopus, and Cochran Library was performed up to October 2020. All randomized controlled trials (RCTs) that examined the effect of Brassica vegetables on blood glucose and lipid profile were included in the study. The search results were limited to English-language publications. Finally, nine RCTs, including 548 participants, were selected for the present study. Pooled analysis indicated a significant reduction in total cholesterol (TC) (SMD = -0.28, 95%CI: 0.48 to 0.08; p = 0.005) following Brassica vegetables consumption. Overall, Brassica vegetables had no significant impact on serum levels of triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood sugar, and glycated hemoglobin. Consumption of Brassica vegetables had a statistically significant effect on TC concentration. However, further high-quality studies are needed to firmly establish the clinical efficacy of these plants., (© 2022 John Wiley & Sons Ltd.)

Aim: To evaluate the effect on glucose control of professional continuous glucose monitoring (p-CGM)-based care as compared with standard care in the management of patients with type 1 and type 2 diabetes., Materials and Methods: The PubMed database was searched comprehensively to identify prospective or retrospective studies evaluating p-CGM as a diagnostic tool for subsequent implementation of lifestyle and/or medication changes and reporting glycated haemoglobin (HbA1c) as an outcome measure., Results: We found 872 articles, 22 of which were included in the meta-analysis. Overall, the use of p-CGM was associated with greater HbA1c reduction from baseline (-0.28%, 95% confidence interval [CI] -0.36% to -0.21%, I 2  = 0%, P < 0.00001) than usual care, irrespective of type of diabetes, length of follow-up, frequency of continuous glucose monitoring (CGM) use and duration of CGM recording. In the few studies describing CGM-derived glucose metrics, p-CGM showed a beneficial effect on change in time in range from baseline (5.59%, 95% CI 0.12 to 11.06, I 2  = 0%, P = 0.05) and a neutral effect on change in time below the target range from baseline (-0.11%, 95% CI -1.76% to 1.55%, I 2  = 33%, P = 0.90)., Conclusions: In patients with type 1 and type 2 diabetes, p-CGM-driven care is superior to usual care in improving glucose control without increasing hypoglycaemia., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

According to the latest statistics, more than 537 million people around the world struggle with diabetes and its adverse consequences. As well as acute risks of hypo- or hyper- glycemia, long-term vascular complications may occur, including coronary heart disease or stroke, as well as diabetic nephropathy leading to end-stage disease, neuropathy or retinopathy. Therefore, there is an urgent need to improve diabetes management to reduce the risk of complications but also to improve patient's quality life. The impact of continuous glucose monitoring (CGM) is well recognized, in this regard. The current review aims at introducing the basic principles of glucose sensing, including electrochemical and optical detection, summarizing CGM technology, its requirements, advantages, and disadvantages. The role of CGM systems in the clinical diagnostics/personal testing, difficulties in their utilization, and recommendations are also discussed. In the end, challenges and prospects in future CGM systems are discussed and non-invasive, wearable glucose biosensors are introduced. Though the scope of this review is CGMs and provides information about medical issues and analytical principles, consideration of broader use will be critical in future if the right systems are to be selected for effective diabetes management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The present study elucidated hepatic molecular and physiological responses of giant gourami to high dietary carbohydrates. Two levels of dietary carbohydrate, normal carbohydrate (34%, NC) and high carbohydrate (53%, HC), were offered to the fish for 60 days. We evaluated the expression of genes that are related to carbohydrate metabolism, lipogenic capacities, amino acid catabolism, Krebs cycle, and energy sensing. In addition, we also observed the digestive enzyme activities, plasma glucose, glycogen content, whole-body composition, and growth performance of the fish. On day 30 after treatment, fish fed with high dietary carbohydrate level has significantly higher expression of gck, pk, hk, and ldh than the NC group (P < 0.05). In contrast, fish in the HC group had lower expression of irs1, igf-1, sdh, fbp, g6pc, gyp, and ampk compared to the NC fish (P < 0.05). On day 60 of the feeding trial, gck and hk expressions were still higher in the HC group (P < 0.05), and gyp, gdh, and ampk became increasingly expressed in the HC group. The increase of dietary carbohydrates resulted in significant increases in amylase and protease activity, plasma glucose, liver glycogen, crude protein, and lipid contents of the fish whole-body (P < 0.05). The high carbohydrate feeding reduced the fish growth rate but increased feed efficiency and did not affect mortality. In conclusion, giant gourami could utilize high carbohydrates due to a high amylase secretion, high modulation of carbohydrate metabolism, and large glucose storage capacity., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Microfluidic paper analytical devices (µPADs) represent one of the most appealing trends in the development of simple and inexpensive analytical systems for diagnostic applications at the point of care (POC). Herein, we describe a smartphone-based origami µPAD for the quantitative determination of glucose in blood samples based on the glucose oxidase-catalyzed oxidation of glucose leading to hydrogen peroxide, which is then detected by means of the luminol/hexacyanoferrate(III) chemiluminescent (CL) system. By exploiting the foldable µPAD format, a two-step analytical procedure has been implemented. First, the diluted blood sample was added, and hydrogen peroxide was accumulated, then the biosensor was folded, and a transport buffer was added to bring hydrogen peroxide in contact with CL reagents, thus promoting the CL reaction. To enable POC applicability, the reagents required for the assay were preloaded in the µPAD so that no chemicals handling was required, and a 3D-printed portable device was developed for measuring the CL emission using the smartphone's CMOS camera. The µPAD was stable for 30-day storage at room temperature and the assay, displaying a limit of detection of 10 µmol L -1 , proved able to identify both hypoglycemic and hyperglycemic blood samples in less than 20 min.

A novel smartphone and paper-based analytical device is constructed for glucose monitoring using acetylene black (AB)-hemin nanozyme as catalyst. [Display omitted] • A significant increase in peroxidase-like activity of acetylene black loaded hemin. • Point of care test can be realized by combined with smartphone for blood monitoring. • Test results in undiluted serum are in good consistency with commercial glucometer. Glucose management is an important part of disease control for diabetes patients, thus the development of a rapid and real-time point of care testing (POCT) device for monitoring blood glucose is of great significance. In this work, a paper-based analytical device (PAD) is constructed by combining acetylene black (AB)-hemin complex modified filter paper as sensing platform with a smartphone as signal detector. Large specific surface area of AB decreases the self-associate and aggregate of hemin in aqueous solution, resulting in improved peroxidase-like activity of hemin. Compared with graphene oxide supported hemin, AB-hemin exhibits superior signal response on paper. Glucose oxidase (GOx) catalyzes the conversion of blood glucose to hydrogen peroxide, and then AB-hemin complex catalyzes the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue TMB oxidized products (TMB+) in the presence of hydrogen peroxide, thus achieving the visual detection of blood glucose. In optimal conditions, PAD provides an applicable linear range from 0.2 mM to 30 mM and a low limit of detection (LOD) (0.06 mM). Notably, the detection accuracy of the developed paper-based sensor is in good agreement with that of the commercially available blood glucose meter (p > 0.05). Moreover, the proposed PAD presents high recoveries from 95.4% to 112% (RSD ≤ 3.2%), and therefore holds great potential for glucose monitoring and diabetes diagnosis. [ABSTRACT FROM AUTHOR]

Continuous glucose monitoring (CGM) is of great importance to the treatment and prevention of diabetes. As a proven commercial technology, electrochemical glucose sensor based on interstitial fluid (ISF) sensing has high sensitivity and wide detection range. Therefore, it has good promotion prospects in noninvasive or minimally-invasive CGM system. However, since there are concentration differences and time lag between glucose in plasma and ISF, the accuracy of this type of sensors are still limited. Typical calibration algorithms rely on simple linear regression which do not account for the variability of the sensitivity of sensors. To enhance the accuracy and stability of CGM based on ISF, optimization of calibration algorithm for sensors is indispensable. While there have been considerable researches on improving calibration algorithms for CGM, they have still received less attention. This article reviews the problem of typical calibration and presents the outstanding calibration algorithms in recent years. Finally, combined with existing research and emerging sensing technologies, this paper makes an outlook on the future calibration algorithms for CGM sensors., Competing Interests: Declaration of competing interest This work was supported by National Key R&D program of China (2022YFB3203700) and the Fundamental Research Funds for the Central Universities, There are no financial/commercial conflicts of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Continuous glucose monitoring (CGM) has become an increasingly important tool for self-management in people with diabetes mellitus (DM). In this paper, we discuss recommendations on how to implement predictive features provided by the Accu-Chek SmartGuide Predict app in clinical practice. The Predict app's features are aimed at ultimately reducing diabetes stress and fear of hypoglycemia in people with DM. Furthermore, we explore the use cases and potential benefits of continuous glucose prediction, predictions of low glucose, and nocturnal hypoglycemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GB, TG, MH, MS, and NW are employees and stockholders of Roche Diabetes Care GmbH. BG received lecture fees and/or consulting of Roche, Dexcom, Abbott, Vitalaire, Diabeloop, Ascensia, and Insulet. DE received lecture fees from Roche Diabetes Care, Sanofi-Aventis, Dexcom; Advisory Board member of Roche Diabetes Care, and Dexcom. MTPM received lecture fees and/or consulting fees from Abbott, Air Liquide, Sanofi, Novo Nordisk, Ascensia, Roche, Lilly, Medtronic, and Liesno Buno. JO received lecture fees from Abbott.

Aims: To evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia., Methods: Patients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the β-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months., Results: We randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was - 2.06 ± 1.37 %, -0.43 ± 0.32 %, and - 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy., Conclusion: A 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Type 1 diabetes (T1D) presents a significant health challenge, requiring patients to actively manage their blood glucose (BG) levels through regular bolus insulin administration. Automated control solutions based on machine learning (ML) models could reduce the need for manual patient intervention. However, the accuracy of current models falls short of what is needed. This is due in part to the fact that these models are often trained on data collected using a basal bolus (BB) strategy, which results in substantial entanglement between bolus insulin and carbohydrate intake. Under standard training approaches, this entanglement can lead to inaccurate forecasts in a control setting, ultimately resulting in poor BG management. To address this, we propose a novel algorithm for training BG forecasters that disentangles the effects of insulin and carbohydrates. By exploiting correction bolus values and leveraging the monotonic effect of insulin on BG, our method accurately captures the independent effects of insulin and carbohydrates on BG. Using an FDA-approved simulator, we evaluated our approach on 10 individuals across 30 days of data. Our approach achieved on average higher time in range compared to standard approaches (81.1% [95% confidence interval (CI) 80.3,81.9] vs 53.6% [95%CI 52.7,54.6], p<0.001), indicating that our approach is able to reliably maintain healthy BG levels in simulated individuals, while baseline approaches are not. Utilizing proxy metrics, our approach also demonstrates potential for improved control on three real world datasets, paving the way for advancements in ML-based BG management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy., Methods: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better β-cell function recovery after CSII therapy., Results: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05)., Conclusions: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better β-cell function recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

GLP-1 receptor agonists (GLP-1RAs) are an innovative class of drugs with significant therapeutic value for type 2 diabetes mellitus (T2DM). The GLP-1RAs currently available on the market are biologic macromolecular peptide agents that are expensive to treat and not easy to take orally. Therefore, the development of small molecule GLP-1RAs is becoming one of the most sought-after research targets for hypoglycemic drugs. In this study, we sought to find a potential oral small molecule GLP-1RA and to evaluate its effect on insulin secretion in rat pancreatic β cells and on blood glucose in mice. We downloaded the mRNA expression profiles of GSE102194 and GSE37936 from the Gene Expression Omnibus database. Subsequently, the small molecule compound idebenone was screened through the connectivity map database. The results of molecular docking, biolayer interferometry, and cellular thermal shift assay indicated that idebenone could bind potently with GLP-1R. Furthermore, ibebenone elevated intracellular cAMP levels. The radioimmunoassay data showed that idebenone enhanced glucose-stimulated insulin secretion via agonism of GLP-1R. Moreover, the results of oral glucose tolerance tests in C57BL/6, Glp-1r -/- , and hGlp-1r mice demonstrated that the glucose-lowering effects of idebenone were mediated by GLP-1R and that there were no species differences in the agonistic effect of idebenone on GLP-1R. In summary, idebenone reduces blood glucose in mice by promoting insulin release through agonism of GLP-1R, suggesting that idebenone is probably a potential GLP-1RA, which is expected to provide a new therapeutic strategy for the prevention and treatment of metabolic diseases such as T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Prediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects., Purpose: This study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy., Study Design and Methods: In this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed., Results: Compared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study., Conclusions: Among prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dazhuo Shi reports article publishing charges was provided by National Natural Science Foundation of China. Jie Gao reports article publishing charges was provided by Fundamental Research Funds for the Central Public Welfare Research Institutes. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Objectives: This study was designed to compare individualized and conventional hyperglycemic thresholds for the risk of acute kidney injury (AKI) after cardiac surgery., Design: This was an observational study., Setting: The study took place in a single-center tertiary teaching hospital., Participants: Adult patients who underwent cardiac surgery between January 2012 and November 2021 were enrolled., Measurements and Main Results: Two blood glucose thresholds were used to define intraoperative hyperglycemia. While the conventional hyperglycemic threshold (CHT) was 180 mg/dL in all patients, the individualized hyperglycemic threshold (IHT) was calculated based on the preoperative hemoglobin A1c level. Various metrics of intraoperative hyperglycemia were calculated using both thresholds: any hyperglycemic episode, duration of hyperglycemia, and area above the thresholds. Postoperative AKI associations were compared using receiver operating characteristic curves and logistic regression analysis. Among the 2,427 patients analyzed, 823 (33.9%) developed AKI. The C-statistics of IHT-defined metrics (0.58-0.59) were significantly higher than those of the CHT-defined metrics (all C-statistics, 0.54; all p < 0.001). The duration of hyperglycemia (adjusted odds ratio, 1.09; 95% confidence interval, 1.02-1.16) and area above the IHT (1.003; 1.001-1.004) were significantly associated with the risk of AKI, except for the presence of any hyperglycemic episode. None of the CHT-defined metrics were significantly associated with the risk of AKI., Conclusions: Individually defined intraoperative hyperglycemia better predicted postcardiac surgery AKI than universally defined hyperglycemia. Intraoperative hyperglycemia was significantly associated with the risk of AKI only for the IHT. Target blood glucose levels in cardiac surgical patients may need to be individualized based on preoperative glycemic status., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Since 2023, guidelines of the AACC/ADA recommend the use of citrate buffer-containing tubes as a first option for glucose measurement. This study aims to assess the pre-analytical stability of glucose under various conditions (room temperature (RT) or at 4 °C) and the potential real-world impact of introducing these tubes on (gestational) diabetes and IFG prevalence., Materials and Methods: 25 healthy volunteers were sampled to assess glucose stability across time, at 4 °C and at RT, before and following centrifugation. 701 patients undergoing fasting plasma glucose analysis and 109 women having OGTT were collected according to current procedures (NaFl K 2 C 2 O 4 (NaFl) tubes) as well as with citrate-containing tubes (FC Mix)., Results: The mean glucose concentration bias between FC Mix and NaFl tubes when centrifugation occurred within 5 min was 0.53 % and this difference raised slowly to reach 2.3 %, six-hours post-centrifugation. When centrifugation was delayed, a rapid decrease in glucose concentrations was observed for NaFl tubes (4.9 % at 30 min) and this trend was only partially reduced by placing samples at 4 °C (3.1 %). The decrease reached 10.8 % (RT) and 7.8 % (4 °C) at 2 h, before reaching a plateau. Samples collected on citrate remained stable during 24 h. In real-life conditions, the mean bias between FC Mix and NaFl tubes increased progressively over time and reached 8.59 % for samples centrifuged between two- and four-hours following sampling. Compared to widespread practices, the use of citrate-containing tubes increased IFG, DM and GDM prevalences by 84.0 %, 36.7 % and 150 %, respectively., Conclusions: Glucose concentrations rapidly decrease in NaFl tubes following collection and placing samples at 4 °C reduces only marginally the decay. Citrate-containing tubes offer a valuable solution for direct and long-lasting glucose stabilization but, before wider adoption, large epidemiologic studies should confirm or redefine current diabetes diagnostic thresholds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Human recombinant insulin is currently the only therapy for children and adolescents with type 1 diabetes (T1D), although not always efficient for the glycemic control of these individuals. The interrelation between the gut microbiome and the glycemic control of apparently healthy populations, as well as various populations with diabetes, is undeniable. Probiotics are biotherapeutics that deliver active components to various targets, primarily the gastrointestinal tract. This systematic review and meta-analysis examined the effect of the administration of probiotics on the glycemic control of pediatric and adolescent individuals with T1D., Materials and Methods: Randomized controlled trials employing the administration of probiotics in children and adolescents with T1D (with ≥10 individuals per treatment arm), written in English, providing parameters of glycemic control, such as mean glucose concentrations and glycosylated hemoglobin (HbA1c), were deemed eligible., Results: The search strategy resulted in six papers with contradictory findings. Ultimately, five studies of acceptable quality, comprising 388 children and adolescents with T1D, were included in the meta-analysis. Employing a random and fixed effects model revealed statistically significant negative effect sizes of probiotics on the glycemic control of those individuals, i.e., higher concentrations of glucose and HbA1c than controls., Conclusions: Children and adolescents with T1D who received probiotics demonstrated worse glycemic control than controls after the intervention. Adequately powered studies, with extended follow-up periods, along with monitoring of compliance and employing the proper strains, are required to unravel the mechanisms of action and the relative effects of probiotics, particularly concerning diabetes-related complications and metabolic outcomes.

Aims: Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D., Methods: In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.7%], body mass index 30.1 kg/m2, age 71 years) underwent, in randomized order, 14 days of metformin and placebo treatment, respectively. Each treatment period was preceded by 14 days without any glucose-lowering medicine and concluded by two 4 h mixed meal tests performed in randomized order and separated by >24 h with either continuous intravenous exendin(9-39)NH2 or saline infusion., Results: Compared to placebo, metformin treatment lowered fasting plasma glucose (mean of differences [MD] 1.4 mmol/L × min [95% CI 0.8-2.0]) as well as postprandial plasma glucose excursions during both saline infusion (MD 186 mmol/L × min [95% CI 64-307]) and exendin(9-39)NH2 infusion (MD 268 mmol/L × min [95% CI 108-427]). The metformin-induced improvement in postprandial glucose tolerance was unaffected by GLP-1R antagonization (MD 82 mmol/L × min [95% CI -6564-170]). Metformin treatment increased fasting plasma GLP-1 (MD 1.7 pmol/L × min [95% CI 0.39-2.9]) but did not affect postprandial GLP-1 responses (MD 820 pmol/L × min [95% CI -1750-111])., Conclusions: Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin's beneficial effect on fasting plasma glucose in T2D. Trial registration: Clinicaltrials.gov NCT03246451., Competing Interests: Conflict of interest: L.S.H., A.B., N.B.D., E.B., S.S., P.H.H., and J.F.R. have nothing to disclose. L.S.G. is a minority shareholder of Antag Therapeutics ApS. B.H. is a board member and cofounder of Bainan Biotech. N.J.W.A. has received funding from and served on scientific advisory panels and/or speakers bureaus for Boehringer Ingelheim, MSD/MERCK, Novo Nordisk, and Mercodia. J.J.H. has served on scientific advisory panels and/or speaker for Novo Nordisk, Eli Lilly, and Zealand Pharma. He has given lectures and received financial support for travel from Novo Nordisk. He has served as a consultant for AlphaSights, Eli Lilly, Structure Therapeutics, and Zealand Pharma. He is currently consulting for GV Management L.L.C. He is a cofounder and on the board of directors of Antag Therapeutics and Bainan Biotech. He is supported by grants from Arla Foods, ERC Advanced Grants, and the Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences University of Copenhagen Denmark. He serves as an investigator for Boehringer Ingelheim and Scohia. T.V. has served on scientific advisory panels, been part of speakers bureaus, and served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Mundipharma, Novo Nordisk, Sanofi, Zealand Pharma, and Sun Pharmaceuticals. All authors declare that the study was conducted without financial or conflicts of interest. F.K.K. has been on the advisory panel of, a consultant for, in the speakers bureau of, owns shares in, and/or has received research support from 89bio, AstraZeneca, Boehringer Ingelheim, Cytoki Pharma, Eli Lilly, Gubra, Novo Nordisk, Merck Sharp & Dohme, Sanofi, Structure Therapeutics, Zealand Pharma, and Zucara and is cofounder of and a minority shareholder in Antag Therapeutics. F.K.K. is currently employed at Novo Nordisk A/S, Bagsværd, Denmark; the present work was done independent of Novo Nordisk A/S. F.K.K. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Diagnosing diabetes by shortening the OGTT to 1-h and substituting 1-h post-load glucose (PG) ≥ 209 mg/dL for 2-h PG≥200 mg/dL has been proposed. One-hour PG≥209 mg/dL is from a meta-analysis without any African-descent populations. Our data suggest 1-h PG≥183 mg/dL maybe more optimal for Africans. As with waist circumference guidelines, population-specific thresholds may be appropriate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Aim: Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients., Methods: We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment., Results: Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of β cell function (HOMA-β), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI., Conclusions: Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-β, IR, and lower Matsuda index were indicators of better hepatic IR improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Recent studies have demonstrated that real-time CGM use reduce the incidence severe hypoglycemic events and impaired awareness of hypoglycemia (IAH) However, there are few real-world studies evaluating the effect of intermittently scanned continuous glucose monitoring (isCGM) on hypoglycemic episodes and hypoglycemia unawareness (IAH). The present study was designed to cover this research-practice gap., Methods: This is a real-world, observational, prospective cohort study with 2 years of follow-up in which 60 subjects with T1D who experienced frequent hypoglycemic events were included. All the patients were invited to use isCGM type Abbott FreeStyle Libre 2® on a continuous basis for 2 years. Glucometric parameters were obtained during the initial 2 weeks using isCGM and compared with data collected for the same period at 1 year and at the end of follow-up. The IAH was evaluated using the Clarke questionnaire, and to assess psychological aspects related to hypoglycemia the Hypoglycemia Fear Survey (HFS) was used., Results: After 2-years of follow-up using isCGM, we observed a decrease in glucose variability (40.3 ± 0.8 % vs. 37.1 ± 0.9 %, p = 0.003), time in low glucose range (54-69 mg/dL) (5.2 ± 0.4 % vs. 3.6 ± 0.3 %, p = 0.001), time in very low glucose range (<54 mg/dL) (3.2 ± 0.5 % vs. 0.8 ± 0.2 %, p < 0.001), less events related to low glucose levels (10.6 ± 1.1 vs 8.0 ± 1.0, p = 0.042) and a short duration of hypoglycemia episodes (106.1 ± 5.9 min vs. 85.7 ± 5.7 min, p = 0.008). In addition, participants presented a reduction of 47 % in the frequency of IAH, assessed by the Clarke questionnaire scores (24.6 % vs. 11.6 %, p = 0.034), as well as hypoglycemia fear (77.8 ± 2.4 vs 68.2 ± 2.1, p < 0.001). Furthermore, a reduction in total insulin dose was also observed (0.64 ± 0.30 UI/Kg/day vs 0.56 ± 0.11 UI/Kg/day, p = 0.018)., Conclusions: In the real-world, long-term use of isCGM could reduce both hypoglycemic episodes and IAH in people with T1D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The development of closed-loop systems for glycemia control in type I diabetes relies heavily on simulated patients. Improving the performances and adaptability of these close-loops raises the risk of over-fitting the simulator. This may have dire consequences, especially in unusual cases which were not faithfully - if at all - captured by the simulator. To address this, we propose to use model-free offline RL agents, trained on real patient data, to perform the glycemia control. To further improve the performances, we propose an end-to-end personalization pipeline, which leverages offline-policy evaluation methods to remove altogether the need of a simulator, while still enabling an estimation of clinically relevant metrics for diabetes., Competing Interests: Declaration of competing interest The authors of this paper declare that they are all affiliated with Diabeloop, and have no other financial or non-financial interests or affiliations that could be perceived as influencing the content or interpretation of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Undaria pinnatifida (UP) contains multiple bioactive substances, such as polyphenols, polysaccharides, and amino acids, which are associated with various biological properties. This study aimed to evaluate the antihyperglycemic effects of three extracts obtained from UP. UP was extracted under three different conditions: a low-temperature water extract at 50 °C (UPLW), a high-temperature water extract at 90 °C (UPHW), and a 70 % ethanol extract (UPE). Nontargeted chemical profiling using high-performance liquid chromatography-triple/time-of-flight mass spectrometry (HPLC-Triple TOF-MS/MS) was conducted on the three UP extracts. Subsequently, α-glucosidase inhibitory (AGI) activity, glucose uptake, and the mRNA expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) were evaluated in Caco-2 cell monolayers. Furthermore, an oral carbohydrate tolerance test was performed on C57BL/6 mice. The mice were orally administered UP at 300 mg/kg body weight (B.W.), and the blood glucose level and area under the curve (AUC) were measured. Compared with glucose, UPLW, UPHW and UPE significantly inhibited both glucose uptake and the mRNA expression of SGLT1 and GLUT2 in Caco-2 cell monolayers. After glucose, maltose, and sucrose loading, the blood glucose levels and AUC of the UPLW group were significantly lower than those of the control group. These findings suggest that UPLW has antihyperglycemic effects by regulating glucose uptake through glucose transporters and can be expected to alleviate postprandial hyperglycemia. Therefore, UPLW may have potential as a functional food ingredient for alleviating postprandial hyperglycemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Xelaglifam, developed as a GPR40/FFAR1 agonist, induces glucose-dependent insulin secretion and reduces circulating glucose levels for Type 2 diabetes treatment. This study investigated the effects of Xelaglifam in comparison with Fasiglifam on the in vitro/in vivo anti-diabetic efficacy and selectivity, and the mechanistic basis. In vitro studies on downstream targets of Xelaglifam were performed in GPR40-expressing cells. Xelaglifam treatment exhibited dose-dependent effects, increasing inositol phosphate-1, Ca 2+ mobilization, and β-arrestin recruitment (EC50: 0.76 nM, 20 nM, 68 nM), supporting its role in Gq protein-dependent and G-protein-independent mechanisms. Despite a lack of change in the cAMP pathway, the Xelaglifam-treated group demonstrated increased insulin secretion compared to Fasiglifam in HIT-T15 β cells under high glucose conditions. High doses of Xelaglifam (<30 mg/kg) did not induce hypoglycemia in Sprague-Dawley rats. In addition, Xelaglifam lowered glucose and increased insulin levels in diabetic rat models (GK, ZDF, OLETF). In GK rats, 1 mg/kg of Xelaglifam improved glucose tolerance (33.4 % and 15.6 % for the 1 and 5 h) after consecutive glucose challenges. Moreover, repeated dosing in ZDF and OLETF rats resulted in superior glucose tolerance (34 % and 35.1 % in ZDF and OLETF), reducing fasting hyperglycemia (18.3 % and 30 % in ZDF and OLETF) at lower doses; Xelaglifam demonstrated a longer-lasting effect with a greater effect on β-cells including 3.8-fold enhanced insulin secretion. Co-treatment of Xelaglifam with SGLT-2 inhibitors showed additive or synergistic effects. Collectively, these results demonstrate the therapeutic efficacy and selectivity of Xelaglifam on GPR40, supportive of its potential for the treatment of Type 2 diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT., Competing Interests: Conflict of interest statement Tobias Warnken is employed by Boehringer Ingelheim Vetmedica GmbH. None of the authors has any other financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim The efficacy of hybrid closed-loop systems (HCLs) in managing glycemic control in pregnant women with type 1 diabetes remains inadequately characterized. We evaluated the use of the Medtronic Minimed 780G HCLs., Methods: The retrospective observational study analyzed the glycemic and perinatal outcomes of pregnant women using the HCLs, followed at our tertiary centre. Independent t-tests were employed to compare data among trimesters based on pre-pregnancy HbA 1c . The associations between glycemic parameters and perinatal outcomes were explored using Spearman rho., Results: Among the 21 women (age: 33.5 ± 4.2 years, diabetes duration: 21.2 ± 7.6 years, pre-pregnancy HbA 1c 7.0 ± 1.1 % (52.9 ± 11.9 mmol/mol)) time in range (pTIR, 63-140 mg/dl; 3.5-7.8 mmol/l) increased progressively throughout pregnancy (trimesters: first: 64.0 ± 9.0 %; second:71.3 ± 11.8 %; third: 75.7 ± 8.1 %). Simultaneously, mean sensor glucose decreased (trimesters: first: 130 ± 10.4 mg/dl (7.2 ± 0.6 mmol/l); second: 120.9 ± 13.4 mg/dl (6.7 ± 0.7 mmol/l); third: 117.3 ± 9.1 mg/dl (6.5 ± 0.5 mmol/l)). Although a majority of women achieved the target pTIR until the third trimester, this did not consistently prevent the delivery of a large-for-gestational-age baby. Notably, one ketoacidosis event occurred, and there were no reported instances of severe hypoglycemia., Conclusion: Use of the Minimed 780G HCLs enabled the attainment of recommended pregnancy glycemic targets for most women with type 1 diabetes in a real-world setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in our paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8)., Methods: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results., Results: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend., Conclusions: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Continuous detection of sudden changes in blood glucose is essential for individuals with diabetes who have difficulty in maintaining optimal control of their blood glucose levels. Hypoglycemic shock or a hyperglycemic crisis are likely to occurs in patients with diabetes and poses a significant threat to their lives. Currently, commercial continuous glucose monitoring (CGM) has limits in the glucose concentration detection range, which is 40-500 mg/dL, making it difficult to prevent the risk of hyperglycemic shock. In addition, current CGMs are invasive, cause pain and irritation during usage, and expensive. In this research, we overcome these limitations by introducing a novel mechanism to detect glucose concentration using supercapacitors. The developed CGM, which is self-powered and minimally invasive due to the use of microneedles, can detect a wider range of glucose concentrations than commercial sensors. In addition, efficacy and stability were proven through in vitro and in vivo experiments. Thus, this self-powered, microneedle and supercapacitive-type CGM can potentially prevent both hypoglycemic and complications of hyperglycemia without pain and with less power consumption than current commercial sensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Determining whether a surrogate marker can be used to replace a primary outcome in a clinical study is complex. While many statistical methods have been developed to formally evaluate a surrogate marker, they generally do not provide a way to examine heterogeneity in the utility of a surrogate marker. Similar to treatment effect heterogeneity, where the effect of a treatment varies based on a patient characteristic, heterogeneity in surrogacy means that the strength or utility of the surrogate marker varies based on a patient characteristic. The few methods that have been recently developed to examine such heterogeneity cannot accommodate censored data. Studies with a censored outcome are typically the studies that could most benefit from a surrogate because the follow-up time is often long. In this paper, we develop a robust nonparametric approach to assess heterogeneity in the utility of a surrogate marker with respect to a baseline variable in a censored time-to-event outcome setting. In addition, we propose and evaluate a testing procedure to formally test for heterogeneity at a single time point or across multiple time points simultaneously. Finite sample performance of our estimation and testing procedure are examined in a simulation study. We use our proposed method to investigate the complex relationship between change in fasting plasma glucose, diabetes, and sex hormones using data from the diabetes prevention program study., (© 2024 John Wiley & Sons Ltd.)

Introduction: Type 1 Diabetes (T1D) affects over 9 million worldwide and necessitates meticulous self-management for blood glucose (BG) control. Utilizing BG prediction technology allows for increased BG control and a reduction in the diabetes burden caused by self-management requirements. This paper reviews BG prediction models in T1D, which include nutritional components., Method: A systematic search, utilizing the PRISMA guidelines, identified articles focusing on BG prediction algorithms for T1D that incorporate nutritional variables. Eligible studies were screened and analyzed for model type, inclusion of additional aspects in the model, prediction horizon, patient population, inputs, and accuracy., Results: The study categorizes 138 blood glucose prediction models into data-driven (54%), physiological (14%), and hybrid (33%) types. Prediction horizons of ≤30 min are used in 36% of models, 31-60 min in 34%, 61-90 min in 11%, 91-120 min in 10%, and >120 min in 9%. Neural networks are the most used data-driven technique (47%), and simple carbohydrate intake is commonly included in models (data-driven: 72%, physiological: 52%, hybrid: 67%). Real or free-living data are predominantly used (83%)., Conclusion: The primary goal of blood glucose prediction in T1D is to enable informed decisions and maintain safe BG levels, considering the impact of all nutrients for meal planning and clinical relevance.

Objectives: Patients with type 1 diabetes (T1D) face unique challenges in glycaemic control due to the complexity and uniqueness of the dietary structure in China, especially in terms of postprandial glycaemic response (PPGR). This study aimed to establish a personalized model for predicting PPGR in patients with T1D., Materials and Methods: Data provided by the First People's Hospital of Yunnan Province, 13 patients with T1D, were recruited and provided with an intervention for at least two weeks. All patients were asked to wear a continuous glucose monitoring (CGM) device under free-living conditions during the study period. To tackle the challenge of incomplete data from wearable devices for CGM measurements, the GAIN method was used in this paper to achieve a more rational interpolation process. In this study, patients' PPGRs were calculated, and a LightGBM prediction model was constructed based on a Bayesian hyperparameter optimisation algorithm and a random search algorithm, which integrated glucose measurement, insulin dose, dietary nutrient content, blood measurement and anthropometry as inputs., Results: The experimental outcomes revealed that the PPGR prediction model presented in this paper demonstrated superior accuracy (R=0.63) compared to both the carbohydrate content only model (R=0.14) and the baseline model emulating the standard of care for insulin administration (R=0.43). In addition, the interpretation of the model using the SHAP method showed that blood glucose levels at meals and blood glucose trends 30 minutes before meals were the most important features of the model., Conclusion: The proposed model offers a heightened precision in predicting PPGR in patients with T1D, so it can better guide the diet plan and insulin intake dose of patients with T1D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiong, Xue, Cai, He and Su.)

The paper "Using Absorption Models for Insulin and Carbohydrates and Deep Leaning to Improve Glucose Level Predictions" ( Sensors 2021 , 5273) proposes a novel approach to predicting blood glucose levels for people with type 1 diabetes mellitus (T1DM). By building exponential models from raw carbohydrate and insulin data to simulate the absorption in the body, the authors reported a reduction in their model's root-mean-square error (RMSE) from 15.5 mg/dL (raw) to 9.2 mg/dL (exponential) when predicting blood glucose levels one hour into the future. In this comment, we demonstrate that the experimental techniques used in that paper are flawed, which invalidates its results and conclusions. Specifically, after reviewing the authors' code, we found that the model validation scheme was malformed, namely, the training and test data from the same time intervals were mixed. This means that the reported RMSE numbers in the referenced paper did not accurately measure the predictive capabilities of the approaches that were presented. We repaired the measurement technique by appropriately isolating the training and test data, and we discovered that their models actually performed dramatically worse than was reported in the paper. In fact, the models presented in the that paper do not appear to perform any better than a naive model that predicts future glucose levels to be the same as the current ones.21 , 5273) proposes a novel approach to predicting blood glucose levels for people with type 1 diabetes mellitus (T1DM). By building exponential models from raw carbohydrate and insulin data to simulate the absorption in the body, the authors reported a reduction in their model's root-mean-square error (RMSE) from 15.5 mg/dL (raw) to 9.2 mg/dL (exponential) when predicting blood glucose levels one hour into the future. In this comment, we demonstrate that the experimental techniques used in that paper are flawed, which invalidates its results and conclusions. Specifically, after reviewing the authors' code, we found that the model validation scheme was malformed, namely, the training and test data from the same time intervals were mixed. This means that the reported RMSE numbers in the referenced paper did not accurately measure the predictive capabilities of the approaches that were presented. We repaired the measurement technique by appropriately isolating the training and test data, and we discovered that their models actually performed dramatically worse than was reported in the paper. In fact, the models presented in the that paper do not appear to perform any better than a naive model that predicts future glucose levels to be the same as the current ones.

Objective: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults., Methods: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups., Results: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower., Conclusion: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Effective diabetes management remains suboptimal in low-resourced countries including Ghana. We determined the effectiveness of hospital-community link diabetes management intervention on glycaemic control and other outcomes., Methods: A retrospective study design, using secondary data from the Ghana-Netherlands for Health Foundation diabetes programme. The z-test was used for proportions, to compare parameters between baseline (2017) and endpoint (2022). The Friedman test was used to assess changes in blood glucose levels, and the multivariable Logistic regression to identify factors associated with blood glucose control., Results: Analyses of 251 clinical records showed decline in median blood glucose levels across six years from 8.8 mmol/L (7.2-12.9) in 2017 to 6.5 mmol/L (5.7-7.2) (p = 0.001) in 2022, recording 43 % increase in patients attaining glycaemic control in 2022 (p = 0.001). The Friedman test showed significant reduction in glucose levels (χ 2  = 319.2, p = 0.001), with an effect size of 0.25 using the Kendall test. The logistic regression analyses revealed that patients on metformin and Glibenclamide combination were more likely to achieve glycaemic control than those on metformin monotherapy (adjusted OR = 7.30, 95 % CI 2.31-23.01, p = 0.001)., Conclusion: The intervention achieved significant reduction in blood glucose levels. Patients with diabetes benefit from the hospital-community link diabetes management intervention regarding glycaemic control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Impaired glycemic control and the subsequent development of Cystic fibrosis Related Diabetes (CFRD) are prevalent complications, affecting up to 50 % of adults with cystic fibrosis (CF). CFTR modulator (CFTRm) therapies improve pulmonary functions, reduce exacerbation rates, increase survival in people with CF (pwCF) and appear to have a positive effect on extrapulmonary manifestations, such as nutritional state, improvements in upper respiratory symptoms, and quality of life. Initial findings indicate that CFTRm may have a positive impact on short-term glycemic control; however, long-term effects remain uncertain at present., Methods: In this retrospective study, data were collected and analyzed on 15 pwCF, ages 13-37 years, started on CFTRm therapy. Oral Glucose Tolerance Test (OGTT) results were compared pre- and post-CFTRm therapy., Results: The 120-min OGTT value decreased from 159.7 mg/dL to 130.4 mg/dL post-CFTRm (p = 0.047). The average time elapsed between the two OGTTs was 49.87 months (ranging 9-157 months, median 38 months). Glycemic status improved in six pwCF (two CFRD to normal (NGT)/indeterminate (INDET) glucose tolerance; two impaired glucose tolerance (IGT) to INDET; two INDET to NGT) and worsened in one (IGT to CFRD). Six pwCF and NGT remained stable with no changes in glycemic status throughout the follow-up period., Conclusions: CFTRm therapy may decelerate the glycemic control deterioration in pwCF over an extended period. These findings indicate the need for periodic OGTTs following the initiation of CFTRm therapy to appropriately adjust insulin requirements and prevent hypoglycemia. Further larger cohorts are required to authenticate and substantiate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)