, Volume 34, Issue 12, pp 877–890 | Cite as

UK prospective diabetes study (UKPDS)

VIII. Study design, progress and performance
  • UK Prospective Diabetes Study Group


The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective, randomised, intervention trial of 5100 newly-diagnosed patients with Type 2 (non-insulin-dependent) diabetes mellitus which aims to determine whether improved blood glucose control will prevent complications and reduce the associated morbidity and mortality. Newly presenting Type 2 diabetic patients aged 25–65 years inclusive, median age 53 years, median body mass index 28 kg/m2 and median fasting plasma glucose 11.3 mmol/l, were recruited and treated initially by diet. Ninety five percent remained hyperglycaemic (fasting plasma glucose > 6 mmol/l) and were randomly allocated to different therapies. In the main randomisation, those who were asymptomatic and had fasting plasma glucose under 15 mmol/l were allocated either to diet policy, or to active policy with either insulin or sulphonylurea aiming to reduce the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with 7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes Study has been included in a factorial design to assess whether improved blood pressure control will be advantageous. Patients with blood pressure ≥ 160/90 mm Hg were randomly allocated to tight control aiming for < 150/85 mm Hg with either an angiotensin-converting enzyme inhibitor or a Beta-blocker or to less tight control aiming for < 200/105 mm Hg. The endpoints of the studies are major clinical events which affect the life and well-being of patients, such as heart attacks, angina, strokes, amputations, blindness and renal failure. To date, 728 patients have had at least one clinical endpoint. Surrogate endpoints include indices of macrovascular and microvascular disease detected by ECG with Minnesota Coding, retinal colour photography and microalbuminuria. The studies also aim to evaluate potential risk factors for the development of diabetic complications such as smoking, obesity, central adiposity, plasma LDL-and HDL-cholesterol, triglyceride, insulin, urate and other biochemical variables. The studies are planned to terminate in 1994, with a median follow-up of 9 years (range 3–16 years) for the glucose study and 5 years (range 2–6 years) for the hypertension study.

Key words

Type 2 (non-insulin-dependent) diabetes mellitus hypertension complications clinical trial glycaemic control blood pressure control 


  1. 1.
    Zimmet P (1982) Type 2 (non-insulin dependent) diabetes: an epidemiological overview. Diabetologia 22: 399–411CrossRefPubMedGoogle Scholar
  2. 2.
    Mather HM, Keen H (1985) The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans. Br Med J 291: 1081–1084Google Scholar
  3. 3.
    Garcia MJ, McNamara PM, Gordon T, Kannell WB (1974) Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 23: 105–111PubMedGoogle Scholar
  4. 4.
    Panzram G (1987) Mortality and survival in Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 30: 123–131CrossRefPubMedGoogle Scholar
  5. 5.
    Panzram G, Zabel-Langhennig R (1981) Prognosis of diabetes mellitus in a geographically defined population. Diabetologia 20: 587–591CrossRefPubMedGoogle Scholar
  6. 6.
    Laing W, Williams DRR (1989) Diabetes, a model for health care management. Office of Health Economics, London UK, No 92: 32–49Google Scholar
  7. 7.
    University Group Diabetes Program. Knatterud GL, Klimt CR, Levin ME, Jacobson ME, Goldner MG (1978) Effects of hypoglycaemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment. JAMA 240: 37–42PubMedGoogle Scholar
  8. 8.
    Jarrett RJ, Keen H (1976) Hyperglycaemia and diabetes mellitus. Lancet II: 1009–1012CrossRefGoogle Scholar
  9. 9.
    Pettitt DJ, Knowler WC, Lisse JR, Bennett PH (1980) Development of retinopathy and proteinuria in relation to plasma glucose concentration in Pima Indians. Lancet II: 1050–1052Google Scholar
  10. 10.
    Dornan TL, Mann JI, Turner RC (1982) Factors protective against retinopathy in insulin-dependent diabetics free of retinopathy for 30 years. Br Med J 285: 1073–1077Google Scholar
  11. 11.
    McCance DR, Hadden DR, Atkinson AB, Archer DB, Kennedy L (1989) Long-term glycaemic control and diabetic retinopathy. Lancet II: 824–828CrossRefGoogle Scholar
  12. 12.
    Lauritzen T, Frost-Larsen K, Larsen HW, Deckert T and the Steno Study Group (1985) Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes 34 [Suppl 3]: 74–79Google Scholar
  13. 13.
    The Kroc Collaborative Study Group (1988) Diabetic retinopathy after two years of intensified insulin treatment. JAMA 260: 37–41Google Scholar
  14. 14.
    Dahl-Jørgensen K, Brinchmann-Hansen O, Hanssen KF et al. (1986) Effect of mean normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy and neuropathy; the Oslo Study. Br Med J 293: 1195–1199Google Scholar
  15. 15.
    Bilous RW, Mauer SM, Sutherland DE, Najarian JS, Goetz FC, Steffes MW (1989) The effects of pancreas transplantation on the glomerular structure of renal allographs in patients with insulin-dependent diabetes. N Engl J Med 321: 80–85PubMedGoogle Scholar
  16. 16.
    Kennedy WR, Navarro X, Goetz FC, Sutherland DER, Najarian JS (1990) Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med 322: 1031–1037PubMedGoogle Scholar
  17. 17.
    Holman RR, Turner RC (1980) The basal plasma glucose: a simple, relevant index of maturity-onset diabetes. Clin Endocrinol 14: 279–286Google Scholar
  18. 18.
    Howe-Davies S, Simpson RW, Turner RC (1980) Control of maturity-onset diabetes by monitoring fasting blood glucose and body weight. Diab Care 3: 607–610Google Scholar
  19. 19.
    Holman RR, Turner RC (1977) Diabetes: the quest for basal normoglycaemia. Lancet I: 469–474CrossRefGoogle Scholar
  20. 20.
    WHO Study Group (1985) Diabetes mellitus. World Health Organisation Technical Report Series No 727. WHO, GenevaGoogle Scholar
  21. 21.
    Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H (1980) Coronary-heart disease risk and impaired glucose tolerance. The Whitehall study. Lancet I: 1373–1376Google Scholar
  22. 22.
    Eschwège E, Richard JL, Thibult N et al. (1985) Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. Horm Metab Res [Suppl 15]: 41–46Google Scholar
  23. 23.
    Stamler R, Stamler J (1979) Asymptomatic hyperglycaemia and coronary heart disease. A series of papers by the International Collaborative Group based on studies in fifteen populations. J Chron Dis 32: 683–837CrossRefPubMedGoogle Scholar
  24. 24.
    Fontbonne A, Charles MA, Thibult N et al. (1991) Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15 year followup. Diabetologia 34: 356–361PubMedGoogle Scholar
  25. 25.
    Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607PubMedGoogle Scholar
  26. 26.
    Fontbonne A, Eschwège E, Cambien F et al. (1989) Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11-year follow-up of the Paris Prospective Study. Diabetologia 32: 300–304CrossRefPubMedGoogle Scholar
  27. 27.
    University Group Diabetic Program (1970) A study of the effects of hypoglycaemic agents on vascular complications on patients with adult-onset diabetes II. Mortality results. Diabetes 19 [Suppl 2]: 789–830Google Scholar
  28. 28.
    Keen H, Jarrett RJ, Fuller J (1973) Tolbutamide and arterial disease in borderline diabetics. Excerpta Medica Int Congress Series 312: 588–602Google Scholar
  29. 29.
    Sartor G, Schersten B, Carlstrom S, Melander A, Norden A, Persson G (1980) Ten-year follow-up of subjects with impaired glucose tolerance. Prevention of diabetes by tolbutamide and diet regulation. Diabetes 29: 41–49PubMedGoogle Scholar
  30. 30.
    The DCCT Research Group (1986) The diabetes control and complications trial (DCCT): design and methodologic considerations for the feasibility phase. Diabetes 35: 530–544Google Scholar
  31. 31.
    Hermann LS (1979) Metformin: a review of its pharmacological properties and therapeutic use. Diab Metab Rev 5: 233–245Google Scholar
  32. 32.
    Standl E, Stiegler H, Roth R, Schulz K, Lehmacher W (1989) On the impact of hypertension on the prognosis of NIDDM. Results of the Schwabing GP-Program. Diab Metab 15: 352–358Google Scholar
  33. 33.
    Medical Research Council Working Party (1985) MRC trial of treatment of mild hypertension: principal results. Br Med J 291: 97–104Google Scholar
  34. 34.
    Australian National Blood Pressure Study Management Committee (1980) The Australian Therapeutic trial in mild hypertension. Lancet I: 1261–1267Google Scholar
  35. 35.
    Collins R, Peto R, MacMahon S et al. (1990) Blood pressure, stroke, and coronary heart disease: part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 335: 827–838CrossRefPubMedGoogle Scholar
  36. 36.
    Chobanian AV (1986) Antihypertensive therapy in evolution. N Engl J Med 314: 1701–1702PubMedGoogle Scholar
  37. 37.
    Christensen CK, Mogensen CE (1987) Antihypertensive treatment: long-term reversal of progression of albuminuria in incipient diabetic nephropathy. A longitudinal study of renal function. J Diab Compl 1: 45–52Google Scholar
  38. 38.
    Mogensen CE (1982) Long term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J 285: 685–688Google Scholar
  39. 39.
    Parving H-H, Anderson AR, Smidt UM, Hommel E, Mathiesen ER, Svendsen PA (1987) Effect of antihypertensive treatment on kidney function in diabetic nephropathy. Br J Med 294: 1443–1447Google Scholar
  40. 40.
    Mathiesen ER, Borch-Johnsen K, Jensen DV, Deckert T (1989) Improved survival in patients with diabetic nephropathy. Diabetologia 32: 884–886CrossRefPubMedGoogle Scholar
  41. 41.
    Yusuf S, Peto R, Lewis J, Collins R, Sleight P (1985) Beta blockade during and after myocardial infarction: an overview of the randomised trials. Prog Cardiovasc Dis 27: 335–371PubMedGoogle Scholar
  42. 42.
    Wilkstrand J, Warnold I, Olsson G, Tuomilehto J, Elmfeldt D, Berglund G (1988) Primary prevention with metoprolol in patients with hypertension. JAMA 259: 1976–1982PubMedGoogle Scholar
  43. 43.
    Hommel E, Parving HH, Mathiesen E, Edsberg B, Nielsen MD, Giese J (1986) Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. Br Med J 293: 467–470Google Scholar
  44. 44.
    Parving HH, Hommel E, Damkjær Nielsen M, Giese J (1989) Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. Br Med J 299: 533–536Google Scholar
  45. 45.
    Hostetter TH, Rennke HG, Brenner BM (1982) The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 72: 375–378CrossRefPubMedGoogle Scholar
  46. 46.
    Zatz R, Rentz Dunn B, Meyer TW, Anderson S, Rennke HG, Brennen BM (1986) Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77: 1925–1930PubMedGoogle Scholar
  47. 47.
    Dzau VJ (1988) Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 77 [Suppl 1]: 4–13Google Scholar
  48. 48.
    Dzau VJ (1986) Significance of the vascular renin-angiotensin pathway. Hypertension 8: 553–559PubMedGoogle Scholar
  49. 49.
    Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM (1991) Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 68: 450–456PubMedGoogle Scholar
  50. 50.
    Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Ranagh JH (1991) Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med 324: 1098–1104PubMedGoogle Scholar
  51. 51.
    Deau VJ (1991) Renin and myocardial infarction in hypertension. N Engl J Med 324: 1128–1130PubMedGoogle Scholar
  52. 52.
    Abert G, Ferrer P (1990) Effects of captopil on atherosclerosis in cynomolgus monkeys. J Cardiovasc Pharm 15: S65-S72Google Scholar
  53. 53.
    Powell JS, Clozel JP, Muller RKM et al. (1989) Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 245: 186–188PubMedGoogle Scholar
  54. 54.
    Sawicki PT, Mühlhauser I, Baba T, Berger M (1990) Do angiotensin converting enzyme inhibitors represent a progress in hypertension care in diabetes mellitus? Diabetologia 33: 121–124PubMedGoogle Scholar
  55. 55.
    United Kingdom Prospective Diabetes Study (1985) III. Prevalence of hypertension and hypotensive therapy in patients with newly diagnosed diabetes. Hypertension 7 [Suppl 2]: 8–13Google Scholar
  56. 56.
    United Kingdom Prospective Diabetes Study (1983) I. Effect of diet, sulphonylurea, insulin or biguanide therapy on fasting plasma glucose and body weight over one year. Diabetologia 24: 404–411Google Scholar
  57. 57.
    Holman RR, Turner RC (1978) Basal normoglycaemia attained with chlorpropamide in mild diabetes. Metabolism 27: 539–547CrossRefPubMedGoogle Scholar
  58. 58.
    Holman RR, Steemson J, Darling P, Reeves WG, Turner RC (1984) Human ultralente insulin. Br Med J 288: 665–668Google Scholar
  59. 59.
    Metropolitan Life Insurance Company (1959) New weight standard for men and women. Stat Bull Metropolitan Life 40: 1–4Google Scholar
  60. 60.
    Holman RR, Turner RC (1985) A practical guide to basal and prandial insulin therapy. Diab Med 2: 45–53Google Scholar
  61. 61.
    Phillips M, Simpson RW, Holman RR, Turner RC (1979) A simple and rational twice daily subcutaneous insulin regime. Distinction between basal and meal insulin requirement. Quart J Med 48: 493–506PubMedGoogle Scholar
  62. 62.
    Turner RC, Holman RR, Matthews DR (1988) Sulphonylurea failure and inadequacy. In: Cameron D, Colagiuri S, Heding L (eds) Excerpta Medica, Amsterdam. Novo Symposium, Hamilton Island, pp 52–56Google Scholar
  63. 63.
    United Kingdom Prospective Diabetes Study (1988) IV. Characteristics of newly-presenting type 2 diabetic patients: male preponderance and obesity at different ages. Diab Med 5: 154–159Google Scholar
  64. 64.
    United Kingdom Prospective Diabetes Study (1990) VI. Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diab Res 13: 1–11Google Scholar
  65. 65.
    Wright BM, Dore CF (1970) A random-zero sphygmomanometer. Lancet I: 33–35Google Scholar
  66. 66.
    Ferris FL, Kassoff A, Bresnick GH, Bailey I (1982) New visual charts for clinical research. Am J Ophthalmol 94: 91–96PubMedGoogle Scholar
  67. 67.
    Davis MD, Hubbard LD, Tarutmann J (1985) Studies of retinopathy; methodology assessment and classification with fundus photographs. Diabetes 35 [Suppl]: 42–49Google Scholar
  68. 68.
    Bloom S, Till S, Sonksen P, Smith S (1984) Use of a biothesiometer to measure individual vibration thresholds and their variation in 519 non-diabetic subjects. Br J Med 288: 1793–1795Google Scholar
  69. 69.
    Ewing DJ, Borsey DQ, Bellavere F, Clarke BF (1981) Cardiac autonomic neuropathy in diabetes: comparison of measures of R-R interval variation. Diabetologia 21: 18–24PubMedGoogle Scholar
  70. 70.
    Ewing DJ, Campbell IW, Murray A, Neilson JMM, Clarke BF (1978) Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. Br Med J 1: 145–147PubMedGoogle Scholar
  71. 71.
    Rose GA, Blackburn H, Gillum RF, Prineas RJ (1982) Cardiovascular survey methods, 2nd edn. World Health Organisation, GenevaGoogle Scholar
  72. 72.
    Davis JE, McDonald JM, Jarett L (1978) A high performance liquid chromatography method for haemoglobin Alc. Diabetes 27: 102–107PubMedGoogle Scholar
  73. 73.
    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, New York London, pp 1831–1835Google Scholar
  74. 74.
    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: 838–839Google Scholar
  75. 75.
    Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11: 583–594PubMedGoogle Scholar
  76. 76.
    Moore JC, Morris JE (1982) A simple automated colorimetric method for determination of N-acetyl-B-D-glucosaminidase. Ann Clin Biochem 19: 157–159PubMedGoogle Scholar
  77. 77.
    Albano JM, Ekins RP, Maritz 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: 487–509PubMedGoogle Scholar
  78. 78.
    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: 465–468PubMedGoogle Scholar
  79. 79.
    Henry RJ, Cannon DC, Winkelman JW (1974) Clinical chemistry; principles and technics. Harper & Row, Hagerstown, pp 552–553Google Scholar
  80. 80.
    Ginsberg JM, Chang BS, Matarese RA, Garella S (1983) Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 309: 1543–1546PubMedGoogle Scholar
  81. 81.
    Yuen CT, Kind PRN, Price RG, Praill PFG, Richardson AC (1984) Colorimetric assay for N-acetyl-beta-D-glucosaminidase (NAG) in pathological urine using the omega W-nitrostyryl substrate: the development of a kit and the comparison of manual procedure with the automated fluorimetric method. Ann Clin Biochem 21: 295–300PubMedGoogle Scholar
  82. 82.
    Westgard JO, Barry PL, Hunt MR (1981) A multi-rule Shewhart chart for quality control in clinical chemistry. Clin Chem 27: 493–501PubMedGoogle Scholar
  83. 83.
    International classification of procedures in medicine (1978) World Health Organisation. GenevaGoogle Scholar
  84. 84.
    Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmus U, Murrells TJ (1984) Microalbuminuria predicts mortality in noninsulin-dependent diabetes. Diab Med 1: 17–19Google Scholar
  85. 85.
    Mogensen CE (1986) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310: 356–360Google Scholar
  86. 86.
    Schmitz A, Vaeth M (1988) Microalbuminuria: a major risk factor in non-insulin-dependent diabetes. A 10-year follow-up study of 503 patients. Diab Med 5: 126–134Google Scholar
  87. 87.
    Stratton IM, Holman RR, Oakes SM, Turner RC for UK Prospective Diabetes Study Group (1991) Randomised trial of tight blood pressure control with ACE inhibitor or B-blocker compared with less tight control in Type II diabetic patients. Diabetes 40 [Suppl 1]: 369 (Abstract)Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • UK Prospective Diabetes Study Group
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
    • 7
    • 8
    • 9
    • 10
    • 11
    • 12
    • 13
    • 14
    • 15
    • 16
    • 17
    • 18
    • 19
    • 20
    • 21
  1. 1.Radcliffe InfirmaryOxford
  2. 2.Royal InfirmaryAberdeen
  3. 3.General HospitalBirmingham
  4. 4.St George's Hospital and Hammersmith HospitalLondon
  5. 5.City HospitalBelfast
  6. 6.North Staffordshire Royal InfirmaryStoke-on-Trent
  7. 7.Royal Victoria HospitalBelfast
  8. 8.St. Helier HospitalCarshalton
  9. 9.Whittington HospitalLondon
  10. 10.Norfolk and Norwich HospitalUK
  11. 11.Lister HospitalStevenage
  12. 12.Ipswich HospitalUK
  13. 13.Ninewells HospitalDundee
  14. 14.Northampton HospitalUK
  15. 15.Torbay Hospital, Peterborough General HospitalUK
  16. 16.Scarborough HospitalUK
  17. 17.Derbyshire Royal InfirmaryUK
  18. 18.Manchester Royal InfirmaryUK
  19. 19.Hope HospitalSalford
  20. 20.Leicester General HospitalUK
  21. 21.Royal Devon and Exeter HospitalExeterUK

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