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. 2020 May 7;11:217. doi: 10.3389/fendo.2020.00217

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Copyright © 2020 Heyman, Bursztyn, Szalat, Muszkat and Abassi.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Two hypothetical examples illustrating the postulated impact of meals on glucose and concomitant sodium uptake in the proximal tubule. (A) A non-diabetic subject with stable glucose levels of 70 mg/dl and a glomerular filtration rate (GFR) of 100 ml/min. This individual will have a glucose reuptake of 70 mg/min (~100 g/day), as demonstrated below: Filtrated Glucose = PGluc × GFR = (70 mg/dl × 100 ml/min) × 24 h = (0.7 mg/ml × 100 ml/min) × 24 h = (70 mg/min) × 24 h = 70 ÷ 1,000 g/min × 1,440 min = 100.8 g/day. (B) This individual, now having three meals per day with three post-prandial increments of glucose levels to 140 mg for an hour will have an extra 12.6 g of glucose reabsorption per day: Filtrated Glucose = PGluc × eGFR = (70 mg/dl × 100 ml/min) × 21 h + (140 mg/dl × 100 ml/min) × 3 h = (0.7 mg/ml × 100 ml/min) × 21 h + (1.4 mg/ml × 100 ml/min) × 3 h = (70 ÷ 1,000 g/min × 1,260 min) + (140 ÷ 1,000 g/min × 180 min) = 88.2 + 25.2 = 113.4 g/day. Thus, ΔGlucose reabsorbed following meals = 113.4 – 100.8 = 12.6 g. (C) A type 2 diabetes mellitus (T2DM) patient with fasting glucose levels of 140 mg/dl without glycosuria and with a GFR of 100 ml/min will reabsorb 140 mg glucose/min, about 200 g/24 h while fasting: Filtrated Glucose = PGluc × eGFR = (140 mg/dl × 100 ml/min) × 24 h = (1.4 mg/ml × 100 ml/min) × 24 h = (140 mg/min) × 24 h = 140 ÷ 1,000 g/min × 1,440 min = 201.6 g/day. (D) Filtrated glucose in this patient post-prandial (three meals) = PGluc × eGFR = (140 mg/dl × 100 ml/min) × 18 h + (210 mg/dl × 100 ml/min) × 6 h = (1.4 mg/ml × 100 ml/min) × 18 h + (2.1 mg/ml × 100 ml/min) × 6 h = (140 ÷ 1,000 g/min × 1,080 min) + (210 ÷ 1,000 g/min × 360 min) = 151.2 + 75.6 = 226.8 g/day. Taking into account that this subject loses ~5 g of glucose per day, ΔGlucose reabsorbed = 226.8–201.6 = 25.2 g–5 g/day = 20.2 g/day.

As proximal tubular transport of Na⁺ and glucose is matched with a 1:1 molar ratio for sodium–glucose co-transporter 2 (SGLT2), the non-diabetic individual (example 1), moving from a 24-h fast to regular eating, will have an additional daily uptake of 70 mEq Na⁺, while the diabetic patient (example 2) will have an enhanced sodium reuptake of 111 mEq. These amounts correspond to additional retentions of 4 and 6.5 g of sodium chloride per day for the non-diabetic and diabetic individuals, respectively. It translates to added water retentions of 0.5 and 0.66 L, respectively, in order to maintain extracellular osmolality, roughly the anecdotal reported acute weight reduction following fasting for a day, immediately reversed upon eating.