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08-15-2018 | Nephropathy | Review | Article

Inpatient Glycemic Management in the Setting of Renal Insufficiency/Failure/Dialysis

Journal: Current Diabetes Reports

Authors: Ravi Iyengar, Jennifer Franzese, Roma Gianchandani

Publisher: Springer US



Purpose of this Review

Chronic diabetic nephropathy and renal dysfunction from other causes are common in hospitalized patients with diabetes. Available diabetes management guidelines aim to reduce hyperglycemia and hypoglycemia, both independent risk factors for hospital outcomes. Renal dysfunction, which increases the risk of hypoglycemia, adds a layer of complexity in diabetes management. Therefore, modified glucose goals and treatment regimens may be required.

Recent Findings

Recent prospective and retrospective studies provide direction on safe insulin therapy for diabetes inpatients with renal compromise. Studies of newer diabetes pharmacotherapy provide data on oral agent use in the inpatient setting.


Diabetes therapy should be modified with changing renal function. Glucose management in patients on peritoneal or hemodialysis is challenging. Reducing weight-based doses of insulin and use of newer insulins can reduce hypoglycemia risk. Safety and efficacy of DPP-4 inhibitors has been evaluated in the hospital and nursing home setting. Metformin, SGLT-2 inhibitors, and GLP1 receptor agonists can be used in several stages of renal dysfunction prior to and at discharge.
Aldukhayel A. Prevalence of diabetic nephropathy among type 2 diabetic patients in some of the Arab countries. Int J Health Sci (Qassim). 2017;11(1):1–4.
Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, et al. Diabetic kidney disease: a report from an ADA consensus conference. Diabetes Care. 2014;37(10):2864–83. CrossRefPubMedPubMedCentral
Thakar CV, Christianson A, Himmelfarb J, Leonard AC. Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus. Clin J Am Soc Nephrol. 2011; https://​doi.​org/​10.​2215/​CJN.​01120211. CrossRefPubMedPubMedCentral
Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16–38. CrossRefPubMed
Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):353–69. CrossRefPubMed
• Hung AM, Siew ED, Wilson OD, Perkins AM, Greevy RA, Horner J, et al. Risk of hypoglycemia following hospital discharge in patients with diabetes and acute kidney injury. Diabetes Care. 2018;41(3):503–12. Important recognition on the risk of hypoglycemic post-discharge in patients with compromised renal function. CrossRefPubMedPubMedCentral
Bakris GL, Molitch M. Are all patients with type 1 diabetes destined for dialysis if they live long enough? Probably Not. Diabetes Care. 2018;41(3):389–90. CrossRefPubMed
• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. The EMPA-REG trial demonstrates cardiovascular benefits in patients with diabetes on empagliflozin, which has significantly increased the improtance and use of SGLT-2 inhibitors in many diabetes regimens. CrossRefPubMed
• Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. The LEADER trial similarly demonstrated improved cardiovascular benefits in patients on liraglutide, increasing the utility of GLP-1 agonists in diabetes regimens. CrossRefPubMedPubMedCentral
Mak R. Renal disease, insulin resistance, and glucose intolerance. Diabetes Rev. 1994;2(1):19–28.
Dzurik R, Spustova V, Lajdova I. Inhibition of glucose utilization in isolated rat soleus muscle by pseudouridine: implications for renal failure. Nephron. 1993;65(1):108–10. CrossRefPubMed
Mak RH. 1, 25-dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia. Kidney Int. 1998;53(5):1353–7. CrossRefPubMed
Mak R, Bettinelli A, Turner C, Haycock GB, Chantler C. The influence of hyperparathyroidism on glucose metabolism in uremia. J Clin Endocrinol Metab. 1985;60(2):229–33. CrossRefPubMed
Mak R, Turner C, Haycock G, Chantler C. Secondary hyperparathyroidism and glucose intolerance in children with uremia. Kidney Int Suppl. 1983;16:S128–33. PubMed
Guthoff M, Wagner R, Vosseler D, Peter A, Nadalin S, Häring H-U, et al. Impact of end-stage renal disease on glucose metabolism—a matched cohort analysis. Nephrol Dial Transplant. 2017;32(4):670–6. CrossRefPubMed
• Gianchandani RY, Neupane S, Heung M. Hypoglycemia in hospitalized hemodialysis patients with diabetes: an observational study. J Diabetes Sci Technol. 2018;12(1):33–8. This study is one of first to highlight the important relationship of hypoglycemia in hospitalized patients on dialysis. CrossRefPubMedPubMedCentral
Association AD. 6. Glycemic targets: standards of medical care in diabetes—2018. Diabetes Care. 2018;41(Supplement 1):S55–64. CrossRef
Shurraw S, Hemmelgarn B, Lin M, Majumdar SR, Klarenbach S, Manns B, et al. Association between glycemic control and adverse outcomes in people with diabetes mellitus and chronic kidney disease: a population-based cohort study. Arch Intern Med. 2011;171(21):1920–7. CrossRefPubMed
Kalantar-Zadeh K, Kopple JD, Regidor DL, Jing J, Shinaberger CS, Aronovitz J, et al. A1C and survival in maintenance hemodialysis patients. Diabetes Care. 2007;30(5):1049–55. CrossRefPubMed
Draznin B. Managing diabetes and hyperglycemia in the hospital setting: a clinician’s guide: American Diabetes Association; 2016.
Kovesdy CP, Park JC, Kalantar-Zadeh K, editors. Glycemic control and burnt-out diabetes in ESRD. Seminars in dialysis; 2010: Wiley Online Library.
Flückiger R, Harmon W, Meier W, Loo S, Gabbay KH. Hemoglobin carbamylation in uremia. N Engl J Med. 1981;304(14):823–7. CrossRefPubMed
Tonyushkina K, Nichols JH. Glucose meters: a review of technical challenges to obtaining accurate results. Journal of diabetes science and technology. 2009;3(4):971–80. CrossRefPubMedPubMedCentral
Perera N, Stewart P, Williams P, Chua E, Yue D, Twigg S. The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis. Diabet Med. 2011;28(10):1272–6. CrossRefPubMed
Sbrignadello S, Pacini G, Tura A. Determination of glucose levels during dialysis treatment: different sensors and technologies. J Sens. 2016;2016:1–8. CrossRef
Guillausseau P, Charles M, Godard V, Timsit J, Chanson P, Paolaggi F, et al. Comparison of fructosamine with glycated hemoglobin as an index of glycemic control in diabetic patients. Diabetes Res (Edinb, Scotl). 1990;13(3):127–31.
Johnson RN, Metcalf PA, Baker JR. Fructosamine: a new approach to the estimation of serum glycosylprotein. An index of diabetic control. Clin Chim Acta. 1983;127(1):87–95. CrossRefPubMed
Armbruster DA. Fructosamine: structure, analysis, and clinical usefulness. Clin Chem. 1987;33(12):2153–63. PubMed
Koga M, Kasayama S. Clinical impact of glycated albumin as another glycemic control marker. Endocr J. 2010;57(9):751–62. CrossRefPubMed
Ansari A, Thomas S, Goldsmith D. Assessing glycemic control in patients with diabetes and end-stage renal failure. Am J Kidney Dis. 2003;41(3):523–31. CrossRefPubMed
Inaba M, Okuno S, Kumeda Y, Yamada S, Imanishi Y, Tabata T, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18(3):896–903. CrossRefPubMed
Peacock T, Shihabi Z, Bleyer A, Dolbare E, Byers J, Knovich M, et al. Comparison of glycated albumin and hemoglobin A1c levels in diabetic subjects on hemodialysis. Kidney Int. 2008;73(9):1062–8. CrossRefPubMed
Okada T, Nakao T, Matsumoto H, Shino T, Nagaoka Y, Tomaru R, et al. Association between markers of glycemic control, cardiovascular complications and survival in type 2 diabetic patients with end-stage renal disease. Intern Med. 2007;46(12):807–14. CrossRefPubMed
Fukuoka K, Nakao K, Morimoto H, Nakao A, Takatori Y, Arimoto K, et al. Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysis. Nephrology. 2008;13(4):278–83. CrossRefPubMed
Charpentier G, Riveline J, Varroud-Vial M. Management of drugs affecting blood glucose in diabetic patients with renal failure. Management. 2011;110897
Dobri GA, Lansang MC. Q: how should we manage insulin therapy before surgery? Cleve Clin J Med. 2013;80(11):702–4. CrossRefPubMed
Rosenblatt SI, Dukatz T, Jahn R, Ramsdell C, Sakharova A, Henry M, et al. Insulin glargine dosing before next-day surgery: comparing three strategies. J Clin Anesth. 2012;24(8):610–7. CrossRefPubMed
Baldwin D, Zander J, Munoz C, Raghu P, DeLange-Hudec S, Lee H, et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care. 2012;35(10):1970–4. CrossRefPubMedPubMedCentral
Kulozik F, Hasslacher C. Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin? Ther Adv Endocrinol Metab. 2013;4(4):113–21. CrossRefPubMedPubMedCentral
Khanna R. Dialysis considerations for diabetic patients. Kidney Int Suppl. 1993;40:S58. PubMed
Sobngwi E, Enoru S, Ashuntantang G, Azabji-Kenfack M, Dehayem M, Onana A, et al. Day-to-day variation of insulin requirements of patients with type 2 diabetes and end-stage renal disease undergoing maintenance hemodialysis. Diabetes Care. 2010;33(7):1409–12. CrossRefPubMedPubMedCentral
Aisenpreis U, Pfützner A, Giehl M, Keller F, Jehle P. Pharmacokinetics and pharmacodynamics of insulin lispro compared with regular insulin in haemodialysis patients with diabetes mellitus. Nephrol Dial Transplant. 1999;14(suppl_4):5–6. CrossRefPubMed
Raz I, Wilson PW, Strojek K, Kowalska I, Bozikov V, Gitt AK, et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009;32(3):381–6. CrossRefPubMedPubMedCentral
Toyoda M, Kimura M, Yamamoto N, Miyauchi M, Umezono T, Suzuki D. Insulin glargine improves glycemic control and quality of life in type 2 diabetic patients on hemodialysis. J Nephrol. 2012;25(6):989–95. CrossRefPubMed
Bouchi R, Babazono T, Onuki T, Mitamura K, Ishikawa Y, Uchigata Y, et al. Administration of insulin glargine thrice weekly by medical staff at a dialysis unit: a new insulin regimen for diabetic management in physically impaired patients undergoing hemodialysis. Diabetol Int. 2011;2(4):197–201. CrossRef
Kiss I, Arold G, Roepstorff C, Bøttcher SG, Klim S, Haahr H. Insulin degludec: pharmacokinetics in patients with renal impairment. Clin Pharmacokinet. 2014;53(2):175–83. CrossRefPubMed
Jacobsen LV, Popescu G, Plum A. Pharmacokinetics of insulin detemir in subjects with renal or hepatic impairment. Diabetes. 2002;51:A102.
Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol. 2005;60(5):469–76. CrossRefPubMedPubMedCentral
Jackson M, Holland M, Nicholas J, Lodwick R, Forster D, Macdonald I. Hemodialysis-induced hypoglycemia in diabetic patients. Clin Nephrol. 2000;54(1):30–4. PubMed
Burmeister JE, Scapini A, da Rosa MD, da Costa MG, Campos BM. Glucose-added dialysis fluid prevents asymptomatic hypoglycaemia in regular haemodialysis. Nephrol Dial Transplant. 2007;22(4):1184–9. CrossRefPubMed
Raimann JG, Kruse A, Thijssen S, Kuntsevich V, Dabel P, Bachar M, et al. Metabolic effects of dialyzate glucose in chronic hemodialysis: results from a prospective, randomized crossover trial. Nephrol Dial Transplant. 2011;27(4):1559–68. CrossRefPubMed
Almalki MH, Mansour AM, Almehthel MS, Sirrs SM. Subcutaneous versus intraperitoneal insulin for patients with diabetes mellitus on continuous ambulatory peritoneal dialysis: meta-analysis of non-randomized clinical trials. Clin Invest Med (Online). 2012;35(3):E132. CrossRef
Quellhorst E. Insulin therapy during peritoneal dialysis: pros and cons of various forms of administration. J Am Soc Nephrol. 2002;13(suppl 1):S92–S6. PubMed
Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, et al. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013;36(11):3430–5. CrossRefPubMedPubMedCentral
• Pasquel FJ, Gianchandani R, Rubin DJ, Dungan KM, Anzola I, Gomez PC, et al. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol. 2017;5(2):125–33. The use of DPP-IV inhibitors in hospitalized patients is a new paradigm to offer easy and effective therapy in the hospital with low risk for hypoglycemia. This study specifically explores the use of sitagliptin. CrossRefPubMed
• Garg R, Schuman B, Hurwitz S, Metzger C, Bhandari S. Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients. BMJ Open Diabetes Res Care. 2017;5(1):e000394. Another exploration into DPP-IV inhibitors, specifically saxaglipitin, as non-inferior to certain diabetes regimens with low risk for hypoglycemia. CrossRefPubMedPubMedCentral
• Vellanki P, Alexanian S, Baldwin D, Rasouli N, Anzola IA, Ramos C, et al. Editors. Efficacy and safety of linagliptin in general surgical patients with type 2 diabetes: linagliptin surgery trial. Diabetes; 2017: American Diabetes Association 1701 N Beauregard St, Alexandria, Va 22311–1717 USA . Demonstration of linagliptin as an effective treatment for mild-to-moderate hyperglycemia with lower incidence of hypoglycemia than basal/bolus regimens.
• Umpierrez GE, Cardona S, Chachkhiani D, Fayfman M, Saiyed S, Wang H, et al. A randomized controlled study comparing a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in patients with type 2 diabetes in long-term care and skilled nursing facilities: linagliptin-LTC trial. J Am Med Dir Assoc. 2017; Incorporating the DPP-IV inhibitor linagliptin as part of diabetes regimens on discharge to nursing homes is particulalry safe with lower incidences of hypoglycemia in this at-risk population.
Meier JJ, Weyhe D, Michaely M, Senkal M, Zumtobel V, Nauck MA, et al. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes. Crit Care Med. 2004;32(3):848–51. CrossRefPubMed
Galiatsatos P, Gibson BR, Rabiee A, Carlson O, Egan JM, Shannon RP, et al. The glucoregulatory benefits of glucagon-like peptide-1 (7-36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study. Crit Care Med. 2014;42(3):638–45. CrossRefPubMedPubMedCentral
• Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): a randomized clinical trial. Diabetes Care. 2016;39(2):222–30. Patients with mild-to-moderate renal impairment can still obtain benefits of the GLP-1 agonist liraglutide without further compromise to renal function. PubMed
• Lalau J-D, Kajbaf F, Bennis Y, Hurtel-Lemaire A-S, Belpaire F, De Broe ME. Metformin treatment in patients with type 2 diabetes and chronic kidney disease stages 3A, 3B, or 4. Diabetes Care. 2018; https://​doi.​org/​10.​2337/​dc17-2231. New data to suggest patients with moderate-to-servere renal impairment can still benefit from metformin in modified doses, without further compromising renal function or increasing the incidence of lactic acidosis. CrossRefPubMed
Metformin prescribing information. Bristol-Meyers Squibb. Available at https://​packageinserts.​bms.​com/​pi/​pi_​glucophage_​xr.​pdfAccessed June 2018.