Clinical characteristics of patients with type 2 diabetes mellitus based on hypoglycemia frequency

Czech version

Authors: Michaela Plichtová; Emil Martinka
Authors‘ workplace: Národný endokrinologický a diabetologický ústav, n. o., Ľubochňa
Published in: Forum Diab 2020; 9(1): 13-21
Category:

Overview

Goal: By means of a retrospective cross-sectional study in the conditions of normal clinical practice, to give a statement on the clinical and laboratory characteristics of patients with DM2T with a more frequent IHG occurrence of iatrogenic hypoglycemia (IHG), and whether a more frequent occurrence is associated with an anamnesis of a more/less frequent occurrence of diabetes complications, atherosclerotic cardiovascular diseases and other selected comorbidities, including endocrinology (ENDO) and oncological (ONCO) diseases.

Cohort and methods: A retrospective cross-sectional study in the conditions of normal clinical practice in hospitalized patients with DM2T. The records of patient self-monitoring during the last month before hospitalization were used to evaluate a IH frequency. All the recorded glycemia values < 3.9 mmol/l were considered to be IH. Based on a IHG occurrence patients were divided into three subgroups: without recorded IHG (0IHG), with 1–2 recorded IHG (1–2IHG) and with three and more recorded IHG (> 3IHG). Clinical and laboratory parameters, incidence of diabetes related complications, CVD, ENDO, ONCO and other chronic comorbidities among the groups were compared, as well as those of antidiabetic, hypolipidemic, antihypertensive and antiplatelet and anticoagulant therapy. Data on patients was obtained from patient documentation and current examinations during hospitalization, within which a IHG occurrence within the initial 7 days of hospitalization was also evaluated based on standard 7-point glycemic profiles and glycemia testing any time during the day when required by the clinical situation.

Results: The study included 294 patients with DM2T. > 3IHG (n = 44) as compared to 0IHG (n = 186) was associated with a lower body weight (BW), a lower BMI, smaller waist circumference (WC), higher HDL-cholesterol levels (HDL), lower triglyceride levels (TAG), a better HDL/TAG index, lower HbA_1c and more frequent treatment with insulin. LDL-cholesterol levels (LDL), the values of blood pressure (BP), glomerular filtration (eGF), urine albumin and creatinine ratio (UACR), the ratio between smokers and patients with hypertension did not differ among the groups, and the proportion of patients with eGF < 60ml/1.73m²was higher in the group with > 3IHG and was not associated with an increased or lower occurrence of CVD, ENDO, ONCO or any other monitored comorbidities.

Conclusion: The results highlighted the heterogeneity of patients with DM2T, which is also shown in a IHG occurrence, while a higher IHG occurrence was associated with a lower BW and BMI, smaller waist circumference, higher HDL levels, lower TAG levels, a lower HbA_1c, a higher proportion of patients with eGF < 60ml/1.73m² and more frequent insulin treatment. These characteristics are probably linked to a lower level of insulin resistance and also a more frequently occurring chronic kidney disease. Other parameters of CV risk, such as LDL-cholesterol levels, BP, eGF, UACR values or the ratio between smokers and patients with hypertension did not differ among the groups. A higher occurrence of IHG was not associated with an increased or lower occurrence of CVD, ENDO, ONCO or any other monitored comorbidities. However the results will need to be verified in a larger cohort of patients.

Keywords:

hypoglycemia – clinical characteristics – complications – type 2 diabetes mellitus

Sources

Adler KG, Bonyhay I, Failing H et al. Antecedent hypoglycemia impairs autonomic cardiovascular function. Implications for rigorous glycemic control. Diabetes 2009; 58(2): 360–366. Dostupné z DOI: <http://dx.doi.org/10.2337/db08–1153>.
Bedenis R, Price AH, Robertson CM et al. Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh Type 2 Diabetes Study. Diabetes Care 2014; 37(12): 3301–3308. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–0908>
Bonds DE, Miller ME, Bergenstal RM et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospecitve epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.b4909>.
Cryer PE. Severe Hypoglycemia Predicts Mortality in Diabetes. Diabetes Care 2012; 35(9): 1814–1816. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0749>
Davies MJ, David A, D‘Alessio DA et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; dci180033. Dostupné z DOI: <https://doi.org/10.2337/dci18–0033>.
Desouza C, Salazar H, Cheong B et al. Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. Diabetes Care 2003; 26(5): 1485–1489. Dostupné z DOI: <http://dx.doi.org/10.2337/diacare.26.5.1485>.
Duckworth W, Abraira C, Moritz T et al. [VADT Investigators]. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360(2): 129–139. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0808431>.
Gerstein HC, Miller ME, Byington RP et al. [Action to Control Cardiovascular Risk in Diabetes Study Group]. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545–2559. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0802743>.
Gill GV, Woodward A, Casson IF et al. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes–the ‘dead in bed’ syndrome revisited. Diabetologia 2009; 52(1): 42–45. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–008–1177–7>.
Goto A, Goto M, Terauchi Y et al. Association between severe hypoglycemia and cardiovascular disease risk in Japanese patients with type 2 diabetes. J Am Heart Assoc 2016; 5(3): e002875. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.115.002875>.
Graveling AJ, Frier BM. Does hypoglycaemia cause cardiovascular events? Br J Diabetes Vasc Dis 2010; 10(1): 5–13. Dostupné z DOI: <https://doi.org/10.1177/1474651409355113>.
Hannefeld M, Frier BM, Pistroschet F al. Hypoglycemia and Cardiovascular Risk: Is there a Major Link? Diabetes Care 2016; 39(Suppl 2): S205–S209. Dostupné z DOI: <http://dx.doi.org/10.2337/dcS15–3014>.
Khunti K, Davies M, Majeed A et al. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care 2015;38(2): 316–322. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–0920>.
Kosibord M, Inzucchi SE, Goyal A et al. Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009; 301(15): 1556–1564. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2009.496>.
Laitinen T, Lyyra-Laitinen T, Huopio H et al. Electrocardiographic alterations during hyperinsulinemic hypoglycemia in healthy subject. Ann Noninvasive Electrocardiol 2008; 13(2): 97–105. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1542–474X.2008.00208.x>.
Lee AK, Warren B, Lee CJ et al. The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes Diabetes Care 2018; 41(1): 104–111. Dostupné z DOI: <https://doi.org/10.2337/dc17–1669>.
Lee AK, Lee CJ, Huang ES et al. Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 2017; 40 (12): 1661–1667. Dostupné z DOI: <http://dx.doi.org/10.2337/dc17–0819>.
Leong A, Berkowitz SA, Triant VA et al. Hypoglycemia in diabetes mellitus as a coronary artery disease risk factor in patients at elevated vascular risk. J Clin Endocrinol Metab 2016; 101(2): 659–668. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2015–3169>.
Mahmoodpoor A, Hamishehkar H, Beigmohammadi M et al. Predisposing Factors for Hypoglycemia and Its Relation With Mortality in Critically Ill PatientsUndergoing Insulin Therapy in an Intensive Care Unit. Anesth Pain Med 2016; 6(1): e33849. Dostupné z DOI: <http://dx.doi.org/10.5812/aapm.33849>.
McCoy RG, Van Houten HK, Ziegenfuss JY et al. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012; 35(9): 1897–1901. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–2054>.
Mellbin LG, Ryd ´en L, Riddle MC et al. [ORIGIN Trial Investigators]. Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial. Eur Heart J 2013; 34(40): 3137–3144. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/eht332>.
[ORIGIN Trial Investigators]. Predictors of nonsevere and severe hypoglycemia during glucose lowering treatment with insulin glargine or standard drugs in the ORIGIN trial. Diabetes Care 2015; 38(1): 22–28. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–1329>.
Patel A, MacMahon S, Chalmers J et al. [ADVANCE Collaborative Group]. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358(24): 2560–2572. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0802987>.
Raz I, Wilson PW, Strojek K et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in tye 2 diabetes. The HEART2D trial. Diabetes Care 2009; 32(3): 381–386. Dostupné z DOI: <http://dx.doi.org/10.2337/dc08–1671>.
Saremi A., Bahn GD, Reaven PE. [Veterans Affairs Diabetes Trial (VADT)]. A Link Between Hypoglycemia and Progression of Atherosclerosis in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care 2016; 39(3), 448–454. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–2107>.
Stahn A, Pistrosch F, Ganz X et al. Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care 2014; 37(2): 516–520. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–0600>.
Svensson AM, McGuire DK, Abrahamsson P et al. Association between hyper and hypoglycaemia and 2 year all-cause mortality risk in diabetic patients with acute coronary events. Eur Heart J 2005; 26(13): 1255–1261. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehi230>.
Tschope D, Bramlage, P, Binz Ch et al. Incidence and predisctors of hypoglycemia in type 2 diabetes – analysis of the prospective DiaRegis registry. BMC Endocrine Disorders 2012; 12: 23. Dostupné z DOI: <http://dx.doi.org/10.1186/1472–6823–12–23>.
Wright RJ, Newby DE, Stirling D et al. Effects of acute insulin induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes. Diabetes Care 2010; 33(7): 1591–1597. Dostupné z DOI: <http://dx.doi.org/10.2337/dc10–0013>,
Yakubovich N, Gerstein H. Serious cardiovascular outcomes in diabetes. The role of hypoglycaemia. Circulation 2011; 123(3): 342–348. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.110.948489>.
Zoungas S, Patel A, Chalmers J et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med, 2010; 363(15):1410–1418. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1003795>.