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The relationship between glucose control and the development and progression of diabetic nephropathy

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Abstract

Diabetic nephropathy is a major cause of morbidity and mortality in patients with diabetes; it occurs in about one third of such patients. The course of nephropathy is better defined and similar for both type 1 and type 2 diabetes. Patients initially develop microalbuminuria (albumin excretion rates [AERs] between 20 and 200 μg/min), then overt nephropathy (AER ≥ 200 μg/min), and finally a decline in glomerular filtration rate (GFR) eventuating in end-stage renal disease. Although metabolic control has long been hypothesized as a contributor to the development of nephropathy, it is only in recent years that this hypothesis has been proven. A number of observational studies have shown correlations between glycemic control and the development of various levels of albuminuria and also declines in GFR. However, large long-term prospective, randomized, interventional studies have now definitely proven that improved metabolic control that achieves nearnormoglycemia can significantly decrease the development and progression of diabetic nephropathy as well as other long-term complications of diabetes, including retinopathy and neuropathy. It is now conceivable that the achievement of near-normoglycemia, plus medications that inhibit the renin-angiotensin system if microalbuminuria develops, may greatly decrease the numbers of patients eventually requiring renal replacement therapy.

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References and Recommended Reading

  1. USRDS 2001 Annual Data Report: Atlas of End-stage Renal Disease in the United States. Bethesda, MD: United States Renal Data System, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2001.

  2. Trevisan R, Viberti GC: Genetic factors in the development of diabetic nephropathy. J Lab Clin Med 1995, 126:342–349.

    PubMed  CAS  Google Scholar 

  3. Mogensen CE: Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. BMJ 1982, 285:685–688.

    PubMed  CAS  Google Scholar 

  4. Parving HH, Andersen AR, Smidt UM, et al.: Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983, 1:1175–1179.

    Article  PubMed  CAS  Google Scholar 

  5. Brenner BM: Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 1983, 23:647–655.

    PubMed  CAS  Google Scholar 

  6. Hostetter TH: Mechanisms of diabetic nephropathy. Am J Kidney Dis 1994, 23:188–192.

    PubMed  CAS  Google Scholar 

  7. Bondy PK, Felig P: Relation of diabetic control to development of vascular complications. Med Clin North Am 1971, 55:889–897.

    Google Scholar 

  8. Cahill GF Jr, Etzwiler DD, Freinkel N: "Control" and diabetes [editorial]. N Engl J Med 1976, 294:1004–1005.

    Article  PubMed  Google Scholar 

  9. Mauer SM, Barbosa J, Vernier RL, et al.: Development of diabetic vascular lesions in normal kidneys transplanted into patients with diabetes mellitus. N Engl J Med 1976, 295:916–920.

    Article  PubMed  CAS  Google Scholar 

  10. Bohman SO, Tyden G, Weilczek H, et al.: Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man. Diabetes 1985, 34:306–308.

    Article  PubMed  CAS  Google Scholar 

  11. Bilous RW, Mauer SM, Sutherland DE, et al.: The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 1989, 321:80–85.

    Article  PubMed  CAS  Google Scholar 

  12. Fioretto P, Steffes MW, Sutherland DE, et al.: Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998, 339:115–117.

    Article  Google Scholar 

  13. Consensus Development Conference on the diagnosis and management of nephropathy in patients with diabetes mellitus. American Diabetes Association and the National Kidney Foundation [no authors listed]. Diabetes Care 1994, 17:1357–1361.

  14. Jacobson HR, Striker GE: Report on a workshop to develop management recommendations for the prevention of progression in chronic renal disease. Am J Kidney Dis 1995, 25:103–106.

    PubMed  CAS  Google Scholar 

  15. Bennett PH, Haffner S, Kasiske BL, et al.: Screening and management of microalbuminuria in patients with diabetes mellitus. Am J Kidney Dis 1995, 25:107–112.

    PubMed  CAS  Google Scholar 

  16. Mogensen CE, Eiskjær H, Vestbo E, et al.: Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care 1995, 18:572–581.

    PubMed  CAS  Google Scholar 

  17. Mogensen CE, Keane WF, Bennett PH, et al.: Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995, 346:1080–1084.

    Article  PubMed  CAS  Google Scholar 

  18. Ballard DJ, Humphrey LL, Melton LJ III, et al.: Epidemiology of persistant proteinuria in type II diabetes mellitus. Diabetes 1988, 37:405–412.

    Article  PubMed  CAS  Google Scholar 

  19. 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 [no authors listed]. N Engl J Med 1993, 329:977–986.

  20. Krolewski AS, Warram JH: Natural history of diabetic nephropathy. Diabetes Rev 1995, 3:446–459.

    Google Scholar 

  21. Savage S, Nagel NJ, Estacio RO, et al.: Clinical factors associated with urinary albumin excretion in type II diabetes. Am J Kidney Dis 1995, 25:836–844.

    PubMed  CAS  Google Scholar 

  22. 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 [no authors listed]. Lancet 1998, 352:837–853.

  23. Caramori ML, Fioretto P, Mauer M: The need for early predictors of diabetic nephropathy risk. Diabetes 2000, 49:1399–1408. A unique review evaluating AER as a predictor of the subsequent development of diabetic nephropathy. The analysis suggests that the risk of progression from normoalbuminuria to microalbuminuria and from microalbuminuria to overt nephropathy is less than originally described for patients with either type 1 or type 2 diabetes.

    Article  PubMed  CAS  Google Scholar 

  24. Mauer M: Structural-functional correlations of diabetic nephropathy. Kidney Int 1994, 45:612–622.

    PubMed  CAS  Google Scholar 

  25. Fioretto P, Steffes M, Mauer M: Glomerular structure in nonproteinuric IDDM patients with various levels of microalbuminuria. Diabetes 1994, 43:1358–1364.

    Article  PubMed  CAS  Google Scholar 

  26. Gambara V, Mecca G, Remuzzi G, Bertani T: Heterogeneous nature of renal lesions in type II diabetes. J Am Soc Nephrol 1993, 3:1458–1466.

    PubMed  CAS  Google Scholar 

  27. Osterby R, Gall M-A, Shmitz A, et al.: Glomerular structure and function in proteinuric type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993, 36:1064–1074.

    Article  PubMed  CAS  Google Scholar 

  28. Brocco E, Fioretto P, Mauer M, et al.: Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria. Kidney Int 1997, 63:S40-S44.

    CAS  Google Scholar 

  29. Hasslacher C, Ritz E, Wahl P, Michael C: Similar risks of nephropathy in patients with type I or type II diabetes mellitus. Nephrol Dial Transplant 1989, 4:859–863.

    PubMed  CAS  Google Scholar 

  30. Kunzelman CL, Knowler WC, Pettitt DJ, Bennett PH: Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians. Kidney Int 1989, 35:681–687.

    PubMed  CAS  Google Scholar 

  31. Parving HH, Oxenboll B, Svendsen PA, et al.: Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol 1982, 100:550–555.

    PubMed  CAS  Google Scholar 

  32. Viberti GC, Hill RD, Jarrett RJ, et al.: Micro-albuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982, 1:1430–1432.

    Article  PubMed  CAS  Google Scholar 

  33. Mathiesen ER, Oxenboll B, Johansen K, et al.: Incipient nephropathy in type 1 insulin-dependent diabetes. Diabetologia 1984, 26:406–410.

    Article  PubMed  CAS  Google Scholar 

  34. Mogensen CE, Christensen CK: Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984, 311:89–93.

    Article  PubMed  CAS  Google Scholar 

  35. Messent JWC, Elliott TG, Hill RD, et al.: Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int 1992, 41:836–839.

    PubMed  CAS  Google Scholar 

  36. Rossing P, Hougaard P, Parving H-H: Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients. Diabetes Care 2002, 25:859–864.

    Article  PubMed  Google Scholar 

  37. Forsblom CM, Groop P-H, Ekstrand A, Groop LC: Predictive value of microalbuminuria in patients with insulin dependent diabetes of long duration. BMJ 1992, 305:1051–1053.

    PubMed  CAS  Google Scholar 

  38. Nelson RG, Bennett PH, Beck GJ, et al.: Development and progression of renal disease in Pima Indians with noninsulin-dependent diabetes mellitus. N Engl J Med 1996, 335:1636–1642.

    Article  PubMed  CAS  Google Scholar 

  39. Ravid M, Lang R, Rachmani R, Lishner M: Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. Arch Intern Med 1996, 156:286–289.

    Article  PubMed  CAS  Google Scholar 

  40. Gaede P, Vedel P, Parving HH, Pedersen O: Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999, 353:617–622.

    Article  PubMed  CAS  Google Scholar 

  41. Estacio RO, Jefers BW, Gifford N, Schrier RW: Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 2000, 23:B54-B64.

    PubMed  Google Scholar 

  42. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators [no authors listed]. Lancet 2000, 355:253–259.

  43. Ordonez JD, Hiatt RA: Comparison of type II and type I diabetics treated for end-stage renal disease in a large prepaid health plan population. Nephron 1989, 51:524–529.

    Article  PubMed  CAS  Google Scholar 

  44. Tuttle KR, Stein JH, DeFronzo RA: The natural history of diabetic nephropathy. Semin Nephrol 1990, 10:184–193.

    PubMed  CAS  Google Scholar 

  45. Gall MA, Nielsen FS, Smitz UM, Parving HH: The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy. Diabetologia 1993, 36:1071–1078.

    Article  PubMed  CAS  Google Scholar 

  46. Hasslacher C, Bostedt-Kiesel A, Kempe HP, Wahl P: Effect of metabolic factors and blood pressure on kidney function in proteinuric type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993, 36:1051–1056.

    Article  PubMed  CAS  Google Scholar 

  47. Biesenbach G, Janko O, Zazgornik J: Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus. Nephrol Dial Transplant 1994, 9:1097–1110.

    PubMed  CAS  Google Scholar 

  48. Krolewski AS, Warram JH, Christlieb AR, et al.: The changing natural history of nephropathy in type 1 diabetes. Am J Med 1985, 78:785–797.

    Article  PubMed  CAS  Google Scholar 

  49. Humphrey LL, Ballard DJ, Frohnert PP, et al.: Chronic renal failure in non-insulin-dependent diabetes mellitus. Ann Intern Med 1989, 111:788–796.

    PubMed  CAS  Google Scholar 

  50. Dinneen SF, Gerstein HC: The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. Arch Intern Med 1997, 157:1413–1418.

    Article  PubMed  CAS  Google Scholar 

  51. Parving HH, Gall MA, Skott P, et al.: Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients. Kidney Int 1992, 41:758–762.

    PubMed  CAS  Google Scholar 

  52. Seaquist ER, Goetz FC, Rich S, et al.: Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989, 320:1161–1165.

    Article  PubMed  CAS  Google Scholar 

  53. Borch-Johnsen K, Nørgaard K, Hommel E, et al.: Is diabetic nephropathy an inherited complication? Kidney Int 1992, 41:719–722.

    PubMed  CAS  Google Scholar 

  54. Quinn M, Angelico MC, Cross A, et al.: Concordance for kidney complications in siblings with IDDM. Diabetes 1992, 41(suppl 1):S2-S8.

    Google Scholar 

  55. Clustering of long-term complications in families with diabetes in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group [no authors listed]. Diabetes 1997, 46:1829–1839.

  56. Pettitt DJ, Saad MF, Bennett PH, et al.: Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1990, 33:438–443.

    Article  PubMed  CAS  Google Scholar 

  57. Haffner SM, Gonzales C, Valdez RA, et al.: Is microalbuminuria part of the prediabetic state? The Mexico City Diabetes Study. Diabetologia 1993, 36:1002–1006.

    Article  PubMed  CAS  Google Scholar 

  58. Freedman BI, Tuttle AB, Spray BJ: Familial predisposition to nephropathy in African-Americans with non-insulin-dependent diabetes mellitus. Am J Kidney Dis 1995, 25:710–713.

    PubMed  CAS  Google Scholar 

  59. The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. The DCCT Research Group [no authors listed]. Diabetes 1986, 35:530–545.

  60. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. The EDIC/DCCT research group [no authors listed]. JAMA 2002, 287:2563–2569. A summary of the findings of the DCCT and the observational follow-up of the DCCT cohort in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, regarding the effect of the intensive therapy on the microvascular complications of type 1 diabetes mellitus.

  61. Ohkubo Y, Kishikawa H, Araki E, et al.: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995, 28:103–117.

    Article  PubMed  CAS  Google Scholar 

  62. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group [no authors listed]. Lancet 1998, 352:854–865.

  63. Nyberg G, Blohme G, Norden G: Impact of metabolic control in progression of clinical diabetic nephropathy. Diabetologia 1987, 30:82–86.

    PubMed  CAS  Google Scholar 

  64. Breyer JA, Bain RP, Evans JK, et al.: Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. Kidney Int 1996, 50:1651–1658.

    Article  PubMed  CAS  Google Scholar 

  65. Mulec H, Blohme G, Grande B, Bjorck S: The effect of metabolic control on rate of decline in renal function in insulindependent diabetes mellitus with overt diabetic nephropathy. Nephrol Dial Transplant 1998, 13:651–655.

    Article  PubMed  CAS  Google Scholar 

  66. Hovind P, Rossing P, Tarnow L, et al.: Progression of diabetic nephropathy. Kidney Int 2001, 59:702–709.

    Article  PubMed  CAS  Google Scholar 

  67. Parving H-H, Rossing P, Hommel E, et al.: Angiotensinconverting enzyme inhibition in diabetic nephropathy: ten years’ experience. Am J Kidney Dis 1995, 26:99–107.

    PubMed  CAS  Google Scholar 

  68. Yokoyama H, Tomonaga O, Hirayama M, et al.: Predictors of the progression of diabetic nephropathy and the beneficial effect of angiotensin-converting enzyme inhibitors in NIDDM patients. Diabetologia 1997, 40:405–411.

    Article  PubMed  CAS  Google Scholar 

  69. Nosadini R, Velussi M, Brocco E, et al.: Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes 2000, 49:476–484.

    Article  PubMed  CAS  Google Scholar 

  70. Morioka T, Emoto M, Tabata T, et al.: Glycemic control is a predictor of survival for diabetic patients on hemodialysis. Diabetes Care 2001, 24:909–913. A recent prospective, observational study showing that good glycemic control predicts better survival of diabetic patients with ESRD starting maintenance hemodialysis.

    Article  PubMed  CAS  Google Scholar 

  71. Adverse events and their association with treatment regimens in the Diabetes Control and Complications Trial [no authors listed]. Diabetes Care 1995, 18:1415–1427.

  72. Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial [no authors listed]. Ann Intern Med 1996 124:379–388.

  73. Influence of intensive diabetes treatment on quality-of-life outcomes in the Diabetes Control and Complications Trial [no authors listed]. Diabetes Care 1996, 19:195–203.

  74. Krolewski AS, Laffel LMB, Krolewski M, et al.: Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. N Engl J Med 1995, 332:1251–1255.

    Article  PubMed  CAS  Google Scholar 

  75. Chase HP, Jackson WE, Hoops SL, et al.: Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA 1989, 261:1155–1160.

    Article  PubMed  CAS  Google Scholar 

  76. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial [no authors listed]. Diabetes 1995, 44:968–983.

  77. 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, 321:405–412. Observational analysis of the UKPDS subjects showing a 37% risk reduction for microvascular complications for each 1% (absolute) reduction in HbA1c value. Those with the lowest risk were those with HbA1c values in the normal range (6.0%).

    Article  PubMed  CAS  Google Scholar 

  78. King H, Aubert RE, Herman WH: Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998, 21:1414–1431.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Endocrinology, Metabolism and Molecular Medicine, The Feinberg School of Medicine of Northwestern University, 303 E. Chicago Avenue (Tarry 15-731), 60611, Chicago, IL, USA

    Carrie A. Phillips MD & Mark E. Molitch MD

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Phillips, C.A., Molitch, M.E. The relationship between glucose control and the development and progression of diabetic nephropathy. Curr Diab Rep 2, 523–529 (2002). https://doi.org/10.1007/s11892-002-0123-1

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