Gaede, 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 353, 617-622

Steno Diabetes Centre, Gentofte, Copenhagen, Denmark.
The Lancet (Impact Factor: 45.22). 03/1999; 353(9153):617-22. DOI: 10.1016/S0140-6736(98)07368-1
Source: PubMed


In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial. We carried out a randomised trial of stepwise intensive treatment or standard treatment of risk factors in patients with microalbuminuria.
In this open, parallel trial patients were allocated standard treatment (n=80) or intensive treatment (n=80). Standard treatment followed Danish guidelines. Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was the development of nephropathy (median albumin excretion rate >300 mg per 24 h in at least one of the two-yearly examinations). Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy.
The mean age was 55.1 years (SD 7.2) and patients were followed up for 3.8 years (0.3). Patients in the intensive group had significantly lower rates of progression to nephropathy (odds ratio 0.27 [95% CI 0-10-0.75]), progression of retinopathy (0.45 [0.21-0.95]), and progression of autonomic neuropathy (0.32 [0.12-0.78]) than those in the standard group.
Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy, and progression of retinopathy and autonomic neuropathy. However, further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality.

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    • "SAH induces vascular damage by promoting endothelial dysfunction and atherosclerosis. Early treatment of hypertension is particularly important in patients with diabetes to prevent cardiovascular disease (CVD) and to minimize the progression of kidney disease and diabetic retinopathy2. "
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    ABSTRACT: Background: Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.
    Arquivos Brasileiros de Cardiologia 07/2014; DOI:10.5935/abc.20140089 · 1.02 Impact Factor
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    • "This is in line with previous findings. In the Steno-2 study, a multifactorial approach of intensive treatment significantly reduced microvascular complications (including diabetic nephropathy and retinopathy) already after a mean monitoring period of 3.8 years [44], whereas the number of macrovascular events was significantly reduced after 13.3 years [45]. Moreover, The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial with a median follow–up of 5 years showed that intensive control reduced major microvascular events, primarily because of a reduction in the incidence of nephropathy, whereas major macrovascular events were not significantly effected [46]. "
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    ABSTRACT: Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes. In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis. Postprandial blood glucose (9.27 +/- 0.4 versus 10.1 +/- 0.4 mmol/L; p = 0.001) and HbA1c (6.84 +/- 0.15 (51 +/- 1.6) versus 7.10 +/- 0.17% (54 +/- 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 +/- 13.2 vs. 314 +/- 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 +/- 12.1 versus 314 +/- 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 +/- 2.3 versus 124 +/- 2.3 mmHg; p = 0.038). Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes.Trial registration: The study was registered at (ID: NCT01319357).
    Cardiovascular Diabetology 01/2014; 13(1):19. DOI:10.1186/1475-2840-13-19 · 4.02 Impact Factor
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    • "Glycaemic control forms only part of the overall management of diabetes. Despite the well documented evidence on the importance of adequate weight management [8] as well as blood pressure [9,10] and lipid control [11-14], gaps currently still exist as evidenced by the large proportion of patients who are obese, with suboptimal blood pressure control and abnormal lipid levels. That may explain partly the reasons for the relatively high prevalence of incipient and overt nephropathy. "
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    ABSTRACT: A territory-wide diabetes management program (Risk Assessment Management Program - RAMP) was recently established, providing comprehensive management for all diabetics, helping to delineate current level of control and complications prevalence among primary care diabetic patients in Hong Kong. This cross-sectional study captured anonymous clinical data from RAMP patients. Data obtained include sociodemographic details, type of diabetes, illness duration, family history, drug usage, coexisting illnesses, diabetic complications and other clinical parameters. Data from 15,856 type 2 diabetic patients were analyzed. 57.1% were above 60 years old, with mean disease duration of 7.3 years. Hypertension was the commonest coexisting chronic illness (57.6%). 30.2% and 61.8% have their systolic and diastolic pressure controlled to below 130 mmHg and 80 mmHg respectively. Over half (51.5%) had an HbA1c level of less than 7.0%. 88.4% did not achieve target lipid level. 15% were on diet control alone . Only 22.2% were on statins. In patients with microalbuminuria and macroalbuminuria, 40.7% and 54.5% were on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) respectively. 12.9%, 38.8% and 2.4% had diabetic retinopathy, nephropathy and neuropathy respectively. Overall, 37.9%, 7.3% and 0.4% had single, two and three concurrent microvascular complications respectively. The level of diabetic control is comparable with other developed countries. We demonstrated a high prevalence of microvascular complications among Chinese primary care patients despite achieving adequate HbA1c levels, highlighting the importance of managing all aspects of diabetes including weight, lipid and blood pressure. Efforts to improve holistic management must be tailored according to the needs of our population, with the challenges that the majority have low educational background and in the older age group.
    BMC Family Practice 01/2014; 15(1):8. DOI:10.1186/1471-2296-15-8 · 1.67 Impact Factor
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