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Research

Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study

Andrea L. Blotsky, Elham Rahme, Mourad Dahhou, Meranda Nakhla and Kaberi Dasgupta
CMAJ April 15, 2019 191 (15) E410-E417; DOI: https://doi.org/10.1503/cmaj.181001
Andrea L. Blotsky
Department of Medicine (Blotsky, Rahme, Dasgupta), McGill University; Centre for Outcomes Research and Evaluation (Blotsky, Rahme, Dahhou, Nakhla, Dasgupta), Research Institute of the McGill University Health Centre; Department of Pediatrics (Nakhla), Division of Endocrinology and Metabolism, McGill University, Montréal, Que.
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Elham Rahme
Department of Medicine (Blotsky, Rahme, Dasgupta), McGill University; Centre for Outcomes Research and Evaluation (Blotsky, Rahme, Dahhou, Nakhla, Dasgupta), Research Institute of the McGill University Health Centre; Department of Pediatrics (Nakhla), Division of Endocrinology and Metabolism, McGill University, Montréal, Que.
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Mourad Dahhou
Department of Medicine (Blotsky, Rahme, Dasgupta), McGill University; Centre for Outcomes Research and Evaluation (Blotsky, Rahme, Dahhou, Nakhla, Dasgupta), Research Institute of the McGill University Health Centre; Department of Pediatrics (Nakhla), Division of Endocrinology and Metabolism, McGill University, Montréal, Que.
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Meranda Nakhla
Department of Medicine (Blotsky, Rahme, Dasgupta), McGill University; Centre for Outcomes Research and Evaluation (Blotsky, Rahme, Dahhou, Nakhla, Dasgupta), Research Institute of the McGill University Health Centre; Department of Pediatrics (Nakhla), Division of Endocrinology and Metabolism, McGill University, Montréal, Que.
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Kaberi Dasgupta
Department of Medicine (Blotsky, Rahme, Dasgupta), McGill University; Centre for Outcomes Research and Evaluation (Blotsky, Rahme, Dahhou, Nakhla, Dasgupta), Research Institute of the McGill University Health Centre; Department of Pediatrics (Nakhla), Division of Endocrinology and Metabolism, McGill University, Montréal, Que.
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  • RE: Diabetes Mellitus Will Always Be a Spectral Illness
    Nevio Cimolai
    Posted on: 23 June 2019
  • RE: Pregnancy a test of beta cell reserve
    Dhastagir Sultan Sheriff
    Posted on: 16 April 2019
  • Posted on: (23 June 2019)
    RE: Diabetes Mellitus Will Always Be a Spectral Illness
    • Nevio Cimolai, physician, Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada

    The retrospective cohort study of Blotsky et al. serves well the epidemiology of diabetes in youth.(1) Their work, and supportive studies otherwise, have used administrative databases to establish diagnoses of diabetes, and they rely on validations previously made that provide some reasonable predictive values for discharge diagnoses as being representative of a gold standard laboratory diagnosis.(2-7) Making extrapolations in this regard has its perils, however, and also has the tendency to bring us further away from the complex clinical entity we recognize as diabetes mellitus.

    Decades ago, criteria for and diagnoses of diabetes mellitus were simplistic and often more clinically-based. Fundamentally, diabetes mellitus is a complex and heterogeneous group of pathologies which are unified by the concepts of disordered carbohydrate metabolism. A major difficulty with harnessing such complexity is the perceived need to create more palpable boundaries for definitions. Such definitions may be more tailored towards assisting epidemiological, administrative, and to some extent clinical usages. There was eventually a move to ascribe the gold standards to strictly laboratory parameters and descriptions. Internationally, the choice of such standards were fraught with controversy, although there was some consensus that the laboratory definitions of diabetes mellitus would strongly rely on the creation of thresholds for the diabetic state as indicated by the frequency of asso...

    Show More

    The retrospective cohort study of Blotsky et al. serves well the epidemiology of diabetes in youth.(1) Their work, and supportive studies otherwise, have used administrative databases to establish diagnoses of diabetes, and they rely on validations previously made that provide some reasonable predictive values for discharge diagnoses as being representative of a gold standard laboratory diagnosis.(2-7) Making extrapolations in this regard has its perils, however, and also has the tendency to bring us further away from the complex clinical entity we recognize as diabetes mellitus.

    Decades ago, criteria for and diagnoses of diabetes mellitus were simplistic and often more clinically-based. Fundamentally, diabetes mellitus is a complex and heterogeneous group of pathologies which are unified by the concepts of disordered carbohydrate metabolism. A major difficulty with harnessing such complexity is the perceived need to create more palpable boundaries for definitions. Such definitions may be more tailored towards assisting epidemiological, administrative, and to some extent clinical usages. There was eventually a move to ascribe the gold standards to strictly laboratory parameters and descriptions. Internationally, the choice of such standards were fraught with controversy, although there was some consensus that the laboratory definitions of diabetes mellitus would strongly rely on the creation of thresholds for the diabetic state as indicated by the frequency of associated complications (then ophthalmological or cardiovascular) at any set time. What was evident nonetheless was that any such laboratory definition underestimated risk and underdiagnosed those who were to suffer any such complications. There are varying paths to diabetes, and the ‘one size-fits all’ applications were often challenged then and continue to be challenged.

    Added to these dilemmae were the findings of glycemic profiles in what would appear to be normal patients. Many such patients have their blood glucose levels in the hyperglycemic range for a considerable time day-to-day.(8) Others found that glycated hemoglobin in a normal population was associated with complications.(9) Among seemingly normal young men, higher fasting blood sugars were risk factors for dysregulated glycemic control.(10) The consequence of these findings is the more balanced and robust view that diabetes mellitus is a continuous spectrum of glycemic dysregulation.(11) There is therefore the onus on the clinician to assess each individual and devise a personalized diabetic profile.(12) Such assessment will include factors such as age, metabolic parameters, family history, medication profile, past history, gestational status, among others in the least and in addition to laboratory measures. The management of this profile will depend on where the patient is on that spectral diagnostic curve.(13,14)

    Effectively, the current knowledge base of molecular, cellular, and genetic bases of disease lead to a unified construct that there is a diabetic spectrum and that the decision to say that a patient has diabetes mellitus is a clinical definition. The junior diagnostician will dwell on absolute markers among fasting blood glucose, hemoglobin A1c, or glucose tolerance testing with the preliminary knowledge that these indicators will signal the initiation of a disease boundary that warrants some form of intervention. The senior diagnostician will already know that diabetes mellitus will always be a spectral disease in which the patient as a whole must be considered. The latter will establish the presence of a metabolic disorder on the basis of several criteria as above and beyond a paper diagnosis. Interventions and/or recommendations will be predicated on that intimate knowledge for the given patient. We then re-reflect on studies such as those from Blotsky et al.(1) What should then be the gold standard – an extrapolated laboratory definition or clinical diagnoses that created the foundation for hospital or outpatient discharge diagnoses?

    References

    1. Blotsky AL, Rahme E, Dahhou M, Nakhla M, Dasgupta K. Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study. CMAJ 2019 April 15;191:E410-7.
    2. Dart AB, Martens PJ, Sellers EA, Brownell MD, Rigatto C, Dean HJ. Validation of a pediatric diabetes care definition using administrative health data in Manitoba, Canada. Diabetes Care 2011;34(4):898-903.
    3. Leong A, Dasgupta K, Chiasson J-L, Rahme E. Estimating the population prevalence of diagnosed and undiagnosed diabetes. Diabetes Care 2013;36(10):3002-8.
    4. Bowker SL, Savu A, Donovan LE, Johnson JA, Kaul P. Validation of administrative and clinical case definitions for gestational diabetes mellitus against laboratory results. Diabet Med 2017;3(6):781-5.
    5. Bowker SL, Savu A, Lam NK, Johnson JA, Kaul P. Validation of administrative data case definitions for gestational diabetes mellitus. Diabet Med 2017;34(1):51-5.
    6. Guttmann A, Nakhla M, Henderson M, et al. Validation of a health administrative data algorithm for assessing the epidemiology of diabetes in Canadian children. Pediatric Diabetes 2010;11(2):122-8.
    7. Leong A, Dasgupta K, Bernatsky S, Lacaille D, Avina-Zubieta A, Rahme E. Systematic review and meta-analysis of validation studies on a diabetes case definition from health administrative records. PLoS One 2013;8(10):e75256.
    8. Borg R, Kuenen JC, Carstensen B, et al. Real-life glycaemic profiles in non-diabetic individuals with low fasting glucose and normal HbA1c: the A1C-derived average glucose (ADAG) study. Diabetologia 2010;53(8):1608-11.
    9. Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010;362(9):800-11.
    10. Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005;353(14):1454-62.
    11. Arky RA. Doctor, is my sugar normal? N Engl J Med 2005;353(14):1511-3.
    12. Bergman M. Prediabetes and diabetes prevention. Med Clin N A 2011;95:xi-xiii.
    13. Brooks-Worrell B, Palmer JP. Is diabetes mellitus a continuous spectrum? Clin Chem 2011;57(2):158-61.
    14. Heianza Y, Arase Y, Fujihara K, et al. Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA1c and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4). Diabet Med 2012;29(9):e270-85.

    Show Less
    Competing Interests: None declared.
  • Posted on: (16 April 2019)
    RE: Pregnancy a test of beta cell reserve
    • Dhastagir Sultan Sheriff, Professor, Reprolabs, Chennai,India

    Pregnancy is considered a test for beta cell reserve. If there is a good function insulin resistance will be overcome. If not gestational will occur. Insulin resistance (IR) that is present in normal pregnancy is to provide nutrients to the growing fetus. There is a rapid increase in insulin in such insulin resistant state.(1-3) The possibility of lipid deposition in muscle fibers( intramyocellular) could be one of the possible mechanism of IR in gestational diabetes mellitus (GDM).(3-4) The poor response of insulin release, possible fat deposition in the skeletal muscle or ectopic fat deposition may cause dysfunctional homeostasis in GDM.(5) This will definitely influence the fine tuning of metabolic machinery of a growing fetus. Children born with such subtle metabolic state probably may be more prone for glucose intolerance and ectopic lipid deposition. The finding that children born to GDM mothers are prone to glucose intolerance may be an eye-opener to monitor such children for beta cell function.

    References:
    1.Ryan EA, Enns L. Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab 1988;67:341-34

    2.Catalano,PM,Huston L, Amini SB,Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal gluocose tolerance and gestational diabetes. Amer J Obstet.Gynecol 1999;180:903-916.

    3.Buchanan TA, Xiang A,Kjos SL, Watanabe R. What is gestational diabetes? Diabetes Care 2007;30:2...

    Show More

    Pregnancy is considered a test for beta cell reserve. If there is a good function insulin resistance will be overcome. If not gestational will occur. Insulin resistance (IR) that is present in normal pregnancy is to provide nutrients to the growing fetus. There is a rapid increase in insulin in such insulin resistant state.(1-3) The possibility of lipid deposition in muscle fibers( intramyocellular) could be one of the possible mechanism of IR in gestational diabetes mellitus (GDM).(3-4) The poor response of insulin release, possible fat deposition in the skeletal muscle or ectopic fat deposition may cause dysfunctional homeostasis in GDM.(5) This will definitely influence the fine tuning of metabolic machinery of a growing fetus. Children born with such subtle metabolic state probably may be more prone for glucose intolerance and ectopic lipid deposition. The finding that children born to GDM mothers are prone to glucose intolerance may be an eye-opener to monitor such children for beta cell function.

    References:
    1.Ryan EA, Enns L. Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab 1988;67:341-34

    2.Catalano,PM,Huston L, Amini SB,Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal gluocose tolerance and gestational diabetes. Amer J Obstet.Gynecol 1999;180:903-916.

    3.Buchanan TA, Xiang A,Kjos SL, Watanabe R. What is gestational diabetes? Diabetes Care 2007;30:2916-2921

    4.Tushuizen ME, Bunck MC, Pouwwels PJ et al. Pancreatic fat content and beta cell function in men with and without type 2 diabetes mellitus. Diabetes Carem2007; 30:2916-2921

    5. Kautzky-Willer A, Krasak M, Winzer C et al. Intramyocellular lipid concentration identifies impaired glucose metabolism in women with previous gestational diabetes. Diabetes 2003;52:244-251.

    Show Less
    Competing Interests: None declared.
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Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study
Andrea L. Blotsky, Elham Rahme, Mourad Dahhou, Meranda Nakhla, Kaberi Dasgupta
CMAJ Apr 2019, 191 (15) E410-E417; DOI: 10.1503/cmaj.181001

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Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study
Andrea L. Blotsky, Elham Rahme, Mourad Dahhou, Meranda Nakhla, Kaberi Dasgupta
CMAJ Apr 2019, 191 (15) E410-E417; DOI: 10.1503/cmaj.181001
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