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Smoking is associated with impaired glucose regulation and a decrease in insulin sensitivity and the disposition index in first-degree relatives of type 2 diabetes subjects independently of the presence of metabolic syndrome

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Abstract

The aim of this study was to investigate glucose tolerance, insulin secretion and insulin resistance according to smoking habits in first-degree relatives of type 2 diabetes patients, a population at high risk for developing diabetes. One thousand three hundred (646 females and 654 males) subjects underwent an oral glucose tolerance test (OGTT) to investigate their glucose metabolism and answered questionnaires about their lifestyle habits. Smoker subjects showed significant impairment compared with non-smoker subjects in 2-h post-oral glucose tolerance test (2hOGTT, 129.3 ± 40.2 vs. 117.7 ± 37.6 mg/dl, p < 0.001), the OGTT insulin sensitivity (386.3 ± 54.9 vs. 400.5 ± 53.4 ml min−1 m2, p < 0.01) method and the insulin sensitivity and secretion index-2 (ISSI-2, 1.7 ± 0.8 vs. 2.0 ± 1.0, p < 0.005). Metabolic syndrome (MS) was higher in the smoker than in the non-smoker group (46.5 vs. 29.7 %, p < 0001), and smokers were more sedentary than non-smokers (3.94 ± 3.77 vs. 4.86 ± 4.41 h/week, p < 0.001). Smokers showed an increased risk of impaired glucose regulation (IGR: impaired glucose tolerance or diabetes mellitus) with a hazard ratio (HR) adjusted by gender, metabolic syndrome and physical activity of 1.78, 95 % CI 1.27–2.47 (p < 0.001). The association between smoking and MS conferred a risk of IGR that was five times higher (HR 5.495, 95 % CI 4.07–7.41, p < 0.001). Smoking habit was a significant explanatory variable in a multiple forward stepwise regression analysis performed using 2hOGTT and ISSI-2 as dependent variables (p < 0.0001, R = 0.313 and p < 0.0001, R = 0.347, respectively). In conclusions, our results show that tobacco smoking is tightly associated with impairments in glucose metabolism and insulin sensitivity and insulin secretion.

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Abbreviations

FDR:

First-degree relatives

MS:

Metabolic syndrome

IGR:

Impaired glucose regulation

IFG:

Impaired fasting glucose

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

QUICKI:

Quantitative insulin sensitivity check index

OGIS:

OGTT insulin sensitivity

ISSI-2:

Insulin sensitivity and secretion index-2

F-ph Ins. Secr:

First-phase insulin secretion

P.A.:

Physical activity

References

  1. Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J (2007) Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 298:2654–2664

    Article  PubMed  CAS  Google Scholar 

  2. Zhang L, Curhan GC, Hu FB, Rimm EB, Forman JP (2011) Association between passive and active smoking and incident type 2 diabetes in women. Diabetes Care 34:892–897

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kowall B, Rathmann W, Strassburger K, Heier M, Holle R, Thorand B, Giani G, Peters A, Meisinger C (2010) Association of passive and active smoking with incident type 2 diabetes mellitus in the elderly population: the KORA S4/F4 cohort study. Eur J Epidemiol 25:393–402

    Article  PubMed  CAS  Google Scholar 

  4. Nakanishi N, Takatorige T, Suzuki K (2005) Cigarette smoking and the risk of the metabolic syndrome in middle-aged Japanese male office workers. Ind Health 43:295–301

    Article  PubMed  Google Scholar 

  5. Eliasson B, Attvall S, Taskinen MR, Smith U (1994) The insulin resistance syndrome in smokers is related to smoking habits. Arterioscler Thromb 14:1946–1950

    Article  PubMed  CAS  Google Scholar 

  6. Ronnemaa T, Ronnemaa EM, Puukka P, Pyorala K, Laakso M (1996) Smoking is independently associated with high plasma insulin levels in nondiabetic men. Diabetes Care 19:1229–1232

    Article  PubMed  CAS  Google Scholar 

  7. Targher G, Alberiche M, Zenere MB, Bonadonna RC, Muggeo M, Bonora E (1997) Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82:3619–3624

    PubMed  CAS  Google Scholar 

  8. Cena H, Fonte ML, Turconi G (2011) Relationship between smoking and metabolic syndrome. Nutr Rev 69:745–753

    Article  PubMed  Google Scholar 

  9. Corwin EJ, McCoy CS, Whetzel CA, Ceballos RM, Klein LC (2006) Risk indicators of metabolic syndrome in young adults: a preliminary investigation on the influence of tobacco smoke exposure and gender. Heart Lung 35:119–129

    Article  PubMed  Google Scholar 

  10. Chen CC, Li TC, Chang PC, Liu CS, Lin WY, Wu MT, Li CI, Lai MM, Lin CC (2008) Association among cigarette smoking, metabolic syndrome, and its individual components: the metabolic syndrome study in Taiwan. Metabolism 57:544–548

    Article  PubMed  CAS  Google Scholar 

  11. Berlin I (2008) Smoking-induced metabolic disorders: a review. Diabetes Metab 34:307–314

    Article  PubMed  Google Scholar 

  12. Bartler PJ (2011) The causes and consequences of low levels of high density lipoproteins in patients with diabetes. Diabetes Metab J 35:101–106

    Article  Google Scholar 

  13. Rafalson L, Donahue RP, Dmochowski J, Rejman K, Dorn J, Trevisan M (2009) Cigarette smoking is associated with conversion from normoglycemia to impaired fasting glucose: the Western New York Health Study. Ann Epidemiol 19:365–371

    Article  PubMed  PubMed Central  Google Scholar 

  14. Oda E (2012) Metabolic syndrome: its history, mechanisms, and limitations. Acta Diabetol 49:89–95

    Article  PubMed  CAS  Google Scholar 

  15. Daniele G, Guardado Mendoza R, Winnier D, Fiorentino V, Pengou Z, Cornell J, Andreozzi F, Jenkinson C, Cersosimo E, Federici M, Tripathy D, Folli F (2014) The inflammatory status score including IL6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51:123–131

    Article  PubMed  CAS  Google Scholar 

  16. Meshkani R, Zargari M, Larijani B (2011) The relationship between uric acid and metabolic syndrome in normal glucose tolerance and normal fasting glucose subjects. Acta Diabetol 48:88–89

    Article  Google Scholar 

  17. Fadini GP, Vigili De Kreutzenberg S, Gjini R, Avogaro A (2011) The metabolic syndrome influences the response to incretin-based therapies. Acta Diabetol 48:219–225

    Article  PubMed  CAS  Google Scholar 

  18. Topolski TD, LoGerfo J, Patrick DL, Williams B, Walwick J, Patrick MMB (2006) The rapid assessment of physical activity (RAPA) among older adults. Prev Chronic Dis 3:1–8

    Google Scholar 

  19. Monti LD, Setola E, Lucotti PCG, Marrocco-Trischitta MM, Comola M, Galluccio E, Poggi A, Mammì S, Catapano AL, Comi G, Chiesa R, Bosi E, Piatti PM (2012) Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomised, double-blind, placebo-controlled trial. Diabetes Obes Metab 14:893–900

    Article  PubMed  CAS  Google Scholar 

  20. Alberti KG, Zimmet P, Shaw J (2005) The metabolic syndrome–a new worldwide definition. IDF epidemiology task force consensus group. Lancet 366:1059–1062

    Article  PubMed  Google Scholar 

  21. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410

    Article  PubMed  CAS  Google Scholar 

  22. Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessment of insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548

    Article  PubMed  CAS  Google Scholar 

  23. Pacini G, Mari A (2003) Methods for clinical assessment of insulin sensitivity and β-cell function. Best Pract Res Clin Endocrinol Metab 17:30–322

    Article  Google Scholar 

  24. Dalfrà MG, Pacini G, Parretti E, Ragazzi E, Mello G, Lapolla A (2011) Elevated insulin sensitivity and β -cell function during pregnancy in mothers of growth-restricted newborns. Am J Physiol Metab 30:E25–E30

    Google Scholar 

  25. Stadler M, Tomann L, Storka A, Wolzt M, Peric S, Bieglmayer C, Pacini G, Dickson SL, Brath H, Bech P, Prager R, Korbonits M (2014) Effects of smoking cessation on b-cell function, insulin sensitivity, body weight, and appetite. Eur J Endocrinol 170:219–227

    Article  PubMed  CAS  Google Scholar 

  26. Stumvoll M, Van Haeften T, Fritsche A, Gerich J (2001) Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care 24:796–797

    Article  PubMed  CAS  Google Scholar 

  27. Retnakaran R, Qi Y, Goran MI, Hamilton J (2009) Evaluation of proposed oral disposition index measures in relation to the actual disposition index. Diabet Med 26:1198–1203

    Article  PubMed  CAS  Google Scholar 

  28. Zinman B, Harris SB, Neuman J, Gerstein HC, Retnakaran RR, Raboud J, Qi Y, Hanley AJG (2010) Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet 376:103–111

    Article  PubMed  CAS  Google Scholar 

  29. Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM (1992) Insulin resistance and cigarette smoking. Lancet 339:1128–1130

    Article  PubMed  CAS  Google Scholar 

  30. Sonmez A, Dogru T, Yilmaz MI, Tasci I, Ocal R, Ozgurtas T, Kilic S, Erbil K, Erikci S, Tsao P (2006) Adiponectin and insulin resistance in young and healthy smokers. Endocr J 53:729–734

    Article  PubMed  CAS  Google Scholar 

  31. Bruin JE, Petre MA, Raha S, Morrison KM, Gerstein HC, Holloway AC (2008) Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction. PLoS ONE 3:e3371

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mennen LI, Balkau B, Charles MA, D’Hour A, le Mauff JM (1999) Gender differences in the relation between fibrinogen, tissue-type plasminogen activator antigen and markers of insulin resistance: effects of smoking. D.E.S.I.R. Study Group. Data from an Epidemiological Study on Insulin Resistance Syndrome. Thromb Haemost 82:1011–1106

    Google Scholar 

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Acknowledgments

We acknowledge the skilful help of Miss Letizia Sonia of the Diabetic Outpatient Clinic, Internal Medicine Department, IRCCS San Raffaele, Milan, Italy.

Conflict of interest

PierMarco Piatti, Emanuela Setola, Elena Galluccio, Sabrina Costa, Barbara Fontana Michela Stuccillo, Valentina Crippa, Alberto Cappelletti, Alberto Margonato, Emanuele Bosi, Lucilla D Monti declare that they have not conflict of interest.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed Consent

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Cardio-Metabolism and Clinical Trials Unit, Diabetes Research Institute, Division of Immunology, Transplantation and Infective Diseases, Department of Internal Medicine, IRCCS San Raffaele, Milan, Italy

    PierMarco Piatti, Emanuela Setola, Michela Stuccillo, Valentina Crippa & Emanuele Bosi

  2. Cardio-Diabetes and Core Lab Unit, Diabetes Research Institute, Division of Immunology, Transplantation and Infective Diseases, Department of Internal Medicine, IRCCS San Raffaele, Milan, Italy

    Elena Galluccio, Sabrina Costa, Barbara Fontana, Emanuele Bosi & Lucilla D. Monti

  3. Cardiac Clinic Unit, Cardio-Thoraco-Vascular Department, IRCCS San Raffaele, Milan, Italy

    Alberto Cappelletti & Alberto Margonato

Authors
  1. PierMarco Piatti
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  2. Emanuela Setola
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  3. Elena Galluccio
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  4. Sabrina Costa
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  5. Barbara Fontana
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Correspondence to PierMarco Piatti.

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Piatti, P., Setola, E., Galluccio, E. et al. Smoking is associated with impaired glucose regulation and a decrease in insulin sensitivity and the disposition index in first-degree relatives of type 2 diabetes subjects independently of the presence of metabolic syndrome. Acta Diabetol 51, 793–799 (2014). https://doi.org/10.1007/s00592-014-0599-6

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  • DOI: https://doi.org/10.1007/s00592-014-0599-6

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