Metabolic disorders in prediabetes: From mechanisms to therapeutic management.

Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.

Vitamin D inhibits ferroptosis and mitigates the kidney injury of prediabetic mice by activating the Klotho/p53 signaling pathway.

Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.

Individualized homeopathic medicines in preventing the progression from pre-diabetes to diabetes: A double-blind, randomized, placebo-controlled, parallel-arm trial.

CONTEXT: Pre-diabetes is a significant public health problem worldwide. India has a very high rate of progression from pre-diabetes to diabetes, 75-78 per thousand persons per year. OBJECTIVE: To study the efficacy of individualized homeopathic medicinal products (HMPs) against placebos in preventing the progression from pre-diabetes to diabetes. DESIGN: Six-month, double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. SETTING: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India. PATIENTS: Sixty participants with pre-diabetes. INTERVENTIONS: Verum: HMPs plus yoga therapy (YT; n = 30); control: identical-looking placebos plus YT (n = 30). MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion of participants progressing from pre-diabetes to diabetes, measured after three and six months. Secondary outcomes comprised of fasting blood glucose (FBS), oral glucose tolerance test (OGTT), glycated hemoglobin percentage (HbA1c%), lipid profile, liver enzymes (alanine transaminase, aspartate transaminase), urea and creatinine, and Measure Yourself Medical Outcome Profile version 2 (MYMOP-2); all measured after 3 and 6 months. RESULTS: The proportion of participants converted from pre-diabetics to diabetics (n/N; n = diabetics, N = prediabetics) was significantly less in the verum group than control: HbA1C% (month 3: verum - 2/30 versus control - 11/30, p = 0.003; month 6: 3/30 vs. 2/30, p = 0.008), OGTT (month 3: 0/30 vs. 8/30, p = 0.015; month 6: 0/30 vs. 1/30, p = 0.008), but not according to FBS (month 3: 1/30 vs. 1/30, p = 0.779; month 6: 1/30 vs. 3/30, p = 0.469). Several secondary outcomes also revealed significant improvements in the verum group than in placebo: HbA1C% (p < 0.001), OGTT (p = 0.001), serum ALT (p = 0.031), creatinine (p = 0.012), and MYMOP-2 profile scores (p < 0.001). Sulphur, Bryonia alba, and Thuja occidentalis were the most frequently indicated medicines. Thus, HMPs outperformed placebos by successfully preventing the progression of pre-diabetes to diabetes. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2022/04/042,026; UTN: U1111-1277-0021.

Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes-Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy.

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.

Effects of vitamin D and/or calcium intervention on sleep quality in individuals with prediabetes: a post hoc analysis of a randomized controlled trial.

PURPOSE: The aim of this study was to evaluate the effects of vitamin D and/or calcium supplementation on sleep quality in individuals with prediabetes. METHODS: A 24-week randomized controlled trial (RCT) was conducted in a 212 Chinese population with prediabetes. Participants were randomly assigned to four groups: vitamin D + calcium group (1600 IU/day + 500 mg/day, n = 53), vitamin D group (1600 IU/day, n = 54), calcium group (500 mg/day, n = 51), and control group (placebo, n = 54). The Pittsburgh Sleep Quality Index (PSQI) was used as the primary outcome to assess sleep quality. Questionnaires and fasting blood samples were collected at baseline and post-intervention for demographic assessment and correlation index analysis. RESULTS: After a 24-week intervention, a significant difference was observed in serum 25(OH)D concentration among the four groups (P < 0.05), and the total PSQI score in vitamin D + calcium group was lower compared to the preintervention levels. Subgroup analyses revealed improved sleep quality with calcium supplementation (P < 0.05) for specific groups, including women, individuals with a low baseline 25(OH)D level (< 30 ng/mL), and individuals in menopause. Moreover, correlation analysis revealed a negative correlation between the extent of change in sleep efficiency scores before and after the calcium intervention and the degree of change in insulin efficiency scores (r = - 0.264, P = 0.007), as well as the magnitude of change in islet beta cell function (r = - 0.304, P = 0.002). CONCLUSIONS: The combined intervention of vitamin D and calcium, as well as calcium interventions alone, exhibits substantial potential for improving sleep quality in individuals with prediabetes. CLINICAL TRIAL REGISTRATION: The trial was registered in August 2019 as ChiCTR190002487.

Akt Signaling and Nitric Oxide Synthase as Possible Mediators of the Protective Effect of N-acetyl-L-cysteine in Prediabetes Induced by Sucrose.

The aim of this work was to evaluate possible mechanisms involved in the protective effect of N-acetyl-L-cysteine (NAC) on hepatic endocrine-metabolic, oxidative stress, and inflammatory changes in prediabetic rats. For that, normal male Wistar rats (60 days old) were fed for 21 days with 10% sucrose in their drinking water and 5 days of NAC administration (50 mg/kg, i.p.) and thereafter, we determined: serum glucose, insulin, transaminases, uric acid, and triglyceride levels; hepatic fructokinase and glucokinase activities, glycogen content, lipogenic gene expression; enzymatic and non-enzymatic oxidative stress, insulin signaling pathway, and inflammatory markers. Results showed that alterations evinced in sucrose-fed rats (hypertriglyceridemia, hyperinsulinemia, and high liver fructokinase activity together with increased liver lipogenic gene expression and oxidative stress and inflammatory markers) were prevented by NAC administration. P-endothelial nitric oxide synthase (P-eNOS)/eNOS and pAKT/AKT ratios, decreased by sucrose ingestion, were restored after NAC treatment. In conclusion, the results suggest that NAC administration improves glucose homeostasis, oxidative stress, and inflammation in prediabetic rats probably mediated by modulation of the AKT/NOS pathway. Administration of NAC may be an effective complementary strategy to alleviate or prevent oxidative stress and inflammatory responses observed in type 2 diabetes at early stages of its development (prediabetes).

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice.

Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12-14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.

Intra-pancreatic fat is associated with high circulating glucagon and GLP-1 concentrations following whey protein ingestion in overweight women with impaired fasting glucose: A randomised controlled trial.

AIM: Intra-pancreatic fat deposition (IPFD) while hypothesised to impair beta-cell function, its impact on alpha-cells remains unclear. We evaluated the association between IPFD and markers of pancreatic cells function using whey protein. METHODS: Twenty overweight women with impaired fasting glucose (IFG) and low or high IPFD (<4.66% vs ≥4.66%) consumed 3 beverage treatments: 0 g (water control), 12.5 g (low-dose) and 50.0 g (high-dose) whey protein, after an overnight fast, in randomised order. Blood glucose, insulin, C-peptide, glucagon, gastric-inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and amylin were analysed postprandially over 4 h. Incremental area-under-the-curve (iAUC), incremental maximum concentration (iCmax), and time to maximum concentration (Tmax) for these were compared between IPFD groups using repeated measures linear mixed models, also controlled for age (pcov). RESULTS: iAUC and iCmax glucose and insulin while similar between the two IPFD groups, high IPFD and ageing contributed to higher postprandial glucagon (iAUC: p = 0.012; pcov = 0.004; iCmax: p = 0.069; pcov = 0.021) and GLP-1 (iAUC: p = 0.006; pcov = 0.064; iCmax: p = 0.011; pcov = 0.122) concentrations. CONCLUSION: In our cohort, there was no evidence that IPFD impaired protein-induced insulin secretion. Conversely, IPFD may be associated with increased protein-induced glucagon secretion, a novel observation which warrants further investigation into its relevance in the pathogenesis of dysglycaemia and type-2 diabetes.

A Narrative Review on Strategies for the Reversion of Prediabetes to Normoglycemia: Food Pyramid, Physical Activity, and Self-Monitoring Innovative Glucose Devices.

In 2019, "Nutrition Therapy for Adults with Diabetes or Prediabetes: A Consensus Report" was published. This consensus report, however, did not provide an easy way to illustrate to subjects with prediabetes (SwPs) how to follow a correct dietary approach. The purpose of this review is to evaluate current evidence on optimum dietary treatment of SwPs and to provide a food pyramid for this population. The pyramid built shows that everyday consumption should consist of: whole-grain bread or potatoes eaten with their skins (for fiber and magnesium) and low glycemic index carbohydrates (GI < 55%) (three portions); fruit and vegetables (5 portions), in particular, green leafy vegetables (for fiber, magnesium, and polyphenols); EVO oil (almost 8 g); nuts (30 g, in particular, pistachios and almonds); three portions of dairy products (milk/yogurt: 300-400 g/day); mineral water (almost 1, 5 L/day for calcium intake); one glass of wine (125 mL); and three cups of coffee. Weekly portions should include fish (four portions), white meat (two portions), protein plant-based food (four portions), eggs (egg portions), and red/processed meats (once/week). At the top of the pyramid, there are two pennants: a green one means that SwPs need some personalized supplementation (if daily requirements cannot be satisfied through diet, vitamin D, omega-3, and vitamin B supplements), and a red one means there are some foods and factors that are banned (simple sugar, refined carbohydrates, and a sedentary lifestyle). Three to four times a week of aerobic and resistance exercises must be performed for 30-40 min. Finally, self-monitoring innovative salivary glucose devices could contribute to the reversion of prediabetes to normoglycemia.

A study on the use of acupoint catgut embedding in the treatment of pre-diabetes: a meta-analysis and data mining approach.

Objective: The efficacy of acupoint catgut embedding (ACE) for the treatment of pre-diabetes remains controversial. Therefore, this study investigated the clinical efficacy and acupoint selection in ACE for the treatment of pre-diabetes. Methods: Eight common databases were searched for relevant literature on ACE for pre-diabetes. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore the protocol for acupoint selection. Results: The meta-analysis revealed that compared with conventional treatment alone, conventional treatment combined with ACE reduced the levels of glycated hemoglobin A1c [mean difference (MD) -0.45, 95% confidence interval (CI) -0.67 to -0.24%, p < 0.001], fasting blood glucose (MD -0.61 mmol/L, 95% CI -0.87 to -0.36 mmol/L, p < 0.001), 2-h postprandial glucose (MD -0.77 mmol/L, 95% CI -0.98 to -0.55 mmol/L, p < 0.001), total cholesterol (MD -0.37 mmol/L, 95% CI -0.74 to 0.00 mmol/L, p = 0.049), triglyceride (MD -0.49 mmol/L, 95% CI -0.77 to -0.20 mmol/L, p < 0.001) and low-density lipoprotein cholesterol (MD -0.23 mmol/L, 95% CI -0.33 to -0.12 mmol/L, p < 0.001), and increased high-density lipoprotein cholesterol levels (MD 0.16 mmol/L, 95% CI 0.05 to 0.27 mmol/L, p = 0.004), whereas changes in the body mass index and the adverse event rates were comparable between groups. Data mining revealed that Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3) were the core acupoints used in ACE for pre-diabetes. Conclusion: ACE can effectively improve blood glucose and lipid levels in pre-diabetes patients and has a good safety profile. ACE consisting of Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3), is a promising complementary strategy for the treatment of pre-diabetes.

The effects of Danzhi Jiangtang capsule on clinical indices and vascular endothelial function in patients with impaired glucose tolerance of Qi-Yin deficiency type.

OBJECTIVE: To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT). METHODS: A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy. RESULTS: In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p < .01) (CI: 1.45, 6.73; Cohen's d: 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p < .001) (CI: -10.28, -6.24; 3.12, 5.18; Cohen's d: 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen's d: 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen's d: 0.40, 0.51). CONCLUSIONS: Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi-Yin deficiency type.

Dietary Consumption on Glycemic Control Among Prediabetes: A Review of the Literature.

Introduction: Prediabetes is a condition that, if left unaddressed, can lead to various complications, such as neuropathy, retinopathy, and nephropathy. Among the critical factors contributing to the development of type 2 diabetes mellitus, dietary choices stand out as particularly significant. Objective: Consequently, our objective is to examine the latest research findings concerning dietary consumption and its impact on glycemic control in individuals with prediabetes. Methods: A literature review of randomized controlled trials was performed using databases such as PubMed, Scopus, and ScienceDirect with searches conducted from January 2019 to 2023. The primary reviewer assessed the quality of the selected studies for bias risk using the Joanna Briggs Institute critical appraisal method for randomized controlled trials. Initially, 975 articles were identified through the search, but after applying the inclusion criteria, only 9 articles were ultimately selected. Results: The review found that a carrageenan-free diet, yogurt with Lactobacillus plantarum OLL2712, Allium hookeri extract (AHE), and delta-tocotrienol improve HbA1C levels. However, salmon, zinc supplement, and balanced deep-sea water were not effective on HbA1C. In addition, studies on the effectiveness of vitamin D in controlling blood glucose levels are inconsistent. Conclusion: Nurses can enhance patient outcomes through collaborative efforts to create individualized dietary strategies. These strategies may encompass the adoption of a carrageenan-free diet, the inclusion of L plantarum OLL2712-enriched yogurt, the utilization of AHE, and the integration of delta-tocotrienol into the dietary plan. This approach is particularly applicable to ambulatory care nurses, health supervisors, and primary care providers.

Health Outcomes Following Engagement With a Digital Health Tool Among People With Prediabetes and Type 2 Diabetes: Prospective Evaluation Study.

BACKGROUND: Diabetes is a worldwide chronic condition causing morbidity and mortality, with a growing economic burden on health care systems. Complications from poorly controlled diabetes are associated with increased socioeconomic costs and reduced quality of life. Smartphones have become an influential platform, providing feasible tools such as health apps to deliver tailored support to enhance the ability of patients with diabetes for self-management. Gro Health is a National Health Service division X-certified digital health tool used to deliver educational and monitoring support to facilitate the development of skills and practices for maintaining good health. OBJECTIVE: This study aims to assess self-reported outcomes of the Gro Health app among users with diabetes and prediabetes and identify the factors that determine engagement with the digital health tool. METHODS: This was a service evaluation of self-reported data collected prospectively by the developers of the Gro Health app. The EQ-5D questionnaire is a standardized tool used to measure health status for clinical and economic appraisal. Gro Health users completed the EQ-5D at baseline and 6 months after using the app. Users provided informed consent for the use of their anonymized data for research purposes. EQ-5D index scores and visual analogue scale (VAS) scores were calculated at baseline and 6 months for individuals with prediabetes and type 2 diabetes. Descriptive statistics and multiple-regression models were used to assess changes in the outcome measures and determine factors that affected engagement with the digital tool. RESULTS: A total of 84% (1767/2114) of Gro Health participants completed EQ-5D at baseline and 6 months. EQ-5D index scores are average values that reflect people's preferences about their health state (1=full health and 0=moribund). There was a significant and clinically meaningful increase in mean EQ-5D index scores among app users between baseline (0.746, SD 0.23) and follow-up (0.792, SD 0.22; P<.001). The greatest change was observed in the mean VAS score, with a percentage change of 18.3% improvement (61.7, SD 18.1 at baseline; 73.0, SD 18.8 at follow-up; P<.001). Baseline EQ-5D index scores, age, and completion of educational modules were associated with significant changes in the follow-up EQ-5D index scores, with baseline EQ-5D index scores, race and ethnicity, and completion of educational modules being significantly associated with app engagement (P<.001). CONCLUSIONS: This study provides evidence of a significant positive effect on self-reported quality of life among people living with type 2 diabetes engaging with a digital health intervention. The improvements, as demonstrated by the EQ-5D questionnaire, are facilitated through access to education and monitoring support tools within the app. This provides an opportunity for health care professionals to incorporate National Health Service-certified digital tools, such as Gro Health, as part of the holistic management of people living with diabetes.

Reinstating acute-phase insulin release among sedentary adults at high risk for type 2 diabetes with Yoga and Walking based lifestyle modification.

BACKGROUND: We compared the impact of 2 lifestyle modifying physical activities, yoga (YBLM) or walking (WBLM) on impaired beta cell function (IBF) or insulin resistance (IR) in restoring acute phase insulin release (APIR) among prediabetes at high risk for type 2 diabetes (HRDM). METHOD: Male and female adults (N = 42, 38.1 ± 4.8 years) with abdominal obesity (Male:103 ± 8.1 cm) Female: 92 ± 11.1 cm), randomized into YBLM (n = 20) and WBLM (n = 22), were monitored for the practice of the intervention, 45 min a day/5 days a week for 12 weeks. Blood sample was collected at 0th minute to estimate the level of Fasting Blood Glucose (FBG), Sr. Insulin and lipid profile and at 10th minute (APIR). IBF, IR and sensitivity (IS) reading were checked in HOMA-2 calculator. RESULT: Wilcoxon sign rank t-test denoted an improved APIR among the subjects with IBF (p = 0.008) and not among the subjects with IR (p = 0.332). However, regression analysis yielded an improved APIR among subjects with IBF (F(1,10) = 7.816, p = 0.002) with the management of body weight and lipid profile and IR (F(1,13) = 17.003, p = 0.001) being found influenced with selected lipid components. In all, during the post assessment period, an impressive boost in APIR was manifested among people shifted to Normoglycemia (n = 14, 35.9%). CONCLUSION: Intriguingly, we postulate the potential role of YBLM over WBLM in the management of lipid profile and body weight on accelerating APIR either through improved Beta cell compensation or by sensitizing skeletal muscles regulating IR, helping improve glucose tolerance resulting in either remission or management of prediabetes.

Lycium barbarum Polysaccharides Improved Glucose Metabolism in Prediabetic Mice by Regulating Duodenal Contraction.

Lycium barbarum polysaccharides (LBPs) have been shown to exert an antiglycemic effect. Emerging evidence suggests that patients with hyperglycemia have a hypercontractility of duodenum, and targeting duodenal contraction of duodenum can be beneficial to glucose metabolism. However, it is unknown whether LBPs can improve glucose metabolism by regulating the hypercontractility of the duodenum. Our aim was to explore the effect of LBPs on duodenal contraction in prediabetic mice and also preliminarily investigate the mechanism. The results showed that LBPs improved glucose homeostasis by decreasing the duodenal amplitude of contraction rather than frequency. Moreover, LBPs ameliorated the gut microbiota composition and the levels of short-chain fatty acids, especially acetic acid, which might bind to the receptor on neurons to regulate the contraction of the duodenum. Acetic acid was hypothesized to play a key role in the above process. Then, acetic acid was determined to exert an antiglycemic effect as expected. In conclusion, LBPs may rely on acetic acid to regulate duodenal contraction to ameliorate glucose metabolism in prediabetic mice, which provides a new therapeutic strategy to treat dysglycemia.

Fish oil supplementation counteracts the effect of high-fat and high-sucrose diets on the carbonylated proteome in the rat cerebral cortex.

High daily intake of saturated fats and refined carbohydrates, which often leads to obesity and overweight, has been associated with cognitive impairment, premature brain aging and the aggravation of neurodegenerative diseases. Although the molecular pathology of obesity-related brain damage is not fully understood, the increased levels of oxidative stress induced by the diet seem to be definitively involved. Being protein carbonylation determinant for protein activity and function and a main consequence of oxidative stress, this study aims to investigate the effect of the long-term high-fat and sucrose diet intake on carbonylated proteome of the cerebral cortex of Sprague-Dawley rats. To achieve this goal, the study identified and quantified the carbonylated proteins and lipid peroxidation products in the cortex, and correlated them with biometrical, biochemical and other redox status parameters. Results demonstrated that the obesogenic diet selectively increased oxidative damage of specific proteins that participate in fundamental pathways for brain function, i.e. energy production, glucose metabolism and neurotransmission. This study also evaluated the antioxidant properties of fish oil to counteract diet-induced brain oxidative damage. Fish oil supplementation demonstrated a stronger capacity to modulate carbonylated proteome in the brain cortex. Data indicated that fish oils did not just decrease carbonylation of proteins affected by the obesogenic diet, but also decreased the oxidative damage of other proteins participating in the same metabolic functions, reinforcing the beneficial effect of the supplement on those pathways. The results could help contribute to the development of successful nutritional-based interventions to prevent cognitive decline and promote brain health.

Combinational application of the natural products 1-deoxynojirimycin and morin ameliorates insulin resistance and lipid accumulation in prediabetic mice.

BACKGROUND: Prediabetes, a stage characterized by chronic inflammation, obesity and insulin resistance. Morin and 1-deoxynojirimycin (DNJ) are natural flavonoids and alkaloids extracted from Morus nigra L., exhibiting anti-hyperglycemic efficacy. However, the benefits of DNJ are shadowed by the adverse events, and the mechanism of morin in anti-diabetes remains under investigation. PURPOSE: In this study, the combinational efficacy and mechanisms of DNJ and morin in ameliorating insulin resistance and pre-diabetes were investigated. METHODS: The mice model with prediabetes and Alpha mouse liver-12 (AML-12) cell model with insulin resistance were established. The anti-prediabetic efficacy of the drug combination was determined via analyzing the blood glucose, lipid profiles and inflammatory factors. The application of network pharmacology provided guidance for the research mechanism. RESULTS: In our study, the intervention of morin ameliorated the insulin resistance via activating the Peroxisome proliferator-activated receptor γ (PPARγ). However, PPARγ activation leaded to the lipid accumulation in prediabetic mice. The combination of 5 mg/kg dose of DNJ and 25 mg/kg morin effectively hindered the progression of T2DM by 87.56%, which was achieved via inhibition of Suppressors of cytokine signaling 3 (SOCS3) and promotion of PPARγ as well as SOCS2 expression. Furthermore, this treatment exhibited notable capabilities in combating dyslipidemia and adipogenesis, achieved by suppressing the Cluster of differentiation 36/ Sterol-regulatory element binding proteins-1/ Fatty acid synthetase (CD36/Serbp1/Fas) signaling. CONCLUSION: This research confirmed that the drug combination of DNJ and morin in ameliorating insulin resistance and lipid accumulation, and revealed the potential mechanisms. In summary, the combination of DNJ and morin is an underlying alternative pharmaceutical composition in T2DM prevention.

The effectiveness of medical nutrition therapy provided by a dietitian in adults with prediabetes: a systematic review and meta-analysis.

BACKGROUND: A total of 374 million adults worldwide are living with prediabetes, 70% of whom will develop type 2 diabetes mellitus (T2DM) in their lifetime. Medical nutrition therapy (MNT) provided by a dietitian, such as that found in lifestyle interventions, has the potential to improve glycemic control and prevent progression to T2DM. OBJECTIVES: The objective of this systematic review was to examine the effectiveness of MNT provided by a dietitian, compared with standard care, on glycemic, cardiometabolic, and anthropometric outcomes in adults with prediabetes. METHODS: Searches were conducted for randomized controlled trials (RCTs) published between 1995 and 2022 using electronic databases MEDLINE, CINHAL, and Cochrane Central. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for RCTs. Meta-analyses were conducted using a random-effects model. The certainty of evidence was assessed for each outcome using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method, and a summary of findings table was created using the GRADEpro Guideline Development Tool. RESULTS: Thirteen RCTs were included in the analysis, showcasing a variety of MNT interventions delivered by dietitians. Intervention durations ranged from 3 to 24 mo. Compared with standard care, MNT improved hemoglobin A1c (HbA1c) (mean difference [95% confidence interval]: -0.30% [-0.49, -0.12]) and fasting blood glucose (FBG) (-4.97 mg/dL [-6.24, -3.71]). Statistically significant improvements were found in anthropometrics (weight, body mass index, and waist circumference), cholesterol (total, high-, and low-density lipoproteins), and blood pressure (systolic and diastolic). No significant effect was found on T2DM or triglycerides. The certainty of evidence was moderate for FBG and low for HbA1c and incidence of T2DM. CONCLUSIONS: In adults with prediabetes, MNT was effective in improving glycemic outcomes, anthropometrics, blood pressure, and most lipid levels. However, most studies had a risk of bias because of the randomization process or deviations from intended interventions. MNT plays a key role in improving cardiometabolic risk factors in adults with prediabetes. TRIAL REGISTRATION NUMBER: This study was registered with the registration ID #351421, available from https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351421.

Effect of Zuo's warming Yang acupuncture therapy combined with lifestyle interventions on prediabetes: A randomized controlled trial.

BACKGROUND: Acupuncture has promising effects on diabetes, but there is limited evidence on prediabetes. The purpose of this study was to evaluate the effect and safety of Zuo's warming Yang acupuncture therapy on prediabetic patients. METHODS: Fifty five individuals with prediabetes were recruited for the study. Participants in the non-acupuncture group received a 12-week lifestyle intervention, while those in the acupuncture group received the same lifestyle intervention in addition to two 50-minute sessions of Zuo's warming Yang acupuncture therapy per week. The primary outcomes measure fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), and Glycated hemoglobin determination (HbA1c) after 12 weeks of treatment. RESULTS: Both acupuncture group and non-acupuncture group showed significant reductions in FPG and 2hPG levels after treatment, with a statistically significant difference between them (FPG:6.25 ± 0.48 vs 5.73 ± 0.50, P < 0.001; 6.21 ± 0.42 vs 6.04 ± 0.41, P = 0.035; 2hPG:8.90(8.44,9.88) vs 7.95(6.93,8.34), P < 0.001; 9.22 ± 1.15 vs 8.70 ± 1.34, P = 0.046; respectively). In addition, FPG and 2hPG in the acupuncture group decreased more significantly than those in the non-acupuncture group after treatment, and the difference was statistically significant (FPG:5.73 ± 0.50 vs 6.04 ± 0.41, P = 0.014;2hPG:7.95(6.93,8.34) vs 8.70 ± 1.34, P = 0.015; respectively). Although both groups showed reductions in HbA1c, only the decrease in the acupuncture group was statistically significant(5.80(5.60,5.90) vs 5.60(5.40,5.80), P = 0.015). No severe adverse events were reported. CONCLUSIONS: Zuo's warming Yang acupuncture therapy conjunction with lifestyle interventions was more effective than lifestyle interventions alone in reducing FPG, 2hPG and HbA1c levels in prediabetic patients. These results suggest that Zuo's warming Yang acupuncture therapy may be a safe and effective treatment option for prediabetes.

A comparative analysis of Vamana and ShamanaChikitsa in prediabetes management: A randomized clinical trial.

BACKGROUND: Prediabetes is a condition before manifestation of diabetes. It is associated with biochemical change in body due to disturbances in food habits, sleep patterns and sedentary lifestyle. Conventional system of medicine has limitations, however Ayurvedic medicines can be effective for management of this condition. OBJECTIVE: To compare the efficacy of Vamana Karma (∼therapeutic emesis) followed by Darvyadi Kwatha (∼herbal decoction) with that of oral medication of Darvyadi Kwatha with lifestyle modification in reducing HbA1c of the prediabetic participants. METHODOLOGY: After approval of IEC and registration under clinical trial registry of India, 40 patients were registered in two groups suffering from prediabetes in the trial. The primary criteria were HBA1c, FBS & PPBS along with secondary criterias like Agnibala (∼strength of digestion and metabolism), Dehabala (physical strength) and Satvabala (mental strength) relief in signs & symptoms of Prameha and quality of life (SF-36 Score). RESULTS: Statistically significant results were observed in both the parameters: (primary & secondary) within the group [VM group (HbA1c (<0.001), FBS (<0.001) & PPBS (<0.001) and SM group (HbA1c (<0.001), FBS (<0.001) & PPBS (<0.001)] and between the group [HbA1c (P < 0.01), FBS (P < 0.01), SF-36 score (P < 0.001) as well. CONCLUSION: The present clinical study suggests that there is significant improvement between the groups. On comparision, it was found that treating prediabete.s Shodhana was more safe & effective than Shamana.