Abstract

The incretin effect in type 2 diabetes is reduced, but the mechanisms behind are uncertain. We hypothesized that the incretin effect associates with degree of enteric autonomic nerve dysfunction and evaluated gastrointestinally mediated glucose disposal (GIGD), as a proxy for the incretin effect, and rectal sensitivity to mechanical distension representing afferent gut signalling. Sixty-six participants with either 1) longstanding type 2 diabetes, 2) newly onset (<1 year), medically untreated diabetes, or 3) healthy controls, underwent a 75 g oral glucose tolerance test (OGTT) and an intravenous isoglycemic glucose infusion to determine GIGD. Earliest sensation to rectal rapid balloon distention was determined as a proxy for autonomic neuropathy. Compared to controls (59.3±14.4%), GIGD was reduced in both early (36.4±14.7%) and longstanding diabetes (17.4±22.3%), with significant difference between all three groups (P<0.01). Both groups of diabetes needed higher pressure during rapid rectal balloon distention (3.7±1.1 kPa for longstanding diabetes, 4.0±1.3 for early diabetes), compared to controls (3.0±0.9 kPa, P<0.01), with no significant difference between the two diabetes groups. GIGD was inversely correlated with pressure at earliest sensation (rho 0.341, P<0.01). For those needing a pressure between 1 and 3 kPa and between 4 and 7 kPa, respectively, GIGD was 46.2%±24.9 and 34.4±23.9% (P=0.05). GIGD was inversely and significantly correlated with glucose values during OGTT, with strongest correlation to the 90-minute value (rho 0.873, P<0.01), and HbA1c (rho 0.653, P<0.01). We show that the degree of rectal hyposensitivity correlates with reduced GIGD and confirm that GIGD correlates with the degree of dysglycemia. These results warrant further studies on the potential role of gut autonomic dysfunction in the reduced incretin effect characterizing type 2 diabetes. Disclosure S.Meling: Consultant; Novo Nordisk, Lilly, AstraZeneca, Boehringer-Ingelheim, Sanofi. E.Tjora: None. N.Ejskjaer: None. S.Carlsen: None. F.K.Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck. P.Njølstad: None. C.Brock: Research Support; Abbott, ElectroCore. R.B.Nedergaard: Other Relationship; Grünenthal Group. E.Søfteland: None. Funding Helse Vest, Norway (F-11637/4800002072); Johan Selmer Kvanes Legat (Legacy)

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