Dubious diagnosis

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Science  08 Mar 2019:
Vol. 363, Issue 6431, pp. 1026-1031
DOI: 10.1126/science.363.6431.1026

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  • RE: Dubious diagnosis
    • Hongli Du, Professor, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
    • Other Contributors:
      • Shuying Fu, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China

    Is it reasonable to lower the fasting glucose threshold for diagnosing prediabetes according to recommendations of American Diabetes Association?

    We read with great interest the news about the diagnosis of prediabetes by Charles Piller that was recently published in the Science (1), and the commentary to this news by the chairs of the American Diabetes Association (ADA) Professional Practice Committee who supported prediabetes treatment (2). Piller reported that prediabetes had little or no harm, and less than 2% of subjects with prediabetes in the ADA range progressed to diabetes each year. Besides, the ADA expanded the impaired fasting glucose (IFG) cutoff resulting in millions of prediabetes patients, which creates a huge economic burden (1). However, chairs of the ADA stated that recommendations for diabetes prevention were based on best current evidence, and prediabetes was a useful term to convey future risk of diabetes. In addition, even a 2% progression rate per year would translate to nearly 1/5 people with prediabetes developing diabetes within 10 years (2). According to extensive literature research, we agree with controlling prediabetes, but we disagree with expanding impaired fasting glucose (IFG) range recommended by the ADA for the diagnosis of prediabetes.

    Lowering the criterion for impaired fasting glucose creating a pandemic of prediabetes
    In 2004, ADA lowered the impaired fasting glucose (IFG) cutoff from 6.0 to 5.6 mmol/L. According...

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    Competing Interests: None declared.
  • RE: Is Prediabetes A “DUBIOUS DIAGNOSIS”?
    • Yuli Huang, Physician, Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, PR China
    • Other Contributors:
      • Qianrong Xiao, Physician, Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, PR China

    Charles Piller reported that ‘prediabetes’ is a “DUBIOUS DIAGNOSIS” and questioned how real is the condition on Science (1) ? We wish to discuss some of our views.
    First, although different definitions of prediabetes are with different sensitive, and specific power for prediction of future diabetes, many studies showed that prediabetes is a high-risk state for progressing to diabetes (2). According to the American daibetes association (ADA) expert panel, up to 70% of them will eventually progress into diabetes. Only 19% people with prediabetes in the control group of Diabetes Prevention Program were converted to normoglycaemia during follow-up. Furthermore, meta-analyses of large prospective cohort studies showed that prediabetes was associated with cardiovascular disease, cancer incidence and all-cause mortality after adjusting multiple risk factors, and the risks were increased even in people with prediabetes defined according to the ADA criteria (3, 4).
    Second, intervention with prediabetes is effective and with cost-effectiveness. Community mobilisation and lifestyle intervention are both with significant reduction in diabetes incidence (5, 6). Furthermore, the 30-year results of the Da Qing Diabetes Prevention Outcome Study showed that lifestyle intervention in people with prediabetes reduced the incidence of cardiovascular events and all-cause mortality, providing strong justification to continue to implement and expand the use of such interventions to cur...

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    Competing Interests: None declared.
  • RE: Dubious Diagnosis
    • Lena Carlsson, Professor, The Sahlgrenska Academy at University of Gothenburg, Sweden
    • Other Contributors:
      • Kajsa Sjöholm, Associate professor, The Sahlgrenska Academy at University of Gothenburg, Sweden
      • Björn Carlsson, Senior Director Physician, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden
      • Markku Peltonen, Professor, National Institute for Health and Welfare, Helsinki, Finland

    In the News article “Dubious diagnosis” (8 March 2019, p. 1027), Charles Piller downplays the importance of prediabetes, stating that it does not strongly predispose to diabetes and that studies demonstrating benefits of treating prediabetes are lacking. However, results from the Swedish Obese Subjects (SOS) study have shown that prediabetes markedly increases the risk of diabetes and that bariatric surgery prevents its progression to diabetes and associated complications.
    The SOS study is a prospective controlled trial comparing the long-term effects of bariatric surgery with usual obesity care. Among patients receiving usual care, 80% with baseline prediabetes and 30% with baseline normoglycemia developed diabetes within 15 years of follow-up (1). In patients with prediabetes, bariatric surgery reduced the risk of diabetes during follow-up by 87%, and the number needed to treat to prevent one new case of diabetes over 10 years was only 1.3 (1). Bariatric surgery also reduced the risk of microvascular complications (affecting eyes, nerves or kidneys) in those with prediabetes, with only 8% of the surgery group requiring hospitalization for a microvascular event compared with 34% of those receiving usual care (2). The number needed to treat to prevent one microvascular event in those with prediabetes was 7 and the relative risk reduction was greater than in those with established diabetes (2). The SOS study also showed that drug costs were reduced by bariatric surger...

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    Competing Interests: L.C. has obtained consulting fees from AstraZeneca and Johnson&Johnson. B.C. is employed by AstraZeneca and holds stocks in the same company.
  • Dubious Diagnosis, Bad Medicine
    • Lewis Kuller, Professor Emeritus of Epidemiology, University of Pittsburgh Graduate School of Public Health

    The recent paper in Science, “Dubious diagnosis. A war on “prediabetes”…”(1) is misleading. The lifetime risk of developing diabetes is about 33% for men, 39% for women.(2) Almost all diabetics went through a period of increased fasting glucose or elevated glycohemoglobin (HbA1c) with increased loss of beta cell function and insulin resistance (IR) leading to metabolic changes associated with increased risk of microvascular and macrovascular disease. By the time of diagnosis of diabetes, the patient has subclinical macro- and microvascular disease.(3-7)

    Blood sugar levels in the population are linear and continuous variables. The risk diabetes is linearly related to the levels of blood glucose. Genetic studies have documented that a combination of polymorphisms and lifestyles are the primary determinants of type 2 diabetes (T2D). Mendelian randomization has shown that genes related to increasing blood glucose are associated with the risk of CVD.(8) Conversion rates from hyperglycemia or elevated HbA1c to diabetes is probably about 5%/year. Some individuals with elevated HbA1c or glucose revert to normal in the short term due to regression to the mean.(9)

    Five approaches can be used to prevent the development of diabetes and reduce burden of CVD among individuals with elevated blood glucose.(10) First, nonpharmacological approaches (DPP).(11, 12) Second, the use of drugs, such as metformin.(13) Third, bariatric surgery.(14) Fourth, treatment of comorbid risk...

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    Competing Interests: None declared.

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