Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2013

Open Access 01-12-2013 | Review

Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review

Authors: Markolf Hanefeld, Eva Duetting, Peter Bramlage

Published in: Cardiovascular Diabetology | Issue 1/2013

Login to get access

Abstract

Background

Hypoglycaemia has been associated with increased cardiovascular (CV) risk and mortality in a number of recent multicentre trials, but the mechanistic links driving this association remain ill defined. This review aims to summarize the available data on how hypoglycaemia may affect CV risk in patients with diabetes.

Methods

This was a systematic review of available mechanistic and clinical studies on the relationship between hypoglycaemia and cardiovascular risk. Study outcomes were compiled from relevant articles, and factors contributing to hypoglycaemia-mediated CVD and its complications are discussed.

Results

Six recent comprehensive clinical trials have reinforced the critical importance of understanding the link between hypoglycaemia and the CV system. In addition, 88 studies have indicated that hypoglycaemia mechanistically contributes to CV risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis. These hypoglycaemia-associated risk factors are conducive to events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes.

Conclusions

Emerging data suggest that there is an impact of hypoglycaemia on CV function and mechanistic link is multifactorial. Further research will be needed to ascertain the full impact of hypoglycaemia on the CV system and its complications.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tu E, Twigg SM, Duflou J, Semsarian C: Causes of death in young Australians with type 1 diabetes: a review of coronial postmortem examinations. Med J Aust. 2008, 188 (12): 699-702.PubMed Tu E, Twigg SM, Duflou J, Semsarian C: Causes of death in young Australians with type 1 diabetes: a review of coronial postmortem examinations. Med J Aust. 2008, 188 (12): 699-702.PubMed
2.
go back to reference Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H: Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia. 2001, 44 (Suppl 2): S14-21.CrossRefPubMed Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H: Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia. 2001, 44 (Suppl 2): S14-21.CrossRefPubMed
3.
go back to reference Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC: Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003, 46 (6): 760-765. 10.1007/s00125-003-1116-6.CrossRefPubMed Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC: Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003, 46 (6): 760-765. 10.1007/s00125-003-1116-6.CrossRefPubMed
4.
go back to reference Wei M, Gibbons LW, Mitchell TL, Kampert JB, Stern MP, Blair SN: Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality. Circulation. 2000, 101 (17): 2047-2052. 10.1161/01.CIR.101.17.2047.CrossRefPubMed Wei M, Gibbons LW, Mitchell TL, Kampert JB, Stern MP, Blair SN: Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality. Circulation. 2000, 101 (17): 2047-2052. 10.1161/01.CIR.101.17.2047.CrossRefPubMed
5.
go back to reference 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 (5): 1164-1170. 10.2337/dc10-1915.PubMedCentralCrossRefPubMed 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 (5): 1164-1170. 10.2337/dc10-1915.PubMedCentralCrossRefPubMed
6.
go back to reference Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M, Heller S: Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010, 363 (15): 1410-1418. 10.1056/NEJMoa1003795.CrossRefPubMed Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M, Heller S: Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010, 363 (15): 1410-1418. 10.1056/NEJMoa1003795.CrossRefPubMed
7.
go back to reference UK Hypoglycaemia Study Group: Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007, 50 (6): 1140-1147.CrossRef UK Hypoglycaemia Study Group: Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007, 50 (6): 1140-1147.CrossRef
8.
go back to reference Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH, Probstfield JL, Simons-Morton DG, Friedewald WT: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008, 358 (24): 2545-2559.CrossRefPubMed Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH, Probstfield JL, Simons-Morton DG, Friedewald WT: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008, 358 (24): 2545-2559.CrossRefPubMed
9.
go back to reference Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008, 358 (24): 2560-2572.CrossRefPubMed Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008, 358 (24): 2560-2572.CrossRefPubMed
10.
go back to reference Moritz T, Duckworth W, Abraira C: Veterans affairs diabetes trial–corrections. N Engl J Med. 2009, 361 (10): 1024-1025.CrossRefPubMed Moritz T, Duckworth W, Abraira C: Veterans affairs diabetes trial–corrections. N Engl J Med. 2009, 361 (10): 1024-1025.CrossRefPubMed
11.
go back to reference Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH, Byington RP, Rosenberg YD, Friedewald WT: Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011, 364 (9): 818-828.CrossRefPubMed Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH, Byington RP, Rosenberg YD, Friedewald WT: Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011, 364 (9): 818-828.CrossRefPubMed
12.
go back to reference Dandona P, Chaudhuri A, Dhindsa S: Proinflammatory and prothrombotic effects of hypoglycemia. Diabetes Care. 2010, 33 (7): 1686-1687. 10.2337/dc10-0503.PubMedCentralCrossRefPubMed Dandona P, Chaudhuri A, Dhindsa S: Proinflammatory and prothrombotic effects of hypoglycemia. Diabetes Care. 2010, 33 (7): 1686-1687. 10.2337/dc10-0503.PubMedCentralCrossRefPubMed
13.
go back to reference Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR: Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes. 2003, 52 (6): 1469-1474. 10.2337/diabetes.52.6.1469.CrossRefPubMed Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR: Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes. 2003, 52 (6): 1469-1474. 10.2337/diabetes.52.6.1469.CrossRefPubMed
14.
go back to reference Wright RJ, Newby DE, Stirling D, Ludlam CA, Macdonald IA, Frier BM: 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. 10.2337/dc10-0013.PubMedCentralCrossRefPubMed Wright RJ, Newby DE, Stirling D, Ludlam CA, Macdonald IA, Frier BM: 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. 10.2337/dc10-0013.PubMedCentralCrossRefPubMed
15.
go back to reference Dave KR, Tamariz J, Desai KM, Brand FJ, Liu A, Saul I, Bhattacharya SK, Pileggi A: Recurrent hypoglycemia exacerbates cerebral ischemic damage in streptozotocin-induced diabetic rats. Stroke. 2011, 42 (5): 1404-1411. 10.1161/STROKEAHA.110.594937.CrossRefPubMed Dave KR, Tamariz J, Desai KM, Brand FJ, Liu A, Saul I, Bhattacharya SK, Pileggi A: Recurrent hypoglycemia exacerbates cerebral ischemic damage in streptozotocin-induced diabetic rats. Stroke. 2011, 42 (5): 1404-1411. 10.1161/STROKEAHA.110.594937.CrossRefPubMed
16.
go back to reference Gimenez M, Gilabert R, Monteagudo J, Alonso A, Casamitjana R, Pare C, Conget I: Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes. Diabetes Care. 2011, 34 (1): 198-203. 10.2337/dc10-1371.PubMedCentralCrossRefPubMed Gimenez M, Gilabert R, Monteagudo J, Alonso A, Casamitjana R, Pare C, Conget I: Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes. Diabetes Care. 2011, 34 (1): 198-203. 10.2337/dc10-1371.PubMedCentralCrossRefPubMed
17.
go back to reference 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 (2): 244-248. 10.4158/EP09260.CR.CrossRefPubMed 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 (2): 244-248. 10.4158/EP09260.CR.CrossRefPubMed
18.
go back to reference McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA: Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012, 35 (9): 1897-1901. 10.2337/dc11-2054.PubMedCentralCrossRefPubMed McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA: Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012, 35 (9): 1897-1901. 10.2337/dc11-2054.PubMedCentralCrossRefPubMed
19.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009, 339: b2700-10.1136/bmj.b2700.PubMedCentralCrossRefPubMed Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009, 339: b2700-10.1136/bmj.b2700.PubMedCentralCrossRefPubMed
21.
go back to reference Swinnen SG, Mullins P, Miller M, Hoekstra JB, Holleman F: Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia. Diabetologia. 2009, 52 (1): 38-41. 10.1007/s00125-008-1147-0.CrossRefPubMed Swinnen SG, Mullins P, Miller M, Hoekstra JB, Holleman F: Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia. Diabetologia. 2009, 52 (1): 38-41. 10.1007/s00125-008-1147-0.CrossRefPubMed
22.
go back to reference American Diabetes Association Workgroup on Hypoglycemia: Defining and reporting hypoglycemia in diabetes: a report from the American diabetes association workgroup on hypoglycemia. Diabetes Care. 2005, 28 (5): 1245-1249.CrossRef American Diabetes Association Workgroup on Hypoglycemia: Defining and reporting hypoglycemia in diabetes: a report from the American diabetes association workgroup on hypoglycemia. Diabetes Care. 2005, 28 (5): 1245-1249.CrossRef
23.
go back to reference Bay C, Kristensen PL, Pedersen-Bjergaard U, Tarnow L, Thorsteinsson B: Nocturnal continuous glucose monitoring: accuracy and reliability of hypoglycemia detection in patients with type 1 diabetes at high risk of severe hypoglycemia. Diabetes Technol Ther. 2013, 15 (5): 371-377. 10.1089/dia.2013.0004.CrossRefPubMed Bay C, Kristensen PL, Pedersen-Bjergaard U, Tarnow L, Thorsteinsson B: Nocturnal continuous glucose monitoring: accuracy and reliability of hypoglycemia detection in patients with type 1 diabetes at high risk of severe hypoglycemia. Diabetes Technol Ther. 2013, 15 (5): 371-377. 10.1089/dia.2013.0004.CrossRefPubMed
24.
go back to reference Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH: Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973, 182 (4108): 171-173. 10.1126/science.182.4108.171.CrossRefPubMed Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH: Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. 1973, 182 (4108): 171-173. 10.1126/science.182.4108.171.CrossRefPubMed
25.
go back to reference Graveling AJ, Frier BM: Impaired awareness of hypoglycaemia: a review. Diabetes Metab. 2010, 36 (Suppl 3): S64-74.CrossRefPubMed Graveling AJ, Frier BM: Impaired awareness of hypoglycaemia: a review. Diabetes Metab. 2010, 36 (Suppl 3): S64-74.CrossRefPubMed
26.
go back to reference Gold AE, MacLeod KM, Frier BM: Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care. 1994, 17 (7): 697-703. 10.2337/diacare.17.7.697.CrossRefPubMed Gold AE, MacLeod KM, Frier BM: Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care. 1994, 17 (7): 697-703. 10.2337/diacare.17.7.697.CrossRefPubMed
27.
go back to reference Jauch-Chara K, Schultes B: Sleep and the response to hypoglycaemia. Best Pract Res Clin Endocrinol Metab. 2010, 24 (5): 801-815. 10.1016/j.beem.2010.07.006.CrossRefPubMed Jauch-Chara K, Schultes B: Sleep and the response to hypoglycaemia. Best Pract Res Clin Endocrinol Metab. 2010, 24 (5): 801-815. 10.1016/j.beem.2010.07.006.CrossRefPubMed
29.
go back to reference Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, Burwood A, Weinger K, Bayless M, Dahms W, Harth J: Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007, 356 (18): 1842-1852.CrossRefPubMed Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, Burwood A, Weinger K, Bayless M, Dahms W, Harth J: Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007, 356 (18): 1842-1852.CrossRefPubMed
30.
go back to reference Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G: Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. 2006, 49 (2): 298-305. 10.1007/s00125-005-0082-6.CrossRefPubMed Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G: Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. 2006, 49 (2): 298-305. 10.1007/s00125-005-0082-6.CrossRefPubMed
31.
go back to reference Tschope D, Bramlage P, Binz C, Krekler M, Deeg E, Gitt AK: Incidence and predictors of hypoglycaemia in type 2 diabetes – an analysis of the prospective DiaRegis registry. BMC Endocr Disord. 2012, 12 (1): 23-10.1186/1472-6823-12-23.PubMedCentralCrossRefPubMed Tschope D, Bramlage P, Binz C, Krekler M, Deeg E, Gitt AK: Incidence and predictors of hypoglycaemia in type 2 diabetes – an analysis of the prospective DiaRegis registry. BMC Endocr Disord. 2012, 12 (1): 23-10.1186/1472-6823-12-23.PubMedCentralCrossRefPubMed
32.
go back to reference Tschope D, Bramlage P, Binz C, Krekler M, Plate T, Deeg E, Gitt AK: Antidiabetic pharmacotherapy and anamnestic hypoglycemia in a large cohort of type 2 diabetic patients–an analysis of the DiaRegis registry. Cardiovasc Diabetol. 2011, 10: 66-10.1186/1475-2840-10-66.PubMedCentralCrossRefPubMed Tschope D, Bramlage P, Binz C, Krekler M, Plate T, Deeg E, Gitt AK: Antidiabetic pharmacotherapy and anamnestic hypoglycemia in a large cohort of type 2 diabetic patients–an analysis of the DiaRegis registry. Cardiovasc Diabetol. 2011, 10: 66-10.1186/1475-2840-10-66.PubMedCentralCrossRefPubMed
33.
go back to reference Bramlage P, Binz C, Gitt AK, Krekler M, Plate T, Deeg E, Tschope D: Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis) - study protocol and patient characteristics at baseline. Cardiovasc Diabetol. 2010, 9: 53-10.1186/1475-2840-9-53.PubMedCentralCrossRefPubMed Bramlage P, Binz C, Gitt AK, Krekler M, Plate T, Deeg E, Tschope D: Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis) - study protocol and patient characteristics at baseline. Cardiovasc Diabetol. 2010, 9: 53-10.1186/1475-2840-9-53.PubMedCentralCrossRefPubMed
34.
go back to reference Gitt AK, Bramlage P, Binz C, Krekler M, Deeg E, Tschope D: Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry. Int J Clin Pract. 2013, doi:10.1111/ijcp.12179 [Epub ahead of print] Gitt AK, Bramlage P, Binz C, Krekler M, Deeg E, Tschope D: Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry. Int J Clin Pract. 2013, doi:10.1111/ijcp.12179 [Epub ahead of print]
35.
go back to reference Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, Band MM, Reekie G, Leese GP: Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population-based study. Diabet Med. 2005, 22 (6): 749-755. 10.1111/j.1464-5491.2005.01501.x.CrossRefPubMed Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, Band MM, Reekie G, Leese GP: Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population-based study. Diabet Med. 2005, 22 (6): 749-755. 10.1111/j.1464-5491.2005.01501.x.CrossRefPubMed
36.
go back to reference Bramlage P, Gitt AK, Binz C, Krekler M, Deeg E, Tschope D: Oral antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for glucose control and the risk of hypoglycemia. Cardiovasc Diabetol. 2012, 11: 122-10.1186/1475-2840-11-122.PubMedCentralCrossRefPubMed Bramlage P, Gitt AK, Binz C, Krekler M, Deeg E, Tschope D: Oral antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for glucose control and the risk of hypoglycemia. Cardiovasc Diabetol. 2012, 11: 122-10.1186/1475-2840-11-122.PubMedCentralCrossRefPubMed
38.
go back to reference Snell-Bergeon JK, Wadwa RP: Hypoglycemia, diabetes, and cardiovascular disease. Diabetes Technol Ther. 2012, 14 (Suppl 1): S51-58.PubMed Snell-Bergeon JK, Wadwa RP: Hypoglycemia, diabetes, and cardiovascular disease. Diabetes Technol Ther. 2012, 14 (Suppl 1): S51-58.PubMed
39.
go back to reference The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the diabetes control and complications trial research group. N Engl J Med. 1993, 329 (14): 977-986.CrossRef The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the diabetes control and complications trial research group. N Engl J Med. 1993, 329 (14): 977-986.CrossRef
40.
go back to reference de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, Steffes MW, Zinman B: Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011, 365 (25): 2366-2376.CrossRefPubMed de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, Steffes MW, Zinman B: Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011, 365 (25): 2366-2376.CrossRefPubMed
41.
go back to reference UK prospective diabetes study (UKPDS) group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK prospective diabetes study (UKPDS) group. Lancet. 1998, 352 (9131): 837-853.CrossRef UK prospective diabetes study (UKPDS) group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK prospective diabetes study (UKPDS) group. Lancet. 1998, 352 (9131): 837-853.CrossRef
42.
go back to reference 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 (15): 1577-1589. 10.1056/NEJMoa0806470.CrossRefPubMed 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 (15): 1577-1589. 10.1056/NEJMoa0806470.CrossRefPubMed
43.
go back to reference Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, Dudl RJ, Ismail-Beigi F, Kimel AR, Hoogwerf B, Horowitz KR, Savage PJ, Seaquist ER, Simmons DL, Sivitz WI, Speril-Hillen JM, Sweeney ME: The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010, 340: b4909-10.1136/bmj.b4909.PubMedCentralCrossRefPubMed Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, Dudl RJ, Ismail-Beigi F, Kimel AR, Hoogwerf B, Horowitz KR, Savage PJ, Seaquist ER, Simmons DL, Sivitz WI, Speril-Hillen JM, Sweeney ME: The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010, 340: b4909-10.1136/bmj.b4909.PubMedCentralCrossRefPubMed
44.
go back to reference Riddle MC, Ambrosius WT, Brillon DJ, Buse JB, Byington RP, Cohen RM, Goff DC, Malozowski S, Margolis KL, Probstfield JL, Schnall A, Seaquist ER: Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010, 33 (5): 983-990. 10.2337/dc09-1278.PubMedCentralCrossRefPubMed Riddle MC, Ambrosius WT, Brillon DJ, Buse JB, Byington RP, Cohen RM, Goff DC, Malozowski S, Margolis KL, Probstfield JL, Schnall A, Seaquist ER: Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010, 33 (5): 983-990. 10.2337/dc09-1278.PubMedCentralCrossRefPubMed
45.
go back to reference Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD: Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009, 360 (2): 129-139. 10.1056/NEJMoa0808431.CrossRefPubMed Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD: Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009, 360 (2): 129-139. 10.1056/NEJMoa0808431.CrossRefPubMed
46.
go back to reference Duckworth WC, Abraira C, Moritz TE, Davis SN, Emanuele N, Goldman S, Hayward R, Huang GD, Marks JB, Reaven PD, Reda DJ, Warren SR, Zieve FJ: The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA diabetes trial. J Diabetes Complications. 2011, 25 (6): 355-361. 10.1016/j.jdiacomp.2011.10.003.CrossRefPubMed Duckworth WC, Abraira C, Moritz TE, Davis SN, Emanuele N, Goldman S, Hayward R, Huang GD, Marks JB, Reaven PD, Reda DJ, Warren SR, Zieve FJ: The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA diabetes trial. J Diabetes Complications. 2011, 25 (6): 355-361. 10.1016/j.jdiacomp.2011.10.003.CrossRefPubMed
47.
go back to reference Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S, ORIGIN Trials Investigators: Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012, 367 (4): 319-328.CrossRefPubMed Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S, ORIGIN Trials Investigators: Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012, 367 (4): 319-328.CrossRefPubMed
48.
go back to reference 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 (7): 1529-1535. 10.2337/dc09-0354.PubMedCentralCrossRefPubMed 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 (7): 1529-1535. 10.2337/dc09-0354.PubMedCentralCrossRefPubMed
49.
go back to reference Dalsgaard-Nielsen J, Madsbad S, Hilsted J: Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects. Thromb Haemost. 1982, 47 (3): 254-258.PubMed Dalsgaard-Nielsen J, Madsbad S, Hilsted J: Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects. Thromb Haemost. 1982, 47 (3): 254-258.PubMed
50.
go back to reference Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV: Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes. 1988, 37 (7): 901-907. 10.2337/diab.37.7.901.CrossRefPubMed Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV: Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes. 1988, 37 (7): 901-907. 10.2337/diab.37.7.901.CrossRefPubMed
51.
go back to reference Schwartz NS, Clutter WE, Shah SD, Cryer PE: Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 1987, 79 (3): 777-781. 10.1172/JCI112884.PubMedCentralCrossRefPubMed Schwartz NS, Clutter WE, Shah SD, Cryer PE: Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 1987, 79 (3): 777-781. 10.1172/JCI112884.PubMedCentralCrossRefPubMed
52.
go back to reference Petersen KG, Schluter KJ, Kerp L: Regulation of serum potassium during insulin-induced hypoglycemia. Diabetes. 1982, 31 (7): 615-617. 10.2337/diab.31.7.615.CrossRefPubMed Petersen KG, Schluter KJ, Kerp L: Regulation of serum potassium during insulin-induced hypoglycemia. Diabetes. 1982, 31 (7): 615-617. 10.2337/diab.31.7.615.CrossRefPubMed
53.
go back to reference Koivikko ML, Karsikas M, Salmela PI, Tapanainen JS, Ruokonen A, Seppanen T, Huikuri HV, Perkiomaki JS: Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes. Diabetologia. 2008, 51 (3): 426-435. 10.1007/s00125-007-0902-y.CrossRefPubMed Koivikko ML, Karsikas M, Salmela PI, Tapanainen JS, Ruokonen A, Seppanen T, Huikuri HV, Perkiomaki JS: Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes. Diabetologia. 2008, 51 (3): 426-435. 10.1007/s00125-007-0902-y.CrossRefPubMed
54.
go back to reference Gill GV, Woodward A, Casson IF, Weston PJ: Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes–the ‘dead in bed’ syndrome revisited. Diabetologia. 2009, 52 (1): 42-45. 10.1007/s00125-008-1177-7.CrossRefPubMed Gill GV, Woodward A, Casson IF, Weston PJ: Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes–the ‘dead in bed’ syndrome revisited. Diabetologia. 2009, 52 (1): 42-45. 10.1007/s00125-008-1177-7.CrossRefPubMed
55.
go back to reference Marques JL, George E, Peacey SR, Harris ND, Macdonald IA, Cochrane T, Heller SR: Altered ventricular repolarization during hypoglycaemia in patients with diabetes. Diabet Med. 1997, 14 (8): 648-654. 10.1002/(SICI)1096-9136(199708)14:8<648::AID-DIA418>3.0.CO;2-1.CrossRefPubMed Marques JL, George E, Peacey SR, Harris ND, Macdonald IA, Cochrane T, Heller SR: Altered ventricular repolarization during hypoglycaemia in patients with diabetes. Diabet Med. 1997, 14 (8): 648-654. 10.1002/(SICI)1096-9136(199708)14:8<648::AID-DIA418>3.0.CO;2-1.CrossRefPubMed
56.
go back to reference Robinson RT, Harris ND, Ireland RH, Macdonald IA, Heller SR: Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with type 1 diabetes. Diabetologia. 2004, 47 (2): 312-315. 10.1007/s00125-003-1292-4.CrossRefPubMed Robinson RT, Harris ND, Ireland RH, Macdonald IA, Heller SR: Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with type 1 diabetes. Diabetologia. 2004, 47 (2): 312-315. 10.1007/s00125-003-1292-4.CrossRefPubMed
57.
go back to reference Ceriello A, Novials A, Ortega E, La Sala L, Pujadas G, Testa R, Bonfigli AR, Esposito K, Giugliano D: Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes. 2012, 61 (11): 2993-2997. 10.2337/db12-0224.PubMedCentralCrossRefPubMed Ceriello A, Novials A, Ortega E, La Sala L, Pujadas G, Testa R, Bonfigli AR, Esposito K, Giugliano D: Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes. 2012, 61 (11): 2993-2997. 10.2337/db12-0224.PubMedCentralCrossRefPubMed
58.
go back to reference Dotson S, Freeman R, Failing HJ, Adler GK: Hypoglycemia increases serum interleukin-6 levels in healthy men and women. Diabetes Care. 2008, 31 (6): 1222-1223. 10.2337/dc07-2243.CrossRefPubMed Dotson S, Freeman R, Failing HJ, Adler GK: Hypoglycemia increases serum interleukin-6 levels in healthy men and women. Diabetes Care. 2008, 31 (6): 1222-1223. 10.2337/dc07-2243.CrossRefPubMed
59.
go back to reference Razavi Nematollahi L, Kitabchi AE, Stentz FB, Wan JY, Larijani BA, Tehrani MM, Gozashti MH, Omidfar K, Taheri E: Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism. 2009, 58 (4): 443-448. 10.1016/j.metabol.2008.10.018.CrossRefPubMed Razavi Nematollahi L, Kitabchi AE, Stentz FB, Wan JY, Larijani BA, Tehrani MM, Gozashti MH, Omidfar K, Taheri E: Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism. 2009, 58 (4): 443-448. 10.1016/j.metabol.2008.10.018.CrossRefPubMed
60.
go back to reference Gruden G, Barutta F, Chaturvedi N, Schalkwijk C, Stehouwer CD, Pinach S, Manzo M, Loiacono M, Tricarico M, Mengozzi G, Witte DR, Fuller JH, Perin PC, Bruno G: NH2-Terminal probrain natriuretic peptide is associated with diabetes complications in the EURODIAB prospective complications study: the role of tumor necrosis factor-alpha. Diabetes Care. 2012, 35 (9): 1931-1936. 10.2337/dc12-0089.PubMedCentralCrossRefPubMed Gruden G, Barutta F, Chaturvedi N, Schalkwijk C, Stehouwer CD, Pinach S, Manzo M, Loiacono M, Tricarico M, Mengozzi G, Witte DR, Fuller JH, Perin PC, Bruno G: NH2-Terminal probrain natriuretic peptide is associated with diabetes complications in the EURODIAB prospective complications study: the role of tumor necrosis factor-alpha. Diabetes Care. 2012, 35 (9): 1931-1936. 10.2337/dc12-0089.PubMedCentralCrossRefPubMed
61.
go back to reference Adler GK, Bonyhay I, Curren V, Waring E, Freeman R: Hypoglycaemia increases aldosterone in a dose-dependent fashion. Diabet Med. 2010, 27 (11): 1250-1255. 10.1111/j.1464-5491.2010.03087.x.PubMedCentralCrossRefPubMed Adler GK, Bonyhay I, Curren V, Waring E, Freeman R: Hypoglycaemia increases aldosterone in a dose-dependent fashion. Diabet Med. 2010, 27 (11): 1250-1255. 10.1111/j.1464-5491.2010.03087.x.PubMedCentralCrossRefPubMed
62.
go back to reference Wright RJ, Frier BM: Vascular disease and diabetes: is hypoglycaemia an aggravating factor?. Diabetes Metab Res Rev. 2008, 24 (5): 353-363. 10.1002/dmrr.865.CrossRefPubMed Wright RJ, Frier BM: Vascular disease and diabetes: is hypoglycaemia an aggravating factor?. Diabetes Metab Res Rev. 2008, 24 (5): 353-363. 10.1002/dmrr.865.CrossRefPubMed
63.
go back to reference Heller SR, Robinson RT: Hypoglycaemia and associated hypokalaemia in diabetes: mechanisms, clinical implications and prevention. Diabetes Obes Metab. 2000, 2 (2): 75-82. 10.1046/j.1463-1326.2000.00050.x.CrossRefPubMed Heller SR, Robinson RT: Hypoglycaemia and associated hypokalaemia in diabetes: mechanisms, clinical implications and prevention. Diabetes Obes Metab. 2000, 2 (2): 75-82. 10.1046/j.1463-1326.2000.00050.x.CrossRefPubMed
64.
go back to reference Hutton RA, Mikhailidis D, Dormandy KM, Ginsburg J: Platelet aggregation studies during transient hypoglycaemia: a potential method for evaluating platelet function. J Clin Pathol. 1979, 32 (5): 434-438. 10.1136/jcp.32.5.434.PubMedCentralCrossRefPubMed Hutton RA, Mikhailidis D, Dormandy KM, Ginsburg J: Platelet aggregation studies during transient hypoglycaemia: a potential method for evaluating platelet function. J Clin Pathol. 1979, 32 (5): 434-438. 10.1136/jcp.32.5.434.PubMedCentralCrossRefPubMed
65.
go back to reference Pfister R, Cairns R, Erdmann E, Schneider CA, Investigators PR: Prognostic impact of electrocardiographic signs in patients with type 2 diabetes and cardiovascular disease: results from the PROactive study. Diabet Med. 2011, 28 (10): 1206-1212. 10.1111/j.1464-5491.2011.03281.x.CrossRefPubMed Pfister R, Cairns R, Erdmann E, Schneider CA, Investigators PR: Prognostic impact of electrocardiographic signs in patients with type 2 diabetes and cardiovascular disease: results from the PROactive study. Diabet Med. 2011, 28 (10): 1206-1212. 10.1111/j.1464-5491.2011.03281.x.CrossRefPubMed
66.
go back to reference Chelliah YR: Ventricular arrhythmias associated with hypoglycaemia. Anaesth Intensive Care. 2000, 28 (6): 698-700.PubMed Chelliah YR: Ventricular arrhythmias associated with hypoglycaemia. Anaesth Intensive Care. 2000, 28 (6): 698-700.PubMed
67.
go back to reference Collier A, Matthews DM, Young RJ, Clarke BF: Transient atrial fibrillation precipitated by hypoglycaemia: two case reports. Postgrad Med J. 1987, 63 (744): 895-897. 10.1136/pgmj.63.744.895.PubMedCentralCrossRefPubMed Collier A, Matthews DM, Young RJ, Clarke BF: Transient atrial fibrillation precipitated by hypoglycaemia: two case reports. Postgrad Med J. 1987, 63 (744): 895-897. 10.1136/pgmj.63.744.895.PubMedCentralCrossRefPubMed
68.
go back to reference DeRosa MA, Cryer PE: Hypoglycemia and the sympathoadrenal system: neurogenic symptoms are largely the result of sympathetic neural, rather than adrenomedullary, activation. Am J Physiol Endocrinol Metab. 2004, 287 (1): E32-41. 10.1152/ajpendo.00539.2003.CrossRefPubMed DeRosa MA, Cryer PE: Hypoglycemia and the sympathoadrenal system: neurogenic symptoms are largely the result of sympathetic neural, rather than adrenomedullary, activation. Am J Physiol Endocrinol Metab. 2004, 287 (1): E32-41. 10.1152/ajpendo.00539.2003.CrossRefPubMed
69.
go back to reference Koivikko ML, Salmela PI, Airaksinen KE, Tapanainen JS, Ruokonen A, Makikallio TH, Huikuri HV: Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes. Diabetes. 2005, 54 (3): 744-750. 10.2337/diabetes.54.3.744.CrossRefPubMed Koivikko ML, Salmela PI, Airaksinen KE, Tapanainen JS, Ruokonen A, Makikallio TH, Huikuri HV: Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes. Diabetes. 2005, 54 (3): 744-750. 10.2337/diabetes.54.3.744.CrossRefPubMed
70.
go back to reference Kamijo Y, Soma K, Aoyama N, Fukuda M, Ohwada T: Myocardial infarction with acute insulin poisoning–a case report. Angiology. 2000, 51 (8): 689-693.PubMed Kamijo Y, Soma K, Aoyama N, Fukuda M, Ohwada T: Myocardial infarction with acute insulin poisoning–a case report. Angiology. 2000, 51 (8): 689-693.PubMed
71.
go back to reference Lindstrom T, Jorfeldt L, Tegler L, Arnqvist HJ: Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus. Diabet Med. 1992, 9 (6): 536-541. 10.1111/j.1464-5491.1992.tb01834.x.CrossRefPubMed Lindstrom T, Jorfeldt L, Tegler L, Arnqvist HJ: Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus. Diabet Med. 1992, 9 (6): 536-541. 10.1111/j.1464-5491.1992.tb01834.x.CrossRefPubMed
72.
go back to reference 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 (5): 1485-1489. 10.2337/diacare.26.5.1485.CrossRefPubMed 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 (5): 1485-1489. 10.2337/diacare.26.5.1485.CrossRefPubMed
73.
go back to reference Gruden G, Giunti S, Barutta F, Chaturvedi N, Witte DR, Tricarico M, Fuller JH, Cavallo Perin P, Bruno G: QTc interval prolongation is independently associated with severe hypoglycemic attacks in type 1 diabetes from the EURODIAB IDDM complications study. Diabetes Care. 2012, 35 (1): 125-127. 10.2337/dc11-1739.PubMedCentralCrossRefPubMed Gruden G, Giunti S, Barutta F, Chaturvedi N, Witte DR, Tricarico M, Fuller JH, Cavallo Perin P, Bruno G: QTc interval prolongation is independently associated with severe hypoglycemic attacks in type 1 diabetes from the EURODIAB IDDM complications study. Diabetes Care. 2012, 35 (1): 125-127. 10.2337/dc11-1739.PubMedCentralCrossRefPubMed
74.
go back to reference Giunti S, Gruden G, Fornengo P, Barutta F, Amione C, Ghezzo G, Cavallo-Perin P, Bruno G: Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based casale monferrato study. Diabetes Care. 2012, 35 (3): 581-583. 10.2337/dc11-1397.PubMedCentralCrossRefPubMed Giunti S, Gruden G, Fornengo P, Barutta F, Amione C, Ghezzo G, Cavallo-Perin P, Bruno G: Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based casale monferrato study. Diabetes Care. 2012, 35 (3): 581-583. 10.2337/dc11-1397.PubMedCentralCrossRefPubMed
75.
go back to reference Christensen TF, Tarnow L, Randlov J, Kristensen LE, Struijk JJ, Eldrup E, Hejlesen OK: QT interval prolongation during spontaneous episodes of hypoglycaemia in type 1 diabetes: the impact of heart rate correction. Diabetologia. 2010, 53 (9): 2036-2041. 10.1007/s00125-010-1802-0.CrossRefPubMed Christensen TF, Tarnow L, Randlov J, Kristensen LE, Struijk JJ, Eldrup E, Hejlesen OK: QT interval prolongation during spontaneous episodes of hypoglycaemia in type 1 diabetes: the impact of heart rate correction. Diabetologia. 2010, 53 (9): 2036-2041. 10.1007/s00125-010-1802-0.CrossRefPubMed
76.
go back to reference The DCCT research group: Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT research group. Am J Med. 1991, 90 (4): 450-459.CrossRef The DCCT research group: Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT research group. Am J Med. 1991, 90 (4): 450-459.CrossRef
77.
go back to reference Murphy NP, Ford-Adams ME, Ong KK, Harris ND, Keane SM, Davies C, Ireland RH, MacDonald IA, Knight EJ, Edge JA, Heller SR, Dunger DB: Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes. Diabetologia. 2004, 47 (11): 1940-1947. 10.1007/s00125-004-1552-y.CrossRefPubMed Murphy NP, Ford-Adams ME, Ong KK, Harris ND, Keane SM, Davies C, Ireland RH, MacDonald IA, Knight EJ, Edge JA, Heller SR, Dunger DB: Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes. Diabetologia. 2004, 47 (11): 1940-1947. 10.1007/s00125-004-1552-y.CrossRefPubMed
78.
go back to reference Tattersall RB, Gill GV: Unexplained deaths of type 1 diabetic patients. Diabet Med. 1991, 8 (1): 49-58. 10.1111/j.1464-5491.1991.tb01516.x.CrossRefPubMed Tattersall RB, Gill GV: Unexplained deaths of type 1 diabetic patients. Diabet Med. 1991, 8 (1): 49-58. 10.1111/j.1464-5491.1991.tb01516.x.CrossRefPubMed
79.
go back to reference Thordarson H, Sovik O: Dead in bed syndrome in young diabetic patients in Norway. Diabet Med. 1995, 12 (9): 782-787. 10.1111/j.1464-5491.1995.tb02080.x.CrossRefPubMed Thordarson H, Sovik O: Dead in bed syndrome in young diabetic patients in Norway. Diabet Med. 1995, 12 (9): 782-787. 10.1111/j.1464-5491.1995.tb02080.x.CrossRefPubMed
80.
go back to reference Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995, 18 (11): 1415-1427. Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995, 18 (11): 1415-1427.
81.
go back to reference Tunbridge WM: Factors contributing to deaths of diabetics under fifty years of age. On behalf of the Medical Services Study Group and British Diabetic Association. Lancet. 1981, 2 (8246): 569-572. Tunbridge WM: Factors contributing to deaths of diabetics under fifty years of age. On behalf of the Medical Services Study Group and British Diabetic Association. Lancet. 1981, 2 (8246): 569-572.
82.
go back to reference Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD: Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes–the EURODIAB prospective complications study. Diabetologia. 2005, 48 (2): 370-378. 10.1007/s00125-004-1628-8.CrossRefPubMed Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD: Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes–the EURODIAB prospective complications study. Diabetologia. 2005, 48 (2): 370-378. 10.1007/s00125-004-1628-8.CrossRefPubMed
83.
go back to reference Zervou S, Wang YF, Laiho A, Gyenesei A, Kytomaki L, Hermann R, Abouna S, Epstein D, Pelengaris S, Khan M: Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully ‘switchable’ in vivo mouse model of diabetes. Diabetologia. 2010, 53 (12): 2676-2687. 10.1007/s00125-010-1887-5.CrossRefPubMed Zervou S, Wang YF, Laiho A, Gyenesei A, Kytomaki L, Hermann R, Abouna S, Epstein D, Pelengaris S, Khan M: Short-term hyperglycaemia causes non-reversible changes in arterial gene expression in a fully ‘switchable’ in vivo mouse model of diabetes. Diabetologia. 2010, 53 (12): 2676-2687. 10.1007/s00125-010-1887-5.CrossRefPubMed
84.
go back to reference Chaudhuri A, Dandona P, Fonseca V: Cardiovascular benefits of exogenous insulin. J Clin Endocrinol Metab. 2012, 97 (9): 3079-3091. 10.1210/jc.2012-1112.CrossRefPubMed Chaudhuri A, Dandona P, Fonseca V: Cardiovascular benefits of exogenous insulin. J Clin Endocrinol Metab. 2012, 97 (9): 3079-3091. 10.1210/jc.2012-1112.CrossRefPubMed
85.
go back to reference Forst T, Hanefeld M, Jacob S, Moeser G, Schwenk G, Pfutzner A, Haupt A: Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res. 2013, 10 (4): 302-14. 10.1177/1479164112465442.CrossRefPubMed Forst T, Hanefeld M, Jacob S, Moeser G, Schwenk G, Pfutzner A, Haupt A: Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res. 2013, 10 (4): 302-14. 10.1177/1479164112465442.CrossRefPubMed
86.
go back to reference Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006, 355 (23): 2427-2443. 10.1056/NEJMoa066224.CrossRefPubMed Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006, 355 (23): 2427-2443. 10.1056/NEJMoa066224.CrossRefPubMed
87.
go back to reference O’Keefe JH, Abuannadi M, Lavie CJ, Bell DS: Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2011, 86 (2): 128-138. 10.4065/mcp.2010.0434.PubMedCentralCrossRefPubMed O’Keefe JH, Abuannadi M, Lavie CJ, Bell DS: Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2011, 86 (2): 128-138. 10.4065/mcp.2010.0434.PubMedCentralCrossRefPubMed
88.
go back to reference Noh RM, Graveling AJ, Frier BM: Medically minimising the impact of hypoglycaemia in type 2 diabetes: a review. Expert Opin Pharmacother. 2011, 12 (14): 2161-2175. 10.1517/14656566.2011.589835.CrossRefPubMed Noh RM, Graveling AJ, Frier BM: Medically minimising the impact of hypoglycaemia in type 2 diabetes: a review. Expert Opin Pharmacother. 2011, 12 (14): 2161-2175. 10.1517/14656566.2011.589835.CrossRefPubMed
89.
go back to reference Drucker DJ, Sherman SI, Bergenstal RM, Buse JB: The safety of incretin-based therapies–review of the scientific evidence. J Clin Endocrinol Metab. 2011, 96 (7): 2027-2031. 10.1210/jc.2011-0599.CrossRefPubMed Drucker DJ, Sherman SI, Bergenstal RM, Buse JB: The safety of incretin-based therapies–review of the scientific evidence. J Clin Endocrinol Metab. 2011, 96 (7): 2027-2031. 10.1210/jc.2011-0599.CrossRefPubMed
Metadata
Title
Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review
Authors
Markolf Hanefeld
Eva Duetting
Peter Bramlage
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-12-135

Other articles of this Issue 1/2013

Cardiovascular Diabetology 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.