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Presence of diabetes-specific autoimmunity in women with gestational diabetes mellitus (GDM) predicts impaired glucose regulation at follow-up

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Abstract

Purpose

Gestational diabetes mellitus (GDM) is the most frequent complication of pregnancy; around 10% of GDM cases may be determined by autoimmunity, and our aims were to establish the role of autoimmunity in a population of Sardinian women affected by GDM, to find predictive factors for autoimmune GDM, and to determine type 1 diabetes (T1D) auto-antibodies (Aabs) together with glucose tolerance after a mean 21.2 months of follow-up.

Methods

We consecutively recruited 143 women affected by GDM and 60 without GDM; clinical data and pregnancy outcomes were obtained by outpatient visit or phone recall. T1D auto-antibodies GADA, IA2-A, IAA, ZnT8-A were measured in the whole population at baseline, and in the Aab-positive women at follow-up.

Results

The overall prevalence of autoimmunity was 6.4% (13/203). No significant difference was found in the prevalence of auto-antibodies between GDM (5.6%) and control (8.3%) women, neither in antibody titres. Highest titres for GADA and ZnT8-A were observed in the control group; no phenotypic factors were predictive for autoimmune GDM. Diabetes-related autoantibodies were still present in all the GDM women at follow-up, and their presence was associated with a 2.65 (p < 0.0016) relative risk (RR) of glucose impairment.

Conclusion

We observed a low prevalence (5.6%) of diabetes-related autoimmunity in our GDM cohort, consistent with the prevalence reported in previous studies. It was not possible to uncover features predictive of autoimmune GDM. However, given the significant risk of a persistent impaired glycemic regulation at follow-up, it is advisable to control for glucose tolerance in GDM women with diabetes-related autoimmunity.

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References

  1. American Diabetes Association (2017) Standards of medical care in diabetes-2017: summary of revisions. Diabetes Care 40:S4–S5

    Article  Google Scholar 

  2. Buchanan TA, Xiang A, Kjos SL, Watanabe R (2007) What is gestational diabetes? Diabetes Care 30(Suppl 2):S105–S111

    Article  PubMed  CAS  Google Scholar 

  3. Ferrara A, Hedderson MM, Quesenberry CP, Selby JV (2002) Prevalence of gestational diabetes mellitus detected by the national diabetes data group or the carpenter and coustan plasma glucose thresholds. Diabetes Care 25:1625–1630

    Article  PubMed  Google Scholar 

  4. O’Sullivan EP, Avalos G, O’Reilly M, Dennedy MC, Gaffney G, Dunne F (2011) Atlantic diabetes in pregnancy (DIP): the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. Diabetologia 54:1670–1675

    Article  PubMed  Google Scholar 

  5. Galtier F (2010) Definition, epidemiology, risk factors. Diabetes Metab 36:628–651

    Article  PubMed  CAS  Google Scholar 

  6. Sacks DA, Hadden DR, Maresh M, Deerochanawong C, Dyer AR, Metzger BE et al (2012) Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care 35:526–528

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lapolla A, Dalfra MG, Lencioni C, Di Cianni G (2004) Epidemiology of diabetes in pregnancy: a review of Italian data. Diabetes Nutr Metab 17:358–367

    PubMed  CAS  Google Scholar 

  8. Murgia C, Berria R, Minerba L, Malloci B, Daniele C, Zedda P et al (2006) Gestational diabetes mellitus in Sardinia: results from an early, universal screening procedure. Diabetes Care 29:1713–1714

    Article  PubMed  Google Scholar 

  9. Di Cianni G, Seghieri G, Lencioni C, Cuccuru I, Anichini R, De Bellis A et al (2007) Normal glucose tolerance and gestational diabetes mellitus: what is in between? Diabetes Care 30:1783–1788

    Article  PubMed  CAS  Google Scholar 

  10. Lapolla A, Dalfra MG, Fedele D (2009) Diabetes related autoimmunity in gestational diabetes mellitus: is it important? Nutr Metab Cardiovasc Dis 19:674–682

    Article  PubMed  CAS  Google Scholar 

  11. Nilsson C, Ursing D, Torn C, Aberg A, Landin-Olsson M (2007) Presence of GAD antibodies during gestational diabetes mellitus predicts type 1 diabetes. Diabetes Care 30:1968–1971

    Article  PubMed  Google Scholar 

  12. Yu SH, Park S, Kim HS, Park SY, Yim CH, Han KO et al (2009) The prevalence of GAD antibodies in Korean women with gestational diabetes mellitus and their clinical characteristics during and after pregnancy. Diabetes Metab Res Rev 25:329–334

    Article  PubMed  CAS  Google Scholar 

  13. Jarvela IY, Juutinen J, Koskela P, Hartikainen AL, Kulmala P, Knip M et al (2006) Gestational diabetes identifies women at risk for permanent type 1 and type 2 diabetes in fertile age: predictive role of autoantibodies. Diabetes Care 29:607–612

    Article  PubMed  CAS  Google Scholar 

  14. Cambuli VM, Incani M, Cossu E, Congiu T, Scano F, Pilia S et al (2010) Prevalence of type 1 diabetes autoantibodies (GADA, IA2, and IAA) in overweight and obese children. Diabetes Care 33:820–822

    Article  PubMed  Google Scholar 

  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  16. Cucca F, Muntoni F, Lampis R, Frau F, Argiolas L, Silvetti M et al (1993) Combinations of specific DRB1, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Hum Immunol 37:85–94

    Article  PubMed  CAS  Google Scholar 

  17. Zavattari P, Lampis R, Mulargia A, Loddo M, Angius E, Todd JA et al (2000) Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia. Hum Mol Genet 9:2967–2972

    Article  PubMed  CAS  Google Scholar 

  18. Bruno G, Maule M, Biggeri A, Ledda A, Mannu C, Merletti F et al (2013) More than 20 years of registration of type 1 diabetes in Sardinian children: temporal variations of incidence with age, period of diagnosis, and year of birth. Diabetes 62:3542–3546

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Murgia C, Orru M, Portoghese E, Garau N, Zedda P, Berria R et al (2008) Autoimmunity in gestational diabetes mellitus in Sardinia: a preliminary case-control report. Reprod Biol Endocrinol 6:24

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dozio N, Beretta A, Belloni C, Castiglioni M, Rosa S, Bosi E et al (1997) Low prevalence of islet autoantibodies in patients with gestational diabetes mellitus. Diabetes Care 20:81–83

    Article  PubMed  CAS  Google Scholar 

  21. Lapolla A, Fedele D, Pedini B, Dal Fra MG, Sanzari M, Masin M et al (2002) Low frequency of autoantibodies to islet cell, glutamic acid decarboxylase, and second-islet antigen in patients with gestational diabetes mellitus: a follow-up study. Ann N Y Acad Sci 958:263–266

    Article  PubMed  CAS  Google Scholar 

  22. Bo S, Menato G, Pinach S, Signorile A, Bardelli C, Lezo A et al (2003) Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens. Diabet Med 20:64–68

    Article  PubMed  CAS  Google Scholar 

  23. Vandewalle CL, Falorni A, Svanholm S, Lernmark A, Pipeleers DG, Gorus FK (1995) High diagnostic sensitivity of glutamate decarboxylase autoantibodies in insulin-dependent diabetes mellitus with clinical onset between age 20 and 40 years. The Belgian Diabetes Registry. J Clin Endocrinol Metab 80:846–851

    PubMed  CAS  Google Scholar 

  24. Dereke J, Nilsson C, Landin-Olsson M, Hillman M (2012) Prevalence of zinc transporter 8 antibodies in gestational diabetes mellitus. Diabet Med 29:e436–e439

    Article  PubMed  CAS  Google Scholar 

  25. Rudland VL, Pech C, Harding AJ, Tan K, Lee K, Molyneaux L et al (2015) Zinc transporter 8 autoantibodies: what is their clinical relevance in gestational diabetes? Diabet Med 32:359–366

    Article  PubMed  CAS  Google Scholar 

  26. de Leiva A, Mauricio D, Corcoy R (2007) Diabetes-related autoantibodies and gestational diabetes. Diabetes Care 30(Suppl 2):S127–S133

    Article  PubMed  Google Scholar 

  27. Incani M, Serafini C, Satta C, Perra L, Scano F, Frongia P et al (2017) High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes. Diabetes Metab Res Rev 33(3):e2864

    Article  CAS  Google Scholar 

  28. Mauricio D, Corcoy R, Codina M, Morales J, Balsells M, de Leiva A (1995) Islet cell antibodies and beta-cell function in gestational diabetic women: comparison to first-degree relatives of type 1 (insulin-dependent) diabetic subjects. Diabet Med 12:1009–1014

    Article  PubMed  CAS  Google Scholar 

  29. Fallucca F, Di Mario U, Gargiulo P, Iavicoli M, Galfo C, Contreas G et al (1985) Humoral immunity in diabetic pregnancy: interrelationships with maternal/neonatal complications and maternal metabolic control. Diabete Metab 11:387–395

    PubMed  CAS  Google Scholar 

  30. Wucher H, Lepercq J, Carette C, Colas C, Dubois-Laforgue D, Gautier JF et al (2011) Poor prognosis of pregnancy in women with autoimmune type 1 diabetes mellitus masquerading as gestational diabetes. Diabetes Metab 37:47–51

    Article  PubMed  CAS  Google Scholar 

  31. Fuchtenbusch M, Ferber K, Standl E, Ziegler AG (1997) Prediction of type 1 diabetes postpartum in patients with gestational diabetes mellitus by combined islet cell autoantibody screening: a prospective multicenter study. Diabetes 46:1459–1467

    Article  PubMed  CAS  Google Scholar 

  32. Hod M, Merlob P, Friedman S, Schoenfeld A, Ovadia J (1991) Gestational diabetes mellitus. A survey of perinatal complications in the 1980s. Diabetes 40(Suppl 2):74–78

    Article  PubMed  Google Scholar 

  33. Whittingham S, Byron SL, Tuomilehto J, Zimmet PZ, Myers MA, Vidgren G et al (1997) Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus in women. Diabet Med 14:678–685

    Article  PubMed  CAS  Google Scholar 

  34. Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Parronchi P, Romagnani S (2016) How pregnancy can affect autoimmune diseases progression? Clin Mol Allergy 14:11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Mauricio D, de Leiva A (2001) Autoimmune gestational diabetes mellitus: a distinct clinical entity? Diabetes Metab Res Rev 17(6):422–428

    Article  PubMed  CAS  Google Scholar 

  36. Hunt KJ, Logan SL, Conway DL, Korte JE (2010) Postpartum screening following GDM: how well are we doing? Curr Diab Rep 10:235–241

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by research Grants from the Regione Autonoma della Sardegna (Grant RAS 2007 n. CRP-59453), from Sapienza Ateneo Scientific Research (Research Projects 2016), and from the Foundation Banca d’Italia (Projects 2015) all awarded to Marco G. Baroni, and from the Foundation di Sardegna (Research Projects 2012-13) to Efisio Cossu.

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Correspondence to M. G. Baroni.

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The study was reviewed and approved by the Ethical Committee of Azienda Ospedaliero-Universitaria of Cagliari, Italy, and conducted in conformance with the Helsinki Declaration.

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Written consent was obtained from all subjects before the study.

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Cossu, E., Incani, M., Pani, M.G. et al. Presence of diabetes-specific autoimmunity in women with gestational diabetes mellitus (GDM) predicts impaired glucose regulation at follow-up. J Endocrinol Invest 41, 1061–1068 (2018). https://doi.org/10.1007/s40618-018-0830-3

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