Clinical Dilemmas in Diabetes

The Prevención con Dieta Mediterránea (PREDIMED) study enrolled older adult subjects at high risk for but without baseline CVD and randomized participants to either a Mediterranean diet supplemented with extra‐virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet based on general advice to reduce fat intake [102]. Compared to the control group, the Mediterranean diet supplemented with extra‐virgin olive oil group had significantly lower progression to DM with a HR of 0.60 (95% CI 0.54–0.85). The beneficial effect seen in this study was thought to be due to dietary composition itself and not attributed to calorie restriction, increased physical activity, or weight loss.

The 2020 ADA guidelines recommend that patients with prediabetes participate in an intensive behavioral lifestyle intervention program modeled on the DPP to achieve and maintain 7% weight loss and to achieve ≥ 150 minutes/week of moderate intensity physical activity (such as brisk walking) [103]. Additionally, the ADA recommends that a variety of eating patterns are acceptable for patients with prediabetes including the Mediterranean diet and a low‐calorie, low‐fat diet. Regarding pharmacologic therapy, the 2020 ADA guidelines state that metformin for prevention of DM should be considered in patients with prediabetes, especially those with BMI ≥ 35 kg/m 2, those aged < 60 years, and women with prior GDM.

In summary, patients with prediabetes have abnormal glucose regulation mediated by impaired insulin secretion and reduced insulin action, as well as an increased risk of progression to DM [18, 25, 26]. Many clinicians screen for diabetes and prediabetes using the combination of FPG and HbA1c. However, even when used together, the combined sensitivity for diagnosing DM and prediabetes is poor [41]. Therefore, omission of a 75‐g OGTT results in both misclassification and under‐diagnosis of DM and prediabetes. The following question then arises: are there clinical consequences to misclassifying diabetes as only prediabetes or prediabetes as normal glucose metabolism?

We conclude that the answer is yes. There is a clear association of increasing microvascular complications with rising glucose concentrations, and patients with prediabetes have an increased prevalence of retinopathy, nephropathy, and neuropathy compared to individuals with normal glucose metabolism [13, 14, 55, 57,59–61, 63,104–106]. There is also an increased prevalence of CVD, cardiovascular mortality, and all‐cause mortality in patients with prediabetes compared to those with normal glucose metabolism [66–68, 70].

Therefore, recognition and treatment of prediabetes is essential to minimize morbidity and mortality. Intensive lifestyle changes emphasizing weight loss and physical activity have been shown to prevent or delay progression to DM, potentially decrease microvascular complications, potentially reduce macrovascular complications, improve comorbidities, improve quality of life, reduce medical costs, and decrease mortality [1875–80]. In addition to lifestyle changes, numerous medications are also effective in preventing or delaying progression to DM including metformin, glipizide, liraglutide, insulin glargine, several thiazolidinediones, orlistat, acarbose, valsartan, and estrogen/progestin [18,82–85,87–92, 107].

The totality of available evidence suggests that prediabetes is not only a risk factor, it is in fact a disease. Perhaps the term “prediabetes” should be changed to “early diabetes” and managed as such clinically.

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