Diabetes Mellitus after Pancreatic Surgery

Aim. To highlight the problem of pathogenesis, diagnostics and treatment of diabetes mellitus in the outcome of surgical interventions on the pancreas.

Key points. Diabetes mellitus can develop as a result of different diseases, including diseases of the exocrine part of the pancreas. Currently, the term “Diabetes of the Exocrine Pancreas” (DEP) is used. One of the causes of DEP is pancreatic surgery. Pancreatectomy is divided into two main types: total pancreatectomy and partial or pancreatic resection. Partial pancreatectomy, in turn, has two main subtypes: resection of the right half of the pancreas — pancreatoduodenal resection (PDR) and resection of the left half of the pancreas — distal resection (DR). When analyzing the literature data, it is clearly seen that the problem of metabolic outcomes of PDR and others is actively studied and is of great interest. Despite the approximately equal volume of resected tissue, diabetes mellitus occurs more often and earlier after DR, while after PDR, remission of pre-existing diabetes is possible in a significant number of patients. With regard to exocrine function, the situation is reversed — after PDR, the probability of developing exocrine pancreatic insufficiency is higher than after DR.

Conclusion. When studying the literature data, it becomes obvious that there is an urgent necessity to develop approaches to the early combination therapy in patients after pancreatic surgery with simultaneous correction of exo- and endocrine pancreatic.

1. Hart P.A., Bellin M.D., Andersen D.K., Bradley D. et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol. Hepatol. 2016;1(3):226–37. DOI: 10.1016/S2468-1253(16)30106-6

2. Niwano F., Hiromine Y., Noso S., Babaya N. et al. Insulin deficiency with and without glucagon: a comparative study between total pancreatectomy and type 1 diabetes. J. Diabetes Investig. 2018;9(5):1084–90. DOI: 10.1111/jdi.12799

3. Andrén-Sandberg Å., Ansorge C., Yadav T.D. Are there indications for total pancreatectomy in 2016? Dig. Surg. 2016;33(4):329–34. DOI: 10.1159/000445018

4. D’Cruz J.R., Misra S., Shamsudeen S. Pancreaticoduodenectomy. Treasure Island (FL): StatPearls Publishing; 2022.

5. Kriger A.G., Gorin D.S., Kaldarov A.R., Paklina O.V. et al. Pancreaticoduodenectomy: methodological aspects and results. P.A. Herzen Journal of Oncology. 2016;5(5):15-21. (in Russian). DOI: 10.17116/onkolog20165515-21

6. Shabunin A.V., Tavobilov M.M. Selecting the most appropriate method of forming pancreatodigestive anastomosis after radical pancreatic head cancer surgery. Journal of Volgograd State Medical University. 2016;13(1):121–5. (in Russian)

7. Schastnyy A.T. Surgical pancreatology: study guide. Vitebsk; 2017. 99 p. (in Russian)

8. Buriev I.M., Ikramov R.Z. Distal pancreatic resection. Annals of HPB Surgery. 1997;2:136–8. (in Russian)

9. Elliott I.A., Epelboym I., Winner M., Allendorf J.D. et al. Populationlevel incidence and predictors of surgically induced diabetes and exocrine insufficiency after partial pancreatic resection. Perm. J. 2017;21:16–095. DOI: 10.7812/TPP/16-095

10. Maxwell D.W., Jajja M.R., Tariq M., Mahmooth Z. et al. Development of diabetes after pancreaticoduodenectomy: results of a 10-year series using prospective endocrine evaluation. J. Am. Coll. Surg. 2019;228(4):400–412.e2. DOI: 10.1016/j.jamcollsurg.2018.12.042

11. Wu L., Nahm C.B., Jamieson N.B., Samra J. et al. Risk factors for development of diabetes mellitus (type 3c) after partial pancreatectomy: a systematic review. Clin. Endocrinol. (Oxf.). 2020;92(5):396–406. DOI: 10.1111/cen.14168

12. Kendall D.M., Sutherland D.E.R., Najarian J.S., Goetz F.C. et al. Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N. Engl. J. Med. 1990;322(13): 898–903. DOI: 10.1056/NEJM199003293221305

13. Kumar A.F., Gruessner R.W.G., Seaquist E.R. Risk of glucose intolerance and diabetes in hemipancreatectomized donors selected for normal preoperative glucose metabolism. Diabetes Care. 2008;31(8):1639–43. DOI: 10.2337/dc07-2453

14. You D.D., Choi S.-H., Choi D.-W., Heo J.-S. et al. Long-term effects of pancreaticoduodenectomy on glucose metabolism. ANZ J. Surg. 2012;82(6):447–51. DOI: 10.1111/j.1445-2197.2012.06080.x

15. Singh A.N., Pal S., Kilambi R., Madhusudhan K.S. et al. Diabetes after pancreaticoduodenectomy: can we predict it? J. Surg. Res. 2018;227:211–19. DOI: 10.1016/j.jss.2018.02.010

16. Kang J.S., Jang J.Y., Kang M.J., Kim E. et al. Endocrine function impairment after distal pancreatectomy: incidence and related factors. World J. Surg. 2016;40(2):440–6. DOI: 10.1007/s00268-015-3228-9

17. Shirakawa S., Matsumoto I., Toyama H., Shinzeki M. et al. Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy. J. Gastrointest. Surg. 2012;16(12): 2212–19. DOI: 10.1007/s11605-012-2039-7

18. Kobayashi I., Miyachi M., Kanai M., Nagino M. et al. Different gastric emptying of solid and liquid meals after pylorus-preserving pancreatoduodenectomy. Br. J. Surg. 1998;85(7):927–30. DOI: 10.1046/j.1365-2168.1998.00738.x

19. Kawai M., Tani M., Hirono S., Miyazawa M. et al. Pylorus ring resection reduces delayed gastric emptying in patients undergoing pancreatoduodenectomy: a prospective, randomized, controlled trial of pylorus-resecting versus pylorus-preserving pancreatoduodenectomy. Ann. Surg. 2011;253(3):495–501. DOI: 10.1097/SLA.0b013e31820d98f1

20. Matsumoto I., Shinzeki M., Asari S., Goto T. et al. A prospective randomized comparison between pylorus- and subtotal stomachpreserving pancreatoduodenectomy on postoperative delayed gastric emptying occurrence and long-term nutritional status. J. Surg. Oncol. 2014;109(7):690–6. DOI: 10.1002/jso.23566

21. Hanna M., Gadde R., Tamariz L., Allen C.J. et al. Delayed gastric emptying after pancreaticoduodenectomy: is subtotal stomach preserving better or pylorus preserving? J. Gastrointest. Surg. 2015;19(8):1542–52. DOI: 10.1007/s11605-015-2816-1

22. Harmuth S., Wewalka M., Holst J.J., Nemecek R. et al. Distal gastrectomy in pancreaticoduodenectomy is associated with accelerated gastric emptying, enhanced postprandial release of GLP-1, and improved insulin sensitivity. J. Gastrointest. Surg. 2014;18(1):52–9. DOI: 10.1007/s11605-013-2283-5

23. Muscogiuri G., Mezza T., Prioletta A., Sorice G.P. et al. Removal of duodenum elicits GLP-1 secretion. Diabetes Care. 2013;36(6): 1641–6. DOI: 10.2337/dc12-0811

24. Kang C.M., Lee J.H. Pathophysiology after pancreaticoduodenectomy. World J. Gastroenterol. 2015;21(19):5794–804. DOI: 10.3748/wjg.v21.i19.5794

25. Holst J.J. Postprandial insulin secretion after gastric bypass surgery: the role of glucagon-like peptide 1. Diabetes. 2011;60(9):2203–5. DOI: 10.2337/db11-0798

26. Holst J.J., Madsbad S., Bojsen-Møller K.N., Svane M.S. et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg. Obes. Relat. Dis. 2018;14(5):708–14. DOI: 10.1016/j.soard.2018.03.003

27. Hutch C.R., Sandoval D. The role of GLP-1 in the metabolic success of bariatric surgery. Endocrinology. 2017;158(12):4139–51. DOI: 10.1210/en.2017-00564

28. Burkhart R.A., Gerber S.M., Tholey R.M., Lamb K.M. et al. Incidence and severity of pancreatogenic diabetes after pancreatic resection. J. Gastrointest. Surg. 2015;19(2):217–25. DOI: 10.1007/s11605-014-2669-z

29. Bock E.A., Hurtuk M.G., Shoup M., Aranha G.V. Late complications after pancreaticoduodenectomy with pancreaticogastrostomy. J. Gastrointest. Surg. 2012;16(5):914–19. DOI: 10.1007/s11605-011-1805-2

30. Menge B.A., Schrader H., Breuer T.G.K., Dabrowski Y. et al. Metabolic consequences of a 50% partial pancreatectomy in humans. Diabetologia. 2009;52(2):306–17. DOI: 10.1007/s00125-008-1219-1

31. Lee B.-W., Kang H.-W., Heo J.-S., Choi S.-H. et al. Insulin secretory defect plays a major role in the development of diabetes in patients with distal pancreatectomy. Metabolism. 2006;55(1):135–41. DOI: 10.1016/j.metabol.2005.08.005

32. Hutchins R.R., Hart R.S., Pacifico M., Bradley N.J. et al. Longterm results of distal pancreatectomy for chronic pancreatitis in 90 patients. Ann. Surg. 2002;236(5):612–18. DOI: 10.1097/00000658-200211000-00011

33. King J., Kazanjian K., Matsumoto J., Reber H.A. et al. Distal pancreatectomy: incidence of postoperative diabetes. J. Gastrointest. Surg. 2008;12(9):1548–53. DOI: 10.1007/s11605-008-0560-5

34. Kodama K., Tojjar D., Yamada S., Toda K. et al. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care. 2013;36(6):1789–96. DOI: 10.2337/dc12-1235

35. Kang M.J., Jung H.S., Jang J.Y., Jung W. et al. Metabolic effect of pancreatoduodenectomy: resolution of diabetes mellitus after surgery. Pancreatology. 2016;16(2):272–7. DOI: 10.1016/j.pan.2016.01.006

36. Niwano F., Babaya N., Hiromine Y., Matsumoto I. et al. Glucose metabolism after pancreatectomy: opposite extremes between pancreaticoduodenectomy and distal pancreatectomy. J. Clin. Endocrinol. Metab. 2021;106(5):E2203–14. DOI: 10.1210/clinem/ dgab036

37. Charlson M.E., Pompei P., Ales K.L., MacKenzie C.R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 1987;40(5):373–83. DOI: 10.1016/0021-9681(87)90171-8

38. Sato N., Yamaguchi K., Chijiiwa K., Tanaka M. Duct-parenchymal ratio predicts exocrine pancreatic function after pancreatoduodenectomy and distal pancreatectomy. Am. J. Surg. 1998;176(3):270–3. DOI: 10.1016/s0002-9610(98)00144-5

39. Lankisch P.G. Exocrine pancreatic function tests. Gut. 1982; 23(9):777–98. DOI: 10.1136/gut.23.9.777

40. Scholten L., Mungroop T.H., Haijtink S.A.L., Issa Y. et al. Newonset diabetes after pancreatoduodenectomy: a systematic review and meta-analysis. Surgery. 2018;164(1):6–16. DOI: 10.1016/j.surg.2018.01.024

41. Fang W.-L., Su C.-H., Shyr Y.-M., Chen T.-H. et al. Functional and morphological changes in pancreatic remnant after pancreaticoduodenectomy. Pancreas. 2007;35(4):361–5. DOI: 10.1097/MPA.0b013e3180d0a8d5

42. Aspelund G., Topazian M.D., Lee J.H., Andersen D.K. et al. Improved outcomes for benign disease with limited pancreatic head resection. J. Gastrointest. Surg. 2005;9(3):400–9. DOI: 10.1016/j.gassur.2004.08.015

43. Wiltberger G., Muhl B., Benzing C., Atanasov G. et al. Preoperative risk stratification for major complications following pancreaticoduodenectomy: Identification of highrisk patients. Int. J. Surg. 2016;31:33–9. DOI: 10.1016/j.ijsu. 2016.04.034

44. Murakami Y., Uemura K., Hayashidani Y., Sudo T. et al. Long-term pancreatic endocrine function following pancreatoduodenectomy with pancreaticogastrostomy. J. Surg. Oncol. 2008;97(6):519–22. DOI: 10.1002/jso.21004

45. Bock E., Hurtuk M.G., Shoup M., Aranha G.V. Long term complications in patients undergoing pancreaticoduodenectomy with pancreaticogastrostomy. Gastroenterology. 2011;140 (5 suppl.1):S1022.

46. Ishida J., Toyama H., Matsumoto I., Shirakawa S. et al. Glucose tolerance after pancreatectomy: a prospective observational followup study of pancreaticoduodenectomy and distal pancreatectomy. J. Am. Coll. Surg. 2021;233(6):753–62. DOI: 10.1016/j.jamcollsurg.2021.08.688

47. Ravi P.K., Singh S.R., Mishra P.R. Redefining the tail of pancreas based on the islets microarchitecture and inter-islet distance: an immunohistochemical study. Medicine. 2021;100(17):E25642. DOI: 10.1097/MD.0000000000025642