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Pancreatic β-cell dysfunction in normoglycemic patients and risk factors

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Abstract

Aims

To evaluate pancreatic β-cell function (βf) in patients with normoglycemia (NG) and normal glucose tolerance (NGT) and related risk factors.

Methods

An observational and comparative study in 527 patients with NG and NGT that were divided by quartiles of βf according to the disposition index derived from OGTT. Anthropometrical, clinical, nutritional, and biochemical variables were measured and associated with βf.

Results

Quartiles of βf were Q1 = DI < 1.93 n = 131, Q2 = DI 1.93–2.45 n = 134, Q3 = DI 2.46–3.1 n = 133, and Q4 = DI > 3.1 n = 129. There was a progressive reduction in pancreatic β-cell function and it is negatively correlated with age, weight, BMI, total body fat and visceral fat, waist circumference, total cholesterol, LDL, and triglycerides (p < 0.01). Glucose levels during OGTT had a negative correlation with βf; the product of fasting glucose by 1-h glucose had the best correlation with βf (r = 0.611, p < 0.001) and was the best predictor of βdf (AUC 0.816, CI 95% 0.774–0.857), even better than 1-h glucose (r = 0.581, p < 0.001). Energy, fat, and carbohydrate intake were negatively correlated with βf (p < 0.05). Glucose levels at 1-h OGTT > 110 mg/dl were positively associated with pancreatic βdf (OR 6.85, CI 95% 3.86–12.4). In the multivariate analysis, glucose levels during OGTT, fasting insulin, and BMI were the main factors associated with βf.

Conclusions

A subgroup of patients with NG and NGT may have a loss of 40% of their βf. Factors related to this βdf were age, adiposity, glucose during OGTT, and the product of fasting and 1-h glucose, as well as food intake.

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References

  1. Alegre-Diaz J, Herrington W, Lopez-Cervantes M et al (2016) Diabetes and cause-specific mortality in Mexico City. N Engl J Med 375(20):1961–1971

    Article  Google Scholar 

  2. Rangel-Baltazar E, Cuevas-Nasu L, Shamah-Levy T et al (2019) Association between high waist-to-height ratio and cardiovascular risk among adults sampled by the 2016 half-way national health and nutrition survey in Mexico (ENSANUT MC 2016). Nutrients 11(6):1402

    Article  Google Scholar 

  3. Villalpando S, de la Cruz V, Rojas R et al (2010) Prevalence and distribution of type 2 diabetes mellitus in Mexican adult population: a probabilistic survey. Salud Publica Mex 52(Suppl 1):S19–S26

    Article  Google Scholar 

  4. Cho NH, Shaw JE, Karuranga S et al (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281

    Article  CAS  Google Scholar 

  5. Classification and Diagnosis of Diabetes (2019) Standards of medical care in diabetes. Diabetes Care 42(Suppl 1):S13–S28

    Google Scholar 

  6. DeFronzo RA (2009) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links The Claude Bernard Lecture. Diabetologia 53(7):1270–1287

    Article  Google Scholar 

  7. Defronzo RA (2009) Banting Lecture From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58(4):773–795

    Article  CAS  Google Scholar 

  8. Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS; DPT-1 Study Group (2010) Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes 59(3):679–685

    Article  CAS  Google Scholar 

  9. Guardado-Mendoza R, Davalli AM, Chavez AO et al (2009) Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. Proc Natl Acad Sci USA 106(33):13992–13997

    Article  CAS  Google Scholar 

  10. Kahn SE, Zraika S, Utzschneider KM, Hull RL (2009) The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia 52(6):1003–1012

    Article  CAS  Google Scholar 

  11. Guardado Mendoza R, Perego C, Finzi G et al (2015) Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas). Diabetologia 58(8):1814–1826

    Article  CAS  Google Scholar 

  12. Folli F, La Rosa S, Finzi G et al (2018) Pancreatic islet of Langerhans’ cytoarchitecture and ultrastructure in normal glucose tolerance and in type 2 diabetes mellitus. Diabetes Obes Metab 20(Suppl 2):137–144

    Article  CAS  Google Scholar 

  13. Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K (2009) Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care 32(3):439–444

    Article  CAS  Google Scholar 

  14. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA (2005) beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 90(1):493–500

    Article  CAS  Google Scholar 

  15. Ahren B (2009) Beta- and alpha-cell dysfunction in subjects developing impaired glucose tolerance: outcome of a 12-year prospective study in postmenopausal Caucasian women. Diabetes 58(3):726–731

    Article  CAS  Google Scholar 

  16. Daniele G, Guardado Mendoza R, Winnier D et al (2014) The inflammatory status score including IL-6, TNF-alpha, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51(1):123–131

    Article  CAS  Google Scholar 

  17. Guardado-Mendoza R, Chavez AO, Jimenez-Ceja LM et al (2017) Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus. Acta Diabetol 54(1):53–61

    Article  CAS  Google Scholar 

  18. DeFronzo RA (2004) Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 88(4):787–835

    Article  CAS  Google Scholar 

  19. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA (2004) Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia 47(1):31–39

    Article  CAS  Google Scholar 

  20. Hannon TS, Kahn SE, Utzschneider KM et al (2018) Review of methods for measuring beta-cell function: design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab 20(1):14–24

    Article  CAS  Google Scholar 

  21. Salunkhe VA, Veluthakal R, Kahn SE, Thurmond DC (2018) Novel approaches to restore beta cell function in prediabetes and type 2 diabetes. Diabetologia 61(9):1895–1901

    Article  CAS  Google Scholar 

  22. Matveyenko AV, Butler PC (2006) Beta-cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in type 2 diabetes. Diabetes 55(7):2106–2114

    Article  CAS  Google Scholar 

  23. Camastra S, Manco M, Mari A et al (2005) Beta-cell function in morbidly obese subjects during free living: long-term effects of weight loss. Diabetes 54(8):2382–2389

    Article  CAS  Google Scholar 

  24. Camastra S, Manco M, Mari A et al (2007) Beta-cell function in severely obese type 2 diabetic patients: long-term effects of bariatric surgery. Diabetes Care 30(4):1002–1004

    Article  CAS  Google Scholar 

  25. Furukawa H, Carroll RJ, Swift HH, Steiner DF (1999) Long-term elevation of free fatty acids leads to delayed processing of proinsulin and prohormone convertases 2 and 3 in the pancreatic beta-cell line MIN6. Diabetes 48(7):1395–1401

    Article  CAS  Google Scholar 

  26. Biggs ML, Mukamal KJ, Luchsinger JA et al (2010) Association between adiposity in midlife and older age and risk of diabetes in older adults. JAMA 303(24):2504–2512

    Article  CAS  Google Scholar 

  27. Niswender KD, Magnuson MA (2007) Obesity and the beta cell: lessons from leptin. J Clin Invest 117(10):2753–2756

    Article  CAS  Google Scholar 

  28. Abdul-Ghani MA, Jayyousi A, DeFronzo RA, Asaad N, Al-Suwaidi J (2019) Insulin resistance the link between T2DM and CVD: basic mechanisms and clinical implications. Curr Vasc Pharmacol 17(2):153–163

    Article  CAS  Google Scholar 

  29. Di Pino A, DeFronzo RA (2019) Insulin resistance and atherosclerosis: implications for insulin sensitizing agents. Endocr Rev. https://doi.org/10.1210/er.2018-00141

    Article  Google Scholar 

  30. Jagannathan R, Buysschaert M, Medina JL et al (2018) The 1-h post-load plasma glucose as a novel biomarker for diagnosing dysglycemia. Acta Diabetol 55(6):519–529

    Article  CAS  Google Scholar 

  31. Abdul-Ghani MA, Lyssenko V, Tuomi T, Defronzo RA (2010) Groop L The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes. Diabetes Metab Res Rev 26(4):280–286

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all the personnel from the Metabolic Research Laboratory at the University of Guanajuato.

Funding

Part of this work was funded by University of Guanajuato through the Research Projects 010/2014 and 018/2015, assigned to Rodolfo Guardado-Mendoza. The funding part was not involved in the design, data collection, analysis, and interpretation, as well as in the writing and submission of the manuscript.

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Authors and Affiliations

  1. Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Guanajuato, Mexico

    Luis H. Vilchis-Flores, Georgina A. Barajas-Medina, Ana Karen Villa-Martínez, Sara S. Salazar López, Gabriela A. Luna-Patiño, María Elena Quiroz-Hernández, María Alejandra Guzmán-Vanegas, Rafael Rodríguez-Cortes, Fabiola Angulo-Romero, Ma. De Lourdes Reyes-Escogido & Lilia M. Jiménez-Ceja

  2. Hospital Regional de Alta Especialidad del Bajío, León, Guanajuato, Mexico

    Alberto Aguilar-García

  3. Dipartimento di Scienze della Salute, Universita’ degli Studi di Milano, Milan, Italy

    Franco Folli

  4. Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato / Hospital Regional de Alta Especialidad del Bajío, Col. San Carlos la Roncha, 37660, León, Guanajuato, Mexico

    Rodolfo Guardado-Mendoza

Authors
  1. Luis H. Vilchis-Flores
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  2. Georgina A. Barajas-Medina
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  11. Alberto Aguilar-García
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Contributions

RGM and LHVH designed the study; RGM, SSSL, GABM, AKVM, GALP, MEQH, MAGV, RRC, and FAR generated the data; LHVH, RGM, MLRE, AAG, and FF analyzed and interpreted the data. All the authors wrote and reviewed the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rodolfo Guardado-Mendoza.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard statement

The protocol was approved by the Institutional Research and Ethical Committee at the University of Guanajuato with the number CIBIUG-P40-2016. All procedures performed were in accordance with the ethical standards of the Institutional Research and Ethical Committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study. The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Informed consent

Informed consent was obtained from all the participants before their inclusion in the present study.

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Vilchis-Flores, L.H., Barajas-Medina, G.A., Villa-Martínez, A.K. et al. Pancreatic β-cell dysfunction in normoglycemic patients and risk factors. Acta Diabetol 56, 1305–1314 (2019). https://doi.org/10.1007/s00592-019-01411-9

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