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.

Plant Extracts as Add-On Therapeutics in Homeopathy: An Open-Label, Randomized Trial Using Mother Tinctures in Prediabetes.

Objectives: Prediabetes is a major public health concern. Different plant extracts are used in homeopathy as mother tinctures (MTs) for the treatment of prediabetes as an adjunct to individualized homeopathic medicines (IHMs); however, their effectiveness remains under-researched. Design: Open-label, randomized (1:1), active-controlled, pragmatic, exploratory trial. Setting: Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Eighty-nine patients with prediabetes. Interventions: Group 1 (n = 45; IHMs plus any one of the following MTs: Cephalandra indica, Gymnema sylvestre, and Syzygium jambolanum; experimental/verum) versus Group 2 (n = 44; IHMs only; control). Outcome measures: Blood parameters, including-the fasting blood sugar (FBS) level, blood sugar level 2 h after ingestion of 75 g of glucose (oral glucose tolerance test [OGTT] result), and glycosylated hemoglobin percentage (HbA1c%), and symptoms, including the Diabetes Symptom Checklist-Revised (DSC-R) score; all of them were measured at baseline and after 3 and 6 months. Results: Although recruitment of 140 patients was initially planned, the target sample size could not be achieved because of coronavirus disease pandemic-related restrictions. Only 89 patients could be enrolled, and the trial had to be terminated prematurely owing to the time constraints of the project. The data of 82 patients (Group 1, n = 40; Group 2, n = 42) were analyzed using a modified intention-to-treat approach. Improvements in all outcomes were greater in Group 1 than in Group 2, but without a significant difference: FBS level (F1, 80 = 4.095, p = 0.046), OGTT result (F1, 80 = 2.399, p = 0.125), HbA1c% (F1, 80 = 1.612, p = 0.208), and DSC-R score (F1, 80 = 0.023, p = 0.880). Conclusions: A promising but nonsignificant trend favored the combination of MTs and IHMs compared with IHMs alone among the patients with prediabetes, especially in FBS. Therefore, further studies are required. Clinical Trial Registration Number: CTRI/2018/08/015319; secondary identifier (UTN): U1111-1218-6016.

A randomized controlled clinical study on Zuo's acupuncture treatment for prediabetes.

INTRODUCTION: Prediabetes is a high-risk stage of transition to type 2 diabetes mellitus. Previous studies suggest that acupuncture has potential to prevent prediabetes' conversion to type 2 diabetes mellitus, which lack of high-quality evidence. Zuo's acupuncture, a kind of acupuncture technique, is formed through long-term and repeated clinical practice by professor Zuo Changbo who integrates the internal meaning of Dong extra acupoints and Taoist medicine principle according to the theories of traditional Chinese medicine. It is used clinically to increase the regression toward normo-glycemi on prediabetes. The objective of this trial is to clarify the clinical effectiveness and safety of Zuo acupuncture for prediabetes. METHODS AND ANALYSIS: This study is a prospective randomized controlled trial in which 60 patients with prediabetes will be randomly allocated in a 1:1 ratio into either an acupuncture treatment group or a control group. Prediabetes patients in the control group will receive prediabetes health education for lifestyle interventions, whereas patients in the acupuncture group will receive lifestyle interventions plus Zuo Daliji and Yueku stitch treatment. Twenty-four treatment sessions will be performed over 3 months. The primary outcome is conversion rate from prediabetes to normal blood glucose. Secondary outcomes include fasting plasma glucose, 2-hour plasma glucose, glycosylated hemoglobin and blood lipid concentration. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (permission number: YF2020-107-01) and the protocol conforms to the principles of the Declaration of Helsinki. Data collection will be completed by June 2022. Publications will be ready for submission in July 2022.

Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes.

CONTEXT: Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on ß-cell function remain unclear. OBJECTIVE: To investigate the effects of vitamin D3 supplementation on insulin sensitivity and ß-cell function. METHODS: This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months. MAIN OUTCOME: Disposition index (DI), as an estimate of ß-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT). RESULTS: Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level <12 ng/mL, the mean percent differences for DI between the vitamin D and placebo groups was 8.5 (95% CI, 0.2-16.8). CONCLUSIONS: Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of ß-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Effect of Vitamin D Supplementation on Glycemic Control in Prediabetes: A Meta-Analysis.

Clinical research results of vitamin D supplementation in the improvement of prediabetes remain controversial. Accordingly, a literature search was conducted of PubMed, Embase (Ovid), and Web of Science prior to 9 November 2021. Randomized controlled studies reported that the following indicators were included: body mass index (BMI), fasting blood glucose (FBG), 2 h oral glucose tolerance test plasma glucose (2h-PG), hemoglobin A1c (HbA1c), insulin resistance by homeostasis model assessment (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-B), and fasting insulin (FINS). Twenty-nine articles (N = 3792) were included in the present meta-analysis. Intriguingly, vitamin D supplementation resulted in a vast improvement in FBG (standardized mean difference (SMD) = -0.38; 95%CI: -0.59, -0.16), HbA1c (SMD = -0.14; 95%CI: -0.22, -0.06) and FINS (SMD = 0.18; 95%CI: -0.26, -0.09), but not in other outcomes. However, preferred changes were observed in subgroups, as follows: Asia (SMD2h-PG = -0.25, 95%CI: -0.45, -0.04), study duration ≥1 year (SMDHOMA-IR = -0.44, 95%CI: -0.81, -0.06) (SMDHOMA-B = 0.34, 95%CI: 0.01, 0.66), baseline 25(OH)D < 50 nmol/L (SMD2h-PG = -0.23, 95%CI: -0.39, -0.06), and baseline 25(OH)D ≥ 50 nmol/L (SMDHOMA-IR = -0.50, 95%CI: -0.96, -0.03). In conclusion, oral supplementation of vitamin D has shown better effects in improving FBG, HbA1c, and FINS compared with controls among prediabetics; long-term vitamin D supplementation could have additional effects in participants with vitamin D deficiency for 2h-PG, HOMA-IR, and HOMA-B.

Effect of Dietary Supplementation with a Natural Extract of Sclerocarya birrea on Glycemic Metabolism in Subjects with Prediabetes: A Randomized Double-Blind Placebo-Controlled Study.

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.

Effect of Yoga on Glucose Control and Quality of Life in Patients of Prediabetes.

Objective: The objective of this study was to evaluate effect of yoga on fasting plasma glucose (FPG), postprandial plasma glucose, and hemoglobin A1C (HbA1C) and also on quality of life (QoL). Research Design and Methods: This was a cohort study in which 100 diagnosed cases of prediabetes were recruited for doing specific yoga, and they themselves act as control for the study. The measurement and comparison of FPG, prandial plasma glucose (PPG), and HbA1C were done at three different time intervals, that is, baseline, 3 months, and at 6 months. The assessment of QoL was done using SF-36 scale. Results: One hundred prediabetic cases were selected for the study in which impaired fasting glucose (IFG) was present more in younger population compared to impaired glucose tolerance (IGT) and IFG plus IGT both of which are more prevalent in middle age group. The yoga therapy was found to have favorable effect on FPG, PPG, and HbA1C along with various anthropometry measures studied in this study. After adjusting correlation coefficient for various anthropometry measures, yoga was found to be effective for controlling glycemic parameters in prediabetics. Conclusions: Yoga is a type of exercise known to improve glycemic control by changing anthropometry measures, but our study aids in knowledge about the beneficial effect beyond this known fact through other mechanisms yet to be explored.

Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial.

BACKGROUND: The potential of a ketone monoester (ß-hydroxybutyrate; KEßHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEßHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES: The primary objective was to investigate the effect of KEßHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of ß-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEßHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [ß-hydroxybutyrate (ßHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS: Blood ßHB concentrations increased to 3.5 mmol/L within 30 minutes after KEßHB supplementation. Plasma glucose AUC was significantly lower after KEßHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEßHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS: Ingestion of the KEßHB-supplemented drink acutely increased the blood ßHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEßHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.

Effects of vitamin D supplementation on the glycemic control of pre-diabetic individuals: a systematic review.

INTRODUCTION: Introduction: research shows the potential effect of vitamin D supplementation with an improvement in the glycemic profile of pre-diabetic patients. Objective: this study evaluates the effects of vitamin D supplementation on glycemic control markers in pre-diabetic individuals. Methods: we analyzed studies published over the last ten years, and indexed in the Science Direct, PubMed, and LILACS databases. We searched studies using health descriptors related to vitamin D, pre-diabetes, and glycemic control markers. We considered randomized controlled trials eligible for inclusion. All phases of selection, data extraction, and risk of bias assessment were carried out by two independent evaluators. Results: we identified 309 articles, of which 4 met the inclusion criteria. Of these, 3 studies have shown that vitamin D supplementation does not alter glycemic control markers in pre-diabetic individuals. Only one study showed a positive effect after supplementation with 60,000 IU/month of vitamin D3 for 12 months, with a significant reduction in the concentrations of glycated hemoglobin, fasting glucose, and two-hour postprandial glucose. Conclusion: there is insufficient scientific evidence to confirm the beneficial effects of vitamin D supplementation on glycemic control markers in pre-diabetic individuals.

INTRODUCCIÓN: Introducción: las investigaciones muestran el efecto potencial de la suplementación con vitamina D con una mejora del perfil glucémico de los pacientes prediabéticos. Objetivo: este estudio evalúa los efectos de la suplementación con vitamina D sobre los marcadores de control glucémico en personas prediabéticas. Métodos: analizamos los estudios publicados en los últimos diez años e indexados en las bases de datos Science Direct, PubMed y LILACS. Se realizaron búsquedas de estudios mediante descriptores de salud relacionados con la vitamina D, la prediabetes y los marcadores de control glucémico. Los ensayos controlados y aleatorizados se consideraron elegibles para su inclusión. Todas las fases de selección, extracción de datos y evaluación del riesgo de sesgos fueron realizadas por dos evaluadores independientes. Resultados: identificamos 309 artículos, de los que 4 cumplieron los criterios de inclusión. De estos, 3 estudios demostraron que la suplementación con vitamina D no altera los marcadores de control glucémico en las personas prediabéticas. Solo un estudio mostró un efecto positivo después de la suplementación de 60.000 UI/mes de vitamina D3 durante 12 meses, con una reducción significativa de las concentraciones de hemoglobina glucosilada, glucosa en ayunas y glucosa posprandial a las dos horas. Conclusión: no hay evidencia científica suficiente para confirmar los efectos beneficiosos de la suplementación de vitamina D sobre los marcadores de control glucémico en las personas prediabéticas.

Moringa oleifera Leaf Supplementation as a Glycemic Control Strategy in Subjects with Prediabetes.

Moringa oleifera (MO) is a multipurpose plant with a high polyphenol content, which is being increasingly consumed to lessen the risk of chronic metabolic diseases such as Type 2 diabetes; however, scientific evidence from clinical trials is scarce. A double-blind, randomized, placebo-controlled, parallel group intervention study with MO leaves as a food supplement was conducted in subjects with prediabetes. They consumed six daily capsules of MO dry leaf powder (2400 mg/day) (MO, n = 31) or placebo (PLC, n = 34) over 12 weeks. Glycemia, appetite-controlling hormones and gut microbiota composition were studied. ANCOVA with the fixed factor "treatment" and the basal value as covariate was used to compare the change score between the groups. The results showed significant differences between groups in the rate of change of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), which showed opposite directions during the intervention, decreasing in MO and increasing in PLC. No different change scores were found between the groups in microbiota, hepatic and renal function markers or the appetite-controlling hormones measured. In conclusion, MO supplementation resulted in favorable changes in glycaemia markers compared to placebo in the subjects with prediabetes studied, suggesting that MO might act as a natural antihyperglycemic agent.

Plasma and Urinary (Poly)phenolic Profiles after 4-Week Red Raspberry (Rubus idaeus L.) Intake with or without Fructo-Oligosaccharide Supplementation.

Red raspberries (RRB) are high in anthocyanin- and ellagitannin- type (poly)phenols. This study aimed to investigate the effect of 4-week RRB supplementation on (poly)phenolic metabolism in adults with prediabetes and insulin-resistance (PreDM-IR); and whether adding fructo-oligosaccharides (FOS), prebiotics, would augment the microbial metabolites of RRB (poly)phenols. In a randomized crossover clinical trial, subjects (n = 35: PreDM-IR, n = 25; healthy Reference group, n = 10) consumed 1 cup RRB (fresh weight equivalence) per day and RRB with 8 g FOS per day each for 4 weeks in random order separated by 4-week washout. Plasma and urinary (poly)phenolic metabolites were characterized after (0-24h) consuming a RRB-based test drink (2 cups RRB) at baseline/week 0 and again after 4-week supplementations. A total of 123 (poly)phenolic metabolites were quantified. After 4-week RRB supplementation, several metabolite groups were significantly increased (p < 0.05), including urolithins, phenyl-γ-valerolactones, and phenolic acids. Supplementing FOS with RRB for 4 weeks enhanced benzoic acid derivatives compared to the baseline (p < 0.05). Specific effects of supplementation by metabolic status indicated 4-week RRB supplementation significantly increased microbial metabolites that were lower in PreDM-IR group. Our results suggest alterations in the capacity of PreDM-IR group to metabolize and render bioavailable raspberry-derived (poly)phenols when consumed regularly.

Urtica Pilulifera in Treating Pre-diabetic Rat Model to Control the Blood Glucose, Lipids and Oxidative Stress.

INTRODUCTION: Pre-diabetic precedes the development of full diabetes. Studying and identification changes in pre-diabetic conditions can give the possibility to decline the development of diabetes and treat conditions associated with diabetes such as cardiovascular diseases. AIM: The main objectives of the present study were to investigate the potential of using Urtica pilulifera in treating the pre-diabetic rat model and to investigate its anti-oxidant impact. METHODS: The pre-diabetic model was induced in rats through daily giving high sucrose diet (35%) for 30 days. The extraction of U. pilulifera leaves was made as described by previous studies. Thirty male Wistar rats were randomly divided into three groups, control group (n=10), pre-diabetic group (n=10), and treated group with the extract of U. pilulifera (n=10). Control group rats received standard diet; pre-diabetic group rats received standard diet and high sucrose (35%) in drinking water, treated group rats received the same conditions as a pre-diabetic group, with intra-peritoneal injection of U. pilulifera injection on daily basis. After one month experiment, blood samples were taken from all rats and tested for glucose, triglycerides, cholesterol, GSH, TAC, and MDA. RESULTS: Both glucose and triglycerides levels were significantly increased in pre-diabetic groups, and significantly reduced in the treated group by the extract of U.pilulifera. The cholesterol level was not significantly changed in all groups. The levels of GSH were significantly reduced in the pre-diabetic group compared with the control group. Treatment with the extract of U. pilulifera increased the levels of GSH significantly compared with the pre-diabetic group. The levels of TAC were not significantly changed between the control group and the pre-diabetic group, but significantly increased in the treated group compared with the pre-diabetic group. The levels of MDA significantly increased in the pre-diabetic group compared with the control group, and significantly reduced in the treated group compared with the control group. CONCLUSION: High sucrose pre-diabetic model is a good model to study diabetes at early stages, and the treatment using U. pilulifera has several benefits in reducing glucose and lipid profile lipids as well as combating oxidative stress.

Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People With Coronary Heart Disease and Impaired Glucose Tolerance: Insights From the ACE Trial.

OBJECTIVE: We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-h PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA1c, FPG, 2-h PG, BMI, estimated glomerular filtration rate, for IGT alone, for IGT + impaired fasting glucose, and for use of thiazides, ACE inhibitors [ACEis]/angiotensin receptor blockers [ARBs], ß-blockers, calcium channel blockers, or statins). RESULTS: Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], P interaction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). CONCLUSIONS: Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

Advanced glycation end products derived from serum albumin modification by glucose (AGE-1) reflect clustering of lipid-associated metabolic abnormalities and are decreased in patients treated with acarbose: A cross-sectional study.

BACKGROUND: Advanced glycation end products (AGEs) are formed during protein modification by a reduction of sugars or reactive aldehydes. Depending on the pathology, various AGEs may be formed. They are stable compounds and are considered as potential diseases markers. OBJECTIVES: The objective of this study was to assess glucose-mediated albumin modification that yields non-standard epitopes of AGEs (AGE-1) in diabetes and in associated metabolic abnormalities. MATERIAL AND METHODS: The AGE-1, expressed as median AGE-1 level and AGE-1 positivity, was determined in 246 individuals (198 with prediabetes/diabetes) using a new slot-dot-blot method (allowing for detection of barely traceable analytes) and related to the presence of diabetes-associated metabolic abnormalities and complications, and treatment. RESULTS: The AGE-1 level was higher in patients with prediabetes/diabetes than in controls. Its elevation was associated with metabolic syndrome (MetS), obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) but not with diabetic control or microand macroangiopathy, except for atherosclerotic plaques formation in carotid arteries. The AGE-1-positive patients had higher triglycerides and lower high-density lipoprotein (HDL)-cholesterol. In patients untreated with aspirin, AGE-1 positivity was associated with higher C-reactive protein (CRP) level. Treatment with aspirin, sulfonylureas and gliptins was associated with higher AGE-1 level and with dyslipidemia medications with higher AGE-1 positivity. In patients with abnormal glucose metabolism, acarbose treatment was associated with lower AGE-1 positivity. Multivariate analysis showed MetS, carotid artery plaques, NAFLD, and treatment with aspirin and acarbose to be independently associated with AGE-1 positivity. CONCLUSIONS: Unlike standard AGEs, AGE-1 is more tightly associated with abnormalities in lipid than glucose metabolism, and lower in patients treated with acarbose but not with other antidiabetics.

Association between vitamin D and prediabetes: A PRISMA-compliant meta-analysis.

BACKGROUND: Previous studies showed conflicting results for associations between vitamin D and prediabetes. The study aimed to make a systematic review and meta-analysis for the association between vitamin D and prediabetes. METHODS: We searched for articles identifying associations between vitamin D and prediabetes published in English until July 2019 in following databases (PubMed, Web of Science, EMBASE, Medline, Google Scholar, and Cochrane databases). Finally, we conducted these analyses (heterogeneities examination, meta-regression analyses, sensitivity analysis, and publication bias examination) using STATA 12.0 software (Stata Corporation, College Station, TX, USA). Q test and I were applied to examine heterogeneities between studies. RESULTS: Twelve studies were finally included in the present study. The study included 4 studies to explore the association between serum levels of 25-hydroxy (OH) vitamin D and risks of prediabetes (including 3094 participants). Additionally, the present study included 8 studies (including 865 individuals with prediabetes treated with vitamin D supplementation and 715 patients treated with placebo) to assess differences in therapeutic effects between individuals with prediabetes treated with vitamin D supplementation and those treated with placebo. The present study showed no significant associations between low serum levels of 25(OH) vitamin D and high risk of prediabetes. Additionally, the study showed no significant differences in changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) between individuals with prediabetes treated with vitamin D and those patients given placebo, whereas meta-analysis showed significantly greater changes in 2-hour oral glucose tolerance test (2HPG) in individuals with prediabetes treated with vitamin D, compared with individuals with prediabetes treated with placebo. CONCLUSION: The study supported that low serum levels of 25(OH) vitamin D increased the risk of prediabetes. In addition, vitamin D supplementation improves impaired glucose tolerance in prediabetes. However, more large-scale clinical trials are essential to explore the association between vitamin D and prediabetes.

Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes.

OBJECTIVE: Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. MEASUREMENTS: A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. RESULTS: The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. CONCLUSIONS: High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.

Cacao extract enriched in polyphenols prevents endocrine-metabolic disturbances in a rat model of prediabetes triggered by a sucrose rich diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting ß-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D. AIM OF THE STUDY: T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose. MATERIALS AND METHODS: We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used. RESULTS: We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05). CONCLUSION: Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes).

Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

BACKGROUND: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control. METHODS: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation. RESULTS: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF. CONCLUSIONS: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

The ongoing D-lemma of vitamin D supplementation for nonskeletal health and bone health.

PURPOSE OF REVIEW: The goal of this review is to give some perspective on the results and conclusions of three recent randomized controlled vitamin D intervention studies that have challenged the health benefit of vitamin D supplementation for reducing risk for cardiovascular disease, cancer, all-cause mortality and type 2 diabetes and improving bone health. RECENT FINDINGS: Vitamin D supplementation to adults who were vitamin D sufficient or insufficient did not reduce risk for developing cardiovascular disease, cancer, type 2 diabetes nor increases bone mineral density (BMD). Patients who were vitamin D deficient with cancer and received vitamin D reduced risk for mortality by 25% and prediabetic adults who were vitamin D deficient and received vitamin D reduced their risk of developing type 2 diabetes by 62%. Older adults receiving 4000 and 10 000 IUs of vitamin D3 daily for 3 years had reduced radial BMD but had no change in either total hip areal bone density or bone strength in the radius and tibia. SUMMARY: Caution is needed when evaluating results and conclusions from randomized controlled trials that investigate health benefits of vitamin D; most studies suggest health benefits when vitamin D supplementation is provided to vitamin D deficient populations and little benefit when given to populations that are vitamin D sufficient/insufficient.

The effect of yoga practice on glycemic control and other health parameters in the prediabetic state: A systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to investigate the effects of yoga on glycemic control, lipid profiles, body composition and blood pressure in people in the pre-diabetic state. Studies on the effectiveness of yoga on population groups under high risk for diabetes, called prediabetic or suffering from metabolic syndromes were extracted from a thorough search of PubMed, Scopus, Cochrane Library, EBSCO and IndMED databases. Both Randomised Controlled Trial (RCT) and non-RCT studies were included in the systematic review and meta-analysis. Studies published between Jan 2002 and Dec 2018 were included. Studies were considered for evaluation if they investigated a yoga intervention to prevent T2DM, against a control group, while also reporting glycemic control and other health parameters of T2DM management. Summary effect sizes and 95% confidence intervals (CI) were calculated using the Comprehensive Meta-Analysis software in addition to publication bias. Of the 46,500 identified studies, 14 studies with 834 participants of whom were 50% women, were found to be eligible for inclusion in our systematic review. Our quantitative synthesis included 12 randomized control trials and 2 non-randomized control trials, with the follow-up period ranging from 4 to 52 weeks. Compared to controls, yoga intervention improved fasting blood glucose (FBG) [Standard Mean Difference (SMD -0.064 mg/dL (95% CI -0.201 to 0.074)]; low density lipoprotein (LDL) [SMD-0.090 mg/dL (95% CI -0.270 to 0.090)]; triglycerides [SMD -0.148 mg/dL (95% CI -0.285 to -0.012)]; total cholesterol [SMD -0.058 mg/dL (95% CI -0.220 to 0.104)] and systolic blood pressure [SMD -0.058 mm Hg (95% CI -0.168 to 0.053)]. This meta-analysis uncovered clinically improved effects of yoga intervention on glycemic control, lipid profiles and other parameters of T2DM management in prediabetic population. These results suggest that yoga intervention may be considered as a comprehensive and alternative approach to preventing T2DM. Further adequately powered, well designed RCTs are needed to support our findings and investigate the long-term effects of yoga in T2DM patients.