Cited by 508Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and ResearchDiabetes Treatment and Management

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Normal Fasting Plasma Glucose Levels and Type 2 Diabetes in Young Men

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Tirosh, Amir, Shai, Iris, Tekes-Manova, Dorit, Israeli, Eran, Pereg, David, Shochat, Tzippora, Kochba, Ilan, Rudich, Assaf·2005·New England Journal of Medicine

DOI 10.1056/nejmoa050080

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Abstract

BACKGROUND: The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. METHODS: We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. RESULTS: A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. CONCLUSIONS: Higher fasting plasma glucose levels within the normoglycemic range constitute an independent risk factor for type 2 diabetes among young men, and such levels may help, along with body-mass index and triglyceride levels, to identify apparently healthy men at increased risk for diabetes.

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Blond, M. B., Færch, K., Herder, C., Ziegler, D., & Stehouwer, C. D. A. (2023) · Diabetologia · doi:10.1007/s00125-023-05890-y · Cited by 33
“Moreover, despite the literature showing no clear threshold for the risk of later diabetes [11], specific but varying cut-off points are used to define prediabetes/intermediate hyperglycaemia (Table 1).”
Background
The paradox of obesity with normal weight; a cross-sectional study
Lahav, Y., Kfir, A., & Gepner, Y. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1173488 · Cited by 45
“This result reinforces previous data presenting high blood lipids and hyperglycemia in the normal range can identify healthy persons at increased risk of developing metabolic syndrome (40).”
Result
Association of ambient particle pollution with gestational diabetes mellitus and fasting blood glucose levels in pregnant women from two Chinese birth cohorts
Hu, Q., Wang, D., Yue, D., Xu, C., Hu, B., Cheng, P., Zhai, Y., Mai, H., Li, P., Gong, J., et al. (2020) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2020.143176 · Cited by 36
Point: Impaired Fasting Glucose: The Case for the New American Diabetes Association Criterion
Shaw, J. E., Zimmet, P., & Alberti, K. G. M. M. (2006) · Diabetes Care · doi:10.2337/dc06-0013 · Cited by 35
Impact of a community based health‐promotion programme in 2‐ to 9‐year‐old children in Europe on markers of the metabolic syndrome, the IDEFICS study
Mårild, S., Russo, P., Veidebaum, T., Tornaritis, M. J., Henauw, S. D., Bourdeaudhuij, I. D., Molnár, D., Moreno, L. A., Bramsved, R., Peplies, J., et al. (2015) · Obesity Reviews · doi:10.1111/obr.12368 · Cited by 34
Predictors of new-onset diabetes mellitus in hypertensive patients: the VALUE trial
Aksnes, T. A., Kjeldsen, S. E., Rostrup, M., Störset, Ö., Hua, T., & Julius, S. (2008) · Journal of Human Hypertension · doi:10.1038/jhh.2008.41 · Cited by 33
Two susceptible diabetogenic variants near/in MTNR1B are associated with fasting plasma glucose in a Han Chinese cohort
Kan, M., Zhou, D., Zhang, D., Zhang, Z., Chen, Z., Yang, Y. F., Guo, X., Xu, H., He, L., & Liu, Y. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2010.02975.x · Cited by 34
Glucose Homeostasis in Hypertensive Subjects
Korhonen, P. E., Aarnio, P. T. T., Saaresranta, T., Jaatinen, P. T., & Kantola, I. M. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.104869 · Cited by 34
Multi-omics approaches for biomarker discovery and precision diagnosis of prediabetes
Song, J., Wang, C., Zhao, T., Zhang, Y., Xing, J., Zhao, X., Zhang, Y., & Zhang, Z. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1520436 · Cited by 36
T2DM: Why Epigenetics?
Fradin, D., & Bougneres, P. F. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/647514 · Cited by 34
“However, losing weight, eating less, and exercising are able to reverse T2DM [14], establishing a clear cause-to-effect relationship between these environmental conditions and T2DM.”
Background
Childhood Metabolic Syndrome
Weiss, R. (2011) · Diabetes Care · doi:10.2337/dc11-s214 · Cited by 33
Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription
Lawrence, M. C., Shao, C., McGlynn, K., Naziruddin, B., Levy, M. F., & Cobb, M. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912596106 · Cited by 32
Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population
Go, M. J., Hwang, J., Park, T. J., Kim, Y. J., Oh, J. H., Kim, Y. J., Han, B., & Kim, B.-J. (2014) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2014.38.5.375 · Cited by 32
“org in fasting glucose variation, β-cell function, and insulin sensitivity as well as T2DM [5-8].”
Background
Effectiveness of citrate buffer-fluoride mixture in Terumo tubes as an inhibitor of in vitro glycolysis
Italian joint SIBioC-SIPMeL Study Group on Diabetes Mellitus, Bonetti, G., Carta, M., Montagnana, M., Cascio, C. L., Bonfigli, A. R., Mosca, A., & Testa, R. (2016) · Biochemia Medica · doi:10.11613/bm.2016.006 · Cited by 32
“Laboratory plasma glucose testing is fundamental for the diagnosis of diabetes mellitus (DM), impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and in particular for the screening and diagnosis of gestational diabetes mellitus (GDM) where HbA1c can’t be used (1-3).”
Method
The triglyceride and glucose index is a useful biomarker to recognize glucose disorders in apparently healthy children and adolescents
Simental‐Mendía, L. E., Gamboa‐Gómez, C. I., Aradillas-García, C., Rodríguez‐Morán, M., & Guerrero‐Romero, F. (2020) · European Journal of Pediatrics · doi:10.1007/s00431-020-03570-2 · Cited by 32
Current diagnostic criteria identify risk for type 2 diabetes too late
Bergman, M., Buysschaert, M., Ceriello, A., Hussain, A., Mohan, V., Sesti, G., & Tuomilehto, J. O. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00039-6 · Cited by 32
Alcohol consumption and higher incidence of impaired fasting glucose or type 2 diabetes in obese Korean men
Roh, W.-G., Shin, H.-C., Choi, J. H., Lee, Y. J., & Kim, K. (2009) · Alcohol · doi:10.1016/j.alcohol.2009.10.005 · Cited by 32
“(Tirosh et al., 2005).”
Background
Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms
Owei, I., UMEKWE, N. A., Wan, J. Y., & Dagogo-Jack, S. E. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216659946 · Cited by 33
Cost-Effectiveness of Alternative Thresholds of the Fasting Plasma Glucose Test to Identify the Target Population for Type 2 Diabetes Prevention in Adults Aged ≥45 Years
Zhuo, X., Zhang, P., Kahn, H. S., & Gregg, E. W. (2013) · Diabetes Care · doi:10.2337/dc13-0497 · Cited by 30
Normal Fasting Plasma Glucose and Risk of Prediabetes and Type 2 Diabetes: The Isfahan Diabetes Prevention Study
Janghorbani, M., & Amini, M. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.490 · Cited by 32
Hunger can be taught: Hunger Recognition regulates eating and improves energy balance
Ciampolini, M., Lovell-Smith, Bianchi, R., & Kenealy, T. W. (2013) · International Journal of General Medicine · doi:10.2147/ijgm.s40655 · Cited by 33
“5 mmol/L).(42) It is interesting that this latter figure corresponds closely to the demarcation point which separated the current study’s low BG and high BG groups.”
Background
Funkcjonalne polimorfizmy genów leptyny i receptora leptyny korelują z długowiecznością oraz z ryzykiem zawału mięśnia serca i cukrzycy 2 typu
Roszkowska-Gancarz, M., Kuryłowicz, A., Połosak, J., Mossakowska, M., Franek, E., & Puzianowska‐Kuźnicka, M. (2014) · Endokrynologia Polska · doi:10.5603/ep.2014.0002 · Cited by 31
“This finding is of great importance since it has been previously found that low-normal fasting glucose levels are associated with lower risk of DM2 compared to high-normal values [52, 54].”
Background
Decision models of prediabetes populations: A systematic review
Leal, J., Morrow, L. M., Khurshid, W., Pagano, E., & Feenstra, T. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13684 · Cited by 30
“Although this was a convenient simplification of reality, it fails to model glycaemia deterioration as a continuum of risk and to account for the differing risk levels of disease progression among individuals with plasma glucose readings towards the upper limit of the normal range.(60) Also, with models informed by a…”
Background
Effects of Montmorency Tart Cherry and Blueberry Juice on Cardiometabolic and Other Health-Related Outcomes: A Three-Arm Placebo Randomized Controlled Trial
SINCLAIR, J. K., Bottoms, L. M., Dillon, S. A., Allan, R., Shadwell, G., & Butters, B. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19095317 · Cited by 30
“Nonetheless, it is important to note that the mean fasting blood glucose values remained within normal ranges [85], and the long-term effects of elevated blood glucose levels remain unknown in healthy individuals.”
Background
Reframing prediabetes: A call for better risk stratification and intervention
Kim, S. H. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13786 · Cited by 31
“For example, although controversy has existed on the appropriate cut point to deﬁne impaired FPG, diabetes risk rises with increasing FPG, even below 5.6 mmol/L (100 mg/dL) [34–36].”
BackgroundInfluential
Does Elevated Plasma Triglyceride Level Independently Predict Impaired Fasting Glucose?
Lin, S. X., Berlin, I., Younge, R. G., Jin, Z., Sibley, C. T., Schreiner, P. J., Szklo, M., & Bertoni, A. G. (2012) · Diabetes Care · doi:10.2337/dc12-0355 · Cited by 32
Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)
Demmer, R. T., Trinh, P., ROSENBAUM, M. S., Li, G., LeDuc, C. A., Leibel, R. L., González, A., Knight, R. D., Paster, B. J., Colombo, P. C., et al. (2019) · Journal of Dental Research · doi:10.1177/0022034519881978 · Cited by 29
A Conceptual Framework for Targeting Prediabetes with Lifestyle, Clinical, And Behavioral Management Interventions
Biuso, T. J., Butterworth, S. W., & Linden, A. (2007) · Disease Management · doi:10.1089/dis.2006.628 · Cited by 28
High Glucose Concentration Stimulates NHE-1 Activity in Distal Nephron Cells: the Role of the Mek/Erk1/2/p90RSKand p38MAPK Signaling Pathways
da Costa-Pessoa, J. M., Damasceno, R. S., Machado, U. F., Beloto-Silva, O., & Oliveira‐Souza, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356673 · Cited by 29
The role of glucose-6-phosphatase activity in glucose homeostasis and its potential for diabetes therapy
Tan, L. S., Lau, H. H., Abdelalim, E. M., Khoo, C. M., O’Brien, R. M., Tai, E. S., & Teo, A. K. K. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.09.005 · Cited by 29
Racial/Ethnic Differences in Association of Fasting Glucose–Associated Genomic Loci With Fasting Glucose, HOMA-B, and Impaired Fasting Glucose in the U.S. Adult Population
Yang, Q., Liu, T., Shrader, P. J., Yesupriya, A., Chang, M., Dowling, N. F., Ned, R. M., Dupuis, J., Florez, J. C., Khoury, M. J., et al. (2010) · Diabetes Care · doi:10.2337/dc10-0898 · Cited by 28
Subclinical Diabetes
Lima, L. M. T. R. (2017) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201720160394 · Cited by 27
Diabetes: Concepts of β-Cell Organ Dysfunction and Failure Would Lead to Earlier Diagnoses and Prevention
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Pathogenesis, Risk Assessment and Prevention of Type 2 Diabetes mellitus
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“Several studies have demonstrated that high-normal blood glucose concentrations are associated with an increased risk for diabetes [30, 46 ].”
Background
Coronary artery disease risk among obese metabolically healthy young men
Twig, G., Gerstein, H. C., Shor, D. B., Derazne, E., Tzur, D., Afek, A. B., & Tirosh, A. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0284 · Cited by 27
Self-citation
Classification and Diagnosis of Diabetes Mellitus
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Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection
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Authors: Tirosh, A., Shai, I., Tekes-Manova, D., Israeli, E., Pereg, D., Shochat, T., Kochba, I., & Rudich, A.
Affiliations: Sheba Medical Center (IL)
Israel Defense Forces Medical Corps (IL)
Meir Medical Center (IL)
Ben-Gurion University of the Negev (IL)
ORCID: Tirosh, Amir
Shai, Iris
Israeli, Eran
Pereg, David
Rudich, Assaf
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2005-10-06
Volume: 353
Issue: 14
Pages: 1454-1462
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa050080
OpenAlex: W2022852506
Semantic Scholar: 6bb2371f0d6168ca3c8b7a7910714ce03e565a83
Cited by: 508
References: 37
Citations by year: 2026: 4 · 2025: 7 · 2024: 17 · 2023: 28 · 2022: 11 · 2021: 17 · 2020: 24 · 2019: 15 · 2018: 24 · 2017: 14 · 2016: 24 · 2015: 21 · 2014: 33 · 2013: 35 · 2012: 31
FWCI: 21.52
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: fasting blood glucose, type 2 diabetes, prediabetes, young men, diabetes risk prediction, serum triglycerides, body mass index, hypertriglyceridemia, military personnel, new-onset diabetes
MeSH terms: Adult, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Follow-Up Studies, Humans, Male, Middle Aged, Reference Values, Risk Factors, Triglycerides, Body Mass Index, Multivariate Analysis, Proportional Hazards Models

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Normal Fasting Plasma Glucose Levels and Type 2 Diabetes in Young Men

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