A Competing Risk Hazard Model for Complications of Diabetes Mellitus
Author(s)
Parvin Akter Khanam*,
Mohammed Ataharul Islam,
Mohammed Abu Sayeed,
Tanjima Begum,
Mohammed Golam Rabbani,
Subhagata Choudhury,
Hajera Mahtab
Affiliation(s)
Department of Epidemiology and Biostatistics, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka, Bangladesh. Department of Applied Statistics, East West University, Dhaka, Bangladesh. Department of Community Medicine, Ibrahim Medical College, Dhaka, Bangladesh. Department of Statistics, Biostatistics and Informatics, University of Dhaka, Dhaka, Bangladesh.
Department of Epidemiology and Biostatistics, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka, Bangladesh. Department of Applied Statistics, East West University, Dhaka, Bangladesh. Department of Community Medicine, Ibrahim Medical College, Dhaka, Bangladesh. Department of Statistics, Biostatistics and Informatics, University of Dhaka, Dhaka, Bangladesh.
ABSTRACT
Diabetes mellitus is a major public health problem globally. It is the cause of serious and sometimes life-threatening complications leading to death. It is one of the most common non communicable diseases and leading cause of death in most developed countries including Bangladesh. It is associated with the increased risk of microvascular (nephropathy and retinopathy), macrovascular (cardiovascular diseases, stroke) and other mixed (cataract, pulmonary tuberculosis, foot ulcer etc.) complications. The aim of this study was to determine the risk factors related to diabetes complications and to propose competing risk models for analyzing complications of diabetes mellitus. We study 2887 diabetic patients from the BIRDEM registry record books for the period from 1984 to 1997 who have at least two follow-up visits and who are free from complications at the first visit. The data on variables such as 2-hBG, age, sex, family history of diabetes, area of residence, educational level, BMI, SBP, DBP and treatment status are obtained. Also, the time from the diagnosis of type 2 diabetes mellitus (T2DM) to the occurrence of complications was recorded. We use the competing risk hazard model and examined the potential risk factors for determining the development of such complications. This study reveals that increase in blood pressure is a potential risk factor for CHD and nephropathy in T2DM. We also found that male and illiterate patients are more affected by nephropathy. In our study, we also revealed that female and illiterate patients are also more influenced by cataract.
Diabetes mellitus is a major public health problem globally. It is the cause of serious and sometimes life-threatening complications leading to death. It is one of the most common non communicable diseases and leading cause of death in most developed countries including Bangladesh. It is associated with the increased risk of microvascular (nephropathy and retinopathy), macrovascular (cardiovascular diseases, stroke) and other mixed (cataract, pulmonary tuberculosis, foot ulcer etc.) complications. The aim of this study was to determine the risk factors related to diabetes complications and to propose competing risk models for analyzing complications of diabetes mellitus. We study 2887 diabetic patients from the BIRDEM registry record books for the period from 1984 to 1997 who have at least two follow-up visits and who are free from complications at the first visit. The data on variables such as 2-hBG, age, sex, family history of diabetes, area of residence, educational level, BMI, SBP, DBP and treatment status are obtained. Also, the time from the diagnosis of type 2 diabetes mellitus (T2DM) to the occurrence of complications was recorded. We use the competing risk hazard model and examined the potential risk factors for determining the development of such complications. This study reveals that increase in blood pressure is a potential risk factor for CHD and nephropathy in T2DM. We also found that male and illiterate patients are more affected by nephropathy. In our study, we also revealed that female and illiterate patients are also more influenced by cataract.
KEYWORDS
Family History of Diabetes, Educational Level, Type 2 Diabetes Mellitus, Coronary Heart Disease, Mean Arterial Blood Pressure
Family History of Diabetes, Educational Level, Type 2 Diabetes Mellitus, Coronary Heart Disease, Mean Arterial Blood Pressure
Cite this paper
Khanam, P. , Islam, M. , Sayeed, M. , Begum, T. , Rabbani, M. , Choudhury, S. and Mahtab, H. (2014) A Competing Risk Hazard Model for Complications of Diabetes Mellitus. Journal of Biosciences and Medicines, 2, 1-11. doi: 10.4236/jbm.2014.25001.
Khanam, P. , Islam, M. , Sayeed, M. , Begum, T. , Rabbani, M. , Choudhury, S. and Mahtab, H. (2014) A Competing Risk Hazard Model for Complications of Diabetes Mellitus. Journal of Biosciences and Medicines, 2, 1-11. doi: 10.4236/jbm.2014.25001.
References
[1] (2012) IDF Diabetes Atlas. 5th Edition. [2] Whiting, D.R., Guariguata, L., Weil, C. and Shaw, J. (2011) IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030. Diabetes Research and Clinical Practice, 94, 311-321.
http://dx.doi.org/10.1016/j.diabres.2011.10.029 [3] Fowler, M.J. (2008) Microvascular and Macrovascular Complications of Diabetes. Clinical Diabetes, 26, 77-82.
http://dx.doi.org/10.2337/diaclin.26.2.77 [4] Cox, D.R. (1972) Regression Models and Life Tables. Journal of the Royal Statistical Society, 34, 187-202. [5] Farewell, V.T. (1979) An Application of Cox’s Proportional Hazard Model to Multiple Infection Data. Applied Statistics, 28, 73-75.
http://dx.doi.org/10.2307/2346815 [6] Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P.D., Zieve, F.J., Marks, J., Davis, S.N., Hayward, R., Warren, S.R., Goldman, S., McCarren, M., Vitek, M.E., Henderson, W.G. and Huang, G.D. (2009) VADT Investigators. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. The New England Journal of Medicine, 360, 129-139. [7] Holman, R.R., Paul, S.K., Bethel, M.A., Matthews, D.R. and Neil, H.A.W. (2008) 10-Year Follow-Up of Intensive Glucose Control in Type 2 Diabetes. The New England Journal of Medicine, 359, 1577-1589.
http://dx.doi.org/10.1056/NEJMoa0806470 [8] Ueda, H., Matsumoto, N., Ishimura, E., Fukumoto, S., Shoji, T., Miki, T., et al. (2003) Factors Affecting Progression of Renal Failure in Patients with Type 2 Diabetes. Diabetes Care, 26, 1530-1534.
http://dx.doi.org/10.2337/diacare.26.5.1530 [9] Boguslawa, N.S., Dariusz, M. and Wladyslaw, G. (2002) Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: Results of Longitudinal Design. Journal of Diabetes and Its Complications, 16, 271-276.
http://dx.doi.org/10.1016/S1056-8727(01)00184-2 [10] Hu, G., Lindstrom, J., Valle, T.T., Eriksson, G., Jousilahti, P., Silventoinen, K., et al. (2004) Physical Activity, Body Mass Index, and Risk of Type 2 Diabetes in Patients with Normal or Impaired Glucose Regulation. Archives of Internal Medicine, 164, 892-896.
http://dx.doi.org/10.1001/archinte.164.8.892 [11] Turner, R.C. (1998) The UK Prospective Diabetes Study. Diabetes Care, 21, C35-C38. [12] Cox, D.R. (1975) Partial Likelihood. Biometrika, 62, 269-276.
http://dx.doi.org/10.1093/biomet/62.2.269 [13] Sasso, F.C., Salvatore, T., Nicola, L.D., et al. (2006) Cardiovascular Risk Factors and Disease Management in Type 2 Diabetic Patients with Diabetic Nephropathy. Diabetes Care, 29, 498-503.
http://dx.doi.org/10.2337/diacare.29.03.06.dc05-1776 [14] Agarwal, N., Senger, N.S., Jain. P.K. and Khare, R. (2011) Nephropathy in Newly Diagnosed Type 2 Diabetes with Special Stress on the Role of Hypertension. Journal of the Association of Physicians of India, 59, 145-147. [15] Matthews, D.R., Stratton, I.M., Aldington, S.J., Holman, R.R. and Khner, E.M. (2004) UK Prospective Diabetes Study Group. Risk of Progression of Retinopathy and Vision Loss Related to Tight Blood Pressure Control in Type 2 Diabetes Mellitus: UKPDS 69. Archives of Ophthalmology, 122, 1631-1640.
http://dx.doi.org/10.1001/archopht.122.11.1631 [16] Leelawattana, R., Pratipanawatr, T., Bunnag, P., Kosachunhanun, N., Suwanwalaikorn, S., Krittiyawong, S., et al. (2006) Thailand Diabetes Registry Project: Prevalence of Vascular Complications in Long-Standing Type 2 Diabetes. Journal of the Medical Association of Thailand, 89, S54-S59. [17] Kim, S.I. and Kim, S.J. (2006) Prevalence and Risk Factors for Cataracts in Persons with Type 2 Diabetes Mellitus. Korean Journal of Ophthalmology, 20, 201-204.
http://dx.doi.org/10.3341/kjo.2006.20.4.201 [18] Javier, F., Perez, C.F., Ruiz, I.M., de Gorospe Pérez-Jáuregui, C., Rodríguez, B.S., Losada, T.G. and Galindo, A.S. (2011) Microvascular Complications and Risk Factors in Patients with Type 2 Diabetes. Endocrinología y Nutrición, 58, 163-168.
http://dx.doi.org/10.1016/j.endonu.2011.01.006 [19] Nathan, D.M., Cleary, P.A., Backlund, J.Y., Genuth, S.M., Lachin, J.M., Orchard, T.J., Raskin, P. and Zinman, B. (2005) Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes. New England Journal of Medicine, 353, 2643-2653.
http://dx.doi.org/10.1056/NEJMoa052187 [20] Sayeed, M.A., Khanam, P.A., Hossain, M.M., et al. (1999) Diabetic Subjects with Severe Hyperglycemia and Proteinuria Are More Prevalent in Rural than Urban and in Poor than Rich People. Diabetes and Endocrine Journal, 27, 35-40. [21] Klein, B.E., Klein, R. and Moss, S.E. (1985) Prevalence of Cataracts in a Population-Based Study of Persons with Diabetes Mellitus. Ophthalmology, 92, 1191-1196.
http://dx.doi.org/10.1016/S0161-6420(85)33877-0 [22] Lehto, S., Ronnemaa, T., Haffner, S.M., Pyörälä, K., Kallio, V. and Laakso, M. (1997) Dislipidemia and Hyperglycemia Predict Coronary Heart Disease Events in Middle-Aged Patients with NIDDM. Diabetes, 46, 1354-1359.
http://dx.doi.org/10.2337/diab.46.8.1354 [23] Gall, M.A., Borch-Johnsen, K., Hougaard, P., Nielsen, F.S. and Parving, H.H. (1995) Albuminuria and Poor Glycemic Control Predict Mortality in NIDDM. Diabetes, 44, 1303-1309.
http://dx.doi.org/10.2337/diab.44.11.1303 [24] Haffner, S.M. (1999) Epidemiological Studies on the Effects of Hyperglycemia and Improvement of Glycemic Control on Macrovascular Events in Type 2 Diabetes. Diabetes Care, 22, C54-C56. [25] Wilson, P.W.F. and Meigs, J.B. (2008) Risk of Type 2 Diabetes Mellitus and Coronary Heart Disease: A Pivotal Role for Metabolic Factors. European Heart Journal, 10, B11-B15. [26] Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P.D., Zieve, F.J., Marks, J., Davis, S.N., Hayward, R., Warren, S.R., Goldman, S., McCarren, M., Vitek, M.E., Henderson, W.G., Huang, G.D. for VADT Investigators (2009) Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. New England Journal of Medicine, 360, 129-139.
http://dx.doi.org/10.1056/NEJMoa0808431 [27] Raman, R., Pal, S.S., Adams, J.S.K., Rani, P.K., Vaitheeswaran, K. and Sharma, T. (2010) Prevalence and Risk Factors for Cataract in Diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study. Investigative Ophthalmology & Visual Science, 51, 6253-6261.
http://dx.doi.org/10.1167/iovs.10-5414 [28] Kuo, H.S., Chang, H.J., Chou, P., Teng, L. and Chen, H.H. (1999) A Markov Chain Model to Assess the Efficacy of Screening for Non-Insulin Dependent Diabetes Mellitus (NIDDM). International Journal of Epidemiology, 28, 233-240.
http://dx.doi.org/10.1093/ije/28.2.233 [29] Weng, J., Li, Y., Shi, L., Zhang, Q., Zhu, D., Hu, Y., Yan, X., Tian, H., et al. (2008) Effect of Intensive Insulin Therapy on β-Cell Function and Glycaemic Control in Patients with Newly Diagnosed Type 2 Diabetes: A Multicentre Randomized Parallel-Group Trial. Lancet, 371, 1753-1760.
http://dx.doi.org/10.1016/S0140-6736(08)60762-X [30] Absood, A., Gandomani, B., Zaki, A., Nasta, V., Michail, A., Habib, P.M. and Hodish, I. (2013) Insulin Therapy for Pre-Hyperglycemic Beta-Cell Endoplasmic Reticulum Crowding. PLoS ONE, 8, Article ID: e54351.
http://dx.doi.org/10.1371/journal.pone.0054351 [31] The Diabetes Control and Complications Trail Research Group (1993) The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. New England Journal of Medicine, 329, 977-986. [32] Alder, A.I., Stevens, R.I., Manley, S.E., Bilous, R.W., Cull, C.A. and Holman, R.R. on Behalf of the UKPDS Group (2003) Development and Progression of Nephropathy in Type 2 Diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney International, 63, 225-232.
http://dx.doi.org/10.1046/j.1523-1755.2003.00712.x
[1] (2012) IDF Diabetes Atlas. 5th Edition. [2] Whiting, D.R., Guariguata, L., Weil, C. and Shaw, J. (2011) IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030. Diabetes Research and Clinical Practice, 94, 311-321.
http://dx.doi.org/10.1016/j.diabres.2011.10.029 [3] Fowler, M.J. (2008) Microvascular and Macrovascular Complications of Diabetes. Clinical Diabetes, 26, 77-82.
http://dx.doi.org/10.2337/diaclin.26.2.77 [4] Cox, D.R. (1972) Regression Models and Life Tables. Journal of the Royal Statistical Society, 34, 187-202. [5] Farewell, V.T. (1979) An Application of Cox’s Proportional Hazard Model to Multiple Infection Data. Applied Statistics, 28, 73-75.
http://dx.doi.org/10.2307/2346815 [6] Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P.D., Zieve, F.J., Marks, J., Davis, S.N., Hayward, R., Warren, S.R., Goldman, S., McCarren, M., Vitek, M.E., Henderson, W.G. and Huang, G.D. (2009) VADT Investigators. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. The New England Journal of Medicine, 360, 129-139. [7] Holman, R.R., Paul, S.K., Bethel, M.A., Matthews, D.R. and Neil, H.A.W. (2008) 10-Year Follow-Up of Intensive Glucose Control in Type 2 Diabetes. The New England Journal of Medicine, 359, 1577-1589.
http://dx.doi.org/10.1056/NEJMoa0806470 [8] Ueda, H., Matsumoto, N., Ishimura, E., Fukumoto, S., Shoji, T., Miki, T., et al. (2003) Factors Affecting Progression of Renal Failure in Patients with Type 2 Diabetes. Diabetes Care, 26, 1530-1534.
http://dx.doi.org/10.2337/diacare.26.5.1530 [9] Boguslawa, N.S., Dariusz, M. and Wladyslaw, G. (2002) Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: Results of Longitudinal Design. Journal of Diabetes and Its Complications, 16, 271-276.
http://dx.doi.org/10.1016/S1056-8727(01)00184-2 [10] Hu, G., Lindstrom, J., Valle, T.T., Eriksson, G., Jousilahti, P., Silventoinen, K., et al. (2004) Physical Activity, Body Mass Index, and Risk of Type 2 Diabetes in Patients with Normal or Impaired Glucose Regulation. Archives of Internal Medicine, 164, 892-896.
http://dx.doi.org/10.1001/archinte.164.8.892 [11] Turner, R.C. (1998) The UK Prospective Diabetes Study. Diabetes Care, 21, C35-C38. [12] Cox, D.R. (1975) Partial Likelihood. Biometrika, 62, 269-276.
http://dx.doi.org/10.1093/biomet/62.2.269 [13] Sasso, F.C., Salvatore, T., Nicola, L.D., et al. (2006) Cardiovascular Risk Factors and Disease Management in Type 2 Diabetic Patients with Diabetic Nephropathy. Diabetes Care, 29, 498-503.
http://dx.doi.org/10.2337/diacare.29.03.06.dc05-1776 [14] Agarwal, N., Senger, N.S., Jain. P.K. and Khare, R. (2011) Nephropathy in Newly Diagnosed Type 2 Diabetes with Special Stress on the Role of Hypertension. Journal of the Association of Physicians of India, 59, 145-147. [15] Matthews, D.R., Stratton, I.M., Aldington, S.J., Holman, R.R. and Khner, E.M. (2004) UK Prospective Diabetes Study Group. Risk of Progression of Retinopathy and Vision Loss Related to Tight Blood Pressure Control in Type 2 Diabetes Mellitus: UKPDS 69. Archives of Ophthalmology, 122, 1631-1640.
http://dx.doi.org/10.1001/archopht.122.11.1631 [16] Leelawattana, R., Pratipanawatr, T., Bunnag, P., Kosachunhanun, N., Suwanwalaikorn, S., Krittiyawong, S., et al. (2006) Thailand Diabetes Registry Project: Prevalence of Vascular Complications in Long-Standing Type 2 Diabetes. Journal of the Medical Association of Thailand, 89, S54-S59. [17] Kim, S.I. and Kim, S.J. (2006) Prevalence and Risk Factors for Cataracts in Persons with Type 2 Diabetes Mellitus. Korean Journal of Ophthalmology, 20, 201-204.
http://dx.doi.org/10.3341/kjo.2006.20.4.201 [18] Javier, F., Perez, C.F., Ruiz, I.M., de Gorospe Pérez-Jáuregui, C., Rodríguez, B.S., Losada, T.G. and Galindo, A.S. (2011) Microvascular Complications and Risk Factors in Patients with Type 2 Diabetes. Endocrinología y Nutrición, 58, 163-168.
http://dx.doi.org/10.1016/j.endonu.2011.01.006 [19] Nathan, D.M., Cleary, P.A., Backlund, J.Y., Genuth, S.M., Lachin, J.M., Orchard, T.J., Raskin, P. and Zinman, B. (2005) Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes. New England Journal of Medicine, 353, 2643-2653.
http://dx.doi.org/10.1056/NEJMoa052187 [20] Sayeed, M.A., Khanam, P.A., Hossain, M.M., et al. (1999) Diabetic Subjects with Severe Hyperglycemia and Proteinuria Are More Prevalent in Rural than Urban and in Poor than Rich People. Diabetes and Endocrine Journal, 27, 35-40. [21] Klein, B.E., Klein, R. and Moss, S.E. (1985) Prevalence of Cataracts in a Population-Based Study of Persons with Diabetes Mellitus. Ophthalmology, 92, 1191-1196.
http://dx.doi.org/10.1016/S0161-6420(85)33877-0 [22] Lehto, S., Ronnemaa, T., Haffner, S.M., Pyörälä, K., Kallio, V. and Laakso, M. (1997) Dislipidemia and Hyperglycemia Predict Coronary Heart Disease Events in Middle-Aged Patients with NIDDM. Diabetes, 46, 1354-1359.
http://dx.doi.org/10.2337/diab.46.8.1354 [23] Gall, M.A., Borch-Johnsen, K., Hougaard, P., Nielsen, F.S. and Parving, H.H. (1995) Albuminuria and Poor Glycemic Control Predict Mortality in NIDDM. Diabetes, 44, 1303-1309.
http://dx.doi.org/10.2337/diab.44.11.1303 [24] Haffner, S.M. (1999) Epidemiological Studies on the Effects of Hyperglycemia and Improvement of Glycemic Control on Macrovascular Events in Type 2 Diabetes. Diabetes Care, 22, C54-C56. [25] Wilson, P.W.F. and Meigs, J.B. (2008) Risk of Type 2 Diabetes Mellitus and Coronary Heart Disease: A Pivotal Role for Metabolic Factors. European Heart Journal, 10, B11-B15. [26] Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P.D., Zieve, F.J., Marks, J., Davis, S.N., Hayward, R., Warren, S.R., Goldman, S., McCarren, M., Vitek, M.E., Henderson, W.G., Huang, G.D. for VADT Investigators (2009) Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. New England Journal of Medicine, 360, 129-139.
http://dx.doi.org/10.1056/NEJMoa0808431 [27] Raman, R., Pal, S.S., Adams, J.S.K., Rani, P.K., Vaitheeswaran, K. and Sharma, T. (2010) Prevalence and Risk Factors for Cataract in Diabetes: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study. Investigative Ophthalmology & Visual Science, 51, 6253-6261.
http://dx.doi.org/10.1167/iovs.10-5414 [28] Kuo, H.S., Chang, H.J., Chou, P., Teng, L. and Chen, H.H. (1999) A Markov Chain Model to Assess the Efficacy of Screening for Non-Insulin Dependent Diabetes Mellitus (NIDDM). International Journal of Epidemiology, 28, 233-240.
http://dx.doi.org/10.1093/ije/28.2.233 [29] Weng, J., Li, Y., Shi, L., Zhang, Q., Zhu, D., Hu, Y., Yan, X., Tian, H., et al. (2008) Effect of Intensive Insulin Therapy on β-Cell Function and Glycaemic Control in Patients with Newly Diagnosed Type 2 Diabetes: A Multicentre Randomized Parallel-Group Trial. Lancet, 371, 1753-1760.
http://dx.doi.org/10.1016/S0140-6736(08)60762-X [30] Absood, A., Gandomani, B., Zaki, A., Nasta, V., Michail, A., Habib, P.M. and Hodish, I. (2013) Insulin Therapy for Pre-Hyperglycemic Beta-Cell Endoplasmic Reticulum Crowding. PLoS ONE, 8, Article ID: e54351.
http://dx.doi.org/10.1371/journal.pone.0054351 [31] The Diabetes Control and Complications Trail Research Group (1993) The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. New England Journal of Medicine, 329, 977-986. [32] Alder, A.I., Stevens, R.I., Manley, S.E., Bilous, R.W., Cull, C.A. and Holman, R.R. on Behalf of the UKPDS Group (2003) Development and Progression of Nephropathy in Type 2 Diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney International, 63, 225-232.
http://dx.doi.org/10.1046/j.1523-1755.2003.00712.x