1564-P: Hepatic Lipid Content Associates with Fasting and Prandial Glucagon Secretion in Recent-Onset Type 2 Diabetes
Authors: HUTTASCH MAXIMILIAN , KAHL SABINE , MORI TIM , HEILMANN GERONIMO , TRINKS NINA , SCHÖN MARTIN , GIANNAKOGEORGOU ANNA , TRENKAMP SANDRA , KUPRIYANOVA YULIYA , SCHRAUWEN-HINDERLING VERA , WEWER ALBRECHTSEN NICOLAI J. , BURKART VOLKER , WAGNER ROBERT , RODEN MICHAEL , THE GDS GROUP FOR 
Published: June 2024

Hyperglycemia in type 2 diabetes (T2D) associates with higher glucagon secretion, which may be further promoted in the presence of metabolic dysfunction-associated steatotic liver disease (MASLD). Thus, we compared fasting and prandial glucagonemia in people with and without recent-onset T2D and MASLD. Participants of the German Diabetes Study (GDS), with T2D (n=50; known duration &lt;1 year) or with normal glucose tolerance (NGT; n=50), underwent mixed meal tolerance tests (MMT; 365 kcal) and hyperinsulinemic-normoglycemic clamps. Early prandial glucose and hormone secretion were quantified by incremental areas under the time curve (iAUC0-60min) and hepatic lipid content (HCL) by 1H-magnetic resonance spectroscopy. Associations of HCL (log) and glucagon secretion in people with T2D were assessed by age, sex and BMI-adjusted multiple linear regression. Both groups were similar in age (~53 yrs), sex (~66% male) and BMI (~29 kg/m2)(all p&gt;0.05), whereas T2D featured lower insulin sensitivity (M-value: 7.2±2.7 vs. 9.8±3.1 mg/kg*min, p&lt;0.001), higher HbA1c (6.3±0.8 vs. 5.3±0.3 % (43.9±8.3 vs. 34.2±2.9 mmol/mol), p&lt;0.001), HCL (6.6±6.8 vs. 4.0±5.0 %, p=0.008), fasting glucagon (9.4±4.9 vs. 7.2±4.6 pmol/L, p=0.021) and C-peptide (2.53±0.94 vs. 1.78±0.95 ng/mL, p&lt;0.001) and - by trend - more likely MASLD (41% vs. 24%, p=0.056). During MMT, iAUC0-60min of glucose (100±52 vs. 37±23 mmol/L*min) and of glucagon (538±261 vs. 306±249 pmol/L*min) were greater, while C-peptide iAUC0-60min (153±69 vs. 235±97 ng/mL*min) was lower than in NGT (all p&lt;0.001). In the regression analyses, an increase in HCL associated with both higher fasting glucagon (β=2.2, p=0.023, model R2= 0.336, p&lt;0.001) and glucagon iAUC0-60min (β=181.4, p=0.002, model R2= 0.204, p=0.033) in people with T2D.
In conclusion, fasting and prandial glucagon secretion is already elevated in recently-diagnosed and near-normoglycemic T2D, which are further exacerbated with rising liver lipid storage.

Disclosure
M. Huttasch: None. S. Kahl: None. T. Mori: None. G. Heilmann: None. N. Trinks: None. M. Schön: None. A. Giannakogeorgou: Research Support; Novo Nordisk. S. Trenkamp: None. Y. Kupriyanova: None. V. Schrauwen-Hinderling: None. N.J. Wewer Albrechtsen: Advisory Panel; Boehringer-Ingelheim. Research Support; Roche Diagnostics, Novo Nordisk A/S. Consultant; Mercodia. V. Burkart: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca.

Funding
The GDS was initiated and financed by the DDZ, which is funded by the German Federal Ministry of Health (Berlin, Germany) and the Ministry of Culture and Science of the State of Northrhine-Westphalia (Dnsseldorf, Germany) and from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e. V.). The GDS is supported in part by funds of the BMBF to the DZD e. V. This project is also receiving funding from the programme ôProfilbildung 2020ö, an initiative of the Ministry of Culture and Science of the State of Northrhine-Westphalia.