Progression of Albuminuria Among Patients with Type 1 Diabetes Mellitus: A Long Term Observational Follow-up Study

Abstract

Background The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up.

Patients and Methods A cohort of 84 patients, 18–76 years of age, a median duration of diabetes of 24 years (1–50 years) and a median follow-up duration of 12 years (1–37 years) were included in the study.

Results Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04–7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too.

Conclusions Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.

Key words

type 1 diabetes - microalbuminuria - alkaline phosphatase - diabetic hepatosclerosis - steatosis

Publication History

Received: 04 May 2018
Received: 04 January 2019

Accepted: 30 January 2019

Article published online:
25 February 2019

• References

• 1 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
• 2 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. N Engl J Med 1993; 329: 977-986
• 3 Andersen AR, Christiansen JS, Andersen JK. et al. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 1983; 25: 496-501
• 4 Krolewski AS, Warram JH, Christlieb AR. et al. The changing natural history of nephropathy in type I diabetes. Am J Med 1985; 78: 785-794
• 5 Groop PH, Thomas MC, Moran JL. et al. FinnDiane Study Group. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes 2009; 58: 1651-1658
• 6 Orchard TJ, Secrest AM, Miller RG. et al. In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: A report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia 2010; 53: 2312-2319
• 7 de Boer, Rue T, Cleary PA. et al. For the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria. an analysis of the diabetes control and complications trial/epidemiology of diabetes interventions and complications cohort. Arch Intern Med 2011; 171: 412-420
• 8 Inker LA, Schmid CH, Tighiouart H. et al. CKD-EPI Investigators. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367: 20-29
• 9 Nelson RG, Tuttle KR. The New KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and CKD screening and diagnosis of diabetic kidney disease. Blood Purif 2007; 25: 112-114
• 10 Lewis EJ, Hunsicker LG, Bain RP. et al. Collaborative study. The effect of angiotensin converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456-1462
• 11 Hirst JA, Taylor KS, Stevens RJ. et al. The impact of renin-angiotensin-aldosterone system inhibitors on type 1 and type 2 diabetic patients with and without early diabetic nephropathy. Kidney Int 2012; 81: 674-683
• 12 Ruggenenti P, Cravedi P, Remuzzi G. The RAAS in the pathogenesiis and treatment of diabetic nephropathy. Nat Rev Nephrol 2010; 6: 319-330
• 13 Rosolowsky ET, Skupien J, Smiles AM. et al. Risk of ESRD in type 1 diabetes remains high in spite of renoprotection. J Am Soc Nephrol 2011; 22: 545-553
• 14 Forsblom C, Harjutsalo V, Thorn L. et al. FinnDiane Study Group. Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol 2011; 22: 537-544
• 15 Viberti G, Mogensen CE, Groop LC. et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group. JAMA 1994; 272: 275-279
• 16 Laffel LM, McGill JB, Gans DJ. The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 1995; 99: 497-504
• 17 de Boer IH. DCCT/EDIC Research Group. Kidney disease and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care 2014; 37: 24-30
• 18 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-dependentdiabetes mellitus. N Engl J Med 1993; 329: 977-986
• 19 Chaturvedi N, Bandinelli S, Mangili R. et al. EURODIAB prospective complications study group: Microalbuminuria in type 1 diabetes: Rates, risk factors and glycemic threshold. Kidney Int 2001; 60: 219-227
• 20 Chokrungvaranon N, Deer J, Reaven PD. Intensive glycemic control and cardiovascular disease; Are there patients who may benefit?. Postgrad Med 2011; 123: 114-123
• 21 Stone ML, Craig ME, Mappstat AKC. et al. Natural history and risk factors for microalbuminuria in adolescents with type 1 diabetes. A longitudinal study. Diabetes Care 2006; 29: 2072-2077
• 22 Perkins BA, Ficociello LH, Silva KH. et al. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003; 348: 2285-2293
• 23 Perkins BA, Ficociello LH, Ostrander BE. et al. Microalbuminuria and risk of early progressive renal function decline in type 1 diabetes. J Am Soc Nephrol 2007; 18: 1353-1361
• 24 Krolewski AS. Progressive Renal Decline: The new paradigm of diabetic nephropathy in type 1 diabetes. Diabetes Care 2015; 38: 954-962
• 25 Marcovecchio ML, Dalton RN, Prevost AT. et al. Prevalence of abnormal lipid profiles and the relationship with the development of microalbuminuria in adolescents with type 1 diabetes. Diabetes Care 2009; 32: 658-663
• 26 Maahs DM, Maniatis AK, Nadeau K. et al. Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus. J Pediatr 2005; 147: 544-546
• 27 Schwab KO, Doerfer J, Hecker W. et al. DPV Initiative of the German Working Group for Pediatric Diabetology. Spectrum and prevalence of atherogenic risk factors in 27,358 children, adolescents, and young adults with type 1 diabetes: Cross-sectional data from the German diabetes documentation and quality management system (DPV). Diabetes Care 2006; 29: 218-225
• 28 Maahs DM, Wadwa RP, McFann K. et al. Longitudinal lipid screening and use of lipid-lowering medications in pediatric type 1 diabetes. J Pediatr 2007; 150: 146-150
• 29 Kershnar AK, Daniels SR, Imperatore G. et al. Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study. J Pediatr 2006; 149: 314-319
• 30 Cruickshanks KJ, Orchard TJ, Becker DJ. The cardiovascular risk profile of adolescents with insulin-dependent diabetes mellitus. Diabetes Care 1985; 8: 118-124
• 31 Lopes-Virella MF, Wohltmann HJ, May-field RK. et al. Effect of metabolic control on lipid, lipoprotein, and apolipoprotein levels in 55 insulin-dependent diabetic patients: A longitudinal study. Diabetes 1983; 32: 20-25
• 32 Attia N, Touzani A, Lahrichi M. et al. Response of apolipoprotein AIV and lipoproteins to glycaemic control in young people with insulin-dependent diabetes mellitus. Diabet Med 1997; 14: 242-247
• 33 Bulum T, Kolarić B, Duvnjak M. et al. Alkaline phosphatase is independently associated with renal function in normoalbuminuric type 1 diabetic patients. Ren Fail 2014; 36: 372-377
• 34 Hanna AN, Waldman WJ, Lott JA. et al. Increased alkaline phosphatase isoforms in autoimmune diseases. Clin Chem 1997; 43: 1357-1364
• 35 Chen G, Brunt EM. Diabetic hepatosclerosis: A 10-year autopsy series. Liver Int 2009; 29: 1044-1050
• 36 King RJ, Harrison L, Gilbey SG. et al. Diabetic hepatosclerosis: Another diabetes microvascular complication?. Diabet Med 2016; 33: e5-e7
• 37 Balakrishnan M, Garcia-Tsao G, Deng Y. et al. Hepatic arteriolosclerosis: A small-vessel complication of diabetes and hypertension. Am J Surg Pathol 2015; 39: 1000-1009