Skip to main content
SpringerLink
Log in

UK Prospective Diabetes Study (UKPDS)

X. Urinary albumin excretion over 3 years in diet-treated Type 2, (non-insulin-dependent) diabetic patients, and association with hypertension, hyperglycaemia and hypertriglyceridaemia

  • Published:
Diabetologia Aims and scope Submit manuscript

Summary

Urinary albumin excretion has been assessed in 585 newly-presenting Type 2 (non-insulin-dependent) diabetic patients (aged 53 (8) years, 67% male) at diagnosis with fasting plasma glucose 10.3 (3.2) mmol/l and over 3 years of dietary treatment. Urinary albumin at diagnosis, geometric mean (1 SD interval) corrected for dilution by regression on urine creatinine concentration of 10 mmol/l, was 17(5–58) mg/l compared with 8 (3–18) mg/l in an agematched non-diabetic reference population. Values greater than 50 mg/l were found in 17% of diabetic patients compared with 4% in the reference group. After diet therapy for 3 months, fasting plasma glucose decreased to 6.9 mmol/l and urinary albumin to 12 (4–31) mg/l (p<0.0001). This suggests that increased urinary albumin excretion at diagnosis is in part functional, possibly secondary to glomerular hyperfiltration caused by hyperglycaemia and raised blood pressure. Over the next 3 years, mean fasting plasma glucose was 7.2 mmol/l, albumin excretion changed little, without significant increase either in patients with raised or normal albumin at diagnosis. Both at diagnosis and over 3 years, urinary albumin excretion was independently associated with fasting plasma glucose and triglyceride levels and with systolic blood pressure, but the combination of these factors only explained 10% of the total variance. This suggests the presence of additional pathological processes in patients with increased urinary albumin. Urinary albumin was not associated with other variables included in syndrome X, such as HDL cholesterol, fasting plasma insulin, obesity or central adiposity. The lack of change in urinary albumin over 3 years, even in subjects with raised excretion and in the highest group for glycaemia, indicates that the pathological processes are only slowly progressive in these asymptomatic patients. Increased cardiovascular mortality associated with raised urinary albumin excretion may in part be secondary to the associated hypertension and elevated triglyceride levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jarrett RJ, Viberti GC, Argyropolous A, Hill RD, Mahmus U, Murrells TJ (1984) Microalbuminuria predicts mortality in noninsulin-dependent diabetics. Diabetic Med 1:17–19

    CAS  PubMed  Google Scholar 

  2. Morrish NJ, Stevens LK, Head J, Fuller JH, Jarrett RJ, Keen H (1990) A prospective study of mortality among middle-aged diabetic patients: the London cohort of the WHO multinational Study of Vascular Disease in Diabetics II: associated risk factors. Diabetologia 33:542–548

    CAS  PubMed  Google Scholar 

  3. Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356–360

    CAS  PubMed  Google Scholar 

  4. Schmitz A, Vaeth M (1987) Microalbuminuria: a major risk factor for non-insulin-dependent diabetes. A 10 year follow-up study of 503 patients. Diabetic Med 5:126–134

    Google Scholar 

  5. Mattock MB, Keen H, Viberti GC et al. (1988) Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 31:82–87

    Article  CAS  PubMed  Google Scholar 

  6. Deckert T, Feldt-Rasmussen B, Borch-Johnson K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32:219–226

    CAS  PubMed  Google Scholar 

  7. Wiseman MJ, Viberti GC, Mackintosh D, Jarrett RJ, Keen H (1984) Glycaemia, arterial pressure and microalbuminuria in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26: 401–405

    Article  CAS  PubMed  Google Scholar 

  8. Mathiesen ER, Oxenbøll B, Johansen K, Svendsen PA, Deckert T (1984) Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia 26:406–410

    Article  CAS  PubMed  Google Scholar 

  9. Gatling W, Mullee MA, Knight C, Hill RD (1988) Microalbu minuria in diabetes: relationship between urinary albumin excretion and diabetes-related variables Diabetic Med 5:348–351

    CAS  PubMed  Google Scholar 

  10. UK Prospective Diabetes Study 6 (1990) Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diabetes Res 13: 1–11

    Google Scholar 

  11. Manley SE, Cull CA, Burton ME et al. (1993) UK Prospective Diabetes Study (UKPDS) IX: Relationships of urinary a albumin and N-acetylglucosaminidase to glycaemia and hypertension at diagnosis of type 2 (non-insulin-dependent) diabetes mellitus and after 3 months diet therapy. Diabetologia 36:835–842

    Google Scholar 

  12. Allawi J, Jarrett RJ (1989) Microalbuminuria and cardiovascular risk factors in type 2 diabetes mellitus. Diabetic Med 7:115–118

    Google Scholar 

  13. Niskanen L, Uusitupa M, Sarlund H, Siitonen O, Voutilainen E, Penttilä I, Pyörälä K (1990) Microalbuminuria predicts the development of serum lipoprotein abnormalities favouring atherogenesis in newly diagnosed type 2 (non-insulin-dependent) diabetic patients. Diabetologia 33:237–243

    Article  CAS  PubMed  Google Scholar 

  14. Mattock MB, Morris NJ, Viberti GC, Keen H, Fitzgerald AP, Jackson PG (1992) Prospective study of microalbuminuria as predictor of mortality in NIDDM. Diabetes 41:736–741

    CAS  PubMed  Google Scholar 

  15. Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHR, Donker AJM, Den Ottolander GJH (1992) Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 340:319–323

    Article  CAS  PubMed  Google Scholar 

  16. Seghieri G, Alviggi L, Caselli P et al. (1990) Serum lipids and lipoproteins in type 2 diabetic patients with persistent microalbuminuria Diabetic Med 7:810–814

    CAS  PubMed  Google Scholar 

  17. Kapelrud H, Bangstad H-J, Dahl-Jørgensen K, Berg K, Hanssen KF (1991) Serum Lp(a) liporrotein concentrations in insulin dependent diabetic patients with microalbuminuria. BMJ 303: 675–678

    CAS  PubMed  Google Scholar 

  18. Jensen T, Stender S, Deckert T (1988) Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type 1 (insulindependent) diabetic patients with increased urinary albumin excretion. Diabetologia 31:142–145

    Article  CAS  PubMed  Google Scholar 

  19. Winocour PH, Bhatnagar D, Ishola M, Arrol S, Durrington PN (1991) Lipoprotein(a) and microvascular disease in type 1 (insulin-dependent) diabetes. Diabetic Med 8:922–927

    CAS  PubMed  Google Scholar 

  20. Dullaart RP, Dikkeschei LD, Doorenbos H (1989) Alterations in serum lipids and apolipoproteins in male type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 32: 685–689

    CAS  PubMed  Google Scholar 

  21. Watts GF, Naumova R, Slavin BM et al. (1989) Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria. Diabetic Med 6:25–30

    CAS  PubMed  Google Scholar 

  22. Patrick AW, Leslie PJ, Clarke BF, Frier BM (1990) The natural history and associations of microalbuminuria in type 2 diabetes during the first year after diagnosis. Diabetic Med 8:902–908

    Google Scholar 

  23. Martin P, Hampton KK, Walton C, Tindall H, Daview JA (1989) Microproteinuria in type 2 diabetes mellitus from diagnosis. Diabetic Med 7:315–318

    Google Scholar 

  24. Vasquez B, Flock EV, Savage PJ et al. (1984) Sustained reduction of proteinuria in type 2 (non-insulin-dependent) diabetes following diet-induced reduction of hyperglycaemia. Diabetologia 26:127–133

    Article  CAS  PubMed  Google Scholar 

  25. Schmitz A, Hvid Hansen H, Christensen T (1989) Kidney function in newly diagnosed type 2 (non-insulin-dependent) diabetic patients, before and during treatment. Diabetologia 32: 434–439.

    Article  CAS  PubMed  Google Scholar 

  26. UK Prospective Diabetes Study Group (1991) UK Prospective Diabetes Study Group (UKPDS). VIII. Study design, progress and performance. Diabetologia 34:877–890.

    Article  Google Scholar 

  27. Wright BM, Dore CF (1970) A random zero sphygmomanometer. Lancet I:33–35.

    Google Scholar 

  28. Westgard JO, Barry PL, Hunt MR (1981) A multi-rule Shewhart chart for quality control in clinical chemistry. Clin Chem 27:493–501.

    CAS  PubMed  Google Scholar 

  29. Woo J, Floyd M, Cannon DC, Kahan B (1978) Radioimmunoassay for urinary albumin. Clin Chem 24:1464–1467

    CAS  PubMed  Google Scholar 

  30. Kearney EM, Mount JN, Watts GF, Slavin BM, Kind PRN (1987) Simple immunoturbidimetric method for determining urinary albumin at low concentrations using Cobas-Bio centrifugal analyser. J. Clin Path 40:465–468.

    CAS  PubMed  Google Scholar 

  31. Jaffé M (1886) Ueber den Neiderschlag, welchen Pikrinsaure in normalen Harn erzeugt und ueber eine neue Reaktion des Kreatinins. Z Physiol Chem 10:391–400

    Google Scholar 

  32. Di Giorgio J (1974) Automated determination of serum and urine creatinine. In: Henry RJ, Cannon DC, Winkelman JW (eds) Clinical chemistry. Principles and techniques. Harper and Row, Hagerstown, pp 552–553

    Google Scholar 

  33. Wahlefeld AW (1974) Triglycerides. Determination after enzymatic hydrolysis. In: Bergmeyer M (ed) Methods of enzymatic analysis. 2nd edn vol 4. Verlag Chemie Weinheim and Academic Press. Inc. New York London, pp 1831–1835

    Google Scholar 

  34. Huang TC, Chen CP, Wefler V, Raftery A (1961) A stable reagent for the Liebermann-Burchard reaction. Application to rapid serum cholesterol determination. Analytical Chem 33:1405–1407

    Article  CAS  Google Scholar 

  35. Siedel J, Schlumberger H, Klose S, Ziegenhorn J, Wahlefeld AW (1981) Improved reagent for the enzymatic determination of serum cholesterol. J Clin Chem Clin Biochem 19:838–839.

    Google Scholar 

  36. Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Research 11:583–594

    CAS  Google Scholar 

  37. Albano JM, Ekins RP, Martiz G, Turner RC (1972) A sensitive precise radio-immunoassay of human insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol 70:487–509

    CAS  PubMed  Google Scholar 

  38. Moore JC, Bown E, Outlaw MC, Jelfs R, Holman RR, Turner RC (1986) Glycosylated haemoglobin: comparison of five different methods including measurement on capillary blood samples. Ann Clin Biochem 23:85–91

    CAS  PubMed  Google Scholar 

  39. Eeley E, Stratton IM, James R, Holman RR (1992) Dietary evaluation in type 2 diabetic subjects randomly allocated to insulin sulphonylurea or diet therapy. Diabetologia 35 [Suppl 1]: A165 (Abstract)

    Google Scholar 

  40. SAS Institute Inc (1990) SAS user guide, Version 6. SAS Institute Inc, Cary

    Google Scholar 

  41. Thompson SG, Barlow RD, Wald NJ, Vunakis HV (1990) How should urinary cotinine concentrations be adjusted for urinary creatinine concentration? Clin Chim Acta 187:289–295

    Article  CAS  PubMed  Google Scholar 

  42. Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37:1595–1607

    CAS  PubMed  Google Scholar 

  43. Mogensen CE, Andersen MJF (1973) Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 22:706–713

    CAS  PubMed  Google Scholar 

  44. Kasiske BL, O'Donnell MP, Cleary MP, Keane WF (1988) Treatment of hyperlipidaemia reduces glomerular injury in obese Zucker rats. Kidney Int 33:667–672

    CAS  PubMed  Google Scholar 

  45. Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, Deckert T (1987) Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia 30:144–148

    Article  CAS  PubMed  Google Scholar 

  46. Damsgaard EM, Frøland A, Jørgensen OD, Mogensen CE (1990) Microalbuminuria as predictor of increased mortality in elderly people. BMJ 300:297–300

    CAS  PubMed  Google Scholar 

  47. Yudkin JS, Forrest RD, Jackson CA (1988) Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Lancet II:530–533

    Google Scholar 

  48. Pettitt DJ, Knowler WC, Lisse JR, Bennett PH (1980) Development of retinopathy and proteinuria in relation to plasma glucose concentrations in Pima Indians. Lancet II:1050–1052

    Google Scholar 

Download references

Author information

Authors and Affiliations

    Consortia

    UK Prospective Diabetes Study Group

    Additional information

    This manuscript was prepared by C. Cull, S. Manley, V. Frighi, R. Holman, R. Turner for the UKPDS Group

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    UK Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS). Diabetologia 36, 1021–1029 (1993). https://doi.org/10.1007/BF02374494

    Download citation

    • Issue Date:

    • DOI: https://doi.org/10.1007/BF02374494

    Key words

    Search

    Navigation