Impact of Esterification with Octenyl Succinic Anhydride on the Structural Characteristics and Glucose Response in Mice of Wheat Starch.

In this study, we investigated the structural properties and digestibility of wheat starch treated with octenyl succinic anhydride (OSA). For the experiment, the samples were reacted with 2, 4, 6, 8, and 10% OSA (pH 8.5-9.0) for 2 h. A light micrograph showed that there was no difference in the morphology and Maltese cross between native and OSA-treated starch. The X-ray diffraction (XRD) patterns of the native and OSA-treated starches showed typical A-type diffraction. In addition, the Fourier transform infrared (FT-IR) spectrum showed a distinct carbonyl peak at approximately 1730 cm-1, indicating the stretching vibration of the C=O bond of the ester group. The degree of substitution (DS) and content of resistant starch (RS) increased with increasing concentrations of treated OSA because of the increase in ester bonds. In particular, RS was thermostable compared to the RS content in uncooked and cooked starch. Blood glucose levels and response in vivo decreased as the OSA concentration increased. Treatment of wheat starch with 8% OSA concentration produced 35.6% heat-stable resistant starch. These results suggest that starch modified with OSA can be used to produce functional foods for diabetes.

Glucose-Responsive Self-Healing Bilayer Drug Microneedles Promote Diabetic Wound Healing Via a Trojan-Horse Strategy.

Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.

Characteristics and Risk of Diabetes in People With Rare Glucose Response Curve During an Oral Glucose Tolerance Test.

CONTEXT: Existing differences in persons with lower 30- or 60-minute plasma glucose (PG) levels during 75-g oral glucose tolerance test (OGTT) than fasting PG remain unclear. OBJECTIVE: To clarify the characteristics of persons whose PG levels decrease after glucose administration during OGTT and their risk of incidence of diabetes in a Japanese general population. METHODS: In this cohort study, a total of 3995 men and 3500 women (mean age 56.7 years) without diabetes were classified into 3 groups: (1) PG at both 30 and 60 minutes ≥ fasting PG; (2) PG at 30 minutes ≥ fasting PG and PG at 60 minutes < fasting PG; (3) PG at 30 minutes < fasting PG. The characteristics and the risk of diabetes onset were analyzed using ordered logistic regression and Cox proportional hazard regression, respectively. RESULTS: Among 7495 participants, the numbers of individuals in the group 1, 2, and 3 were 6552, 769, and 174, respectively. The glucose response curve of the group 3 was boat shaped. Group 3 had the youngest age, lowest percentage of men, and best health condition, followed by groups 2 and 1. Among 3897 participants analyzed prospectively, 434 developed diabetes during the mean follow-up period of 5.8 years. The hazard ratio for diabetes onset in the group 2 was 0.30 with reference to the group 1. No-one in group 3 developed diabetes. CONCLUSION: People with lower 30-minute PG than fasting PG tended to be women, young, healthy, and at low risk of diabetes onset.

Minimal Effective Dose of Beans Required to Elicit a Significantly Lower Glycemic Response Than Commonly Consumed Starchy Foods: Predictions Based on In Vitro Digestion and Carbohydrate Analysis.

Beans elicit lower glycemic responses (GRs) than other starchy foods, but the minimum effective dose (MED) to reduce GR is unknown. We sought to determine the MED of beans compared to common starchy foods. Overnight-fasted healthy volunteers consumed »c (phase 1, n = 24) or ½c (phase 2, n = 18) of black, cranberry, great northern, kidney, navy and pinto beans and corn, rice, pasta and potato (controls), with blood glucose measured before and for 2 h after eating. GRs (incremental areas under the curves, iAUCs) after beans were consumed were compared to those of controls by ANOVA followed by Dunnett's test. To qualify for MED, beans had to elicit an effective reduction in GR, defined as a statistically significant reduction in iAUC of ≥20% (i.e., a relative glycemic response, RGR, ≤80). Outcomes from in vitro digestion were compared with in vivo RGR. Both doses of all six beans effectively reduced GR versus all four starchy controls, except for »c and ½c cranberry and pinto vs. corn, »c great northern and navy vs. corn and »c navy and pinto vs. potato. MED criteria were met for 18 comparisons of the »c servings, with four of the remaining six met by the ½c servings. The overall mean ± SEM RGR vs. controls was similar for the »c and ½c servings: 53 ± 4% and 56 ± 3%, respectively. By multiple regression analysis, RGR = 23.3 × RDS + 8.3 × SDS - 20.1 × RS + 39.5 × AS - 108.2 (rapidly digested starch, p < 0.001; slowly digested starch, p = 0.054; resistant starch, p = 0.18; available sugars, p = 0.005; model r = 0.98, p = 0.001). RGR correlated with in vitro glucose release (r = 0.92, p < 0.001). The MED of beans is » cup. For n = 30 comparisons (n = 24 beans vs. controls, n = 6 controls vs. each other), an effective reduction in GR was predicted from in vitro carbohydrate analysis with 86% sensitivity and 100% specificity.

KATP channel activity and slow oscillations in pancreatic beta cells are regulated by mitochondrial ATP production.

Pancreatic beta cells secrete insulin in response to plasma glucose. The ATP-sensitive potassium channel (KATP ) links glucose metabolism to islet electrical activity in these cells by responding to increased cytosolic [ATP]/[ADP]. It was recently proposed that pyruvate kinase (PK) in close proximity to beta cell KATP locally produces the ATP that inhibits KATP activity. This proposal was largely based on the observation that applying phosphoenolpyruvate (PEP) and ADP to the cytoplasmic side of excised inside-out patches inhibited KATP . To test the relative contributions of local vs. mitochondrial ATP production, we recorded KATP activity using mouse beta cells and INS-1 832/13 cells. In contrast to prior reports, we could not replicate inhibition of KATP activity by PEP + ADP. However, when the pH of the PEP solutions was not corrected for the addition of PEP, strong channel inhibition was observed as a result of the well-known action of protons to inhibit KATP . In cell-attached recordings, perifusing either a PK activator or an inhibitor had little or no effect on KATP channel closure by glucose, further suggesting that PK is not an important regulator of KATP . In contrast, addition of mitochondrial inhibitors robustly increased KATP activity. Finally, by measuring the [ATP]/[ADP] responses to imposed calcium oscillations in mouse beta cells, we found that oxidative phosphorylation could raise [ATP]/[ADP] even when ADP was at its nadir during the burst silent phase, in agreement with our mathematical model. These results indicate that ATP produced by mitochondrial oxidative phosphorylation is the primary controller of KATP in pancreatic beta cells. KEY POINTS: Phosphoenolpyruvate (PEP) plus adenosine diphosphate does not inhibit KATP activity in excised patches. PEP solutions only inhibit KATP activity if the pH is unbalanced. Modulating pyruvate kinase has minimal effects on KATP activity. Mitochondrial inhibition, in contrast, robustly potentiates KATP activity in cell-attached patches. Although the ADP level falls during the silent phase of calcium oscillations, mitochondria can still produce enough ATP via oxidative phosphorylation to close KATP . Mitochondrial oxidative phosphorylation is therefore the main source of the ATP that inhibits the KATP activity of pancreatic beta cells.

A sensitive non-enzymatic dual-conductive biosensor for continuous glucose monitoring.

BACKGROUND: Diabetes and diabetic wound management have always been urgent issues for global healthcare. In the demand for blood glucose monitoring and wound management, phenylboronic acid (PBA)-based glucose biosensors are effective assistance due to their excellent glucose specificity, high sensitivity, and response stability. Nevertheless, PBA-based glucose biosensors still have challenges in terms of wide linearity and large deformation requirements. Therefore, it is necessary to develop PBA-based glucose biosensors with satisfactory mechanical properties, high response sensitivity, excellent stability, and wide linearity. RESULTS: In this work, a glucose-responsive PBA-based biosensor was successfully synthesized for the first time. The sensor materials exhibited excellent mechanical properties with an elongation at break reached up to 1000%, and the healing efficiency was over 90% within 30 min at 45 °C. Furthermore, the biosensor exhibited exceptional electromechanical responsiveness, stability, high sensitivity, and wide linearity due to the specificity of phenylboronic acid to glucose and the construction of a special HCNT/PEDOT:PSS dual conductive structure. In addition, the assembled biosensor displayed remarkable glucose, pH and temperature responses, exhibiting a linear response to glucose concentration range from 0.20 mM to 2.0 mM, with a sensitivity coefficient of 47.11 mA mM-1 and regression coefficient of 0.942. Moreover, the sensor materials showed satisfactory cytocompatibility, hemocompatibility, and antibacterial properties against Escherichia coli and Staphylococcus aureus. SIGNIFICANCE: For the first time, a dual conductive structural glucose biosensor based on PBA-based copolymer was synthesized. In addition to excellent glucose sensitivity and response stability, the biosensor has a wide linearity range, excellent self-healing property, and satisfactory mechanical performance. As a promising substitute for non-enzymatic glucose biosensors, this new material with special structure and characteristics would also be beneficial to wound management in diabetic patients.

The effects of Mediterranean diets with low or high glycemic index on plasma glucose and insulin profiles are different in adult men and women: Data from MEDGI-Carb randomized clinical trial.

BACKGROUND & AIMS: Recent evidence suggests that the ability to regulate glucose and insulin homeostasis is different in men and women. Against this background, it has been hypothesized that the impact on daily plasma glucose and insulin profiles of the glycemic index (GI) of the habitual diet may differ according to sex. The aim of this study is to evaluate whether 8-h average plasma glucose and insulin profiles during a low- or a high-GI diet in individuals at high risk of developing type 2 diabetes are influenced by sex. METHODS: We conducted a randomized, controlled, parallel group dietary intervention, comparing high-versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of 156 adults at risk for type 2 diabetes. For 12 weeks, 82 vs 74 participants consumed either a low-GI or high-GI Mediterranean diet, respectively. The two experimental diets contained the same quantity of available carbohydrate (270 g/d) and fiber (35 g/d) and the same foods and beverages, except for the major sources of starch that was specific to the low-GI and high-GI groups (pasta, brown rice, flatbread, all bran, and wheat bread plus rye and seeds, vs jasmine rice, potato, couscous, wholegrain bread, and rusks). At baseline and after the intervention plasma glucose and insulin profiles were evaluated for 8 h in the two intervention groups - separately for men and women - with both breakfast and lunch resembling food choices of the assigned diet. RESULTS: One hundred fifty-six adults (82 women, 74 men) with at least two traits of the metabolic syndrome completed the intervention. In women, the high-GI induced significantly higher (23%, p < 0.05) 8-h average plasma glucose concentrations in comparison to the low-GI diet already on the first day of the intervention; the difference increased up to 37% (p < 0.05) after 12 weeks of diet. Conversely, there were no significant differences between the two diets in men. These results were confirmed by the two-way analysis of variance showing a statistically significant interaction between the effects of sex and diet on the glucose profile after breakfast and lunch (F = 7.887, p = 0.006). CONCLUSION: The results of our intervention show that women, compared to men, are more sensitive to the metabolic effects of the dietary GI. This has a strong clinical and scientific relevance and, if confirmed in further studies, it might have important implications for dietary strategies for diabetes and cardiovascular disease prevention in the context of personalized nutrition. REGISTRATION NUMBER OF CLINICAL TRIAL: Clinicaltrials.gov n. NCT03410719.

Cross-linked phosphorylated RS4 wheat starch reduces glucose and insulin responses after 3 days of pre-feeding in healthy adults: an acute, double-blind, randomized controlled clinical trial.

When this project was designed, there was no evidence that adding resistant starch to available carbohydrate (avCHO) reduced glycaemic and insulinaemic responses (GIR). We compared GIR elicited by a cookie containing cross-linked phosphorylated RS4 wheat starch (Fibersym®) (RS4XL) versus an avCHO-matched control-cookie (CC) after n = 15 adults had consumed RS4XL or CC daily for 3-days using a double-blind, randomised, cross-over design. The difference in glucose iAUC over 0-2 h (primary endpoint) (mmol × min/L) after RS4XL, (mean ± SEM) 106 ± 16, versus CC, 124 ± 16, was not significant (p = 0.087). However, RS4XL reduced 0-90 min glucose iAUC (72 ± 9 vs 87 ± 9, p = 0.022), peak glucose concentration (6.05 ± 0.36 vs 6.57 ± 0.31 mmol/L, p = 0.017) and 0-2 h insulin iAUC (189 ± 21 vs 246 ± 24 nmol × h/L, p = 0.020). These results show that RS4XL reduced postprandial glycaemic and insulinaemic responses when added to avCHO, but do not prove that the products of its colonic fermentation are required for this effect.

pH-Responsive Hexa-Histidine Metal Assembly (HmA) with Enhanced Biocatalytic Cascades as the Vehicle for Glucose-Mediated Long-Acting Insulin Delivery.

Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, especially controlling LBG in the long-term by a single injection. Herein, the pH-responsive hexa-histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose-mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H2 O2 ). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long-acting hypoglycemic agent with prospective clinical application.

Glucose-Responsive Microparticle-Loaded Dissolving Microneedles for Selective Delivery of Metformin: A Proof-of-Concept Study.

Diabetes mellitus (DM) is a metabolic disorder that is one of the most common health problems in the world, primarily type 2 DM (T2DM). Metformin (MTF), as the first-line treatment of DMT2, is effective in lowering glucose levels, but its oral administration causes problems, including gastrointestinal side effects, low bioavailability, and the risk of hypoglycemia. In this study, we formulated MTF into microparticles incorporating a glucose-responsive polymer (MP-MTF-GR), which could potentially increase the bioavailability and extend and control the release of MTF according to glucose levels. This system was delivered by dissolving microneedles (MP-MTF-GR-DMN), applied through the skin, thereby preventing gastrointestinal side effects of orally administered MTF. MP-MTF-GR was formulated using various concentrations of gelatin as a polymer combined with phenylboronic acid (PBA) as a glucose-responsive material. MP-MTF-GR was encapsulated in DMN using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as DMN polymers. The physicochemical evaluation of MP-MTF-GR showed that MTF could be completely entrapped in MP with the percentage of MTF trapped increasing with increasing gelatin concentration without changing the chemical structure of MTF and producing stable MP. In addition, the results of the physicochemical evaluation of MP-MTF-GR-DMN showed that DMN had adequate mechanical strength properties and penetration ability and was stable to environmental changes. The results of the in vitro release and ex vivo permeation study on media with various concentrations of glucose showed that the release and permeation of MTF from the formula increased with increasing glucose levels in the media. The MP-MTF-GR-DMN formula successfully delivered MTF through the skin at 11.30 ± 0.29, 23.31 ± 1.64, 36.12 ± 3.77, and 53.09 ± 3.01 µg from PBS, PBS + glucose 1%, PBS + glucose 2%, and PBS + glucose 4%, respectively, at 24 h, which indicates glucose-responsive permeation and release behavior. The formula developed was also proven to be nontoxic based on hemolysis tests. Importantly, the in vivo study on the rat model showed that this combination approach could provide a better glucose reduction compared to other routes, reducing the blood glucose level to normal levels after 3 h and maintaining this level for 8 h. Furthermore, this approach did not change the skin moisture of the rats. This MP-MTF-GR-DMN is a promising alternative to MTF delivery to overcome MTF problems and increase the effectiveness of T2DM therapy.

Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped.

AIMS/HYPOTHESIS: The rapid remission of type 2 diabetes by a diet very low in energy correlates with a marked improvement in glucose-stimulated insulin secretion (GSIS), emphasising the role of beta cell dysfunction in the early stages of the disease. In search of novel mechanisms of beta cell dysfunction after long-term exposure to mild to severe glucotoxic conditions, we extensively characterised the alterations in insulin secretion and upstream coupling events in human islets cultured for 1-3 weeks at ~5, 8, 10 or 20 mmol/l glucose and subsequently stimulated by an acute stepwise increase in glucose concentration. METHODS: Human islets from 49 non-diabetic donors (ND-islets) and six type 2 diabetic donors (T2D-islets) were obtained from five isolation centres. After shipment, the islets were precultured for 3-7 days in RPMI medium containing ~5 mmol/l glucose and 10% (vol/vol) heat-inactivated FBS with selective islet picking at each medium renewal. Islets were then cultured for 1-3 weeks in RPMI containing ~5, 8, 10 or 20 mmol/l glucose before measurement of insulin secretion during culture, islet insulin and DNA content, beta cell apoptosis and cytosolic and mitochondrial glutathione redox state, and assessment of dynamic insulin secretion and upstream coupling events during acute stepwise stimulation with glucose [NAD(P)H autofluorescence, ATP/(ATP+ADP) ratio, electrical activity, cytosolic Ca2+ concentration ([Ca2+]c)]. RESULTS: Culture of ND-islets for 1-3 weeks at 8, 10 or 20 vs 5 mmol/l glucose did not significantly increase beta cell apoptosis or oxidative stress but decreased insulin content in a concentration-dependent manner and increased beta cell sensitivity to subsequent acute stimulation with glucose. Islet glucose responsiveness was higher after culture at 8 or 10 vs 5 mmol/l glucose and markedly reduced after culture at 20 vs 5 mmol/l glucose. In addition, the [Ca2+]c and insulin secretion responses to acute stepwise stimulation with glucose were no longer sigmoid but bell-shaped, with maximal stimulation at 5 or 10 mmol/l glucose and rapid sustained inhibition above that concentration. Such paradoxical inhibition was, however, no longer observed when islets were acutely depolarised by 30 mmol/l extracellular K+. The glucotoxic alterations of beta cell function were fully reversible after culture at 5 mmol/l glucose and were mimicked by pharmacological activation of glucokinase during culture at 5 mmol/l glucose. Similar results to those seen in ND-islets were obtained in T2D-islets, except that their rate of insulin secretion during culture at 8 and 20 mmol/l glucose was lower, their cytosolic glutathione oxidation increased after culture at 8 and 20 mmol/l glucose, and the alterations in GSIS and upstream coupling events were greater after culture at 8 mmol/l glucose. CONCLUSIONS/INTERPRETATION: Prolonged culture of human islets under moderate to severe glucotoxic conditions markedly increased their glucose sensitivity and revealed a bell-shaped acute glucose response curve for changes in [Ca2+]c and insulin secretion, with maximal stimulation at 5 or 10 mmol/l glucose and rapid inhibition above that concentration. This novel glucotoxic alteration may contribute to beta cell dysfunction in type 2 diabetes independently from a detectable increase in beta cell apoptosis.

Preparation, physicochemical properties, and in vivo digestibility of thermostable resistant starch from malic acid-treated wheat starch.

In this study, malic acid treatment under different conditions, including molarity level (2-4 M), temperatures (90-130 °C), and time (2-12 h), was evaluated to prepare a modified wheat starch that is rich in resistant starch (RS). The physicochemical characteristics of the modified starch were also investigated. The application of 4 M malic acid and a heat treatment at 130 °C for 7 h produced a malic acid-treated (MT) wheat starch composed of 99.5 % RS. Fourier-transform infrared spectroscopy of MT wheat starch displayed a distinct carbonyl peak at around 1,740 cm-1, is formed due to the stretching vibration of the CO bond of the ester group. The crystalline and double-helix structures of the MT wheat starch were extensively destroyed, resulting in its enhanced degree of substitution, number of cross-linking bonds, and thermostable RS content (99 %) as well as its reduced viscosity. Furthermore, its consumption in vivo reduced the blood glucose level and response. The starch modification method reported herein could be applied when preparing RS-rich wheat starch for use in the production of heat-processed foods with high fiber contents and low calories.

Postprandial glucose variability in type 1 diabetes: The individual matters beyond the meal.

AIM: To explore intraindividual (between-meals) and interindividual (between-subjects) variability of postprandial glucose response (PGR) in type 1 diabetes (T1DM). METHODS: Data were taken from five cross-over trials in 61 subjects with T1DM on insulin pump wherein the effects of different dietary components or the intraindividual-variability of PGR to the same meal were evaluated by CGM. Predictors (type of meal or nutrient composition) of early (iAUC0-3h), late (iAUC3-6h), total (iAUC0-6h), and time-course of postprandial blood glucose changes (iAUC3-6hminus0-3h) were evaluated using two mixed-effect linear regression models considering the patient's identification number as random-effect. RESULTS: High-glycemic-index (HGI) and low-glycemic-index meals were the best positive and negative predictors of glucose iAUC0-3h, respectively. A Low-Fat-HGI meal significantly predicted iAUC3-6hminus0-3h (Estimate 3268; p = 0.017). Among nutrients, dietary fiber was the only significant negative predictor of iAUC0-3h (Estimate -550; p < 0.001) and iAUC0-6h (Estimate -742; p = 0.01) and positive predictor of iAUC3-6hminus0-3h (Estimate 336; p = 0.043). For all models, the random-effect patient was statistically significant (p < 0.001 by ANOVA). CONCLUSION: Beyond the meal characteristics (including glycemic index, fat and fiber content), individual traits significantly influence PGR. Specific interindividual factors should be further identified to properly predict glucose response to meals with different composition in individuals with T1DM.

The Cdc25/Ras/cAMP-dependent protein kinase A signaling pathway regulates proline utilization in wine yeast Saccharomyces cerevisiae under a wine fermentation model.

Proline is a predominant amino acid in grape must, but it is poorly utilized by the yeast Saccharomyces cerevisiae in wine-making processes. This sometimes leads to a nitrogen deficiency during fermentation and proline accumulation in wine. In this study, we clarified that a glucose response is involved in an inhibitory mechanism of proline utilization in yeast. Our genetic screen showed that strains with a loss-of-function mutation on the CDC25 gene can utilize proline even under fermentation conditions. Cdc25 is a regulator of the glucose response consisting of the Ras/cAMP-dependent protein kinase A (PKA) pathway. Moreover, we found that activation of the Ras/PKA pathway is necessary for the inhibitory mechanism of proline utilization. The present data revealed that crosstalk exists between the carbon and proline metabolisms. Our study could hold promise for the development of wine yeast strains that can efficiently assimilate proline during the fermentation processes.

Transdermal Insulin Delivery and Microneedles-based Minimally Invasive Delivery Systems.

Diabetes has become a serious threat to human health, causing death and pain to numerous patients. Transdermal insulin delivery is a substitute for traditional insulin injection to avoid pain from the injection. Transdermal methods include non-invasive and invasive methods. As the non-invasive methods could hardly get through the stratum corneum, minimally invasive devices, especially microneedles, could enhance the transappendageal route in transcutaneous insulin delivery, and could act as connectors between the tissue and outer environment or devices. Microneedle patches have been in quick development in recent years and with different types, materials and functions. In those patches, the smart microneedle patch could perform as a sensor and reactor responding to glucose to regulate the blood level. In the smart microneedles field, the phenylboronic acid system and the glucose oxidase system have been successfully applied on the microneedle platform. Insulin transdermal delivery strategy, microneedles technology and smart microneedles' development would be discussed in this review.

Use of a Continuous Glucose Monitor to Determine the Glycaemic Index of Rice-Based Mixed Meals, Their Effect on a 24 h Glucose Profile and Its Influence on Overweight and Obese Young Adults' Meal Preferences.

Postprandial hyperglycaemia is associated with an increased risk of type-2 diabetes. This study aims to determine the glycaemic index (GI) of three varieties of rice-based mixed meals and their effects on glycaemic variability (GV), 24 h mean glucose levels and target ranges, and rice variety preferences among overweight and obese young adults using real-time continuous glucose monitoring (rtCGM). In a randomised controlled crossover design, 14 participants (22.8 ± 4.6 years, 32.9 ± 5.8 kg/m2) were randomly assigned to receive 3 rice-based mixed meals containing 50 g of available carbohydrates (white rice meal = WRM; brown rice meal = BRM; and parboiled basmati rice meal = PBRM) and 50 g of a glucose reference drink on alternate days. GI, GV, 24 h mean glucose levels and target ranges were measured. Rice variety preferences were compared with those of baseline data and determined at the end of the study period. Results: The analysis found that PBRM was low in GI (45.35 ± 2.06), BRM medium in GI (56.44 ± 2.34), and WRM high in GI (83.03 ± 2.19). PBRM had a significantly (p < 0.05) lower 24 h mean glucose level, higher in-target 24 h glucose level percentage and non-significantly (p > 0.05) lower GV compared to WRM. Prior to observing their postprandial glucose levels generated by rtCGM, the participants preferred WRM (64.3%) over other meals, whereas this preference changed significantly (p < 0.05) at the endpoint (PBRM, 71.4%). PBRM reduced 24 h glucose level and GV of overweight and obese young adults. The rtCGM is proven to be reliable in measuring GI, while providing robust continuous glycaemic information. This may serve as an educational tool that motivates eating behaviour changes among overweight and obese young adults.

Complete nutrition drink with retrograded starch is low glycemic, and the individual glucose response to the low glycemic complete nutrition drink depends on fasting insulin levels and HOMA-IR in a randomized cross-over control trial.

Complete nutrition drinks with a low glycemic index (GI) provide nutritional support and prevent hyperglycaemia. The present study identified GI and factors predicting individual glucose response to a new complete nutrition drink. A randomised cross-over controlled trial was conducted in eighteen healthy volunteers (FPG < 100 mg/dl). Complete nutrition drinks containing retrograded starch, glucose solution and white bread were assigned in a random sequence with 14-day wash-out intervals. Plasma glucose and insulin levels were measured from baseline to 180 min after consuming each food. Results show the adjusted GIs of the drink was 48.2 ± 10.4 and 46.7 ± 12.7 with glucose and white bread as the reference, respectively. While the drink has low GI (<55), the individual glucose responses varied (GI: 7-149). Comparing characters in individual GI < 55 (n = 12) and GI ≥ 55 (n = 6) groups revealed significantly higher baseline insulin in the low GI group (14.86 ± 16.51 µIU/ml v. 4.9 ± 3.4 µIU/ml, P < 0·05). The correlation matrix confirms only two predictive factors for having individual GI <55 were baseline insulin (r = 0·5, P = 0·03) and HOMA-IR (r = 0·55, P = 0·02). ROC curve reveals fasting insulin above 1.6 µIU/ml and HOMA-IR above 1.05 as the cut-off values. The findings suggest that the complete nutrition drink has a low GI, but there was wide variability in individual responses partly explained by fasting insulin levels and HOMA-IR. Screening for fasting insulin and HOMA-IR may be encouraged to maximise the functional benefit of the drink.

A Decentralized Study Setup Enables to Quantify the Effect of Polymerization and Linkage of α-Glucans on Post-Prandial Glucose Response.

The complexity of the carbohydrate structure is associated with post-prandial glucose response and diverse health benefits. The aim of this study was to determine whether, thanks to the usage of minimally invasive glucose monitors, it was possible to evaluate, in a decentralized study setup, the post-prandial glycemic response (PPGR) of α-glucans differing systematically in their degree of polymerization (DP 3 vs. DP 60) and in their linkage structure (dextrin vs. dextran). Ten healthy subjects completed a double-blind, randomized, decentralized crossover trial, testing at home, in real life conditions, four self-prepared test beverages consisting of 25 g α-glucan dissolved in 300 mL water. The incremental area under the curve of the 120 min PPGR (2h-iAUC) was the highest for Dextrin DP 3 (163 ± 27 mmol/L*min), followed by Dextrin DP 60 (-25%, p = 0.208), Dextran DP 60 (-59%, p = 0.002), and non-fully caloric Resistant Dextrin (-68%, p = 0.002). These results show that a fully decentralized crossover study can be successfully used to assess the influence of both polymerization and structure of α-glucans on PPGR.

Glucose sensitive konjac glucomannan/concanavalin A nanoparticles as oral insulin delivery system.

Compared with injection, oral drug delivery is a better mode of administration because of its security, low pain and simplicity. Insulin is the first choice for clinical treatment of type 1 diabetes, but, because insulin inability to resist gastrointestinal (GI) digestion results in poor oral bioavailability of insulin. Herein, we developed a targeted oral delivery system for diabetes. ConA-INS-KGM nanoparticles were prepared, loaded with insulin, fabricated from konjac glucomannan (KGM) and concanavalin A (ConA) through a crosslinking method, as an insulin oral delivery system in response to different blood glucose levels. The size of nanoparticles was characterized by TEM, which showed that these nanoparticles were formed spherical particles with a diameter of about 500 nm. In vitro release of insulin from these nanoparticles was studied, which indicated that insulin release is reversible at different glucose concentrations. In vivo tests demonstrated that they are safe and have high biocompatibility. Using the nanoparticles to treat diabetic mice, we found that they can control blood sugar levels for 6 h, retaining their glucose-sensitive properties during this time. Therefore, these nanoparticles have significant potential as glucose-responsive systems for diabetes and show great applications in biomedical fields.

The northeast glucose drift: Stratification of post-breakfast dysglycemia among predominantly Hispanic/Latino adults at-risk or with type 2 diabetes.

Background: There is minimal experience in continuous glucose monitoring (CGM) among underserved racial/ethnic minority populations with or at risk of type 2 diabetes (T2D), and therefore a lack of CGM-driven insight for these individuals. We analyzed breakfast-related CGM profiles of free-living, predominantly Hispanic/Latino individuals at-risk of T2D, with pre-T2D, or with non-insulin treated T2D. Methods: Starting February 2019, 119 participants in Santa Barbara, CA, USA, (93 female, 87% Hispanic/Latino [predominantly Mexican-American], age 54·4 [±12·1] years), stratified by HbA1c levels into (i) at-risk of T2D, (ii) with pre-T2D, and (iii) with non-insulin treated T2D, wore blinded CGMs for two weeks. We compared valid CGM profiles from 106 of these participants representing glucose response to breakfast using four parameters. Findings: A "northeast drift" was observed in breakfast glucose responses comparing at-risk to pre-T2D to T2D participants. T2D participants had a significantly higher pre-breakfast glucose level, glucose rise, glucose incremental area under the curve (all p < 0·0001), and time to glucose peak (p < 0·05) compared to pre-T2D and at-risk participants. After adjusting for demographic and clinical covariates, pre-breakfast glucose and time to peak (p < 0·0001) were significantly associated with HbA1c. The model predicted HbA1c within (0·55 ± 0·67)% of true laboratory HbA1c values. Interpretation: For predominantly Hispanic/Latino adults, the average two-week breakfast glucose response shows a progression of dysglycemia from at-risk of T2D to pre-T2D to T2D. CGM-based breakfast metrics have the potential to predict HbA1c levels and monitor diabetes progression. Funding: US Department of Agriculture (Grant #2018-33800-28404), a seed grant from the industry board fees of the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (Award #1648451), and the Elsevier foundation.