Prediabetes

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    Last Updated: October 13, 2024

    Prediabetes is the intermediate stage between healthy blood glucose levels and diabetes. It is associated with an increased risk of cardiovascular disease and type 2 diabetes. Weight loss induced by lifestyle intervention is the primary treatment and is very effective.

    Prediabetes falls under the Diabetes & Blood Sugar category.

    What is prediabetes?

    Prediabetes is a condition characterized by elevated blood glucose levels that do not meet the criteria for type 2 diabetes. Prediabetes increases the risk of cardiovascular disease and type 2 diabetes and is associated with the presence of obesity (especially abdominal or visceral obesity), dyslipidemia, and high blood pressure.[1]

    What are the main signs and symptoms of prediabetes?

    Prediabetes is an asymptomatic condition. Signs, or indications that an individual should undergo testing to determine whether they have prediabetes, include overweight or obesity in combination with at least one of the following risk factors: family history of diabetes, high-risk race/ethnicity (i.e., Black, Latino/Hispanic, Native American, Asian American, Pacific Islander), history of gestational diabetes, polycystic ovary syndrome, high blood pressure, low high-density lipoprotein cholesterol (HDL-C) levels, or elevated triglycerides.[1][2] Universal screening irrespective of the presence of risk factors is recommended for adults at least 35 years old. If initial screening results meet the criteria for prediabetes, it is recommended to repeat screenings yearly. If the results are normal, it is recommended to repeat screenings at least every three years, or sooner if symptoms of diabetes (e.g., excessive thirst) or other risk factors (e.g., hypertension) develop. [1]

    How is prediabetes diagnosed?

    Prediabetes is diagnosed based on either fasting plasma glucose, 2-hour plasma glucose during a 75-gram oral glucose tolerance test (OGTT), or HbA1c. According to the American Diabetes Association, an individual should be diagnosed with prediabetes if they have one of the following:[1]

    • Fasting glucose of 100–125 mg/dL (5.6–6.9 mmol/L)
    • 2-hour glucose during an OGTT of 140–199 mg/dL (7.8–11.0 mmol/L)
    • HbA1c of 5.7%–6.4%

    Notably, the World Health Organization defines the lower limit for impaired fasting glucose as 110 mg/dL (6.1 mmol/L).

    Evidence suggests that an OGTT is the most sensitive diagnostic test for prediabetes, and reliance on either fasting glucose or HbA1c alone may result in significant underdiagnosis of prediabetes.[3][4]

    What are some of the main medical treatments for prediabetes?

    Lifestyle intervention (i.e., weight loss, exercise, healthy eating, reduction or cessation of alcohol intake) is the cornerstone of prediabetes treatment, but metformin is considered the first-line pharmacological intervention. It’s recommended that metformin be added for people with prediabetes who have a BMI of at least 35, higher glucose levels (e.g., fasting glucose ≥ 110 mg/dL, HbA1c ≥ 6.0%), and/or a history of gestational diabetes.[5] Metformin may also be considered in cases where lifestyle intervention is ineffective.[6] Weight-loss drugs (e.g., semaglutide) are another increasingly popular option to enhance the efficacy of lifestyle intervention.[7][8]

    How could diet affect prediabetes?

    A hypocaloric diet is a powerful intervention for people with prediabetes and overweight or obesity, as achieving and maintaining significant weight loss (at least 5% of initial body weight) can prevent or delay the development of type 2 diabetes.[9] In the context of significant weight loss, there does not appear to be an ideal macronutrient distribution, so the diet should be customized to the individual’s dietary preferences and metabolic goals to maximize adherence.[10] Plant-based dietary patterns that emphasize the consumption of whole grains, legumes, nuts, fruits, and vegetables may be particularly beneficial for reducing the risk of type 2 diabetes.[5]

    Have any supplements been studied for prediabetes?

    A wide variety of supplements hypothesized to improve glycemic control have been studied in people with prediabetes, including zinc, vitamin D, cinnamon, berberine, curcumin, probiotics, panax ginseng, vitamin K, omega-3 fatty acids, aloe vera, and mulberry leaf extract.[11][12]

    Are there any other treatments for prediabetes?

    Physical activity is pivotal for preventing or delaying the development of type 2 diabetes. At least 150 minutes of moderate-intensity physical activity (e.g., brisk walking) plus two resistance exercise sessions should be performed each week to promote further improvements in insulin sensitivity.[5][13][14] Additionally, breaking up periods of sitting with standing or walking can improve postprandial (after-meal) glucose levels.[15] Tobacco cessation is also recommended.[5]

    What causes prediabetes?

    The causes of prediabetes overlap with those of type 2 diabetes, as the physiological defects that underlie the latter — insulin resistance and loss of pancreatic beta-cell (cells that produce and secrete insulin) function — are also present in prediabetes,[16][17] albeit to a lesser extent than in type 2 diabetes.

    The causes of prediabetes are multifactorial and are influenced by genetic predisposition and environment. However, excess energy intake and sedentary behavior, leading to the accumulation of more visceral fat than the individual can tolerate, are primarily responsible for the hyperglycemia that defines prediabetes.[18]

    Examine Database: Prediabetes

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    Frequently asked questions

    What is prediabetes?

    Prediabetes is a condition characterized by elevated blood glucose levels that do not meet the criteria for type 2 diabetes. Prediabetes increases the risk of cardiovascular disease and type 2 diabetes and is associated with the presence of obesity (especially abdominal or visceral obesity), dyslipidemia, and high blood pressure.[1]

    What are the main signs and symptoms of prediabetes?

    Prediabetes is an asymptomatic condition. Signs, or indications that an individual should undergo testing to determine whether they have prediabetes, include overweight or obesity in combination with at least one of the following risk factors: family history of diabetes, high-risk race/ethnicity (i.e., Black, Latino/Hispanic, Native American, Asian American, Pacific Islander), history of gestational diabetes, polycystic ovary syndrome, high blood pressure, low high-density lipoprotein cholesterol (HDL-C) levels, or elevated triglycerides.[1][2] Universal screening irrespective of the presence of risk factors is recommended for adults at least 35 years old. If initial screening results meet the criteria for prediabetes, it is recommended to repeat screenings yearly. If the results are normal, it is recommended to repeat screenings at least every three years, or sooner if symptoms of diabetes (e.g., excessive thirst) or other risk factors (e.g., hypertension) develop. [1]

    Do clinical features differ between people with prediabetes?

    Prediabetes can be diagnosed using either fasting plasma glucose, 2-hour plasma glucose during an oral glucose tolerance test (OGTT), or HbA1c. The clinical features displayed by people with impaired fasting glucose (IFG) differ from those with impaired glucose tolerance (IGT) or elevated 2-hour plasma glucose levels during an OGTT.

    Both are characterized by insulin resistance, but differ in the primary site of insulin resistance. In IFG, there is insulin resistance in the liver and normal insulin resistance in skeletal muscle, whereas IGT exhibits little to no insulin resistance in the liver and severe insulin resistance in skeletal muscle.[19] There are also differences in insulin secretion. In response to oral glucose, people with IFG have an impaired early-phase (first 30 minutes) insulin response, whereas people with IGT have an impaired late-phase insulin response.[20] During an OGTT, people with IFG exhibit higher plasma glucose levels than people with IGT at 30–60 minutes. Plasma glucose levels then return to around baseline at 120 minutes, while they remain significantly elevated in people with IGT.[20]

    How is prediabetes diagnosed?

    Prediabetes is diagnosed based on either fasting plasma glucose, 2-hour plasma glucose during a 75-gram oral glucose tolerance test (OGTT), or HbA1c. According to the American Diabetes Association, an individual should be diagnosed with prediabetes if they have one of the following:[1]

    • Fasting glucose of 100–125 mg/dL (5.6–6.9 mmol/L)
    • 2-hour glucose during an OGTT of 140–199 mg/dL (7.8–11.0 mmol/L)
    • HbA1c of 5.7%–6.4%

    Notably, the World Health Organization defines the lower limit for impaired fasting glucose as 110 mg/dL (6.1 mmol/L).

    Evidence suggests that an OGTT is the most sensitive diagnostic test for prediabetes, and reliance on either fasting glucose or HbA1c alone may result in significant underdiagnosis of prediabetes.[3][4]

    What are some of the main medical treatments for prediabetes?

    Lifestyle intervention (i.e., weight loss, exercise, healthy eating, reduction or cessation of alcohol intake) is the cornerstone of prediabetes treatment, but metformin is considered the first-line pharmacological intervention. It’s recommended that metformin be added for people with prediabetes who have a BMI of at least 35, higher glucose levels (e.g., fasting glucose ≥ 110 mg/dL, HbA1c ≥ 6.0%), and/or a history of gestational diabetes.[5] Metformin may also be considered in cases where lifestyle intervention is ineffective.[6] Weight-loss drugs (e.g., semaglutide) are another increasingly popular option to enhance the efficacy of lifestyle intervention.[7][8]

    How could diet affect prediabetes?

    A hypocaloric diet is a powerful intervention for people with prediabetes and overweight or obesity, as achieving and maintaining significant weight loss (at least 5% of initial body weight) can prevent or delay the development of type 2 diabetes.[9] In the context of significant weight loss, there does not appear to be an ideal macronutrient distribution, so the diet should be customized to the individual’s dietary preferences and metabolic goals to maximize adherence.[10] Plant-based dietary patterns that emphasize the consumption of whole grains, legumes, nuts, fruits, and vegetables may be particularly beneficial for reducing the risk of type 2 diabetes.[5]

    How does a high-protein diet affect people with prediabetes?

    Evidence suggests that a high-protein diet promotes superior improvements in glycemic control than a lower-protein, higher-carbohydrate diet. In two 6-month randomized controlled trials that provided all meals to participants, a high-protein diet (30% of energy from protein, 40% from carbohydrate, 30% from fat) and a high-carbohydrate diet (15% of energy from protein, 55% from carbohydrate, 30% from fat) facilitated similar weight loss, and both diets facilitated improvements in markers of glycemic control and beta-cell function compared to baseline, but improvements were greater with the high-protein diet.[21][22] Furthermore, in one of these studies, which only included participants with prediabetes, 100% of participants in the high-protein diet group no longer met the criteria for prediabetes at the end of the study, while only 33% of participants in the high-carbohydrate diet group accomplished this feat.[22] This result may be a consequence of body composition differences: lean mass percentage increased in the high-protein group, while it decreased in the high-carbohydrate group, despite similar weight loss.

    In support of these findings, an acute (2-day intervention) crossover trial in people with prediabetes or normal glucose levels found reduced postprandial glucose levels with a high-protein diet compared to a high-carbohydrate diet.[23] The beneficial effects of a high-protein diet on glycemic control may be due to protein’s ability to enhance the secretion of incretin hormones[22][23]glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) — which potentiate insulin secretion and increase glucose disposal.[24]

    Have any supplements been studied for prediabetes?

    A wide variety of supplements hypothesized to improve glycemic control have been studied in people with prediabetes, including zinc, vitamin D, cinnamon, berberine, curcumin, probiotics, panax ginseng, vitamin K, omega-3 fatty acids, aloe vera, and mulberry leaf extract.[11][12]

    Are there any other treatments for prediabetes?

    Physical activity is pivotal for preventing or delaying the development of type 2 diabetes. At least 150 minutes of moderate-intensity physical activity (e.g., brisk walking) plus two resistance exercise sessions should be performed each week to promote further improvements in insulin sensitivity.[5][13][14] Additionally, breaking up periods of sitting with standing or walking can improve postprandial (after-meal) glucose levels.[15] Tobacco cessation is also recommended.[5]

    What causes prediabetes?

    The causes of prediabetes overlap with those of type 2 diabetes, as the physiological defects that underlie the latter — insulin resistance and loss of pancreatic beta-cell (cells that produce and secrete insulin) function — are also present in prediabetes,[16][17] albeit to a lesser extent than in type 2 diabetes.

    The causes of prediabetes are multifactorial and are influenced by genetic predisposition and environment. However, excess energy intake and sedentary behavior, leading to the accumulation of more visceral fat than the individual can tolerate, are primarily responsible for the hyperglycemia that defines prediabetes.[18]

    References

    1. ^American Diabetes Association Professional Practice Committee2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022Diabetes Care.(2022 Jan 1)
    2. ^, Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Krist AH, Kubik M, Li L, Ogedegbe G, Owens DK, Pbert L, Silverstein M, Stevermer J, Tseng CW, Wong JBScreening for Prediabetes and Type 2 Diabetes: US Preventive Services Task Force Recommendation Statement.JAMA.(2021-Aug-24)
    3. ^Meijnikman AS, De Block CEM, Dirinck E, Verrijken A, Mertens I, Corthouts B, Van Gaal LFNot performing an OGTT results in significant underdiagnosis of (pre)diabetes in a high risk adult Caucasian population.Int J Obes (Lond).(2017-Nov)
    4. ^Sacks DBA1C versus glucose testing: a comparison.Diabetes Care.(2011-Feb)
    5. ^American Diabetes Association Professional Practice Committee3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: Standards of Medical Care in Diabetes-2022Diabetes Care.(2022 Jan 1)
    6. ^Moin TShould Adults with Prediabetes Be Prescribed Metformin to Prevent Diabetes Mellitus? Yes: High-Quality Evidence Supports Metformin Use in Persons at High Risk.Am Fam Physician.(2019-Aug-01)
    7. ^Handelsman Y, Anderson JE, Bakris GL, Ballantyne CM, Beckman JA, Bhatt DL, Bloomgarden ZT, Bozkurt B, Budoff MJ, Butler J, Dagogo-Jack S, de Boer IH, DeFronzo RA, Eckel RH, Einhorn D, Fonseca VA, Green JB, Grunberger G, Guerin C, Inzucchi SE, Jellinger PS, Kosiborod MN, Kushner P, Lepor N, Mende CW, Michos ED, Plutzky J, Taub PR, Umpierrez GE, Vaduganathan M, Weir MRDCRM Multispecialty Practice Recommendations for the management of diabetes, cardiorenal, and metabolic diseases.J Diabetes Complications.(2022-Feb)
    8. ^Dungan KMA New Bar for Pharmacologic Weight Loss: Type 2 Diabetes Prevention.Diabetes Care.(2022-Oct-01)
    9. ^Guess NDDietary Interventions for the Prevention of Type 2 Diabetes in High-Risk Groups: Current State of Evidence and Future Research Needs.Nutrients.(2018-Sep-06)
    10. ^Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, Mitri J, Pereira RF, Rawlings K, Robinson S, Saslow L, Uelmen S, Urbanski PB, Yancy WS JrNutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus ReportDiabetes Care.(2019 May)
    11. ^Derosa G, D'Angelo A, Maffioli PThe role of selected nutraceuticals in management of prediabetes and diabetes: An updated review of the literature.Phytother Res.(2022-Oct)
    12. ^Rendell MPharmacotherapeutic options for prediabetes.Expert Opin Pharmacother.(2021-Jan)
    13. ^Hrubeniuk TJ, Bouchard DR, Goulet EDB, Gurd B, Sénéchal MThe ability of exercise to meaningfully improve glucose tolerance in people living with prediabetes: A meta-analysis.Scand J Med Sci Sports.(2020-Feb)
    14. ^Strasser B, Pesta DResistance training for diabetes prevention and therapy: experimental findings and molecular mechanisms.Biomed Res Int.(2013)
    15. ^Aidan J Buffey, Matthew P Herring, Christina K Langley, Alan E Donnelly, Brian P CarsonThe Acute Effects of Interrupting Prolonged Sitting Time in Adults with Standing and Light-Intensity Walking on Biomarkers of Cardiometabolic Health in Adults: A Systematic Review and Meta-analysisSports Med.(2022 Feb 11)
    16. ^Brannick B, Dagogo-Jack SPrediabetes and Cardiovascular Disease: Pathophysiology and Interventions for Prevention and Risk Reduction.Endocrinol Metab Clin North Am.(2018-Mar)
    17. ^Abdul-Ghani MA, DeFronzo RAPathophysiology of prediabetes.Curr Diab Rep.(2009-Jun)
    18. ^Roy Taylor, Ambady Ramachandran, William S Yancy Jr, Nita G ForouhiNutritional basis of type 2 diabetes remissionBMJ.(2021 Jul 7)
    19. ^Faerch K, Borch-Johnsen K, Holst JJ, Vaag APathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?Diabetologia.(2009-Sep)
    20. ^Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, Pratley R, Zinman B,Impaired fasting glucose and impaired glucose tolerance: implications for care.Diabetes Care.(2007-Mar)
    21. ^Abbas E Kitabchi, Kristin A McDaniel, Jim Y Wan, Frances A Tylavsky, Crystal A Jacovino, Chris W Sands, Ebenezer A Nyenwe, Frankie B StentzEffects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trialDiabetes Care.(2013 Jul)
    22. ^Stentz FB, Mikhael A, Kineish O, Christman J, Sands CHigh protein diet leads to prediabetes remission and positive changes in incretins and cardiovascular risk factors.Nutr Metab Cardiovasc Dis.(2021-Apr-09)
    23. ^Amirsalar Samkani, Mads J Skytte, Mads N Thomsen, Arne Astrup, Carolyn F Deacon, Jens J Holst, Sten Madsbad, Jens F Rehfeld, Thure Krarup, Steen B HaugaardAcute Effects of Dietary Carbohydrate Restriction on Glycemia, Lipemia and Appetite Regulating Hormones in Normal-Weight to Obese SubjectsNutrients.(2018 Sep 12)
    24. ^Michael A Nauck, Juris J MeierIncretin hormones: Their role in health and diseaseDiabetes Obes Metab.(2018 Feb)

    Examine Database References

    1. HbA1c - Jing Guo, Hongdong Chen, Xueqin Zhang, Wenjiao Lou, Pingna Zhang, Yuheng Qiu, Chao Zhang, Yaoxian Wang, Wei Jing LiuThe Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled TrialsOxid Med Cell Longev.(2021 Dec 15)
    2. HbA1c - Thota RN, Acharya SH, Garg MLCurcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: a randomised controlled trialLipids Health Dis.(2019 Jan 26)
    3. HbA1c - Miñambres I, Cuixart G, Gonçalves A, Corcoy REffects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trialsClin Nutr.(2019 Jun)
    4. HbA1c - Bruls Y, et alCarnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trialEBioMedicine.()
    5. HbA1c - Zamani M, Pahlavani N, Nikbaf-Shandiz M, Rasaei N, Ghaffarian-Ensaf R, Asbaghi O, Shiraseb F, Rastgoo SThe effects of L-carnitine supplementation on glycemic markers in adults: A systematic review and dose-response meta-analysis.Front Nutr.(2022)
    6. HbA1c - Gheysari R, Nikbaf-Shandiz M, Hosseini AM, Rasaei N, Hosseini S, Bahari H, Asbaghi O, Rastgoo S, Goudarzi K, Shiraseb F, Behmadi RThe effects of L-carnitine supplementation on cardiovascular risk factors in participants with impaired glucose tolerance and diabetes: a systematic review and dose-response meta-analysis.Diabetol Metab Syndr.(2024 Jul 31)
    7. HbA1c - Karimi-Nazari E, et alEffect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trialClin Nutr ESPEN.()
    8. Oxidative Stress Biomarkers - Abedi A, Ghobadi H, Sharghi A, Iranpour S, Fazlzadeh M, Aslani MREffect of saffron supplementation on oxidative stress markers (MDA, TAC, TOS, GPx, SOD, and pro-oxidant/antioxidant balance): An updated systematic review and meta-analysis of randomized placebo-controlled trials.Front Med (Lausanne).(2023)
    9. Sperm Count - Elham Karimi-Nazari, Azadeh Nadjarzadeh, Roghayyeh Masoumi, Ameneh Marzban, Seyed Ahmad Mohajeri, Nahid Ramezani-Jolfaie, Amin Salehi-AbargoueiEffect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trialClin Nutr ESPEN.(2019 Dec)
    10. HbA1c - Dludla PV, Nyambuya TM, Orlando P, Silvestri S, Mxinwa V, Mokgalaboni K, Nkambule BB, Louw J, Muller CJF, Tiano LThe impact of coenzyme Q on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta-analysis of randomized controlled trials.Endocrinol Diabetes Metab.(2020-Apr)
    11. HbA1c - Wang L, Yang H, Huang H, Zhang C, Zuo HX, Xu P, Niu YM, Wu SSInulin-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.J Transl Med.(2019-Dec-05)
    12. HbA1c - Salehidoost R, Taghipour Boroujeni G, Feizi A, Aminorroaya A, Amini MEffect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial.Sci Rep.(2022-Oct-28)
    13. HbA1c - Xiong K, Wang J, Kang T, Xu F, Ma AEffects of resistant starch on glycaemic control: a systematic review and meta-analysis.Br J Nutr.(2021-Jun-14)
    14. HbA1c - Parry-Strong A, Wright-McNaughton M, Weatherall M, Hall RM, Coppell KJ, Barthow C, Krebs JDVery low carbohydrate (ketogenic) diets in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.Diabetes Obes Metab.(2022-Dec)
    15. HbA1c - N Suksomboon, N Poolsup, S PunthanitisarnEffect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes: a systematic review and meta-analysisJ Clin Pharm Ther.(2016 Apr)
    16. HbA1c - Yiyi Zhang, Wen Liu, Dan Liu, Tieyun Zhao, Haoming TianEfficacy of Aloe Vera Supplementation on Prediabetes and Early Non-Treated Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled TrialsNutrients.(2016 Jun 23)
    17. HbA1c - Effects of Panax ginseng on hyperglycemia, hypertension, and hyperlipidemia: A systematic review and meta-analysis.()
    18. HbA1c - Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom ZFlaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials.Nutr Rev.(2018 Feb 1)
    19. HbA1c - Villarreal-Renteria AI, Herrera-Echauri DD, Rodríguez-Rocha NP, Zuñiga LY, Muñoz-Valle JF, García-Arellano S, Bernal-Orozco MF, Macedo-Ojeda GEffect of flaxseed (Linum usitatissimum) supplementation on glycemic control and insulin resistance in prediabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.Complement Ther Med.(2022 Nov)
    20. Leptin - Abbasi S, Karimi K, Hossein Moridpour A, Musazadeh V, Faghfouri AH, Jozi HCan flaxseed supplementation affect circulating adipokines in adults? An updated systematic review and meta-analysis of randomized controlled trials.Front Nutr.(2023)
    21. Insulin Resistance - Mihoko Yoshino, Jun Yoshino, Brandon D Kayser, Gary J Patti, Michael P Franczyk, Kathryn F Mills, Miriam Sindelar, Terri Pietka, Bruce W Patterson, Shin-Ichiro Imai, Samuel KleinNicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic womenScience.(2021 Jun 11)
    22. Insulin Resistance - Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CMEarly Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with PrediabetesCell Metab.(2018 Jun 5)
    23. Insulin Resistance - Wallace HJ, Holmes L, Ennis CN, Cardwell CR, Woodside JV, Young IS, Bell PM, Hunter SJ, McKinley MCEffect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial.Am J Clin Nutr.(2019-Nov-01)
    24. Glycemic Control - Harris SS, Pittas AG, Palermo NJA randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African AmericansDiabetes Obes Metab.(2012 Sep)
    25. Glycemic Control - Shaban Nazarian, John V St Peter, Raymond C Boston, Sidney A Jones, Cary N MariashVitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucoseTransl Res.(2011 Nov)
    26. Fasting Glucose - Lari A, Sohouli MH, Fatahi S, Cerqueira HS, Santos HO, Pourrajab B, Rezaei M, Saneie S, Rahideh STThe effects of the Dietary Approaches to Stop Hypertension (DASH) diet on metabolic risk factors in patients with chronic disease: A systematic review and meta-analysis of randomized controlled trials.Nutr Metab Cardiovasc Dis.(2021 Sep 22)
    27. High-density lipoprotein (HDL) - Alaei-Shahmiri F, Soares MJ, Zhao Y, Sherriff JThe impact of thiamine supplementation on blood pressure, serum lipids and C-reactive protein in individuals with hyperglycemia: a randomised, double-blind cross-over trialDiabetes Metab Syndr.(2015 Oct-Dec)
    28. Glycemic Control - Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai NPilot Study of Resveratrol in Older Adults With Impaired Glucose ToleranceJ Gerontol A Biol Sci Med Sci.(2012 Jan 4)
    29. Insulin - Johnston CS, Kim CM, Buller AJVinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetesDiabetes Care.(2004 Jan)
    30. Endothelial Function - Shannon OM, Mendes I, Köchl C, Mazidi M, Ashor AW, Rubele S, Minihane AM, Mathers JC, Siervo MMediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.J Nutr.(2020-May-01)