1 Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: 1384–95.
2 Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545–59.
3 Bliss M. The discovery of insulin. Chicago: University of Chicago Press, 1982.
4 Tunbridge WMG. Factors contributing to deaths of diabetics under fifty years of age. Lancet 1981; 318: 569–72.
5 Gagnum V, Stene LC, Jenssen TG, et al. Causes of death in childhood-onset type 1 diabetes: long-term follow-up. Diabet Med 2017; 34: 56–63.
6 Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405–12.
7 Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577–89.
8 Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360: 129–39.
9 Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucosa control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358: 2560–72.
10 Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363: 1410–18.
11 Pieber TR, Marso SP, McGuire DK, et al. DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality. Diabetologia 2018; 61: 58–65.
12 Heller SR, Bergenstal RM, White WB, et al. Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: the EXAMINE trial. Diabetes Obes Metab 2017;19: 664–71.
13 Mellbin LG, Ryden L, Riddle MC, et al. Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial. Eur Heart J 2013; 34: 3137–44.
14 Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909.
15 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: 104–11.
16 Lu CL, Shen HN, Hu SC, Wang JD, Li CY. A population-based study of all-cause mortality and cardiovascular disease in association with prior history of hypoglycemia among patients with type 1 diabetes. Diabetes Care 2016; 39: 1571–78.
17 Goto A, Goto M, Terauchi Y, Yamaguchi N, Noda M. Association between severe hypoglycemia and cardiovascular disease risk in Japanese patients with type 2 diabetes. J Am Heart Assoc 2016; 5: e002875.
18 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: 659–68.
19 Cha SA, Yun JS, Lim TS, et al. Severe hypoglycemia and cardiovascular or all-cause mortality in patients with type 2 diabetes. Diabetes Metab J 2016; 40: 202–10.
20 Sejling AS, Schouwenberg B, Faerch LH, Thorsteinsson B, de Galan BE, Pedersen-Bjergaard U. Association between hypoglycaemia and impaired hypoglycaemia awareness and mortality in people with type 1 diabetes mellitus. Diabet Med 2016; 33: 77–83.
21 Luk AO, Ho TS, Lau ES, et al. Association of self-reported recurrent mild hypoglycemia with incident cardiovascular disease and all-cause mortality in patients with type 2 diabetes: prospective analysis of the Joint Asia Diabetes Evaluation Registry. Medicine (Baltimore) 2016; 95: e5183.
22 Freemantle N, Danchin N, Calvi-Gries F, Vincent M, Home PD. Relationship of glycaemic control and hypoglycaemic episodes to 4-year cardiovascular outcomes in people with type 2 diabetes starting insulin. Diabetes Obes Metab 2016; 18: 152–58.
23 Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. 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: 316–22.
24 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: 3301–08.
25 Lung TW, Petrie D, Herman WH, et al. Severe hypoglycemia and mortality after cardiovascular events for type 1 diabetic patients in Sweden. Diabetes Care 2014; 37: 2974–81.
26 Rathmann W, Kostev K, Gruenberger JB, Dworak M, Bader G, Giani G. Treatment persistence, hypoglycaemia and clinical outcomes in type 2 diabetes patients with dipeptidyl peptidase-4 inhibitors and sulphonylureas: a primary care database analysis. Diabetes Obes Metab 2013; 15: 55–61.
27 Hsu PF, Sung SH, Cheng HM, et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 2013; 36: 894–900.
28 Zhao Y, Campbell CR, Fonseca V, Shi L. Impact of hypoglycemia associated with antihyperglycemic medications on vascular risks in veterans with type 2 diabetes. Diabetes Care 2012; 35: 1126–32. 29 Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care 2011; 34: 1164–70.
30 Nunes AP, Iglay K, Radican L, et al. Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users. Diabetes Obes Metab 2017; 19: 1425–35.
31 Smith L, Chakraborty D, Bhattacharya P, Sarmah D, Koch S, Dave KR. Exposure to hypoglycemia and risk of stroke. Ann N Y Acad Sci 2018; 1431: 25–34.
32 Goto A, Arah OA, Goto M, Terauchi Y, Noda M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ 2013; 347: f4533.
33 Yeh JS, Sung SH, Huang HM, et al. Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis. Acta Diabetol 2016; 53: 377–92.
34 Huang CJ, Wang WT, Sung SH, et al. Blood glucose reduction by diabetic drugs with minimal hypoglycaemia risk for cardiovascular outcomes: evidence from meta-regression analysis of randomized controlled trials. Diabetes Obes Metab 2018; 20: 2131–39.
35 Muller N, Khunti K, Kuss O, et al. Is there evidence of potential overtreatment of glycaemia in elderly people with type 2 diabetes? Data from the GUIDANCE study. Acta Diabetol 2017; 54: 209–14.
36 de Decker L, Hanon O, Boureau AS, et al. Association between hypoglycemia and the burden of comorbidities in hospitalized vulnerable older diabetic patients: a cross-sectional, population-based study. Diabetes Ther 2017; 8: 1405–13.
37 Heald AH, Anderson SG, Cortes GJ, et al. Hypoglycaemia in the over 75s: understanding the predisposing factors in type 2 diabetes (T2DM). Prim Care Diabetes 2018; 12: 133–38.
38 Huang ES, Laiteerapong N, Liu JY, John PM, Moffet HH, Karter AJ. Rates of complications and mortality in older patients with diabetes mellitus: the Diabetes and Aging Study. JAMA Intern Med 2014;174: 251–58.
39 Chi MJ, Liang CK, Lee WJ, Peng LN, Chou MY, Chen LK. Association of new-onset diabetes mellitus in older people and mortality in Taiwan: a 10-year nationwide population-based study. J Nutr Health Aging 2017; 21: 227–32.
40 Jones TB, Savasan ZA, Johnson Q, Bahado-Singh R. Management of pregnant patients with diabetes with ischemic heart disease. Clin Lab Med 2013; 33: 243–56.
41 Kimmerle R, Heinemann L, Delecki A, Berger M. Severe hypoglycemia; incidence and predisposing factors in 85 pregnancies of type 1 diabetic women. Diabetes Care 1992;15: 1034–37.
42 Leinonen PJ, Hiilesmaa VK, Kaaja RJ, Teramo KA. Maternal mortality in type 1 diabetes. Diabetes Care 2001;24: 1501–02.
43 NICE. Diabetes in pregnancy: anagement from preconception to the postnatal period. NICE guideline [NG3]. London: National Institute for Health and Care Excellence, 2015.
44 Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990–96. Arch Dis Child 1999;81: 318–23.
45 O’Grady MJ, Delaney J, Jones TW, Davis EA. Standardised mortality is increased three-fold in a population-based sample of children and adolescents with type 1 diabetes. Pediatr Diabetes 2013;14: 13–17.
46 Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 2010; 33: 1389–94. 47 Dahlquist G, Kallen B. Mortality in childhood-onset type 1 diabetes: a population-based study. Diabetes Care 2005; 28: 2384–87.
48 Fisher BM, Gillen G, Hepburn DA, Dargie HJ, Frier BM. Cardiac responses to acute insulin-induced hypoglycemia in humans. Am J Physiol 1990; 258: H1775–79.
49 Sommerfield AJ, Wilkinson IB, Webb DJ, Frier BM. Vessel wall stiffness in type 1 diabetes and the central hemodynamic effects of acute hypoglycemia. Am J Physiol Endocrinol Metab 2007; 293: E1274–79.
50 Petersen KG, Schluter KJ, Kerp L. Regulation of serum potassium during insulin-induced hypoglycemia. Diabetes 1982; 31: 615–17. 51 Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011; 34 (suppl 2): S132–37.
52 Wright RJ, Newby DE, Stirling D, Ludlam CA, Macdonald IA, Frier BM. Effects of acute insulin-induced hypoglycemia on índices of inflammation: putative m echanism for aggravating vascular disease in diabetes. Diabetes Care 2010; 33: 1591–97.
53 Adler GK, Bonyhay I, Failing H, Waring E, Dotson S, Freeman R. Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control. Diabetes 2009; 58: 360–66.
54 Chow E, Iqbal A, Walkinshaw E, Phoenix F, Macdonald IA, Storey RF, Ajjan R, Heller SR. Prolonged prothrombotic effects of antecedent hypoglycemia in individuals with type 2 diabetes. Diabetes Care 2018; 41: 2625–33.
55 Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev 2008; 24: 353–63.
56 Desouza C, Salazar H, Cheong B, Murgo J, Fonseca V. Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. Diabetes Care 2003; 26: 1485–89.
57 Adler GK, Bonyhay I, Curren V, Waring E, Freeman R. Hypoglycaemia increases aldosterone in a dose-dependent fashion. Diabet Med 2010; 27: 1250–55.
58 Gogitidze Joy N, Hedrington MS, Briscoe VJ, Tate DB, Ertl AC, Davis SN. Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals. Diabetes Care 2010; 33: 1529–35.
59 Beall C, Ashford ML, McCrimmon RJ. The physiology and pathophysiology of the neural control of the counterregulatory response. Am J Physiol Regul Integr Comp Physiol 2012; 302: R215–23.
60 Fritsche A, Stumvoll M, Grub M, et al. Effect of hypoglycemia on beta-adrenergic sensitivity in normal and type 1 diabetic subjects. Diabetes Care 1998; 21: 1505–10.
61 Gimenez M, Gilabert R, Monteagudo J, et al. Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes. Diabetes Care 2011;34: 198–203.
62 McNeilly AD, Gallagher JR, Dinkova-Kostova AT, et al. Nrf2-mediated neuroprotection again t recurrent hypoglycemia is insufficient to prevent cognitive impairment in a rodent model of type 1 diabetes. Diabetes 2016; 65: 3151–60.
63 Ratter JM, Rooijackers HM, Tack CJ, et al. Proinflammatory effects of hypoglycemia in humans with or without diabetes. Diabetes 2017;66: 1052–61.
64 Cwikiel J, Seljeflot I, Berge E, Njerve IU, Ulsaker H, Arnesen H, Flaa A. Effect of strenuous exercise on mediators of inflammation in patients with coronary artery disease. Cytokine 2018; 105: 17–22.
65 Ceriello A, Novials A, Ortega E, et al. Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls. Nutr Metab Cardiovasc Dis 2014; 24: 116–23.
66 Reno CM, VanderWeele J, Bayles J, et al. Severe hypoglycemia-induced fatal cardiac arrhythmias are augmented by diabetes and attenuated by recurrent hypoglycemia. Diabetes 2017;66: 3091–97.
67 Tattersall RB, Gill GV. Unexplained deaths of type 1 diabetic patients. Diabet Med 1991; 8: 49–58.
68 Secrest AM, Becker DJ, Kelsey SF, Laporte RE, Orchard TJ. Characterizing sudden death and dead-in-bed syndrome in type 1 diabetes: analysis from two childhood-onset type 1 diabetes registries. Diabet Med 2011; 28: 293–300.
69 Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the “dead-in-bed” syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract 2010; 16: 244–48.
70 Marques JLB, George E, Peacey SR, et al. Altered ventricular repolarization during hypoglycaemia in patients with diabetes. Diabet Med 1997; 14: 648–54.
71 Landstedt-Hallin L, Englund A, Adamson U, Lins PE. Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus. J Intern Med 1999; 246: 299–307.
72 Tu E, Bagnall RD, Duflou J, Lynch M, Twigg SM, Semsarian C. Post-mortem pathologic and genetic studies in “dead in bed syndrome” cases in type 1 diabetes mellitus. Hum Pathol 2010;41: 392–400.
73 Novodvorsky P, Bernjak A, Chow E, et al. Diurnal differences in risk of cardiac arrhythmias during spontaneous hypoglycemia in young people with type 1 diabetes. Diabetes Care 2017; 40: 655–62. 74 Reno CM, Daphna-Iken D, Chen YS, VanderWeele J, Jethi K, Fisher SJ. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation. Diabetes 2013; 62: 3570–81.
75 Chow E, Bernjak A, Williams S, et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes 2014; 63: 1738–47.
76 Chow E, Bernjak A, Walkinshaw E, et al. Cardiac autonomic regulation and repolarization during acute experimental hypoglycemia in type 2 diabetes. Diabetes 2017; 66: 1322–33.
77 Fisher BM, Gillen G, Dargie HJ, Inglis GC, Frier BM. The effects of insulin-induced hypoglycaemia on cardiovascular function in normal man: studies using radionuclide ventriculography. Diabetologia 1987; 30: 841–45.
78 Rao AD, Bonyhay I, Dankwa J, et al. Baroreflex sensitivity impairment during hypoglycemia: implications for cardiovascular control. Diabetes 2016; 65: 209–15.
79 Hendrieckx C, Halliday JA, Bowden JP, et al. Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics. Diabetes Res Clin Pract 2014; 103: 430–36.
80 Evans M, Khunti K, Mamdani M, et al. Health-related quality of life associated with daytime and nocturnal hypoglycaemic events: a time trade-off survey in five countries. Health Qual Life Outcomes 2013; 11: 90.
81 Anderbro T, Gonder-Frederick L, Bolinder J, et al. Fear of hypoglycemia: relationship to hypoglycemic risk and psychological factors. Acta Diabetol 2015; 52: 581–89.
82 Gonder-Frederick L, Nyer M, Shepard JA, Vajda K, Clarke W. Assessing fear of hypoglycemia in children with type 1 diabetes and their parents. Diabetes Manag (Lond) 2011; 1: 627–39.
83 Driscoll KA, Raymond J, Naranjo D, Patton SR. Fear of hypoglycemia in children and adolescents and their parents with type 1 diabetes. Curr Diab Rep 2016; 16: 77.
84 Gonder-Frederick LA, Vajda KA, Schmidt KM, et al. Examining the behaviour subscale of the Hypoglycaemia Fear Survey: an international study. Diabet Med 2013; 30: 603–09.
85 Barnard K, Thomas S, Royle P, Noyes K, Waugh N. Fear of hypoglycaemia in parents of young children with type 1 diabetes: a systematic review. BMC Pediatr 2010; 10: 50.
86 International Hypoglycaemia Study Group. Understanding hypoglycaemia. https://ihsgonline.com/resources (accessed Feb 21, 2019).
87 Yeoh E, Choudhary P, Nwokolo M, Ayis S, Amiel SA. Interventions that restore awareness of hypoglycemia in adults with type 1 diabetes: a systematic review and meta-analysis. Diabetes Care 2015;38: 1592–609.
88 Lane W, Bailey TS, Gerety G, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA 2017;318: 33–44.
89 Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA 2017; 318: 45–56.
90 Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med 2017; 377: 723–32.
91 Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med 2008; 25: 765–74.
92 Beck RW, Riddlesworth TD, Ruedy K, et al. Continuous glucosa monitoring versus usual care in patients with type 2 diabetes receiving multiple daily insulin injections: a randomized trial. Ann Intern Med 2017; 167: 365–74.
93 Bergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 2013; 369: 224–32.
94 Bergenstal RM, Garg S, Weinzimer SA, et al. Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes. JAMA 2016; 316: 1407–08.
95 Rickels MR, Peleckis AJ, Markmann E, et al. Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes. J Clin Endocrinol Metab 2016;101: 4421–30.
96 American Diabetes Association. American Diabetes Association 6: glycemic targets: standards of medical care in diabetes—2019. Diabetes Care 2019; 42 (suppl 1): S61–70.
97 Lowe G, Woodward M, Hillis G, et al. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes 2014; 63: 1115–23.
98 Keating ST, van Diepen JA, Riksen NP, El-Osta A. Epigenetics in diabetic nephropathy, immunity and metabolism. Diabetologia 2018; 61: 6–20.
99 Rooijackers HM, Wiegers EC, Tack CJ, van der Graaf M, de Galan BE. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies. Cell Mol Life Sci 2016; 73: 705–22.
100 Joy NG, Tate DB, Younk LM, Davis SN. Effects of acute and antecedent hypoglycemia on endothelial function and markers of atherothrombotic balance in healthy humans. Diabetes 2015;64: 2571–80.
101 Reno CM, Tanoli T, Bree A, et al. Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats. Am J Physiol Endocrinol Metab 2013; 304: E1331–37.
102 Puente EC, Silverstein J, Bree AJ, et al. Recurrent moderate hypoglycemia ameliorates brain damage and cognitive dysfunction induced by severe hypoglycemia. Diabetes 2010; 59: 1055–62.
103 Milani-Nejad N, Janssen PM. Small and large animal models in cardiac contraction research: advantages and disadvantages. Pharmacol Ther 2014; 141: 235–49.
104 Campbell M, Heller SR, Jacques RM. Response to Comment on Novodvorsky et al. Diurnal differences in risk of cardiac arrhythmias during spontaneous hypoglycemia in young people with type 1 diabetes. Diabetes Care 2017; 40: 655–662.
105 Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481–89.
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