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Exp Clin Endocrinol Diabetes 2022; 130(01): 55-60
DOI: 10.1055/a-1220-6160
Article

Glucagon and Liver Fat are Downregulated in Response to Very Low-calorie Diet in Patients with Obesity and Type-2 Diabetes

Stephan L. Haas
1   Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
,
Patrik Löfgren
1   Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
,
Per Stål
1   Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
,
Johan Hoffstedt
1   Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
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Abstract

Background and Study Aims In patients with obesity and type-2 diabetes, short-time very low-calorie diet may ameliorate hyperglycemia and hepatic steatosis. Whether this also implies the glucose-regulating hormone glucagon remains to be elucidated. This study investigated the effects of a very low-calorie diet on plasma levels of glucagon and liver fat in obese patients with type-2 diabetes.

Patients and Methods Ten obese patients with type-2 diabetes, 6 men and 4 women, were included. At baseline, fasting plasma glucagon, insulin and glucose were determined, and liver fat and stiffness evaluated by transient elastography. The subjects were then prescribed a very low-calorie diet of maximum 800 kcal/day for 7 weeks and reexamined after 7 weeks and 12 months.

Results At baseline, BMI was 42±4 kg/m2 and fasting glucose 10.6±3.4 mmol/l. All patients had hepatic steatosis. Plasma glucagon was strongly related to liver fat (r2=0.52, p=0.018). After 7 weeks of very low-calorie diet, plasma glucagon was significantly decreased by nearly 30% (p=0.004) along with reductions of BMI (p<0.0001), glucose (p=0.02), insulin (p=0.03), liver fat (p=0.007) and liver stiffness (p=0.05). At 12 months follow-up, both glucagon and liver fat increased and were not different to basal levels, despite persistent reductions of BMI (p<0.002) and glucose (p=0.008).

Conclusion In obese type-2 diabetic subjects, plasma glucagon and liver fat are correlated and similarly affected by a very low-calorie diet, supporting a role of hepatic steatosis in glucagon metabolism.

Key words

fatty liver - glucose - insulin - liver stiffness - weight reduction


Publication History

Received: 26 May 2020
Received: 02 July 2020

Accepted: 13 July 2020

Article published online:
06 August 2020

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
    CrossrefPubMedGoogle Scholar
  • 2 Byrne CD, Targher G. NAFLD: A multisystem disease. Journal of Hepatology 2015; 62: 47-64
    CrossrefPubMedGoogle Scholar
  • 3 Tilg H, Moschen AR, Roden M. NAFLD and diabetes mellitus. Nature Reviews Gastroenterology & Hepatology 2017; 14: 32-42
    CrossrefPubMedGoogle Scholar
  • 4 Meex RCR, Watt MJ. Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol 2017; 13: 509-520
    CrossrefPubMedGoogle Scholar
  • 5 Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: Causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019; 7: 313-324
    CrossrefPubMedGoogle Scholar
  • 6 Liljenquist JE, Mueller GL, Cherrington AD. et al. Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J Clin Invest 1977; 59: 369-374
    CrossrefPubMedGoogle Scholar
  • 7 Reaven GM, Chen YD, Golay A. et al. Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1987; 64: 106-110
    CrossrefPubMedGoogle Scholar
  • 8 Junker AE, Gluud L, Holst JJ. et al. Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting Hyperglucagonemia. J Intern Med 2016; 279: 485-493
    CrossrefPubMedGoogle Scholar
  • 9 Anoop S, Misra A, Bhatt S. et al. High Plasma glucagon levels correlate with waist-to-hip ratio, suprailiac skinfold thickness, and deep subcutaneous abdominal and intraperitoneal adipose tissue depots in nonobese Asian Indian Males with type 2 diabetes in North India. 2017; 2017: 2376016
    PubMedGoogle Scholar
  • 10 Petersen KF, Dufour S, Befroy D. et al. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005; 54: 603-608
    CrossrefPubMedGoogle Scholar
  • 11 Lim EL, Hollingswirth KG, Aribisala BS. et al. Reversal of type 2 diabetes: Normalization of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54: 2506-2514
    CrossrefPubMedGoogle Scholar
  • 12 Steven S, Taylor R. Restoring normoglycaemia by use of a very low calorie diet in long- and short-duration type 2 diabetes. Diabet Med 2015; 32: 1149-1155
    CrossrefPubMedGoogle Scholar
  • 13 Steven S, Hollingsworth KG, Al-Mrabeh A. et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: Pathophysiological changes in responders and nonresponders. Diabetes Care 2016; 39: 808-815
    CrossrefPubMedGoogle Scholar
  • 14 Taylor R, Al-Mrabeh A, Zhyzhneuskaya S. et al. Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for beta cell recovery. Cell Metabolism 2018; 28: 547-556
    CrossrefPubMedGoogle Scholar
  • 15 Lee K, Lee S, Kim YJ. Waist circumference, dual-energy X-ray absortiometrically measured abdominal adiposity, and computed tomographically derived intra-abdominal fat area on detecting metabolic risk factors in obese women. Nutrition 2008; 24: 625-631
    CrossrefPubMedGoogle Scholar
  • 16 de Ledinghen V, Wong GL, Vergniol J. et al. Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology 2016; 31: 848-855
    CrossrefPubMedGoogle Scholar
  • 17 de Ledinghen V, Hiriart JB, Vergniol J. et al. Controlled Attenuation Parameter (CAP) with the XL Probe of the Fibroscan((R)): A Comparative Study with the M Probe and Liver Biopsy. Dig Dis Sci 2017; 62: 2569-2577
    CrossrefPubMedGoogle Scholar
  • 18 Eddowes PJ, Sasso M, Allison M. et al. Accuracy of fibroscan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 2019; 156: 1717-1730
    CrossrefPubMedGoogle Scholar
  • 19 EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63: 237-264
    CrossrefPubMedGoogle Scholar
  • 20 Castera L, Friedrich-Rust M, Lomba R. Non-invasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology 2019; 156: 1264-1281
    CrossrefPubMedGoogle Scholar
  • 21 Myers RP, Pomier-Layrargues G, Kirsch R. et al. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology 2012; 55: 199-208
    CrossrefPubMedGoogle Scholar
  • 22 Williams CD, Stengel J, Asike MI. et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study. Gastroenterology 2011; 140: 124-131
    CrossrefPubMedGoogle Scholar
  • 23 Loomba R, Abraham M, Unalp A. et al. Nonalcoholic Steatohepatitis Clinical Research Network. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 2012; 56: 943-951
    CrossrefPubMedGoogle Scholar
  • 24 Suppli MPA, Bagger JI, Vilsbøll T. et al. Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia. Medical Hypotheses 2016; 86: 100-103
    CrossrefPubMedGoogle Scholar
  • 25 Knop FK. EJE PRIZE 2018: A gut feeling about glucagon. European Journal of Endocrinology 2018; 178: R267-R280
    CrossrefPubMedGoogle Scholar
  • 26 Faerch K, Vistisen D, Pacini G. et al. Insulin resistance is accompanied by increased fasting glucagon and delayed glucagon suppression in individuals with normal and impaired glucose regulation. Diabetes 2016; 65: 3473-3481
    CrossrefPubMedGoogle Scholar
  • 27 Bannas P, Kramer H, Hernando D. et al. Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers. Hepatology 2015; 62: 1444-1455
    CrossrefPubMedGoogle Scholar
  • 28 Wang JH, Ou HY, Yen YH. et al. Usefulness of controlled attenuation parameter in detecting and monitoring hepatic steatosis with MRI-PDFF as Reference. Dig Dis Sci 2020; 65: 1512-1519
    CrossrefPubMedGoogle Scholar