Abstract
Results from many single risk factor intervention trials and the multi-targeted Steno-2 trial in the last few years have provided a strong case that management of type 2 diabetes in all age groups requires a structured and intensified approach that is far more than just glucocentric, an approach addressing additional cardiovascular risk factors including hypertension, dyslipidaemia, sedentary behaviour, smoking and dietary habits causing insulin resistance and pro-inflammation. This type of integrated therapy applied for almost 8 years to high-risk type 2 diabetic patients has cut the relative risk of macro-and microangiopathy by half. The treatment algorithms for multifactorial therapeutic packages do not harbour any revolutionizing novel drugs or previously untested behaviour modelling, but the success criteria seem to include an individualized and stepwise introduction of target-driven polypharmacy and simple but focused behaviour modelling with continuous education, motivation and trouble-shooting for treatment barriers identified for the patient and the care giver. It is high time we transfer these experiences and major health benefits gained in the ‘green house’ of controlled clinical trials to the community level. To facilitate this process it is of crucial importance to offer not only postgraduate training of diabetes care providers but also to identify and eliminate treatment barriers.
Key words
Type 2 diabetes · Multifactorial intervention · Cardiovascular disease · Polypharmacy · Drug concordance · Education · Risk factors · Albuminuria
References
-
1
Fabre J, Balant L P, Dayer P G, Fox H M, Vernet A T.
The kidney in maturity onset diabetes mellitus: a clinical study of 510 patients.
Kidney Int.
1982;
21
730-738
-
2 Wingard D L, Barrett-Connor E L. Heart disease and diabetes. In: Harris MI, Cowie CC, Stern MS, Boyko EJ, Rieber GE, Bennet PH (eds) Diabetes in America, 2nd ed. Washington; National Institutes of Health 1995: 429-448
-
3
Laakso M, Lehto S.
Epidemiology of macrovascular disease in diabetes.
Diabet Rev.
1997;
5
294-315
-
4
Gu K, Cowie C C, Harris M I.
Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971 - 1993.
Diabet Care.
1998;
21
1138-1145
-
5
Gæde P, Vedel P, Larsen N, Jensen G V, Parving H H, Pedersen O.
Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.
N Engl J Med.
2003;
348
383-393
-
6
UKPDS Study Group .
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.
Lancet.
1998;
352
837-853
-
7
UK Prospective Diabetes Study Group .
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.
BMJ.
1998;
317
703-713
-
8
Hansson L, Zanchetti A, Carruthers S G, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn K H, Wedel H, Westerling S.
Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.
Lancet.
1998;
351
1755-1762
-
9
Curb J D, Pressel S L, Cutler J A, Savage P J, Applegate W B, Black H, Camel G, Davis B R, Frost P H, Gonzalez N, Guthrie G, Oberman A, Rutan G H, Stamler J.
Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.
JAMA.
1996;
276
1886-1892
-
10
Staessen J A, Fagard R, Thijs L, Celis H, Arabidze G G, Birkenhager W H, Bulpitt C J, de Leeuw P W, Dollery C T, Fletcher A E, Forette F, Leonetti G, Nachev C, O’Brien E T, Rosenfeld J, Rodicio J L, Tuomilehto J, Zanchetti A.
Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.
Lancet.
1997;
350
757-764
-
11
UK Prospective Diabetes Study Group .
Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39.
BMJ.
1998;
317
713-720
-
12
Hansson L, Lindholm L H, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg B E, Wester P O, Bjorck J E.
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.
Lancet.
1999;
353
611-616
-
13
Estacio R O, Jeffers B W, Hiatt W R, Biggerstaff S L, Gifford N, Schrier R W.
The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.
N Engl J Med.
1998;
338
645-652
-
14
Tatti P, Pahor M, Byington R P, Di Mauro P, Guarisco R, Strollo G, Strollo F.
Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM.
Diabet Care.
1998;
21
597-603
-
15
Lindholm L H, Ibsen H, Dahlof B, Devereux R B, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen S E, Kristiansson K, Lederballe-Pedersen O, Nieminen M S, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S,. The LIFE Study Group .
Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.
Lancet.
2002;
359
1004-1010
-
16
Hansson L, Lindholm L H, Ekbom T, Dahlof B, Lanke J, Schersten B, Wester P O, Hedner T, de Faire U.
Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study.
Lancet.
1999;
354
1751-1756
-
17
Brown M J, Palmer C R, Castaigne A, de Leeuw P W, Mancia G, Rosenthal T, Ruilope L M.
Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).
Lancet.
2000;
356
366-372
-
18
Hansson L, Hedner T, Lund-Johansen P, Kjeldsen S E, Lindholm L H, Syvertsen J O, Lanke J, de Faire U, Dahlof B, Karlberg B E.
Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.
Lancet.
2000;
356
359-365
-
19
Pyörälä K, Pedersen T R, Kjekshus J, Faergeman O, Olsson A G, Thorgeirsson G.
Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S).
Diabet Care.
1997;
20
614-620
-
20
Sacks F M, Pfeffer M A, Moye L A, Rouleau J L, Rutherford J D, Cole T G, Brown L, Warnica J W, Arnold J M, Wun C C, Davis B R, Braunwald E.
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
N Engl J Med.
1996;
335
1001-1009
-
21
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels .
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.
N Engl J Med.
1998;
339
1349-1357
-
22
Heart Protection Study Collaborative Group .
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
Lancet.
2002;
360
7-22
-
23
Athyros V G, Papageorgiou A A, Mercouris B R, Athyrou V V, Symeonidis A N, Basayannis E O, Demitriadis D S, Kontopoulos A G.
Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.
Curr Med Res Opin.
2002;
18
220-228
-
24
Rubins H B, Robins S J, Collins D, Fye C L, Anderson J W, Elam M B, Faas F H, Linares E, Schaefer E J, Schectman G, Wilt T J, Wittes J.
Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.
N Engl J Med.
1999;
341
410-418
-
25
Colhoun H M, Betteridge D J, Durrington P N, Hitman G A, Neil H A, Livingstone S J, Thomason M J, Mackness M I, Charlton-Menys V, Fuller J H.
Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.
Lancet.
2004;
364
685-696
-
26
Parving H H, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P.
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.
N Engl J Med.
2001;
345
870-878
-
27
Brenner B M, Cooper M E, de Zeeuw D, Keane W F, Mitch W E, Parving H H, Remuzzi G, Snapinn S M, Zhang Z, Shahinfar S.
RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
N Engl J Med.
2001;
345
861-869
-
28
Lewis E J, Hunsicker L G, Clarke W R, Berl T, Pohl M A, Lewis J B, Ritz E, Atkins R C, Rohde R, Raz I. Collaborative Study Group .
Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
N Engl J Med.
2001;
345
851-860
-
29
EUROASPIRE .
A European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. EUROASPIRE Study Group. European Action on Secondary Prevention through Intervention to Reduce Events.
Eur Heart J.
1997;
18
1569-1582
-
30
Gæde P, Vedel P, Parving H H, 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
-
31 Griffin S, Kinmonth A L. Systems for routine surveillance for people with diabetes mellitus (Cochrane Review). In: The Cochrane Library. Oxford; Update Software 2002
-
32
Olivarius N F, Beck-Nielsen H, Andreasen A H, Horder M, Pedersen P A.
Randomised controlled trial of structured personal care of type 2 diabetes mellitus.
BMJ.
2001;
323
970-975
-
33
Hippisley-Cox J, Pringle M.
Prevalence, care, and outcomes for patients with diet-controlled diabetes in general practice: cross sectional survey.
Lancet.
2004;
364
423-428
-
34
Glasgow R E, McCaul K D, Schafer L C.
Barriers to regimen adherence among persons with insulin-dependent diabetes.
J Behav Med.
1986;
9
65-77
-
35
Logan A G, Milne B J, Achber C, Campbell W P, Haynes R B.
Work-site treatment of hypertension by specially trained nurses. A controlled trial.
Lancet.
1979;
2
1175-1178
-
36
Johansen J, Claudi T, Holtedahl K.
Insulin treatment for poorly regulated diabetic patients in general practice. Better regulation and symptom relief?.
Scand J Prim Health Care.
1999;
17
244-249
-
37
Tashkin D P.
Multiple dose regimens. Impact on compliance.
Chest.
1995;
107
176S-182S
-
38
Wald N J, Law M R.
A strategy to reduce cardiovascular disease by more than 80 %.
BMJ.
2003;
326
1419
-
39
Snoek F J.
Barriers to good glycaemic control: the patient’s perspective.
Int J Obes.
2000;
24
S12-S20
-
40
Hiss R G.
Barriers to care in non-insulin-dependent diabetes mellitus. The Michigan experience.
Ann Intern Med.
1996;
124
146-148
-
41
Kenny S J, Smith P J, Goldschmid M G, Newman J M, Herman W H.
Survey of physician practice behaviors related to diabetes mellitus in the U. S. Physician adherence to consensus recommendations.
Diabet Care.
1993;
16
1507-1510
-
42
Lauritzen T, Griffin S, Borch-Johnsen K, Wareham N J, Wolffenbuttel B H, Rutten G.
Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care. The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening.
Int J Obes.
2000;
24 Suppl 3
S6-11
-
43
Anderson K M, Odell P M, Wilson P W, Kannel W B.
Cardiovascular disease risk profiles.
Am Heart J.
1991;
121
293-298
-
44
Gæde P, Pedersen O.
Intensive integrated therapy of type 2 diabetes. Implications for long-term prognosis.
Diabetes.
2004;
Suppl. 3
S39-S47
-
45
Huang E S, Meigs J B, Singer D E.
The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus.
Am J Med.
2001;
111
633-642
-
46
Antithrombotic Trialists' Collaboration .
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
BMJ.
2002;
324
71-86
-
47
Turner R C, Millns H, Neil H A, Stratton I M, Manley S E, Matthews D R, Holman R R.
Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23).
BMJ.
1998;
316
823-828
-
48
Poulsen M K, Henriksen J E, Hother-Nielsen O, Beck-Nielsen H.
The combined effect of triple therapy with rosiglitazone, metformin, and insulin aspart in type 2 diabetic patients.
Diabet Care.
2003;
26
3273-3279
-
49
Brousseau M E, Schaefer E J, Wolfe M L, Bloedon L T, Digenio A G, Clark R W, Mancuso J P, Rader D J.
Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol.
N Engl J Med.
2004;
350
1505-1515
-
50
Gæde P, Beck M, Vedel P, Pedersen O.
Limited impact of lifestyle education in patients with Type 2 diabetes mellitus and microalbuminuria: results from a randomized intervention study.
Diabet Med.
2001;
18
104-108
O. Pedersen
Steno Diabetes Center
Niels Steensens Vej 2 · 2820 Gentofte · Denmark
Phone: +45 44 43 90 59
Email: oluf@steno.dk