Non-obese patients with type 2 diabetes and prediabetic subjects: distinct phenotypes requiring special diabetes treatment and (or) prevention?
Open accessAbstract
A major reason for the increased incidence of type 2 diabetes mellitus (T2DM) across the world is the so-called obesity epidemic, which occurs both in developed and developing countries. However, a large proportion of patients with T2DM in European and, in particular, Asian countries are non-obese. The non-obese T2DM phenotype is characterized by disproportionally reduced insulin secretion and less insulin resistance, as compared with obese patients with T2DM. Importantly, non-obese patients with T2DM have a similar increased risk of cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese patients is influenced by genetics as well as factors operating in utero indicated by low birth weight. Furthermore, this phenotype is slightly more prevalent among patients with latent autoimmune diabetes in adults, characterized by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism resulting in low insulin secretion influences the risk of T2DM in both obese and non-obese subjects, but is relatively more prevalent among non-obese patients with T2DM. Furthermore, the Pro12Ala polymorphism of the PPARγ gene influencing insulin action increases the risk of T2DM in non-obese subjects. Despite a “normal” body mass index, non-obese patients with T2DM are generally characterized by a higher degree of both abdominal and total fat masses (adiposity). Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to insulin treatment more rapidly as compared with obese patients with T2DM.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The insulin resistance in peripheral and hepatic tissues is present in obese and non-obese T2D patients, but not to the same extent.
“The insulin resistance in peripheral and hepatic tissues is present in obese and non-obese T2D patients, but not to the same extent.115”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [115]
Peripheral and hepatic insulin resistance is present in obese and non-obese T2D patients, but not to the same extent in non-obese subjects.
“Peripheral and hepatic insulin resistance is present in obese and non-obese T2D patients, but not to the same extent in non-obese subjects.115”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [115]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Global Burden of Diabetes, 1995–2025: Prevalence, numerical estimates, and projections
King, H. O. M., Aubert, R. E., & Herman, W. H. (1998) · Diabetes Care · doi:10.2337/diacare.21.9.1414 · Cited by 6,267 · see citing works
Diet, nutrition and the prevention of chronic diseases
Joint, W. (2002) · Medical Entomology and Zoology · Cited by 4,889 · see citing works
Pan, X.-R., Li, G.-W., Hu, Y.-H., Wang, J.-X., Yang, W.-Y., An, Z.-X., Hu, Z.-X., Juan-Lin, Xiao, J.-Z., Cao, H.-B., et al. (1997) · Diabetes Care · doi:10.2337/diacare.20.4.537 · Cited by 4,320 · see citing works
A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. (2007) · Nature · doi:10.1038/nature05616 · Cited by 2,993 · see citing works
Yusuf, S., Hawken, S., Ôunpuu, S., Bautista, L., Franzosi, M. G., Commerford, P., Lang, C. C., Rumboldt, Z., Onen, C. L., Lisheng, L., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67663-5 · Cited by 2,903 · see citing works
U.K. Prospective Diabetes Study Group (1995) · Diabetes · doi:10.2337/diab.44.11.1249 · Cited by 1,923 · see citing works
Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects
Graham, T. E., Yang, Q., Blüher, M., Hammarstedt, A., Ciaraldi, T. P., Henry, R. R., Wason, C. J., Oberbach, A., Jansson, P.-A., Smith, U., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054862 · Cited by 1,319 · see citing works
Willett, W. C., Dietz, W. H., & Colditz, G. A. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908053410607 · Cited by 1,141 · see citing works
Kirpichnikov, D., McFarlane, S. I., & Sowers, J. R. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-1-200207020-00009 · Cited by 1,084 · see citing works
Oral Antihyperglycemic Therapy for Type 2 Diabetes
Inzucchi, S. E. (2002) · JAMA · doi:10.1001/jama.287.3.360 · Cited by 1,057 · see citing works
Turner, R., Stratton, I., Horton, V., Manley, S., Zimmet, P., Mackay, I. R., Shattock, M., Bottazzo, G. F., & Holman, R. (1997) · The Lancet · doi:10.1016/s0140-6736(97)03062-6 · Cited by 779 · see citing works
Manson, J. E. (1991) · Archives of Internal Medicine · doi:10.1001/archinte.1991.00400060077013 · Cited by 675 · see citing works
Dalton, M., Cameron, A. J., Zimmet, P., Shaw, J. E., Jolley, D., Dunstan, D. W., & Welborn, T. A. (2003) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2003.01229.x · Cited by 666 · see citing works
Poulsen, P., Kyvik, K. O., Vaag, A. A., & Beck‐Nielsen, H. (1999) · Diabetologia · doi:10.1007/s001250051131 · Cited by 617 · see citing works
Self-citationYki-Järvinen, H., Ryysy, L., Nikkilä, K., Tulokas, T., Vanamo, R., & Heikkilä, M. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-5-199903020-00002 · Cited by 433 · see citing works
Nathan, D. M., Buse, J. B., Davidson, M. B., Heine, R. J., Holman, R. R., Sherwin, R., & Zinman, B. (2006) · Diabetologia · doi:10.1007/s00125-006-0316-2 · Cited by 420 · see citing works
Adiposity and Hyperinsulinemia in Indians Are Present at Birth
Yajnik, C. S., Lubree, H., Rege, S., Naik, S. S., Deshpande, J. A., Deshpande, S. S., Joglekar, C. V., & Yudkin, J. S. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020434 · Cited by 412 · see citing works
Butler, A. E., Janson, J., Soeller, W. C., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2304 · Cited by 411 · see citing works
Saxena, R., Gianniny, L., Burtt, N. P., Lyssenko, V., Giuducci, C., Sjögren, M., Florez, J. C., Almgren, P., Isomaa, B., Orho‐Melander, M., et al. (2006) · Diabetes · doi:10.2337/db06-0381 · Cited by 373 · see citing works
Vaag, A., Henriksen, J. E., & Beck-Nielsen, H. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115656 · Cited by 299 · see citing works
Self-citationLow birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs
Poulsen, P., Vaag, A. A., Kyvik, K. O., Jensen, D. M., & Beck‐Nielsen, H. (1997) · Diabetologia · doi:10.1007/s001250050698 · Cited by 295 · see citing works
Self-citationLow birthweight is associated with specific changes in muscle insulin-signalling protein expression
Ozanne, S. E., Jensen, C. B., Tingey, K., Storgaard, H., Madsbad, S., & Vaag, A. A. (2005) · Diabetologia · doi:10.1007/s00125-005-1669-7 · Cited by 286 · see citing works
Self-citationYajnik, C. S., & Yudkin, J. S. (2004) · The Lancet · doi:10.1016/s0140-6736(03)15269-5 · Cited by 267 · see citing works
Age, body mass index and Type 2 diabetes?associations modified by ethnicity
Group, T. D.-D. S. (2003) · Diabetologia · doi:10.1007/s00125-003-1158-9 · Cited by 215 · see citing works
Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of men in Uppsala.
Skarfors, E., Selinus, K. I., & Lithell, H. (1991) · BMJ · doi:10.1136/bmj.303.6805.755 · Cited by 211 · see citing works
Vaag, A., Henriksen, J. E., Madsbad, S., Holm, N., & Beck-Nielsen, H. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117715 · Cited by 206 · see citing works
Self-citationRelationship Between β-Cell Mass and Fasting Blood Glucose Concentration in Humans
Ritzel, R. A., Butler, A. E., Rizza, R. A., Veldhuis, J. D., & Butler, P. C. (2006) · Diabetes Care · doi:10.2337/diacare.29.03.06.dc05-1538 · Cited by 197 · see citing works
Jensen, C. B., Storgaard, H., Dela, F., Holst, J. J., Madsbad, S., & Vaag, A. A. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1271 · Cited by 182 · see citing works
Self-citationVaag, A. A., Holst, J. J., Vølund, A., & Beck‐Nielsen, H. (1996) · European Journal of Endocrinology · doi:10.1530/eje.0.1350425 · Cited by 154 · see citing works
Self-citationAn Update on The Diabetes Prevention Program
Ratner, R. E. (2006) · Endocrine Practice · doi:10.4158/ep.12.s1.20 · Cited by 141 · see citing works
Tuomi, T. (2005) · Diabetes · doi:10.2337/diabetes.54.suppl_2.s40 · Cited by 129 · see citing works
Hollenbeck, C., Chen, Y., & Reaven, G. (1984) · Diabetes · doi:10.2337/diab.33.7.622 · Cited by 116 · see citing works
Mojiminiyi, O. A., Abdella, N., Arouj, M. A., & Nakhi, A. B. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803355 · Cited by 110 · see citing works
Adlerberth, A., Rosengren, A., & Wilhelmsen, L. (1998) · Diabetes Care · doi:10.2337/diacare.21.4.539 · Cited by 97 · see citing works
Altered Fat Tissue Distribution in Young Adult Men Who Had Low Birth Weight
Rasmussen, E. L., Malis, C., Jensen, C. B., Jensen, J. B., Storgaard, H., Poulsen, P., Pilgaard, K. A., Schou, J. H., Madsbad, S., Astrup, A. V., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.1.151 · Cited by 93 · see citing works
Self-citationThe effect of obesity on glycaemic response to metformin or sulphonylureas in Type 2 diabetes
Donnelly, L. A., Doney, A. S. F., Hattersley, A. T., Morris, A. D., & Pearson, E. R. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01755.x · Cited by 88 · see citing works
Prevalence of NIDDM and impaired glucose tolerance in Italy: an OGTT-based population study
Garancini, M. P., Calori, G., Ruotolo, G., Manara, E., Izzo, A., Ebbli, E., Bozzetti, A., Boari, L., Lazzari, P., & Gallus, G. (1995) · Diabetologia · doi:10.1007/bf00400635 · Cited by 86 · see citing works
Antiatherogenic properties of metformin: the experimental evidence
Mamputu, J., Wiernsperger, N. F., & Renier, G. (2003) · Diabetes & Metabolism · doi:10.1016/s1262-3636(03)72790-6 · Cited by 81 · see citing works
Clinical profile of lean NIDDM in South India
Mohan, V., Vijayaprabha, R., Rema, M., Premalatha, G., Poongothai, S., Deepa, R., Bhatia, E., Mackay, I. R., & Zimmet, P. (1997) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(97)00088-0 · Cited by 80 · see citing works
Metabolic Aspects of Insulin Resistance in Individuals Born Small for Gestational Age
Vaag, A. A., Jensen, C. B., Poulsen, P., Brøns, C., Pilgaard, K. A., Grunnet, L. G., Vielwerth, S., & Alibegovic, A. C. (2006) · Hormone Research in Paediatrics · doi:10.1159/000091519 · Cited by 77 · see citing works
Self-citationLong-Term Efficacy of Metformin Therapy in Nonobese Individuals With Type 2 Diabetes
Ong, C. R., Molyneaux, L. M., Constantino, M., Twigg, S. M., & Yue, D. K. (2006) · Diabetes Care · doi:10.2337/dc06-0827 · Cited by 76 · see citing works
Long-term efficacy of sulfonylureas: a United Kingdom Prospective Diabetes Study perspective
Holman, R. R. (2006) · Metabolism · doi:10.1016/j.metabol.2006.02.006 · Cited by 72 · see citing works
Chang, S. A., Kim, H. S., Yoon, K. H., Ko, S. H., Kwon, H. S., Kim, S. R., Lee, W. C., Yoo, S. J., Son, H. S., Cha, B. Y., et al. (2004) · Metabolism · doi:10.1016/s0026-0495(03)00314-7 · Cited by 66 · see citing works
Hermann, T. S., Rask‐Madsen, C., Ihlemann, N., Domínguez, H., Jensen, C. B., Storgaard, H., Vaag, A. A., Køber, L., & Torp-Pedersen, C. T. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021550 · Cited by 65 · see citing works
Self-citationLower-body fat mass as an independent marker of insulin sensitivity—the role of adiponectin
Buemann, B., Sørensen, T. I. A., Pedersen, O. B., Black, E., Holst, J. J., Toubro, S., Echwald, S. M., Holst, J. J., Rasmussen, C. E., & Astrup, A. V. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0802929 · Cited by 64 · see citing works
Lund, S. S., Tarnow, L., Stehouwer, C. D. A., Schalkwijk, C., Frandsen, M., Smidt, U., Pedersen, O. B., Parving, H. ‐., & Vaag, A. A. (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00713.x · Cited by 45 · see citing works
Self-citationAdipocytokines and the expanding 'Asian Indian Phenotype'.
Mohan, V., & Deepa, R. (2006) · PubMed · Cited by 44 · see citing works
Vaag, A. A. (1999) · PubMed · Cited by 41 · see citing works
Self-citationHollenbeck, C. B., Chen, Y. D., & Reaven, G. M. (1984) · Diabetes · doi:10.2337/diabetes.33.7.622 · Cited by 30 · see citing works
Bourn, D. M. (1996) · Diabetic Medicine · doi:10.1002/(sici)1096-9136(199611)13:11 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Fernandez-Castaner, M., Biarnes, J., Camps, I., Ripolles, J., Gomez, N., and Soler, J. 1996. Beta-cell dysfunction in first-degree rela- tives of patients with non-insulin-dependent diabetes mellitus. Dia- bet. Med. 13: 953-959. doi:10.1002/(SICI)1096-9136(199611) 13:11<953::AID-DIA257>3.0.CO;2-V. PMID:8946153. · DOI
- Kirpichnikov, D., McFarlane, S.I., and Sowers, J.R. 2002. Metfor- min: an update. Ann. Intern. Med. 137: 25-33. PMID:12093242.
Cited by
Sorted by citations
Reed, J., Bain, S., & Kanamarlapudi, V. (2021) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s319895 · Cited by 441 · see citing works
Normal weight individuals who develop Type 2 diabetes: the personal fat threshold
Taylor, R., & Holman, R. R. (2014) · Clinical Science · doi:10.1042/cs20140553 · Cited by 190 · see citing works
Lean diabetes mellitus: An emerging entity in the era of obesity
George, A. M., Jacob, A. G., & Fogelfeld, L. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i4.613 · Cited by 177 · see citing works
Hypothalamic inflammation: a double‐edged sword to nutritional diseases
Cai, D., & Liu, T. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06388.x · Cited by 159 · see citing works
Lankatillake, C., Huynh, T. T., & Dias, D. A. (2019) · Plant Methods · doi:10.1186/s13007-019-0487-8 · Cited by 159 · see citing works
Understanding the cause of type 2 diabetes
Taylor, R. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00157-8 · Cited by 83 · see citing works
Taylor, R., Barnes, A. C., Hollingsworth, K. G., Irvine, K. M., Solovyova, A. S., Clark, L., Kelly, T., Martin-Ruiz, C., Romeres, D., Koulman, A., et al. (2023) · Clinical Science · doi:10.1042/cs20230586 · Cited by 71 · see citing works
The anti-diabetic activity of oat β-d-glucan in streptozotocin–nicotinamide induced diabetic mice
Liu, M., Zhang, Y., Zhang, H., Hu, B., Wang, L., Qian, H., & Qi, X. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.06.083 · Cited by 56 · see citing works
Lee, J., Yee, S., Kim, J.-J., Choi, M., Kwon, E.-Y., Seo, K., & Lee, M. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.09.019 · Cited by 53 · see citing works
Overview of Metformin and Neurodegeneration: A Comprehensive Review
Kruczkowska, W., Gałęziewska, J., Buczek, P., Płuciennik, E., Kciuk, M., & Śliwińska, A. (2025) · Pharmaceuticals · doi:10.3390/ph18040486 · Cited by 50 · see citing works
Raised Serum Adenosine Deaminase Level in Nonobese Type 2 Diabetes Mellitus
Khemka, V. K., Bagchi, D., Ghosh, A., Sen, O., Bir, A., Chakrabarti, S., & Banerjee, A. (2013) · The Scientific World JOURNAL · doi:10.1155/2013/404320 · Cited by 45 · see citing works
“However, obesity is not always linked to T2DM as ascertained by studies that indicate that the Asian T2DM phenotype is commonly less obese when defined by Body Mass Index (BMI) and around 20%of north EuropeanT2DM cases are of the nonobese type [3, 4].”
BackgroundResveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats
Szkudelska, K., Okulicz, M., Hertig, I., & Szkudelski, T. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110026 · Cited by 45 · see citing works
Gu, Y., Hu, K., Huang, Y., Zhang, Q., Liu, L., Ge, M., Wu, H., Xia, Y., Bao, X., Shi, H., et al. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.04.041 · Cited by 41 · see citing works
Sihota, P., Yadav, R. N., Poleboina, S., Mehandia, V., Bhadada, S. K., Tikoo, K., & Kumar, N. (2020) · JBMR Plus · doi:10.1002/jbm4.10379 · Cited by 43 · see citing works
“Importantly, nonobese patients with T2D have a similar increased risk of cardiovascular disease as obese T2D patients.((7,63))”
BackgroundDiabetic neuropathy research: from mouse models to targets for treatment
Ito, S., Pham, V. M., Matsumura, S., Katano, T., & Funatsu, N. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.259603 · Cited by 39 · see citing works
“(2006), we have recently and successfully established a mouse model of non-obese type 2 diabetes that is frequently found in Asia (Vaag and Lund, 2007).”
Kannan, M., Sarva, S., Kandadai, R. M., Paturi, V. R., Jabeen, S., & Borgohain, R. (2014) · Neurology India · doi:10.4103/0028-3886.149393 · Cited by 36 · see citing works
Lee, J., Lee, H.-I., Seo, K.-I., Cho, H. W., Kim, M., Park, E., & Lee, M. (2014) · PubMed · Cited by 35 · see citing works
Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats
Sárközy, M., Szűcs, G., Fekete, V., Pipicz, M., Éder, K., Gáspár, R., Sója, A., Pipis, J., Ferdinandy, P., Csonka, C., et al. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0424-3 · Cited by 35 · see citing works
“One of the major pathologies of the aforementioned CVD is diabetic cardiomyopathy (DCM) [15, 16].”
BackgroundInfluentialKashima, S., Inoue, K., Matsumoto, M., & Akimoto, K. (2014) · Journal of Diabetes · doi:10.1111/1753-0407.12213 · Cited by 34 · see citing works
“History of cardiovascular disease [n (%)] 19 (9)*** 20 (8)* 24 (15)** 12 (11)”
A Glimpse into Milestones of Insulin Resistance and an Updated Review of Its Management
Aedh, A. I., Alshahrani, M. S., Huneif, M. A., Pryme, I. F., & Oruch, R. (2023) · Nutrients · doi:10.3390/nu15040921 · Cited by 32 · see citing works
“The dilemma of IR cannot be explained as being simply dependent on obesity, as many prediabetes individuals in certain societies are skinny or have lean bodies [84].”
BackgroundDiabetes risk assessment with imaging: a radiomics study of abdominal CT
Lu, C., Wang, Y., Meng, X., Zhao, H.-T., Zeng, C. H., Xu, W., Gao, Y., & Ju, S. (2018) · European Radiology · doi:10.1007/s00330-018-5865-5 · Cited by 29 · see citing works
Wang, C., Yatsuya, H., Tamakoshi, K., Toyoshima, H., Wada, K., Li, Y., Hilawe, E. H., Uemura, M. Y., Chiang, C., Zhang, Y., et al. (2015) · Preventive Medicine · doi:10.1016/j.ypmed.2015.07.021 · Cited by 27 · see citing works
“However, some non-obese individuals develop T2DM, suggesting the existence of a familial influence (Paolo, 2007; Vaag and Lund, 2007).”
BackgroundEffects of long-term exposure to CO and PM2.5 on microalbuminuria in type 2 diabetes
Chin, W., Chang, Y., Huang, L.-F., Tsui, H.-C., Hsu, C.-C., & Guo, Y. L. (2018) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2018.04.009 · Cited by 25 · see citing works
Trends in the Prevalence of Lean Diabetes Among U.S. Adults, 2015–2020
Adesoba, T. P., & Brown, C. C. (2023) · Diabetes Care · doi:10.2337/dc22-1847 · Cited by 25 · see citing works
Periodontitis is associated with diabetic retinopathy in non-obese adults
Song, S. J., Lee, S., Han, K., & Park, J. (2016) · Endocrine · doi:10.1007/s12020-016-1215-z · Cited by 25 · see citing works
Epigenetic regulation of HGK/MAP4K4 in T cells of type 2 diabetes patients
Chuang, H., Wang, J., Lee, I., Sheu, W. H., & Tan, T. (2016) · Oncotarget · doi:10.18632/oncotarget.7686 · Cited by 23 · see citing works
“However, not all obese individuals develop diabetes, and not all T2D patients are obese (body mass index (BMI) greater than 30) [1].”
BackgroundMethodInfluentialCalorie restriction and reversal of type 2 diabetes
Taylor, R. (2016) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2016.1239525 · Cited by 23 · see citing works
Sanit, J., Prompunt, E., Adulyaritthikul, P., Nokkaew, N., Mongkolpathumrat, P., Kongpol, K., Kijtawornrat, A., Petchdee, S., Barrère‐Lemaire, S., & Kumphune, S. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.7763 · Cited by 23 · see citing works
“In particular, there have been several reports that type 2 diabetes was commonly occurs in non-obese people within Asia (30-32).”
BackgroundLean diabetes is one end of the spectrum of type 2 diabetes and not a separate entity
Mohan, V., Pramodkumar, T. A., Deepa, M., Pradeepa, R., Ranjit Unnikrishnan, I., Routray, P., Tharunika, S., Lakshmi, N., Killivalavan, D., Ganesan, S., et al. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.112387 · Cited by 20 · see citing works
Burden and spectrum of disease in people with diabetes in Tonga
Matoto, V., Viney, K. A., Roseveare, C., Colaguiri, R., & Marais, B. J. (2014) · Public Health Action · doi:10.5588/pha.13.0080 · Cited by 20 · see citing works
Yu, H., Ho, M. M., Liu, X., Yang, J., Chau, P. H., & Fong, D. (2023) · Journal of Global Health · doi:10.7189/jogh.13.04088 · Cited by 20 · see citing works
Haghighatdoost, F., Amini, M., Aminorroaya, A., Abyar, M., & Feizi, A. (2019) · World Journal of Diabetes · doi:10.4239/wjd.v10.i6.350 · Cited by 21 · see citing works
Dwivedi, K. K., Lakhani, P., Sihota, P., Tikoo, K., Kumar, S., & Kumar, N. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.12.037 · Cited by 19 · see citing works
Tice, M., Bailey, S., Sroga, G. E., Gallagher, E. J., & Vashishth, D. (2021) · JBMR Plus · doi:10.1002/jbm4.10583 · Cited by 20 · see citing works
“The progression of diabetes in the MKR model mirrors the respective progression observed in humans displaying “normal” body mass index (BMI),((100)) and it also reflects the development of complications, such as dyslipidemia.”
MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes
Chuang, H., & Tan, T. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-016-0307-7 · Cited by 19 · see citing works
“5, more than 60% of T2D patients in Asia are still classified as having non-obese T2D [1].”
BackgroundZhou, J., Wang, Y., He, Y., Gao, Y., Wan, R., Cai, M., Li, W., Chen, R., Walker, E., Zhai, X., et al. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.03.008 · Cited by 19 · see citing works
Phenotypic characterization of nonautoimmune diabetes in adult Ugandans with low body mass index
Kibirige, D., Sekitoleko, I., Lumu, W., Thomas, N., Hawkins, M. A., Jones, A. G., Hattersley, A. T., Smeeth, L. L., & Nyirenda, M. (2024) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188241252314 · Cited by 18 · see citing works
Domon, A., Katayama, K., Sato, T., Tochigi, Y., Tazaki, H., & Suzuki, H. (2021) · PLoS ONE · doi:10.1371/journal.pone.0251135 · Cited by 18 · see citing works
“However, many type 2 DM patients, especially in Asia, are nonobese [29].”
BackgroundMondal, S., Basu, S., Ghosh, S., Guria, S., & Mukherjee, S. (2023) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23561 · Cited by 15 · see citing works
Terada, T., Boulé, N. G., Forhan, M. A., Prado, C. M. M., Kenny, G. P., Prud’homme, D., Ito, E., & Sigal, R. J. (2017) · Obesity · doi:10.1002/oby.21808 · Cited by 15 · see citing works
“Our results are similar to a previous study showing reduced insulin secretion and lower insulin resistance in the nonobese type 2 diabetes phenotype compared to the obese type 2 diabetes phenotype (31).”
ResultSong, S. J., Han, K., Lee, S., & Park, J. (2017) · Medicine · doi:10.1097/md.0000000000008694 · Cited by 15 · see citing works
Duan, B., Zhao, Z., Lin, L., Jin, J., Zhang, L., Xiong, H., Ta, N., Gao, T., & Mei, Z. (2017) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2017/7302965 · Cited by 14 · see citing works
“The “neutral” effect of TFKS on body weight is rather surprising (Figure 2(b)); however, considering that a relatively large proportion of T2DM patients are not obese at all particularly in Asian countries [26], TKFS could be an adequate therapeutic for the population of not obese T2DM patients.”
BackgroundMayurasakorn, K., Hasanah, N., Homma, T., Homma, M., Rangel, I. K., Garza, A., Romero, J. R., Adler, G. K., Williams, G. H., & Pojoga, L. H. (2018) · Metabolism · doi:10.1016/j.metabol.2018.01.012 · Cited by 14 · see citing works
Janota, O., Mantovani, M., Kwiendacz, H., Irlik, K., Bucci, T., Lam, S. H. M., Huang, B., Alam, U., Boriani, G., Hendel, M., et al. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02420-x · Cited by 14 · see citing works
“…obese normal weight (MONW) phenotype, a term used to describe individuals who present obesity alterations (e.g. reduced insulin sensitivity, hypertension, DM, and hypertriglyceridemia), despite having normal weight, present a higher risk of adverse outcomes compared to people without DM [11, 12].”
BackgroundChen-chen, F., Ding, Y., Li-qin, T., Gui, Y., Shen, X. Y., He, L., Lu, X., & Leung, W. K. (2021) · Journal of Periodontal Research · doi:10.1111/jre.12938 · Cited by 13 · see citing works
Personality traits and diabetes incidence among postmenopausal women
Luo, J., Manson, J. E., Weitlauf, J. C., Shadyab, A. H., Rapp, S. R., García, L., Jonasson, J. M., Tindle, H. A., Nassir, R., Wactawski‐Wende, J., et al. (2019) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001296 · Cited by 13 · see citing works
Body Mass Index and Health Care Utilization in Diabetic and Nondiabetic Individuals
Jerant, A. F., Bertakis, K. D., & Franks, P. J. (2015) · Medical Care · doi:10.1097/mlr.0000000000000343 · Cited by 12 · see citing works
“22 Heavier diabetic persons could have better health status than their leaner counterparts, owing to the same factors invoked in explaining the BMI mortality paradox, 1,8 – 10 or to uncharacterized factors.”
BackgroundNaidoo, P., & Islam, M. S. (2014) · Pharmacological Reports · doi:10.1016/j.pharep.2014.02.019 · Cited by 10 · see citing works
“During obesity, insulin resistance is high which causes excessive breakdown of triglycerides into fatty acids in the adipose tissue leading to a state of hyperlipidemia, however, in the case of nonobese and lean individuals they tend to have less insulin resistance and relatively lower rates of lipolysis occurring (Gr…”
BackgroundInfluentialDiabetes induced internal organs inflammation in non-obese type 2 diabetic rat
Mongkolpathumrat, P., Nokkaew, N., Adulyaritthikul, P., Kongpol, K., Sanit, J., Pankhong, P., & Kumphune, S. (2019) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2019.90307 · Cited by 10 · see citing works
“T2DM is commonly associated with obesity, which is determined by a body mass index of greater than 25 kg/m2 (DeFronzo et al., 2015; Kashima et al., 2015; Seshadri, 2013; Vaag and Lund, 2007).”
BackgroundBody mass index and health status in diabetic and non-diabetic individuals
Jerant, A. F., Bertakis, K. D., & Franks, P. W. (2015) · Nutrition and Diabetes · doi:10.1038/nutd.2015.2 · Cited by 11 · see citing works
Different β‐cell secretory phenotype in non‐obese compared to obese early type 2 diabetes
Gudipaty, L., Rosenfeld, N. K., Fuller, C. S., Cuchel, M., & Rickels, M. R. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3295 · Cited by 9 · see citing works
Yu, H., Ho, M. M., Chau, P. H., & Fong, D. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15173 · Cited by 8 · see citing works
“Moreover, clinical studies have indicated that lifestyle interventions for diabetes are less effective in non-obese individuals.(8,36,37)”
BackgroundDurst, M., Könczöl, K., Ocskay, K., Sípos, K., Várnai, P., Szilvásy‐Szabó, A., Fekete, C., & Tóth, Z. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.828571 · Cited by 8 · see citing works
Garg, D., & Dutta, M. K. (2019) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_331_18 · Cited by 7 · see citing works
“[14] Moreover, the risk of diabetes among nonobese individuals is influenced by genetics.[15]”
BackgroundType 2 diabetes mellitus alters cardiac mitochondrial content and function in a non-obese mice model
Guirao, A. R. D. Y., Martins, E. L., LOPEZ-ALARCON, M., Braga, B. C., Vera, N., Lopes, J. A., Galina, A., Takiya, C. M., Lindoso, R. S., Vieyra, A. R., et al. (2020) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202020191340 · Cited by 7 · see citing works
“Furthermore, it is well described that metabolic disturbance is a typical finding in T2DM (Wang et al. 2010).”
BackgroundAdenosine deaminase gene variant in diabetes and obesity
Dayani, S. B., Asgarbeik, S., Asadi, M., & Amoli, M. M. (2022) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-022-00978-5 · Cited by 6 · see citing works
“Because a significant proportion of T2DM patients are non-obese [19], therefore in non-obese subjects the role of inflammation is thought to be less important for decreased amount of adipose tissue [28].”
BackgroundGaffney, C. J., Mansell, P., Stephens, F. B., Macdonald, I. A., & Tsintzas, K. (2017) · Journal of Diabetes Research · doi:10.1155/2017/8248725 · Cited by 6 · see citing works
“360,000 UK-based nonobese patients with T2D (BMI < 25 kg/m(2)) (based on the data in [4]), which still possess a significant risk of secondary complications [5] and have an equal risk of cardiovascular disease to their obese counterparts [6].”
BackgroundZolkeflee, N. K. Z., Wong, P. L., Maulidiani, M., Ramli, N. S., Azlan, A., Mediani, A., Tham, C. L., & Abas, F. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149778 · Cited by 5 · see citing works
Prenatal Development and Adolescent Obesity: Two Distinct Pathways to Diabetes in Adulthood
Boone‐Heinonen, J., Sacks, R. M., Takemoto, E. E., Hooker, E. R., Dieckmann, N. F., Harrod, C. S., & Thornburg, K. L. R. (2018) · Childhood Obesity · doi:10.1089/chi.2017.0290 · Cited by 5 · see citing works
“Pathways stemming from these prenatally induced characteristics may underlie the diabetes phenotype that occurs in the absence of obesity.(26) Moreover, the BMI-independent pathway may be heterogeneous, involving multiple prenatally induced pathways that can be studied in populations with repeated measurements of body…”
BackgroundMir, S. A., Narasimhan, K., Annadurai, J. K., Vaitheeswari, Ji, S., Cameron‐Smith, D., Eriksson, J. G., Leow, M. K., Wenk, M. R., Torta, F. T., et al. (2025) · Diabetes · doi:10.2337/db25-0010 · Cited by 4 · see citing works
Padmakumar, R., Pai, M., Shams, F., Kumar, P. M., Shaji, P. G., Anithadevi, T., J, S. P., & Krishna, V. (2015) · Surgical Innovation · doi:10.1177/1553350615589523 · Cited by 4 · see citing works
“Nonobese T2DM patients may progress to insulin treatment more rapidly than obese patients.(1) According to the International Diabetes Federation, metabolic surgery is an appropriate treatment for people with T2DM and body mass index (BMI) >35 kg/m(2) who fail to achieve the recommended treatment targets with medical t…”
BackgroundEffect of Weight Change on the Progression to Diabetes among Non-obese Individuals
Seki, R., Inoue, K., Takao, S., & Akimoto, K. (2018) · Annals of Biomedical Research · doi:10.61545/abr-1-102 · Cited by 4 · see citing works
“The development of T2DM in non-obese individuals has been reported to be characterized by impaired pancreatic insulin secretion and less severe insulin resistance, as compared with obese individuals [13,14].”
BackgroundInfluentialda Costa, T. S., Pontes, J. G. D. M., Delgado, G. G., Omage, F. B., Santana, G. O., Rodrigues, G. T., Scervino, M. V. M., Pithon‐Curi, T. C., Cruzat, V. F., Bazotte, R. B., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118826 · Cited by 3 · see citing works
Phenotypical Classification of Type 2 Diabetes Mellitus
Adhikari, P., Devang, N., & Nandini, M. (2018) · Journal of Endocrinology and Diabetes · doi:10.15226/2374-6890/5/6/001119 · Cited by 3 · see citing works
“Causes are genetics, sedentary lifestyle, autoimmunity, stress, inflammation and fatty liver [4].”
BackgroundFang, C. Y., Rao, A. D., Handorf, E. A., Deng, M., Cheung, P., & Tseng, M. (2024) · Annals of Behavioral Medicine · doi:10.1093/abm/kaae056 · Cited by 2 · see citing works
Zinn, C., Campbell, J. L., Fraser, L., Davies, G., Hawkins, M., Currie, O., Cannons, J., Unwin, D., Crofts, C., Stewart, T., et al. (2025) · Nutrients · doi:10.3390/nu17243953 · Cited by 2 · see citing works
“Driven largely by unhealthy lifestyle factors such as energy-dense, nutrient-poor diets, excessive alcohol consumption, smoking, and physical inactivity, these behaviours contribute to insulin resistance, hyperinsulinemia, obesity, and ultimately T2D [3–7].”
Cai, Y., Zhao, N., Mi, J., Du, H., Wan, Z., Liu, Z., Pan, Y., Yan, X., Fan, Z., Li, J., et al. (2026) · Insights into Imaging · doi:10.1186/s13244-026-02206-7 · Cited by 4 · see citing works
“NIDDM is widely acknowledged as having heterogeneous roots [27], although epidemiological studies consistently show a strong correlation with overnutrition [28, 29].”
Interaction entre facteurs d’environnement et fonds génétique dans le diabète de type 2
Bernard, C., Della‐Zuana, O., & Ktorza, A. (2013) · médecine/sciences · doi:10.1051/medsci/2013298020 · Cited by 2 · see citing works
Role of Adenosine Deaminase and Insulin in Type 2 Diabetes Mellitus in Eastern India
Malathi, R. (2017) · Journal of Medical Science And clinical Research · doi:10.18535/jmscr/v5i4.123 · Cited by 2 · see citing works
Oo, S., Rakhmanin, Y. A., Zi, Z., Аксенова, М. Г., Kirillov, A. V., Бурд, С. Г., & Ilyukova, I. I. (2018) · Hygiene and Sanitation · doi:10.18821/0016-9900-2018-97-3-197-203 · Cited by 2 · see citing works
Yamaguchi, F., Akieda‐Asai, S., Nakamura, E., Uchida, H., Yamashita, A., & Date, Y. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.03.009 · Cited by 1 · see citing works
“However, a cohort study conducted in northern European countries [5] showed that 20% of patients with diabetes were nonobese, with a BMI 25.”
Tripathi, P., VYAWAHARE, A. R., KADAM, N. S., Tiwari, D., Sharma, B., Kathrikolly, T., GANLA, M. H., & Saboo, B. (2025) · Journal of Diabetes Research · doi:10.1155/jdr/3783469 · Cited by 1 · see citing works
“The prevalence of Type 2 diabetes (T2D) in India is rising, largely due to the global obesity epidemic a ff ecting both developed and developing countries [1].”
Metz, C. N., Hudson, L., & Pavlov, V. A. (2016) · Springer eBooks · doi:10.1007/978-3-319-20797-1_11-1 · Cited by 1 · see citing works
Li, L., Wang, Z., Ruan, H., Zhang, M., Zhou, L., Wei, X., Zhu, Y., Wei, J., Chen, X., & He, S. (2022) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2022.109213 · Cited by 1 · see citing works
Adhikary, P., Banerjee, M., Banerjee, S., Kaiser, S., Gargari, P., Chowdhury, J., & Chowdhury, S. (2023) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-023-01184-6 · Cited by 1 · see citing works
Health in an ecological civilization towards a process understanding of the dialectics of health
McLaren, G. (2019) · Swinburne figshare (Swinburne University of Technology) · Cited by 1 · see citing works
Metz, C. N., Hudson, L., & Pavlov, V. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-18741-9_11 · Cited by 1 · see citing works
Lundgren, V. (2013) · Työväentutkimus Vuosikirja · Cited by 1 · see citing works
Mosa, R. (2017) · The University of Queensland · doi:10.14264/uql.2017.998
Is Urinary Calprotectin a Useful Tool to Detect the Therapeutic Control of Type II Diabetes?
Sayed, H. A., Ghabra, T., Marwan Abdulrahman Mohammed, B., Rafeeq, M. M., & Eid, S. S. (2019) · International Journal of Pharmacology · doi:10.3923/ijp.2019.295.300
Shaibu, S., Longdet, I. Y., Luka, C. D., Ortswen, J. F., Eneojo-Abah, G., Oguche, J., Salami, T., Akor, S. E., & Abah, S. E. (2020) · medRxiv · doi:10.1101/2020.09.09.20186791
“INTRODUCTION Diabetes is a chronic metabolic disorder characterized with an abnormally high sugar level in the blood and are of different types, type-1-diabetes; type-2diabetes; gestational diabetes and autoimmune diabetes(1,2).”
BackgroundEffects of exercise on reducing diabetes risk in Korean women according to menopausal status
Cho, J. H., Kwon, H., Park, S. E., Yoo, J., Han, K., Rhee, E., & Lee, W. (2022) · Cardiovascular Prevention and Pharmacotherapy · doi:10.36011/cpp.2022.4.e8
“Patients with a nonobese type 2 diabetes phenotype are characterized by a disproportionate decrease in insulin secretion, more beta-cell dysfunction, and less insulin resistance than in obese patients [37], which is widely known as a component of the pathophysiology of type 2 diabetes [38].”
BackgroundSyndromes of severe insulin resistance: lessons from nature
Krentz, A. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91707-0.00005-x
Non-obese genetic type 2 diabetes causes brain and behavioral hallmarks of chronic stressPreprint
Romaní‐Pérez, M., Henry, M. S., Pajot, C., Bailbé, D., Brossaud, J., Buyannemekh, K., Prado, L., Foury, A., Rincel, M., Lépinay, A. L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.08.658427
“Given that not all T2D patients are overweight [18] it is essential to explore lean diabetic animal models to better understand the link between T2D and emotional disorders.”
Kanazashi, M., Tanaka, M., & Tsumori, T. (2026) · Microcirculation · doi:10.1111/micc.70054
“First, we employed a non-obese T2DM model, which is more common in Asian populations [52]; therefore, the present findings cannot be directly generalized to patients with type 1 diabetes or obese type 2 diabetes mellitus.”
Akar, E. A. (2022) · theses.fr (ABES) · doi:10.70675/a7b15e3fz84e7z4915z9447zc112181e06e4
Yamaguchi, F., Kiyonaga, T., Nitta, S., Yoshinaga, N., Akieda‐Asai, S., Date, Y., & Sawada, H. (2026) · Journal of Public Health Research · doi:10.1177/22799036261471211
“9 Obesity is conventionally defined as BMI ≥ 30 kg/m 2 by the World Health Organization (WHO), whereas the Japan Society for the Study of Obesity uses a lower threshold of BMI ≥ 25 kg/m 2 .”
- Authors
- Vaag, A., & Lund, S. S.
- Affiliations
- Lund University (SE)
- ORCID
- Vaag, Allan
- Venue
- Applied Physiology, Nutrition, and Metabolism
- Publisher
- Canadian Science Publishing
- Published
- 2007-10
- Volume
- 32
- Issue
- 5
- Pages
- 912-920
- ISSN
- 1715-5312 (ISSN-L)
- 1715-5320
- OpenAlex
- W2158286241
- Cited by
- 89
- References
- 51
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 10 · 2018: 9 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 3
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Applied Physiology, Nutrition, and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- European Commission
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, non-obese patients, prediabetes, insulin secretion, insulin resistance, cardiovascular risk, low birth weight, latent autoimmune diabetes in adults, glutamic acid decarboxylase antibodies, adiposity, lifestyle intervention, metformin, insulin therapy, genetic risk factors
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Phenotype, Prediabetic State
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
