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?
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
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]
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]
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]
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]
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]
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]
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]
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]
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
Examine Database References
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- 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)
- 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)
- HbA1c - Bruls Y, et alCarnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trialEBioMedicine.()
- 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)
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- 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.()
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- HbA1c - Effects of Panax ginseng on hyperglycemia, hypertension, and hyperlipidemia: A systematic review and meta-analysis.()
- 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)
- 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)
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- 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)
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