Enhancing levan biosynthesis by destroying the strongly acidic environment caused by membrane-bound glucose dehydrogenase (mGDH) in Gluconobacter sp. MP2116.

Levan produced by Gluconobacter spp. has great potential in biotechnological applications. However, Gluconobacter spp. can synthesize organic acids during fermentation, resulting in environmental acidification. Few studies have focused on the effects of environmental acidification on levan synthesis. This study revealed that the organic acids, mainly gluconic acid (GA) and 2-keto-gluconic acid (2KGA) secreted by Gluconobacter sp. MP2116 created a highly acidic environment (pH < 3) that inhibited levan biosynthesis. The levansucrase derived from strain MP2116 had high enzyme activity at pH 4.0 âˆ¼ pH 6.5. When the ambient pH was less than 3, the enzyme activity decreased by 67 %. Knocking out the mgdh gene of membrane-bound glucose dehydrogenase (mGDH) in the GA and 2KGA synthesis pathway in strain MP2116 eliminated the inhibitory effect of high acid levels on levansucrase function. As a result, the levan yield increased from 7.4 g/l (wild-type) to 18.8 g/l (Δmgdh) during fermentation without pH control. This study provides a new strategy for improving levan production by preventing the inhibition of polysaccharide synthesis by environmental acidification.

Melastoma dodecandrum lour. Protects against cerebral ischemia-reperfusion injury by ameliorating oxidative stress and endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Melastoma dodecandrum Lour. (MD), a traditional Chinese medicine used by the She ethnic group, has been used to treat cerebral ischemia-reperfusion (CIR) injury due to its efficacy in promoting blood circulation and removing blood stasiss; however, the therapeutic effects and mechanisms of MD in treating CIR injury remain unclear. AIM: To investigate the protective effects of MD on CIR injury, in addition to its impact on oxidative stress, endoplasmic reticulum (ER) stress, and cell apoptosis. MATERIALS AND METHODS: The research was conducted using both cell experiments and animal experiments. The CCK-8 method, immunofluorescence staining, and flow cytometry were used to analyze the effects of MD-containing serum on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cell viability, reactive oxygen species (ROS) clearance, anti-inflammatory, neuroprotection and inhibition of apoptosis. Furthermore, 2,3,5-Triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, Nissl staining, and immunohistochemistry were used to detect infarct size, pathological changes, Nissl corpuscula and neuronal protein expression in middle cerebral artery occlusion (MCAO) rats. Polymerase chain reaction and Western Blotting were conducted in cell and animal experiments to detect the expression levels of ER stress-related genes and proteins. RESULTS: The MD extract enhanced the viability of PC12 cells under OGD/R modeling, reduced ROS and IL-6 levels, increased MBP levels, and inhibited cell apoptosis. Furthermore, MD improved the infarct area in MCAO rats, increased the number of Nissl bodies, and regulated neuronal protein levels including Microtubule-Associated Protein 2 (MAP-2), Myelin Basic Protein (MBP), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament 200 (NF200). Additionally, MD could regulate the expression levels of oxidative stress proteins malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT). Both cell and animal experiments demonstrated that MD could inhibit ER stress-related proteins (GRP78, ATF4, ATF6, CHOP) and reduce cell apoptosis. CONCLUSION: This study confirmed that the therapeutic mechanism of the MD extract on CIR injury was via the inhibition of oxidative stress and the ER stress pathway, in addition to the inhibition of apoptosis.

Associations of dietary inflammation index and composite dietary antioxidant index with preserved ratio impaired spirometry in US adults and the mediating roles of triglyceride-glucose index: NHANES 2007-2012.

BACKGROUND: Previous studies have shown that inflammatory and antioxidant dietary patterns can modify the risk of COPD, yet few studies have examined the association of these diets with its early signs (PRISm), and the potential role of metabolic disorders remains to be elucidated. METHODS: Data from 9529 individuals who participated in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. The Dietary Inflammation Index (DII) and the Dietary Antioxidant Composite Index (CDAI) were assessed using 24-h dietary recall, multiple metabolic indicators were calculated according to biochemical markers, and lung function parameters defined PRISm cases. Individual and joint effects of DII and CDAI were evaluated by generalized linear models and binary logistic regression models, and mediation effects of metabolic indicators were further explored by causal mediation analysis. RESULTS: Increased DII was associated with decreased lung function (FEV1: ß = -18.82, FVC: ß = -29.2; OR = 1.04) and increased metabolic indicators (ß = 0.316, 0.036, 0.916, 0.033, and 0.145 on MAP, UA, TC, TyG, and MS, respectively). Contrary to this, CDAI were positively and negatively associated with lung function (FEV1: ß = 3.42; FVC: ß = 4.91; PRISm: OR = 0.99) and metabolic indicators (ß < 0), respectively. Joint effects of DII and CDAI indicated the minimal hazard effects of DII on TyG (ß = -0.11), FEV1 (ß = 72.62), FVC (ß = 122.27), and PRISm (OR = 0.79) in subjects with high CDAI when compared with those with low CDAI (low DII + high CDAI vs. high DII + low CDAI). Furthermore, TyG mediated 13.74 %, 8.29 %, and 21.70 % of DII- and 37.30 %, 20.90 %, and 12.32 % of CDAI-FEV1, -FVC, and -PRISm associations, respectively. CONCLUSIONS: These findings indicated that CDAI can attenuate the adverse effects of DII on metabolic disorders and lung function decline, which provides new insight for diet modification in preventing early lung dysfunction.

Mechanism study of Dual-Emission ratiometric fluorescent pH-Sensitive carbon quantum dots and its application on mornitoring enzymatic catalysis.

Carbon dots (CQD) have received significant attention as a novel ratiometric fluorescent pH nanoprobe, owing to their favorable optical properties and excellent biocompatibility. Despite their appealing features, the precise mechanism behind the pH-sensitive photoluminescence of CQDs remains to be fully understood. This study endeavors to unravel the mechanism underlying the pH-responsive ratiometric fluorescence in dual-emission CQDs, synthesized through a one-step hydrothermal method using o-phenylenediamine and oxalic acid as precursors. The resultant CQDs exhibit inherent dual-emission at wavelengths of 383 nm and 566 nm, with the ratiometric fluorescence response tailored by the ratio of precursors, providing a robust tool for pH sensing across a range of 2 to 6. Detailed characterizations, including chemical, morphological, and optical analyses, alongside theoretical insights from time-dependent density functional theory (TD-DFT), elucidate the mechanism underlying the pH-dependent luminescence, attributed to the electron cloud transmission between amide and adjacent carboxyl groups on the CQD surface. The superior performance of these CQDs in real-time pH monitoring is demonstrated through their application in glucose oxidase-catalyzed reactions, showcasing their potential as efficient, reliable nanoprobes for biomedical research and diagnostic applications.

Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity.

BACKGROUND & AIMS: Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic OXPHOS capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases. METHODS: We analysed 65 humans without diabetes (BMI 50±7 kg/m2, HbA1c 5.5±0.4%) undergoing bariatric surgery. MASLD stages were assessed by histology, whole-body insulin sensitivity (PREDIcted-M index) by oral glucose tolerance tests, and maximal ADP-stimulated mitochondrial OXPHOS capacity by high-resolution respirometry of liver samples. RESULTS: Prediabetes was present in 30 participants, and MASLD in 46 participants. Thereof, 25 had metabolic dysfunction-associated steatohepatitis (MASH), and seven had F2-F3 fibrosis. While simple regression did not detect an association of insulin sensitivity with hepatic OXPHOS capacity, interaction analyses revealed that the regression coefficient of OXPHOS capacity depended on fasting plasma glucose (FPG) and liver lipid content. Interestingly, the respective slopes were negative for FPG ≤100 mg/dl, but positive for FPG >100 mg/dl. Liver lipid content displayed similar behavior, with a threshold value of 24%. Post-challenge glycemia affected the association between insulin sensitivity and OXPHOS capacity normalized for citrate synthase activity. Presence of prediabetes affected hepatic insulin signaling, mitochondrial dynamics and fibrosis prevalence, while the presence of MASLD related to higher biomarkers of hepatic inflammation, cell damage and lipid peroxidation in people with normal glucose tolerance. CONCLUSIONS: Rising liver lipid contents and plasma glucose concentrations, even in the non-diabetic range, are associated with a progressive decline of hepatic mitochondrial adaptation in people with obesity and insulin resistance. CLINTRIALS. GOV IDENTIFIER: NCT01477957.

The Intake of Dietary Lipids Improves Glucose Tolerance via Modulating Gut Microbiota.

The composition of gut microbiota is determined not only by genetic factors but also by environmental factors, such as diet, exercise, and disease conditions. Among these factors, diet is crucial in changing the gut microbial composition. Dietary lipids composed of different fatty acids not only alter host metabolism but also have a significant impact on the composition of gut microbiota. However, the molecular mechanisms underlying the relationship between these host effects and their impact on gut microbiota remain unclear. Here, we demonstrated that intake of different dietary lipids improved glucose tolerance by modulating gut microbiota. The results of our analysis show that the taxa of bacteria that increase in number as a result of dietary lipid intake play an important role in glucose metabolism. Thus, we have identified a new mechanism underlying the function of dietary lipids in regulating glucose homeostasis. Our findings contribute to possible new methods to prevent and treat metabolic disorders by modifying the composition of gut microbiota.

Loss of glucose-stimulated ß-cell Nr4a1 expression impairs insulin secretion and glucose homeostasis.

A central aspect of type 2 diabetes is decreased functional ß-cell mass. The orphan nuclear receptor Nr4a1 is critical for fuel utilization, but little is known regarding its regulation and function in the ß-cell. Nr4a1 expression is decreased in type 2 diabetes rodent ß-cells and type 2 diabetes patient islets. We have shown that Nr4a1 deficient mice have reduced ß-cell mass and that Nr4a1 knock-down impairs glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 ß-cells. Here, we demonstrate that glucose concentration directly regulates ß-cell Nr4a1 expression. We show that 11 mM glucose increases Nr4a1 expression in INS-1 832/13 ß-cells and primary mouse islets. We show that glucose functions through the cAMP/PKA/CREB pathway to regulate Nr4a1 mRNA and protein expression. Using Nr4a1-/- animals, we show that Nr4a1 is necessary for GSIS and systemic glucose handling. Using RNA-seq, we define Nr4a1-regulated pathways in response to glucose in the mouse islet, including Glut2 expression. Our data suggests that Nr4a1 plays a critical role in the ß-cells response to the fed state.

Physical environment and blood glucose level of diabetic patients: A cross-sectional study.

Objective: To determine the correlation between physical environment and blood glucose levels in diabetic patients. METHODS: The quantitative, cross-sectional study was conducted from July to October 2022 at the Rejosari Pekanbaru Community Health Centre, Indonesia, and comprised diabetic patients of either gender with a disease history of at least 3 years. Environmental temperature was considered acceptable at 18-20°C, while environmental light was considered acceptable at 60-120 lux. Random blood glucose level <60mg/dL was taken as low, 70-130 mg/dL normal, and >140 mg/dL high. The correlation between physical environment and blood glucose level was worked out. Data was analysed using SPSS 20. RESULTS: Of the 125 subjects, 89(71.2%) were females and 36(28.8%) were males. There were 45 patients aged 56-65 years and 11(8.8%) were aged <11 years. Overall, 90(72%) patients had high random blood sugar and 35(28%) had normal level. The disease duration was <5 years in 79(63.2%) cases and >5 years in 46(36.8%). Of the 80(64%) patients who lived in an unacceptable living room temperature, 63(78.8%) had high random blood glucose levels (p=00042). Of the 73(58.4%) patients who lived in an unacceptable living room light, 59(80.8%) had high random blood glucose (p=0.016). Conclusion: A significant effect of temperature and light was found on blood glucose levels in diabetic patients.

Beyond glucose: The crucial role of redox signaling in ß-cell metabolic adaptation.

OBJECTIVE: Redox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic ß-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in ß-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for ß-cell function and health. METHODS: We employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic ß-cells. RESULTS: Glucose stimulation significantly increases ROS levels in ß-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation. CONCLUSIONS: Proper functioning of pancreatic ß-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic ß-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in ß-cell function.

Pathophysiological characteristics of subjects with intermediate hyperglycemia and type 2 diabetes identified by 1-hour plasma glucose during an oral glucose tolerance test.

AIMS: The International Diabetes Federation (IDF) has recently recommended determination of 1-hour plasma glucose (1-hPG) during an oral glucose tolerance test (OGTT) to diagnose intermediate hyperglycemia (IH) and type 2 diabetes (T2DM). Herein, we investigated the cardiometabolic characteristics of individuals with IH and T2DM according to IDF criteria. METHODS: We studied 3086 individuals stratified on the basis of fasting, 1-hPG and 2-hPG in four groups: 1) normal glucose tolerance (NGT), 2) isolated impaired fasting glucose (iIFG,), 3) IH (fasting glucose < 126 mg/dL, 1-hPG 155-208 mg/dL, and/or 2-hPG 140-199 mg/dL, and 4) newly diagnosed T2DM (fasting glucose, 1-hPG and/or 2-hPG≥126 mg/dL, 209 mg/dL and 200 mg/dL, respectively). RESULTS: Individuals with IH and T2DM exhibited higher adiposity, blood pressure, uric acid, a worse lipid and inflammatory profile and a progressive reduction in Matsuda index of insulin sensitivity, insulinogenic index, and disposition index as compared to the NGT group. Moreover, individuals with IH and T2DM exhibited lower Matsuda, insulinogenic, and disposition indexes as compared to the iIFG group. CONCLUSIONS: 1-h PG-based criteria for diagnosis of IH and diabetes identify individuals having an unfavorable cardiometabolic risk profile with a progressive reduction in insulin sensitivity associated with impaired ß cell function.

A Systematic Approach to Evaluating Instrumental Variable Assumptions: Applied Example of Glucose-lowering Medications and Risk for Hospitalized Heart Failure in Older Adults.

One obstacle to adopting instrumental variable (IV) methods in pharmacoepidemiology is their reliance on strong, unverifiable assumptions. We can falsify IV assumptions by leveraging the causal structure, which can strengthen or refute their plausibility and increase the validity of effect estimates. We illustrate a systematic approach to evaluate calendar time IV assumptions in estimating the known effect of thiazolidinediones on hospitalized heart failure. Using cohort entry time before and after 09/2010, when the U.S. Food and Drug Administration issued a safety communication as a proposed IV, we estimated IV and propensity score-weighted 2-year risk differences (RDs) using Medicare data (2008-2014). We (i) performed inequality tests, (ii) identified the negative control IV/outcome using causal assumptions, (iii) estimated RDs after narrowing the calendar time range and excluding patients likely associated with unmeasured confounding, (iv) derived bounds for RDs, and (v) estimated the proportion of compliers and their characteristics. The findings revealed that IV assumptions were violated and RDs were extreme, but the assumptions became more plausible upon narrowing the calendar time range and restricting the cohort by excluding prevalent heart failure (the strongest measured predictor of outcome). Systematically evaluating IV assumptions could help detect bias in IV estimators and increase their validity.

Efficacy and safety of dapagliflozin add-on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled study.

AIM: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. PATIENTS AND METHODS: In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. RESULTS: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. CONCLUSION: Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.

Artificial Intelligence-Enhanced Metasurfaces for Instantaneous Measurements of Dispersive Refractive Index.

Measurements of the refractive index of liquids are in high demand in numerous fields such as agriculture, food and beverages, and medicine. However, conventional ellipsometric refractive index measurements are too expensive and labor-intensive for consumer devices, while Abbe refractometry is limited to the measurement at a single wavelength. Here, a new approach is proposed using machine learning to unlock the potential of colorimetric metasurfaces for the real-time measurement of the dispersive refractive index of liquids over the entire visible spectrum. The platform with a proof-of-concept experiment for measuring the concentration of glucose is further demonstrated, which holds a profound impact in non-invasive medical sensing. High-index-dielectric metasurfaces are designed and fabricated, while their experimentally measured reflectance and reflected colors, through microscopy and a standard smartphone, are used to train deep-learning models to provide measurements of the dispersive background refractive index with a resolution of ≈10-4, which is comparable to the known index as measured with ellipsometry. These results show the potential of enabling the unique optical properties of metasurfaces with machine learning to create a platform for the quick, simple, and high-resolution measurement of the dispersive refractive index of liquids, without the need for highly specialized experts and optical procedures.

Novel Supramolecular Hydrogel for Infected Diabetic Foot Ulcer Treatment.

Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4) hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.

Preclinical toxicity studies supporting 2DG for treatment of status epilepticus.

2-deoxy-D-glucose (2DG) has been proposed as a potential antiseizure treatment based on seizure suppressive actions in multiple acute and chronic seizure models, including models of status epilepticus (SE). Here we summarize recently completed preclinical toxicological studies of single doses of an intravenous formulation of 2DG supporting potential safety of 2DG for acute treatment of SE and acute repetitive seizures (ARS).

Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort.

OBJECTIVE: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation. METHODS: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed. RESULTS: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05). CONCLUSIONS: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Effects of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control: a systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Web of Science, PubMed/MEDLINE and SPORTDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials involving exercise, metformin or their combined treatments in individuals with prediabetes or type 2 diabetes mellitus (T2DM) were included. Outcomes included haemoglobin A1c (HbA1c), 2-hour glucose during oral glucose tolerance test, fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: 407 articles with 410 randomised controlled trials (n=33 802) were included. In prediabetes, the exercise showed greater efficacy than metformin on HbA1c levels (mean difference -0.16%, 95% CI (-0.23 to -0.09) vs -0.10%, 95% CI (-0.21 to 0.02)), 2-hour glucose (-0.68 mmol/L, 95% CI (-0.97 to -0.39) vs 0.01 mmol/L, 95% CI (-0.38 to 0.41)) and HOMA-IR (-0.54, 95% CI (-0.71 to -0.36) vs -0.23, 95% CI (-0.55 to 0.10)), while the efficacy on fasting glucose was comparable (-0.26 mmol/L, 95% CI (-0.32 to -0.19) vs -0.33 mmol/L, 95% CI (-0.45 to -0.21)). In T2DM, metformin was more efficacious than exercise on HbA1c (-0.88%, 95% CI (-1.07 to -0.69) vs -0.48%, 95% CI (-0.58 to -0.38)), 2-hour glucose (-2.55 mmol/L, 95% CI (-3.24 to -1.86) vs -0.97 mmol/L, 95% CI (-1.52 to -0.42)) and fasting glucose (-1.52 mmol/L, 95% CI (-1.73 to -1.31) vs -0.85 mmol/L, 95% CI (-0.96 to -0.74)); exercise+metformin also showed greater efficacy in improving HbA1c (-1.23%, 95% CI (-2.41 to -0.05)) and fasting glucose (-2.02 mmol/L, 95% CI (-3.31 to -0.74)) than each treatment alone. However, the efficacies were modified by exercise modality and metformin dosage. CONCLUSION: Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be superior to exercise in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42023400622.

Personal and Social-Built Environmental Factors of Glucose Variability Among Multiethnic Groups of Adults With Type 2 Diabetes: Research Protocol Using Ecological Momentary Assessment, Continuous Glucose Monitoring, and Actigraphy.

Glucose variability (GV)-the degree of fluctuation in glucose levels over a certain period of time-is emerging as an important parameter of dynamic glycemic control. Repeated glycemic oscillations have been reported to be the link to diabetes complications. This prospective observational study aims to: (1) identify multilevel risk factors (personal and social-built environmental factors) associated with high GV; (2) identify "within-person predictors" of high GV leveraging the intra-person data to inform future personalized diabetes interventions; and (3) examine which lifestyle factors either mediate or moderate the relationship between emotional well-being and GV among diverse adults with type 2 diabetes (T2D). We will recruit 200 adults with T2D from the community. All participants will complete baseline surveys assessing demographics, lifestyle, social-built environmental, and clinical factors. Real-time dynamic glucose levels will be measured using continuous glucose monitoring (CGM). Sleep, physical activity, diet/eating, and emotional well-being will be measured with an actigraphy device and a real-time self-report tool (ecological momentary assessment [EMA]) across 14 days. Two 24-h dietary recall data will be collected by online video calls. Generalized linear models, multilevel models, and structural equation models will be developed to achieve the study aims. The findings from the study will identify high-risk groups of high GV who would benefit from CGM to improve diabetes outcomes and inform the future development of personalized just-in-time interventions targeting lifestyle behaviors with an increased understanding of GV and by supporting healthcare providers' clinical decisions.

Continuous glucose monitoring metrics in people with liver glycogen storage disease and idiopathic ketotic hypoglycemia: A single-center, retrospective, observational study.

BACKGROUND: Cohort data on continuous glucose monitoring (CGM) metrics are scarce for liver glycogen storage diseases (GSDs) and idiopathic ketotic hypoglycemia (IKH). The aim of this study was to retrospectively describe CGM metrics for people with liver GSDs and IKH. PATIENTS AND METHODS: CGM metrics (descriptive, glycemic variation and glycemic control parameters) were calculated for 47 liver GSD and 14 IKH patients, categorized in cohorts by disease subtype, age and treatment status, and compared to published age-matched CGM metrics from healthy individuals. Glycemic control was assessed as time-in-range (TIR; ≥3.9 - ≤7.8 and ≥3.9 - ≤10.0 mmol/L), time-below-range (TBR; <3.0 mmol/L and ≥3.0 - ≤3.9 mmol/L), and time-above-range (TAR; >7.8 and >10.0 mmol/L). RESULTS: Despite all patients receiving dietary treatment, GSD cohorts displayed significantly different CGM metrics compared to healthy individuals. Decreased TIR together with increased TAR were noted in GSD I, GSD III, and GSD XI (Fanconi-Bickel syndrome) cohorts (all p < 0.05). In addition, all GSD I cohorts showed increased TBR (all p < 0.05). In GSD IV an increased TBR (p < 0.05) and decreased TAR were noted (p < 0.05). In GSD IX only increased TAR was observed (p < 0.05). IKH patient cohorts, both with and without treatment, presented CGM metrics similar to healthy individuals. CONCLUSION: Despite dietary treatment, most liver GSD cohorts do not achieve CGM metrics comparable to healthy individuals. International recommendations on the use of CGM and clinical targets for CGM metrics in liver GSD patients are warranted, both for patient care and clinical trials.