curcumin and Prediabetic-State

This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms.. An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms.. Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis.. CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS.. PROSPERO (CRD42016042131).

Topics: Adult; Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Humans; Meta-Analysis as Topic; Metabolic Syndrome; Prediabetic State; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Dysglycemia is a disease state preceding the onset of diabetes and includes impaired fasting glycemia and impaired glucose tolerance. This review aimed to collect and analyze the literature reporting the results of clinical trials evaluating the effects of selected nutraceuticals on glycemia in humans. The results of the analyzed trials, generally, showed the positive effects of the nutraceuticals studied alone or in association with other supplements on fasting plasma glucose and post-prandial plasma glucose as primary outcomes, and their efficacy in improving insulin resistance as a secondary outcome. Some evidences, obtained from clinical trials, suggest a role for some nutraceuticals, and in particular Berberis, Banaba, Curcumin, and Guar gum, in the management of prediabetes and diabetes. However, contradictory results were found on the hypoglycemic effects of Morus, Ilex paraguariensis, Omega-3, Allium cepa, and Trigonella faenum graecum, whereby rigorous long-term clinical trials are needed to confirm these data. More studies are also needed for Eugenia jambolana, as well as for Ascophyllum nodosum and Fucus vesiculosus which glucose-lowering effects were observed when administered in combination, but not alone. Further trials are also needed for quercetin.

Topics: Blood Glucose; Curcumin; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Supplements; Glucose Intolerance; Humans; Hypoglycemic Agents; Prediabetic State; Quercetin

Studies have demonstrated inconsistent effects of curcumin on glycemic outcomes and lipid parameters in patients with prediabetes and type 2 diabetes mellitus (T2DM). This study aimed to assess the effect of curcumin on glycemic control and lipid profile in prediabetes and T2DM.. A systematic search of randomized controlled trials (RCTs) was conducted from inception to June 2018 in electronic sources including AMED, ANZCTR, BioMed Central, CENTRAL, CINAHL, ClinicalTrials.gov, Expanded Academic Index, Google Scholar, ISRCTN, LILACS, MEDLINE, NCCIH, Science Direct, Scopus, Web of Science, and WHO ICTRP. Hand search was also performed. Of the total 486 records, four trials (N = 508) and eight trials (N = 646) were eligible for the meta-analysis of individuals with prediabetes and T2DM, respectively. Curcumin significantly reduced glycosylated hemoglobin (HbA1c) in prediabetics (MD: -0.9%, 95% CI: -1.7 to -0.1%, p = 0.03). Furthermore, T2DM subjects gained favorable reduction in both HbA1c (MD: -0.5%, 95% CI: -1.0 to -0.0%, p = 0.04) and fasting plasma glucose (MD: -11.7 mg/dL, 95% CI: -22.1 to -1.3 mg/dL, p = 0.03). Tendency of lipid profile improvement was also observed.. Our findings may encourage curcumin supplementation based on its meaningful effect on glycemic control and positive trend on lipid outcomes in prediabetes and T2DM.

Topics: Blood Glucose; Cholesterol; Curcumin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Lipids; Prediabetic State

Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA

Topics: Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Supplements; Double-Blind Method; Humans; Insulin; Insulin Resistance; Obesity; Overweight; Prediabetic State; Zinc

The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients.. The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.. A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.. Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019.

Topics: Adolescent; Adult; Antioxidants; Biomarkers; Blood Glucose; Clinical Trials, Phase II as Topic; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Lipids; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Quality of Life; Randomized Controlled Trials as Topic; Young Adult; Zinc

Lifestyle interventions, including increase in physical activity and dietary counselling, have shown the ability to prevent type 2 diabetes (T2D) in high-risk state individuals, but the prevalence is still skyrocketing in Australia, in line with global prevalence. Currently, no medicines are approved by the Therapeutic Goods Administration in Australia for the management of prediabetes. Therefore, there is a need of developing a safer, biologically efficacious and cost-effective alternative for delaying the transition of individual health state from prediabetes into T2D. In the current trial we propose to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids on improving glycosylated haemoglobin as a primary outcome, along with secondary outcomes of glycaemic indices, lipid profile and inflammatory parameters.. Eighty individuals diagnosed with prediabetes, aged between 30 and 70 years, will be randomly assigned to double placebo, curcumin alone, fish oil alone or double active groups according to a computer-generated randomisation sequence for 12 weeks. At baseline and post-intervention visits participants will be asked to provide blood samples and undergo body composition measurements. A blood sample is used for estimating glycaemic profiles, lipid profiles and inflammatory parameters (C-reactive protein, whole blood cell count, adiponectin, leptin, interleukin-6). The interim visit includes review on compliance with supplements based on capsule log and capsule count, adverse events and anthropometric measurements. In addition to these procedures, participants provide self-reported questionnaires on dietary intake (using a 3-day food record), a physical activity questionnaire and medical history.. This trial aims to determine whether curcumin and/or long-chain omega-3 polyunsaturated fatty acids affect surrogate markers of glycaemic control which is relevant to delaying T2D. To date 38 participants completed the trial. No changes have been made to the clinical protocol post recruitment. If successful, this trial will provide considerable evidence for performing a larger trial to investigate whether this combination can be administered for preventing or delaying the onset of T2D in high-risk individuals.. ACTRN12615000559516 , registered on 29 May 2015).

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Composition; Clinical Protocols; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Glycated Hemoglobin; Humans; Inflammation Mediators; Lipids; Male; Middle Aged; New South Wales; Prediabetic State; Research Design; Risk Factors; Time Factors; Treatment Outcome

Cognitive impairment develops with pre-diabetes and dementia is a complication of diabetes. Natural products like turmeric and cinnamon may ameliorate the underlying pathogenesis.. People ≥ 60 years (n=48) with newly-recognised untreated pre-diabetes were randomised to a double-blind metabolic study of placebo, turmeric (1 g), cinnamon (2 g) or both (1 g & 2 g respectively), ingested at a white bread (119 g) breakfast. Observations were made over 6 hours for pre- and post-working memory (WM), glycaemic and insulin responses and biomarkers of Alzheimer's disease (AD)(0, 2, 4 and 6 hours): amyloid precursor protein (APP), γ-secretase subunits presenilin-1 (PS1), presenilin-2 (PS2), and glycogen synthase kinase (GSK-3β). Differences between natural product users and non-users were determined by Students t and chi square tests; and between pre-test and post-test WM by Wilcoxon signed rank tests. Interaction between turmeric and cinnamon was tested by 2-way ANOVA. Multivariable linear regression (MLR) took account of BMI, glycaemia, insulin and AD biomarkers in the WM responses to turmeric and cinnamon.. No interaction between turmeric and cinnamon was detected. WM increased from 2.6 to 2.9 out of 3.0 (p=0.05) with turmeric, but was unchanged with cinnamon. WM improvement was inversely associated with insulin resistance (r=-0.418, p<0.01), but not with AD biomarkers. With MLR, the WM responses to turmeric were best predicted with an R2 of 34.5%; and with significant turmeric, BMI and insulin/glucose AUC beta-coefficients.. Co-ingestion of turmeric with white bread increases working memory independent of body fatness, glycaemia, insulin, or AD biomarkers.. 背景：認知功能失調伴隨糖尿病前期與失智症是糖尿病的併發症之ㄧ。天然食品如薑黃及 肉桂可改善此致病機轉。本研究為評估薑黃肉桂如何影響糖尿病前期患者認知功能之代謝 研究。方法：對象為三軍總醫院參加老人健檢者，納入條件為其空腹血糖介於100-126 mg/dL，共計48 位參與者。經由雙盲性別分層隨機分派至服用口服降血糖藥物或其組合、 薑黃、肉桂或其組合及控制組共4 組，每組12 名，男女各半。參與者須於報到後抽取空 腹血液、實施工作記憶前測及測量基本體位資料。再於8 時服用早餐及受試藥物，各組分 別為安慰劑、薑黃1 克、肉桂2 克、肉桂2 克與薑黃1 克等。隨後每隔2 小時採集血液， 共4 次，於最後1 次抽血完畢後，再測工作記憶分數。利用RT-PCR 技術測得APP、 PS1、PS2、GSK-3βmRNA 表現量。利用t 檢定及卡方檢定比較天然食品使用者及非使用 者平均值之差異；魏克森符號等級檢定工作記憶前測及後測的分數。利用雙因子變異數分 析檢定薑黃與肉桂兩植物成分之交互作用。複迴歸模式分析校正身體質量指數、血糖、胰 島素濃度、阿茲海默症相關之生物標記後，薑黃肉桂對工作記憶之影響。結果：薑黃與肉 桂兩植物成分並無交互作用產生。有服用薑黃者工作記憶平均分數由2.6 增加至2.9 分， 為邊緣性顯著（p=0.05），服用肉桂者工作記憶前後測平均分數沒有顯著差異。工作記憶 分數之改善與胰島素阻抗呈負相關 （r=-0.418, p<0.01），但與阿茲海默症之相關生物標記 無顯著相關。複迴歸分析結果顯示服用薑黃、BMI 及胰島素阻抗為工作記憶分數最佳預測 因子。結論：本研究觀察到的薑黃改善認知效果，可能並非透過假設之降血糖途徑或降低 生物標記基因表現量而來，推測薑黃有其他保護神經元機制。

Topics: Aged; Alzheimer Disease; Biomarkers; Blood Glucose; Body Mass Index; Bread; Cinnamomum zeylanicum; Curcuma; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Male; Memory; Middle Aged; Phytotherapy; Placebos; Plant Preparations; Postprandial Period; Prediabetic State

To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population.. This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention.. After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group.. A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.

Topics: Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Male; Middle Aged; Plant Extracts; Prediabetic State; Treatment Outcome

The polyphenols resveratrol (RSV) and curcumin (Cur) are phytoalexines and natural antibiotics with numerous pharmacological functions and metabolic impacts. Recent evidences show a broad control of gut microbiota by polyphenols which could influence glycemic regulation. The aim of this work is to estimate the respective effect of RSV and Cur alone or in association on the control of glycemia and on gut microbiota. A 5-week chronic treatment of hyperglycemic mice with RSV and/or Cur resulted in a differential effect on glucose tolerance test and modified gut microbiome. We precisely identified groups of bacteria representing a specific signature of the glycemic effect of RSV. Inferred metagenomic analysis and metabolic pathway prediction showed that the sulfur and branched-chain amino-acid (BCAA) metabolic activities are tightly correlated with the efficacy of RSV for the control of glycaemia. The impact on BCAA metabolism was further validated by serum metabolomics analysis. Altogether, we show that polyphenols specifically impact gut microbiota and corresponding metabolic functions which could be responsible for their therapeutic role.

Topics: Amino Acids, Branched-Chain; Animals; Blood; Curcumin; Diet, High-Fat; Drug Therapy, Combination; Gastrointestinal Microbiome; Hyperglycemia; Male; Mice, Inbred C57BL; Prediabetic State; Resveratrol

Lifestyle modification pivoting on nutritional management holds tremendous potential to meet the challenge of management of diabetes. The current study hypothesizes that regular uptake of curcumin lowers the incidence of diabetes by functional regulation of pancreatic adrenergic receptor subtypes. The specific objective of the study was to identify the regulatory pathways implicated in the antidiabetogenesis effect of curcumin in multiple low-dose streptozotocin (MLD-STZ)-induced diabetic Wistar rats. Administration of MLD-STZ to curcumin-pretreated rats induced a prediabetic condition. Scatchard analysis, real-time polymerase chain reaction, and confocal microscopic studies confirmed a significant increase in α2-adrenergic receptor expression in the pancreas of diabetic rats. Pretreatment with curcumin significantly decreased α2-adrenergic receptor expression. The diabetic group showed a significant decrease in the expression of β-adrenergic receptors when compared with control. Pretreatment significantly increased β-adrenergic receptor expression to near control. When compared with the diabetic rats, a significant up-regulation of CREB, phospholipase C, insulin receptor, and glucose transporter 2 were observed in the pretreated group. Curcumin pretreatment was also able to maintain near control levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, and inositol triphosphate. These results indicate that a marked decline in α2-adrenergic receptor function relents sympathetic inhibition of insulin release. It also follows that escalated signaling through β-adrenergic receptors mediates neuronal stimulation of hyperglycemia-induced β-cell compensatory response. Curcumin-mediated functional regulation of adrenergic receptors and modulation of key cell signaling molecules improve pancreatic glucose sensing, insulin gene expression, and insulin secretion.

Topics: Adrenergic Agents; Animals; Blood Glucose; Curcuma; Curcumin; Diabetes Mellitus, Experimental; Gene Expression; Hyperglycemia; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Pancreas; Phytotherapy; Plant Extracts; Prediabetic State; Rats, Wistar; Receptors, Adrenergic, alpha-2; Receptors, Adrenergic, beta; Signal Transduction; Streptozocin

Long-term dietary curcumin (>12 wk) improves metabolic homeostasis in obese mice by sensitizing insulin signaling and reducing hepatic gluconeogenesis. Whether these occur only secondary to its chronic anti-inflammatory and antioxidative functions is unknown.. In this study, we assessed the insulin sensitization effect of short-term curcumin gavage in a rapid dexamethasone-induced insulin resistance mouse model, in which the chronic anti-inflammatory function is eliminated.. Six-week-old male C57BL/6 mice received an intraperitoneal injection of dexamethasone (100 mg/kg body weight) or phosphate-buffered saline every day for 5 d, with or without simultaneous curcumin gavage (500 mg/kg body weight). On day 7, insulin tolerance tests were performed. After a booster dexamethasone injection and curcumin gavage on day 8, blood glucose and insulin concentrations were measured. Liver tissues were collected on day 10 for quantitative polymerase chain reaction and Western blotting to assess gluconeogenic gene expression, insulin signaling, and the expression of fibroblast growth factor 21 (FGF21). Primary hepatocytes from separate, untreated C57BL/6 mice were used for testing the in vitro effect of curcumin treatment.. Dexamethasone injection impaired insulin tolerance (P < 0.05) and elevated ambient plasma insulin concentrations by ~2.7-fold (P < 0.01). Concomitant curcumin administration improved insulin sensitivity and reduced hepatic gluconeogenic gene expression. The insulin sensitization effect of curcumin was demonstrated by increased stimulation of S473 phosphorylation of protein kinase B (P < 0.01) in the dexamethasone-treated mouse liver, as well as the repression of glucose production in primary hepatocytes (P < 0.001). Finally, curcumin gavage increased FGF21 expression by 2.1-fold in the mouse liver (P < 0.05) and curcumin treatment increased FGF21 expression in primary hepatocytes.. These observations suggest that the early beneficial effect of curcumin intervention in dexamethasone-treated mice is the sensitization of insulin signaling, involving the stimulation of FGF21 production, a known insulin sensitizer.

Topics: Animals; Antioxidants; Blood Glucose; Cells, Cultured; Curcumin; Dexamethasone; Dietary Supplements; Fibroblast Growth Factors; Gene Expression Regulation, Enzymologic; Glucocorticoids; Gluconeogenesis; Hep G2 Cells; Humans; Insulin; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Prediabetic State; Random Allocation; Recombinant Proteins; Signal Transduction