Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2014

Open Access 01-12-2014 | Research article

Visit-to-visit variability of fasting plasma glucose as predictor of ischemic stroke: competing risk analysis in a national cohort of Taiwan Diabetes Study

Published in: BMC Medicine | Issue 1/2014

Login to get access

Abstract

Background

Glycemic variation as an independent predictor of ischemic stroke in type 2 diabetic patients remains unclear. This study examined visit-to-visit variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), for predicting ischemic stroke independently, regardless of glycated hemoglobin (HbA1c) and other conventional risk factors in such patients.

Methods

Type 2 diabetic patients enrolled in the National Diabetes Care Management Program, ≥30 years old and free of ischemic stroke (n = 28,354) in 2002 to 2004 were included, and related factors were analyzed with extended Cox proportional hazards regression models of competing risk data on stroke incidence.

Results

After an average 7.5 years of follow-up, there were 2,250 incident cases of ischemic stroke, giving a crude incidence rate of 10.56/1,000 person-years (11.64 for men, 9.63 for women). After multivariate adjustment, hazard ratios for the second, third and fourth versus first FPG-CV quartile were 1.11 (0.98, 1.25), 1.22 (1.08, 1.38) and 1.27 (1.12, 1.43), respectively, without considering HbA1c, and 1.09 (0.96, 1.23), 1.16 (1.03, 1.31) and 1.17 (1.03, 1.32), respectively, after considering HbA1c.

Conclusions

Besides HbA1c, FPG-CV was a potent predictor of ischemic stroke in type 2 diabetic patients, suggesting that different therapeutic strategies now in use be rated for their potential to (1) minimize glucose fluctuations and (2) reduce HbA1c level in type 2 diabetic patients to prevent ischemic stroke.
Appendix
Available only for authorised users
Literature
1.
Rautio A, Eliasson M, Stegmayr B: Favorable trends in the incidence and outcome in stroke in nondiabetic and diabetic subjects: findings from the Northern Sweden MONICA Stroke Registry in 1985 to 2003. Stroke. 2008, 39: 3137-3144. 10.1161/STROKEAHA.107.504100.CrossRefPubMed
2.
Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR: Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes: a population-based cohort study. Stroke. 2007, 38: 1739-1743. 10.1161/STROKEAHA.106.481390.CrossRefPubMed
3.
Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, Hinchey JA, Howard VJ, Jauch EC, Levine SR, Meschia JF, Moore WS, Nixon JV, Pearson TA: Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011, 42: 517-584. 10.1161/STR.0b013e3181fcb238.CrossRefPubMed
4.
Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA, Howard BV, Kirkman MS, Kosiborod M, Reaven P, Sherwin RS: Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation. 2009, 119: 351-357. 10.1161/CIRCULATIONAHA.108.191305.CrossRefPubMed
5.
Standards of medical care in diabetes-2010. Diabetes Care. 2010, 33: S11-S61. 10.2337/dc10-S011.
6.
Ceriello A, Ihnat MA: `Glycemic variability’: a new therapeutic challenge in diabetes and the critical care setting. Diabet Med. 2010, 27: 862-867. 10.1111/j.1464-5491.2010.02967.x.CrossRefPubMed
7.
Siegelaar SE, Holleman F, Hoekstra JB, DeVries JH: Glucose variability; does it matter?. Endocr Rev. 2010, 31: 171-182. 10.1210/er.2009-0021.CrossRefPubMed
8.
9.
Kohnert KD, Freyse EJ, Salzsieder E: Glycaemic variability and pancreatic β-cell dysfunction. Curr Diabetes Rev. 2012, 8: 345-354. 10.2174/157339912802083513.CrossRefPubMed
10.
Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D: Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008, 57: 1349-1354. 10.2337/db08-0063.CrossRefPubMed
11.
Muggeo M, Verlato G, Bonora E, Bressan F, Girotto S, Corbellini M, Gemma ML, Moghetti P, Zenere M, Cacciatori V, Zoppini G, De Marco R: The Verona Diabetes Study: a population-based survey on known diabetes mellitus prevalence and 5-year all-cause mortality. Diabetologia. 1995, 38: 318-325. 10.1007/BF00400637.CrossRefPubMed
12.
Muggeo M, Zoppini G, Bonora E, Brun E, Bonadonna RC, Moghetti P, Verlato G: Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients: the verona diabetes Study. Diabetes Care. 2000, 23: 45-50. 10.2337/diacare.23.1.45.CrossRefPubMed
13.
Lin CC, Li CI, Yang SY, Liu CS, Chen CC, Fuh MM, Chen W, Li TC: Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. Am J Med. 2012, 125: e9-e18. 10.1016/j.amjmed.2011.07.027.PubMed
14.
Lin CC, Li CI, Liu CS, Lin WY, Chen CC, Yang SY, Lee CC, Li TC: Annual fasting plasma glucose variation increases risk of cancer incidence and mortality in patients with type 2 diabetes: the Taichung Diabetes Study. Endocr Relat Cancer. 2012, 19: 473-483. 10.1530/ERC-12-0038.CrossRefPubMed
15.
Nalysnyk L, Hernandez-Medina M, Krishnarajah G: Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature. Diabetes Obes Metab. 2010, 12: 288-298. 10.1111/j.1463-1326.2009.01160.x.CrossRefPubMed
16.
Wu VC, Huang TM, Wu PC, Wang WJ, Chao CT, Yang SY, Shiao CC, Hu FC, Lai CF, Lin YF, Han YY, Chen YS, Hsu RB, Young GH, Wang SS, Tsai PR, Chen YM, Chao TT, Ko WJ, Wu KD: Preoperative proteinuria is associated with long-term progression to chronic dialysis and mortality after coronary artery bypass grafting surgery. PLoS One. 2012, 7: e27687-10.1371/journal.pone.0027687.CrossRefPubMedPubMedCentral
17.
18.
Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML: Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011, 20: 236-242. 10.1002/pds.2087.CrossRefPubMed
19.
Kilpatrick ES, Rigby AS, Atkin S: A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care. 2008, 31: 2022-2198. 10.2337/dc08-0864.CrossRef
20.
Lunn M, McNeil D: Applying Cox regression to competing risks. Biometrics. 1995, 51: 524-532. 10.2307/2532940.CrossRefPubMed
21.
Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan DM, Peterson CM: Tests of glycemia in diabetes. Diabetes Care. 2003, 26: S106-S108. 10.2337/diacare.26.3.777.CrossRefPubMed
22.
Heo SH, Lee SH, Kim BJ, Kang BS, Yoon BW: Does glycated hemoglobin have clinical significance in ischemic stroke patients?. Clin Neurol Neurosurg. 2010, 112: 98-102. 10.1016/j.clineuro.2009.08.024.CrossRefPubMed
23.
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000, 321: 405-412. 10.1136/bmj.321.7258.405.CrossRefPubMedPubMedCentral
24.
Selvin E, Coresh J, Shahar E, Zhang L, Steffes M, Sharrett AR: Glycaemia (haemoglobin A1c) and incident ischaemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Lancet Neurol. 2005, 4: 821-826. 10.1016/S1474-4422(05)70227-1.CrossRefPubMed
25.
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: 2545-2559. 10.1056/NEJMoa0802743.CrossRefPubMed
26.
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: 129-139. 10.1056/NEJMoa0808431.CrossRefPubMed
27.
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: 2560-2572. 10.1056/NEJMicm066227.CrossRefPubMed
28.
Brownlee M, Hirsch IB: Glycemic variability: a hemoglobin A1c independent risk factor for diabetic complications. JAMA. 2006, 295: 1707-1708. 10.1001/jama.295.14.1707.CrossRefPubMed
29.
Gimeno-Orna JA, Castro-Alonso FJ, Boned-Juliani B, Lou-Arnal LM: Fasting plasma glucose variability as a risk factor of retinopathy in type 2 diabetic patients. J Diabetes Complications. 2003, 17: 78-81. 10.1016/S1056-8727(02)00197-6.CrossRefPubMed
30.
Zoppini G, Verlato G, Targher G, Bonora E, Trombetta M, Muggeo M: The Verona Diabetes Study. Variability of body weight, pulse pressure and glycaemia strongly predict total mortality in elderly type 2 diabetic patients. Diabetes Metab Res Rev. 2008, 24: 624-628. 10.1002/dmrr.897.CrossRefPubMed
31.
Hirsch IB, Brownlee M: Should minimal blood glucose variability become the gold standard of glycemic control?. J Diabetes Complications. 2005, 19: 178-181. 10.1016/j.jdiacomp.2004.10.001.CrossRefPubMed
32.
Eslami S, Taherzadeh Z, Schultz MJ, Abu-Hanna A: Glucose variability measures and their effect on mortality: a systematic review. Intensive Care Med. 2011, 37: 583-593. 10.1007/s00134-010-2129-5.CrossRefPubMedPubMedCentral
33.
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C: Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006, 295: 1681-1687. 10.1001/jama.295.14.1681.CrossRefPubMed
34.
Hu Y, Liu W, Huang R, Zhang X: Postchallenge plasma glucose excursions, carotid intima-media thickness, and risk factors for atherosclerosis in Chinese population with type 2 diabetes. Atherosclerosis. 2010, 210: 302-306. 10.1016/j.atherosclerosis.2009.11.015.CrossRefPubMed
35.
Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanefeld M: Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care. 2000, 23: 1830-1834. 10.2337/diacare.23.12.1830.CrossRefPubMed
36.
Barbieri M, Rizzo MR, Marfella R, Boccardi V, Esposito A, Pansini A, Paolisso G: Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. Atherosclerosis. 2013, 227: 349-354. 10.1016/j.atherosclerosis.2012.12.018.CrossRefPubMed
37.
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: 1410-1418. 10.1056/NEJMoa1003795.CrossRefPubMed
38.
Yakubovich N, Gerstein HC: Serious cardiovascular outcomes in diabetes: the role of hypoglycemia. Circulation. 2011, 123: 342-348. 10.1161/CIRCULATIONAHA.110.948489.CrossRefPubMed
39.
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: 2993-2997. 10.2337/db12-0224.CrossRefPubMedPubMedCentral
40.
41.
42.
Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001, 161: 397-405. 10.1001/archinte.161.3.397.
43.
Meigs JB, Nathan DM, D'Agostino RB, Wilson PW: Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. Diabetes Care. 2002, 25: 1845-1850. 10.2337/diacare.25.10.1845.CrossRefPubMed
Metadata
Title
Visit-to-visit variability of fasting plasma glucose as predictor of ischemic stroke: competing risk analysis in a national cohort of Taiwan Diabetes Study
Publication date
01-12-2014
Published in
BMC Medicine / Issue 1/2014
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-014-0165-7

Other articles of this Issue 1/2014

BMC Medicine 1/2014 Go to the issue

Research article

Stroke, multimorbidity and polypharmacy in a nationally representative sample of 1,424,378 patients in Scotland: implications for treatment burden

Review

Managing the changing burden of cancer in Asia

Research article

Comparative effectiveness and cost-effectiveness of antiretroviral therapy and pre-exposure prophylaxis for HIV prevention in South Africa

Reviewer acknowledgement

Reviewer acknowledgements for 2013

Research article

Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis

Commentary

The value of screening in patient populations with high prevalence of a disorder