Poboljšanje glikoregulacije, snižavanje broja hipoglikemija, telesne mase i nivoa C-reaktivnog proteina kod bolesnika sa dijabetesom melitusom tipa 1 na intenziviranoj insulinskoj terapiji analozima insulina
Sažetak
Uvod/Cilj. Dobra metabolička kontrola može odložiti nastanak i napredovanje hroničnih komplikacija dijabetesa melitusa (DM). Intenzivirana insulinska terapija (IIT) je kamen temeljac dobre metaboličke kontrole u lečenju bolesnika sa tipom 1 DM (T1DM), uz izbegavanje hipoglikemije i povećanja telesne mase (TM) kod tih bolesnika. Cilj rada bio je da se procene efekti primene IIT analozima insulina (aspart i glargin) na obolele od T1DM. Metode. Prospektivnim kliničkim istraživanjem obuhvaćeno je 49 bolesnika sa T1DM u trajanju od najkraće jedne godine, koji su tada bili na IIT humanim insulinima. Uveden im je insulin aspart u trajanju od tri meseca, a zatim insulin glargin takođe u trajanju od tri meseca. Urađena im je analiza nivoa glukoze u krvi (GK) (glikoziliranog hemoglobina – HbA1c, srednjeg nivoa GK, GK natašte, postprandijalne GK i glikemijske varijabilnosti) i analiza TM, broja hipoglikemija i nivoa C-reaktivnog proteina (CRP). Rezultati. Nivo HbA1c je posle tri meseca terapije insulinom aspart bio neznatno (bez značajnosti) snižen (sa 9,28% na 8,83%), a posle kombinacije aspart/glargin bio je značajno snižen (na 8,08%; p < 0,001). Posle prva tri meseca, zabeleženo je značajno ublažavanje nivoa postprandijalne GK nakon sva tri glavna obroka. Srednji postprandijalni porast GK bio je značajno smanjen. Varijabilnost dnevne GK je bila značajno smanjena (standardna devijacija dnevne GK smanjena je sa 2,28 mmol/L na 1,90 mmol/L; p < 0,05). Srednja vrednost GK u profilima je opala (sa 9,11 mmol/L na 8,31 mmol/L; p < 0,05). Sve vrednosti GK u profilima posle šest meseci bile su statistički značajno niže u odnosu na početne vrednosti, kao i srednje vrednosti GK (6,88 mmol/L; p < 0,001) i varijabilnost dnevne GK (1,49 mmol/L; p < 0,01). Naši rezultati pokazali su značajno smanjenje broja hipoglikemija posle tri meseca, a posebno nakon uvođenja terapije insulinskim analogom glargin (značajno smanjenje broja simptomatskih, asimptomatskih i noćnih hipoglikemija). Rezultati su pokazali diskretno, ali značajno smanjenje TM i značajno sniženje nivoa CRP (sa 3,43 mg/L na 2,25 mg/L; p < 0,001). Zaključak. Terapija obolelih od T1DM analozima insulina (insulin aspart i insulin glargin) u IIT dovodi do poboljšanja kontrole GK sa smanjenjem broja hipoglikemija, TM i nivoa CRP.
Reference
Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977–86.
Rodbard HW, Rodbard D. Biosynthetic Human Insulin and Insulin Analogs. Am J Ther 2020; 27(1): e42–51.
Bolli GB, Cheng AYY, Owens DR. Insulin: evolution of insulin formulations and their application in clinical practice over 100 years. Acta Diabetol 2022; 59(9): 1129–44.
Anand SS, Dagenais GR, Mohan V, Diaz R, Probstfield J, Freeman R, et al. Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study. Eur J Prev Cardiol 2012; 19(4): 755–64.
Milicevic Z, Raz I, Beattie SD, Campaigne BN, Sarwat S, Gromniak E, et al. Natural history of cardiovascular disease in patients with diabetes: role of hyperglycemia. Diabetes Care 2008; 31(Suppl 2): S155–60.
Lazar S, Ionita I, Reurean-Pintilei D, Timar R, Luca SA, Timar B. To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study. J Clin Med 2024; 13(2): 450.
Meng X, Gong C, Cao B, Peng X, Wu D, Gu Y, et al. Glucose fluctuations in association with oxidative stress among children with T1DM: comparison of different phases. J Clin Endocrinol Metab 2015; 100(5): 1828–36.
McDonnell ME, Umpierrez GE. Insulin therapy for the management of hyperglycemia in hospitalized patients. Endocrinol Metab Clin North Am 2012; 41(1): 175–201.
Ceriello A, Colagiuri S. International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations. Diabet Med 2008; 25(10): 1151–6.
Ceriello A, Ihnat MA. 'Glycaemic variability': a new therapeutic challenge in diabetes and the critical care setting. Diabet Med 2010; 27(8): 862–7.
Suh S, Kim JH. Glycemic Variability: How Do We Measure It and Why Is It Important? Diabetes Metab J 2015; 39(4): 273–82.
Ratner RE. Hypoglycemia: New Definitions and Regulatory Implications. Diabetes Technol Ther 2018; 20(S2): S250–3.
Gerstein HC, Rutty CJ. Insulin Therapy: The Discovery That Shaped a Century. Can J Diabetes 2021; 45(8): 798–803.
Hegele RA, Maltman GM. Insulin's centenary: the birth of an idea. Lancet Diabetes Endocrinol 2020; 8(12): 971–7.
Bogun M, Inzucchi SE. Inpatient management of diabetes and hyperglycemia. Clin Ther 2013; 35(5): 724–33.
Johnson ML, Bergenstal RM, Levy BL, Dreon DM. A Safe and Simple Algorithm for Adding and Adjusting Mealtime Insulin to Basal-Only Therapy. Clin Diabetes 2022; 40(4): 489–97.
Guerci B, Sauvanet JP. Subcutaneous insulin: pharmacokinetic variability and glycemic variability. Diabetes Metab 2005; 31(4 Pt 2): 4S7–24.
Holl RW, Swift PG, Mortensen HB, Lynggaard H, Hougaard P, Aanstoot HJ, et al. Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidore study group. Eur J Pediatr 2003; 162(1): 22–9.
Goldman J, Kapitza C, Pettus J, Heise T. Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice. Curr Med Res Opin 2017; 33(10): 1821–31.
Peterson GE. Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir. Curr Med Res Opin 2006; 22(12): 2613–9.
Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Diabetes Care 2000; 23(5): 639–43.
Devries JH, Nattrass M, Pieber TR. Refining basal insulin therapy: what have we learned in the age of analogues? Diabetes Metab Res Rev 2007; 23(6): 441–54.
Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007; (2): CD005613. Update in: Cochrane Database Syst Rev 2020; 11: CD005613.
Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev 2006; (2): CD003287.
Gough SC. A review of human and analogue insulin trials. Diabetes Res Clin Pract 2007; 77(1): 1–15.
Hermansen K, Fontaine P, Kukolja KK, Peterkova V, Leth G, Gall MA. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. Diabetologia 2004; 47(4): 622–9.
Ashwell SG, Amiel SA, Bilous RW, Dashora U, Heller SR, Hepburn DA, et al. Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes. Diabet Med 2006; 23(3): 285–92.
Murphy NP, Keane SM, Ong KK, Ford-Adams M, Edge JA, Acerini CL, et al. Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens. Diabetes Care 2003; 26(3): 799–804.
Gerich JE. Clinical significance, pathogenesis, and management of postprandial hyperglycemia. Arch Intern Med 2003; 163(11): 1306–16.
DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 2003; 26(3): 688–96.
Shaefer C, Reid T, Vlajnic A, Zhou R, DiGenio A. Fasting Versus Postprandial Hyperglycemia As A Treatment Target To Lower Elevated Hemoglobin A1C. Endocr Pract 2015; 21(12): 1323–32.
National Clinical Guideline Centre (UK). Type 1 Diabetes in Adults: Diagnosis and Management. National Clinical Guideline NG17. London: National Institute for Health and Care Excellence (NICE); 2015.
Radenković S, Golubović M, Radojković D, Ćirić V, Kocić R. Treatment Satisfaction in Patients with Diabetes Mellitus Type 1 Treated with Intensified Insulin Therapy with Insulin Analogues. Acta Fac Med Naiss 2021; 38(3): 240–6.
Lin YK, Fisher SJ, Pop-Busui R. Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies. J Diabetes Investig 2020; 11(6): 1388–402.
Macon EL, Devore MH, Lin YK, Music MB, Wooten M, McMullen CA, et al. Current and future therapies to treat impaired awareness of hypoglycemia. Front Pharmacol 2023; 14: 1271814.
Hashmi HZ, Khowaja A, Moheet A. Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review. Front Pharmacol 2024; 15: 1349004.
Hölzen L, Schultes B, Meyhöfer S, Meyhöfer S. Hypoglycemia Unawareness-A Review on Pathophysiology and Clinical Implications. Biomedicines 2024; 12(2): 391.
Pesić M, Zivić S, Radenković S, Velojić M, Dimić D, Antić S. [Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy]. Vojnosanit Pregl 2007; 64(4): 247–52. (Serbian)
Kilpatrick ES, Rigby AS, Goode K, Atkin SL. Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetes. Diabetologia 2007; 50(12): 2553–61.
Sarteau AC, Kahkoska AR, Crandell J, Igudesman D, Corbin KD, Kichler JC, et al. More hypoglycemia not associated with increasing estimated adiposity in youth with type 1 diabetes. Pediatr Res 2023; 93(3): 708–14.
Brown RJ, Wijewickrama RC, Harlan DM, Rother KI. Uncoupling intensive insulin therapy from weight gain and hypoglycemia in type 1 diabetes. Diabetes Technol Ther 2011; 13(4): 457–60.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107(3): 499–511.
Colak A, Akinci B, Diniz G, Turkon H, Ergonen F, Yalcin H, et al. Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes. Scand J Clin Lab Invest 2013; 73(5): 422–7.
Emerson SR, Kurti SP, Harms CA, Haub MD, Melgarejo T, Logan C, et al. Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review. Adv Nutr 2017; 8(2): 213–25.
Jialal I, Devaraj S. Anti-inflammatory Strategies to Prevent Diabetic Cardiovascular Disease. Clin Pharmacol Ther 2015; 98(2): 121–3.
Schaumberg DA, Glynn RJ, Jenkins AJ, Lyons TJ, Rifai N, Manson JE, et al. Effect of intensive glycemic control on levels of markers of inflammation in type 1 diabetes mellitus in the diabetes control and complications trial. Circulation 2005; 111(19): 2446–53.