RYGB and SLG have a similar impact on diabetes remission, of which baseline β-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

In morbid obesity, Roux-en-Y gastric bypass causes rapid and profound metabolic adaptations; insulin sensitivity improves in proportion to the weight loss, and β-cell glucose sensitivity increases independently of weight loss. Over a period of 1 yr after surgery, diabetes remission depends on the starting degree of β-cell dysfunction.

OBJECTIVEPharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODSWe measured fasting and postmeal urinary excretion of glucose, b-hydroxybutyrate (b-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ‡60 mL · min 21 · 1.73 m 22 ) and in control subjects without diabetes at baseline and following empagliflozin treatment. RESULTSWith chronic (4 weeks) sodium-glucose cotransporter 2 inhibition, baseline fractional glucose excretion (<2%) rose to 38 6 12% and 46 6 11% (fasting vs. postmeal, respectively; P < 0. ) all increased (P £ 0.001 for all) and were each positively related to glycosuria (P £ 0.001). These parameters changed in the same direction in subjects without diabetes, but changes were smaller than in the patients with diabetes. Although plasma N-terminal pro-B-type natriuretic peptide levels were unaltered, plasma erythropoietin concentrations increased by 31 (64)% (P = 0.0078). CONCLUSIONSWe conclude that the sodium-glucose cotransporter 2 inhibitor-induced increase in b-HB is not because of reduced renal clearance but because of overproduction. The increased lactate excretion contributes to lower plasma lactate levels, whereas the increased natriuresis may help in normalizing the exchangeable sodium pool. Taken together, glucose loss through joint inhibition of glucose and sodium reabsorption in the proximal tubule induces multiple changes in renal metabolism.

Aims/hypothesis Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusion, designed to achieve physiological postprandial levels, directly affects endogenous glucose production (EGP) under conditions mimicking the fasting state in diabetes. Methods In 14 healthy volunteers, we applied the pancreatic clamp technique, whereby plasma insulin and glucagon levels are clamped using somatostatin and hormone replacement. The clamp was applied in paired, 4 h experiments, during which saline (control) or GLP-1(7-37)amide (0.4 pmolmin −1 kg −1 ) was infused. Results During the control study, plasma insulin and glucagon were maintained at basal levels and plasma C-peptide was suppressed, such that plasma glucose rose to a plateau of ∼10.5 mmol/l and tracer-determined EGP increased by ∼60%. During GLP-1 infusion at matched plasma glucose levels, the rise of EGP from baseline was fully prevented. Lipolysis (as indexed by NEFA concentrations and tracerdetermined glycerol rate of appearance) and substrate utilisation (by indirect calorimetry) were similar between control and GLP-1 infusion. Conclusions/interpretation GLP-1 inhibits EGP under conditions where plasma insulin and glucagon are not allowed to change and glucose concentrations are matched, indicating either a direct effect on hepatocytes or neurally mediated inhibition.

2 , P ϭ 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 Ϯ 0.02-vs. 0.92 Ϯ 0.02-fold, P ϭ 0.006), the increment being higher in Study II (ϩ36 Ϯ 5%) than Study I (ϩ19 Ϯ 6%, P Ͻ 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rhoϭ0.60, P ϭ 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 Ϯ 6 g for the first load and 52 Ϯ 5 g for the second load (P ϭ not significant). Fasting endogenous glucose production [13.3 Ϯ 0.6 mol ⅐ min Ϫ1 ⅐ kg fat-free mass (FFM) Ϫ1 ] averaged 6.0 Ϯ 3.8 mol ⅐ min Ϫ1 ⅐ kg FFM Ϫ1 between 0 and 180 min and 1.7 Ϯ 2.6 between 180 and 360 min (P Ͻ 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect. glucose potentiation; glucose absorption; glucose tolerance IMPROVEMENT OF CARBOHYDRATE tolerance following repeated glucose administration was first reported by Hamman and Hirschman in 1919 (10) and subsequently confirmed by Staub in 1921 (24) and by Traugott in 1922 (27). This effect has since been known as the Staub-Traugott effect and has been demonstrated after oral (8,24,27) and intravenous administration of glucose (5-9).Despite the fact that this facilitated glucose disposal is an important physiological determinant of overall glycemic exposure, its mechanisms have not been established conclusively. Increased plasma insulin response has been reported by some studies (2, 3, 25), but not others (1,7,14,21,23,26,30); decreased hepatic clearance of insulin (30) and enhanced insulin sensitivity (13, 14) have also been proposed.On theoretical grounds, a lower glycemic response to a glucose load that follows another glucose challenge could be due to: 1) increased insulin secretion, 2) enhanced peripheral insulin sensitivity, 3) enhanced hepatic insulin sensitivity, 4) reduced absorption of oral glucose, or 5) a combination of the above. In the present study, we explored each of these mechanisms in healthy volunteers. MATERIALS AND METHODSSubjects. Seventeen healthy subjects (Table 1) volunteered for the study. They gave no history of preexisting metabolic disorder or familial diabetes and were not taking any medication. None of them had lost weight or changed dietary habits during the 3 mo preceding the study. All subjects had resting arterial blood pressure Ͻ140/90 mmHg and normal results for liver and renal function tests. The study protocol was approved by the local Ethics Committee, and all subjects gave their informed consent to participate.Study protocol. Two studies were carried out in each subject after an overnight (12-to 14-h) fast, with a 2-wk interval. In the first study (Study I), subjects received two sequential oral glucose loads (75 g), the first at time 0 min and the second at time 180 min. Venous blood was sampled at timed intervals for plasma glucose, insulin, C-peptide, glucagon-...