Aims/hypothesisThe aim of this work was to study the potential long-term impact of a 7.8 years intensified, multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria in terms of gained years of life and years free from incident cardiovascular disease.MethodsThe original intervention (mean treatment duration 7.8 years) involved 160 patients with type 2 diabetes and microalbuminuria who were randomly assigned (using sealed envelopes) to receive either conventional therapy or intensified, multifactorial treatment including both behavioural and pharmacological approaches. After 7.8 years the study continued as an observational follow-up with all patients receiving treatment as for the original intensive-therapy group. The primary endpoint of this follow-up 21.2 years after intervention start was difference in median survival time between the original treatment groups with and without incident cardiovascular disease. Non-fatal endpoints and causes of death were adjudicated by an external endpoint committee blinded for treatment allocation.ResultsThirty-eight intensive-therapy patients vs 55 conventional-therapy patients died during follow-up (HR 0.55 [95% CI 0.36, 0.83], p = 0.005). The patients in the intensive-therapy group survived for a median of 7.9 years longer than the conventional-therapy group patients. Median time before first cardiovascular event after randomisation was 8.1 years longer in the intensive-therapy group (p = 0.001). The hazard for all microvascular complications was decreased in the intensive-therapy group in the range 0.52 to 0.67, except for peripheral neuropathy (HR 1.12).Conclusions/interpretationAt 21.2 years of follow-up of 7.8 years of intensified, multifactorial, target-driven treatment of type 2 diabetes with microalbuminuria, we demonstrate a median of 7.9 years of gain of life. The increase in lifespan is matched by time free from incident cardiovascular disease.Trial registration:ClinicalTrials.gov registration no. NCT00320008.Funding:The study was funded by an unrestricted grant from Novo Nordisk A/S.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-4065-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The TMAO pathway and its metabolites are possibly involved in the development of two major health problems: insulin resistance and cancer. Within these pathways novel therapeutic targets may be identified. Further research is needed in order to verify existing or develop new pharmacological agents that modify these pathways and reduce the risk of insulin resistance and GIC.

In the present post hoc analyses we studied the impact of intensified, multifactorial treatment on renal outcomes in patients with type 2 diabetes and microalbuminuria enrolled in the Steno-2 Study. Outcome measures were progression to macroalbuminuria, decline in the glomerular filtration rate (GFR), and development of end stage renal disease (ESRD). In total, 160 patients with type 2 diabetes and microalbuminuria were recruited and assigned to conventional or intensified therapy targeting multiple risk factors. The mean duration of the intervention was 7.8 years after which all patients were offered intensified therapy over a total follow-up up to 21 years on albuminuria, GFR, ESRD and mortality. Progression to macroalbuminuria was significantly reduced in the intensive-therapy group with a hazard ratio of 0.51 [95% confidence interval 0.32, 0.84]. The decline in GFR was significantly different with 3.1 ml/min/year in the intensive-therapy group compared to 4.0 in the conventional-therapy group. Progression to ESRD trended towards a decreased hazard with an adjusted ratio in the intensive group of 0.36 [0.12, 1.05]. ESRD combined with death had a significantly reduced hazard ratio of 0.53 [0.35, 0.8]. Thus, intensified, multifactorial treatment slowed progression in nephropathy and renal function loss reducing the risk of ESRD.