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Purpose <p>Reactive hypoglycemia (RH) is characterized by the occurrence of Whipple’s triad within hours after carbohydrate ingestion, whereas pseudo-hypoglycemia (PH) involves hypoglycemic-like symptoms without pathological reductions in plasma glucose. Differentiating between these conditions is essential to avoid misdiagnosis and unnecessary testing.</p> Methods <p>We analyzed 74 patients who underwent a prolonged oral glucose tolerance test (OGTT) for suspected RH. RH was defined as plasma glucose &lt; 55&#xa0;mg/dL between 180 and 300&#xa0;min, and PH as hypoglycemic-like symptoms with glucose ≥ 55&#xa0;mg/dL at all time points. Clinical, glycemic, and insulinemic parameters were compared between groups.</p> Results <p>83% of the participants were women. Median age was 45 years, and median BMI was 25&#xa0;kg/m<sup>2</sup>. Confirmed RH occurred in 26% of patients, and PH in 20%. All PH subjects reported symptoms, which were associated with higher nadir glucose levels (76 vs. 50&#xa0;mg/dL). Compared with PH patients, RH patients exhibited higher 1-hour glucose levels (146 vs. 123&#xa0;mg/dL), and a lower Matsuda index (5.7 vs. 18.6). RH also showed greater ΔGLU0–1 (74 vs. 34&#xa0;mg/dL) and greater ΔINS0–2 (63 vs. 44 µU/mL). A higher proportion of RH patients had 1-hour glucose &gt; 155&#xa0;mg/dL (44% vs. 13%). The ΔGLU0–1 emerged as the strongest predictor of RH (OR 1.69, <i>p</i> = 0.041).</p> Conclusions <p>Dynamic OGTT parameters—particularly ΔGLU0–1 and Matsuda index—distinguish RH from PH more effectively than nadir glucose alone and symptoms referral. Incorporating these markers may enhance diagnostic accuracy, reduce misclassification and inform clinical decision-making, optimizing the use of OGTT.</p> Clinical trial number <p>Not applicable.</p>

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Early glucose and insulin dynamics during prolonged oral glucose tolerance test (OGTT) distinguish reactive hypoglycemia from Pseudo-Hypoglycemia

  • 期刊论文

  • 发表日期：

    2025年11月4日

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  • Alberto Vassallo,
  • Matteo Acanfora,
  • Fanny Valsecchi,
  • Vincenzo Franzese

摘要

Purpose

Reactive hypoglycemia (RH) is characterized by the occurrence of Whipple’s triad within hours after carbohydrate ingestion, whereas pseudo-hypoglycemia (PH) involves hypoglycemic-like symptoms without pathological reductions in plasma glucose. Differentiating between these conditions is essential to avoid misdiagnosis and unnecessary testing.

Methods

We analyzed 74 patients who underwent a prolonged oral glucose tolerance test (OGTT) for suspected RH. RH was defined as plasma glucose < 55 mg/dL between 180 and 300 min, and PH as hypoglycemic-like symptoms with glucose ≥ 55 mg/dL at all time points. Clinical, glycemic, and insulinemic parameters were compared between groups.

Results

83% of the participants were women. Median age was 45 years, and median BMI was 25 kg/m2. Confirmed RH occurred in 26% of patients, and PH in 20%. All PH subjects reported symptoms, which were associated with higher nadir glucose levels (76 vs. 50 mg/dL). Compared with PH patients, RH patients exhibited higher 1-hour glucose levels (146 vs. 123 mg/dL), and a lower Matsuda index (5.7 vs. 18.6). RH also showed greater ΔGLU0–1 (74 vs. 34 mg/dL) and greater ΔINS0–2 (63 vs. 44 µU/mL). A higher proportion of RH patients had 1-hour glucose > 155 mg/dL (44% vs. 13%). The ΔGLU0–1 emerged as the strongest predictor of RH (OR 1.69, p = 0.041).

Conclusions

Dynamic OGTT parameters—particularly ΔGLU0–1 and Matsuda index—distinguish RH from PH more effectively than nadir glucose alone and symptoms referral. Incorporating these markers may enhance diagnostic accuracy, reduce misclassification and inform clinical decision-making, optimizing the use of OGTT.

Clinical trial number

Not applicable.