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Pathophysiology of Prediabetes

Our goal is to understand the causes and consequences of impaired metabolic health in obesity and normal weight and the role of metabolic dysfunction-associated steatotic liver disease (MASLD) in the pathogenesis of prediabetes, type 2 diabetes and cardiovascular diseases.

In this respect, in 2008, we published the first large cohort study addressing precise phenotyping in metabolically healthy obesity (MHO) and then extended our research to subphenotypes of impaired metabolic in normal weight. To address the mechanisms how MASLD impacts on cardiometabolic diseases, in 2008, we were the first to introduce the concept of hepatokines and are studying their cardiometabolic role in the organ cross-talk.

Our goal is to understand the causes and consequences of impaired metabolic health in obesity and normal weight, and the role of metabolic dysfunction-associated steatotic liver disease (MASLD) in the pathogenesis of prediabetes, type 2 diabetes, and cardiovascular diseases.

In this respect, in 2008, we published the first large cohort study addressing precise phenotyping in metabolically healthy obesity (MHO) and then extended our research to subphenotypes of impaired metabolic in normal weight. To address the mechanisms how MASLD impacts cardiometabolic diseases, in 2008, we were the first to introduce the concept of hepatokines and are studying their cardiometabolic role in the organ cross-talk.

Scientists at Pathophysiology of Prediabetes

Prof_Stefan_ Porträt 1(1)
Prof. Dr. Norbert Stefan

Head of Section, IDM

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Fritz_Schick_Med_Mitarbeiter_ 74
Prof. Dr. Dr. Fritz Schick

Group Leader, Scientist

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Juergen_Machann_Med_Mitarbeiter_ 15
Prof. Dr. Jürgen Machann

Senior Scientist

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Costas_Kartazis
Dr. Konstantinos Kantartzis

Physician Scientist

Portraitfoto Angela_Lehn_Stefan
Dr. Angela Lehn-Stefan

Physician Scientist

Dr. Sebastian Schuth

Physician Scientist

Karin Waneck

TA

Our Topics

Causes, consequences, and treatment of metabolically unhealthy fat distribution

Energy storage capacity under positive energy balance is important for metabolic health. An increased energy intake, particularly after consuming increased amounts of glucose, fructose, and saturated fat, and when energy expenditure is low, results in the storage of energy mostly in the form of triglycerides in adipose tissue.

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Causes and cardiometabolic consequences of NAFLD

An unhealthy diet results in increased hepatic de novo lipogenesis and hepatic inflammation. This process is amplified by a lipodystrophy-like phenotype with expansion of visceral adipose tissue. By increased secretion of very low-density lipoproteins, ceramides, pro-coagulants, glucose, and dysregulated secretion of microRNAs and hepatokines, the fatty liver impacts metabolically important organs and tissues and the cardiovascular system.

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Treatment of NAFLD

Pathophysiological targeted treatment of hepatic steatosis, e.g. by inhibiting cortisol production in metabolically active tissues, such as the liver, is effective to fight the epidemic of NAFLD.

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Recent Publications

Lancet Diabet. Endocrinol. 14, 594-607 (2026)

Magkos, F. ; Stefan, N.

Is weight cycling clinically harmful?
Lancet Reg. Health-Eur. 65:101722 (2026)

Pugliese, N. ; White, T.M. ; Brennan, P.N. ; Pannain, S. ; Hagström, H. ; Michel, M. ; Rice-Duek, L. ; Targher, G. ; Caussy, C. ; Dillon, J.F. ; Tacke, F. ; Kopka, C.J. ; Sebastiani, G. ; Boursier, J. ; Tsochatzis, E.A. ; Brouwer, W.P. ; Guaraldi, G. ; Vettor, R. ; Thiele, M. ; Roden, M. ; Stefan, N. ; Jarvis, H. ; Gines, P. ; Schattenberg, J.M. ; Pose, E. ; Buttigieg, S. ; Byrne, C.D. ; Lazarus, J.V.

Diagnostic innovation and models of care to improve fibrosis detection and risk stratification in steatotic liver disease.
Diabetologie 22, 219-220 (2026)

Stefan, N. ; Roden, M.

Fettlebererkrankungen (Teil 1).
Diabetes 75, 965-973 (2026)

Meier, C.Z. ; Wagner, R. ; Ganslmeier, M. ; Kantartzis, K. ; Heni, M. ; Peter, A. ; Jumpertz von Schwartzenberg, R. ; Machann, J. ; Schick, F. ; Birkenfeld, A.L. ; Häring, H.U. ; Fritsche, A. ; Stefan, N.

Different metabolic responses to long-term weight loss after lifestyle intervention among type 2 diabetes risk clusters: Results from the TULIP Study.
Exp. Clin. Endocrinol. Diabet., DOI: 10.1055/a-2766-3214 (2026)

Stefan, N. ; Roden, M.

Diabetes and metabolic dysfunction-associated steatotic liver disease.
Am. J. Physiol. Endocrinol. Metab. 330, E411-E421 (2026)

Heider, S. ; Gohlke, S. ; Kuxhaus, O. ; Haueise, T. ; Stefan, N. ; Birkenfeld, A.L. ; Machann, J. ; Schulz, T.J.

Bone marrow adipose tissue mass and dipeptidyl peptidase-4 link aging and metabolic health to biomarkers of bone turnover.
Lancet Gastroenterol. Hepatol. 11, 521-537 (2026)

Zhou, X.D. ; Lazarus, J.V. ; Krittanawong, C. ; Targher, G. ; Byrne, C.D. ; Younossi, Z.M. ; Tacke, F. ; Chen, Q.F. ; Mantzoros, C.S. ; Tilg, H. ; Mehal, W.Z. ; Sperling, L.S. ; Lip, G.Y.H. ; Stefan, N. ; Zheng, M.H.

Pharmacotherapy for metabolic dysfunction-associated steatohepatitis: Heart-liver co-management.
Biomark. Res. 14:19 (2026)

Singh, A. ; Jumpertz von Schwartzenberg, R. ; Wagner, R ; Sandforth, L. ; Sandforth, A. ; Jähnert, M. ; Ganslmeier, M. ; Kabisch, S. ; Perakakis, N. ; Preissl, H. ; Fritsche, A. ; Stefan, N. ; Walter, D. ; Ouni, M. ; Birkenfeld, A.L. ; Schürmann, A.

Stratifying high-risk prediabetes clusters using blood-based epigenetic markers.
Lancet Diabet. Endocrinol. 14, 137-148 (2025)

Vazquez Arreola, E. ; Gong, Q. ; Hanson, R.L. ; Wang, J. ; Sandforth, L. ; He, S. ; Sandforth, A. ; Qian, X. ; Giacca, M. ; Bornstein, S.R. ; Fritsche, A. ; Stefan, N. ; Preissl, H. ; Gregg, E.W. ; Marx, N. ; Jumpertz von Schwartzenberg, R. ; Li, G. ; Birkenfeld, A.L.

Prediabetes remission and cardiovascular morbidity and mortality: Post-hoc analyses from the Diabetes Prevention Program Outcome study and the DaQing Diabetes Prevention Outcome study.

Contact

Prof_Stefan_ Porträt 1(1)
Prof. Dr. Norbert Stefan

Head of Section, IDM

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Networks and Affiliations

University of Florida

University of Florida

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Boston Children’s Hospital

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National Institutes of Health

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Stratification of obese phenotypes to optimize future obesity therapy

SOPHIA IMI EU Consortium

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German Center for Diabetes Research

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