Intensive Intervention in Type 2 Diabetes Leads to Long-Term Gains

A doctor, testing the sensibility of a patient`s foot. This test is often used for checking neuropathy of diabetic patients.

Steno Type 2 Trial: Striking long-term benefits of multiple risk factor intervention in type 2 DM.

By Martina M. McGrath, MD
April 14, 2017

Risk factor management in patients with diabetes is challenging, and despite best medical efforts, few achieve the targets set out by society guidelines1. Two recently published papers reporting long-term follow up of Steno-2 are a timely reminder as to what can be achieved with a structured, well-resourced approach to caring for these patients.

The Steno Type 2 trial enrolled 160 Danish patients with type 2 DM and albuminuria in 19932. Patients were randomized to conventional care versus intensive intervention. This consisted of treating multiple risk factors to predefined targets, listed below.

Risk Factor Conventional Arm Intensive Arm
HbA1c <7.5% <6.5%
Total cholesterol < 250mg/dL <190mg/dL
HDL cholesterol >35mg/dL >42mg/dL
BP Target <160/95mmHg <140/85mmHg
Treatment with ACEi regardless of BP No Yes
Aspirin Yes if known Coronary Artery Disease Yes if known Coronary Artery Disease or Peripheral Vascular Disease
Behavioral interventions for diet, exercise, smoking cessation No Yes

The intervention arm continued for eight years, up to 2001. At that time, all participants were offered intensive treatment and follow up continued until 2014.

The research group has recently published their 21-year follow up data3,4 and it makes for very impressive reading. Only one patient, who emigrated, was lost to follow-up. Complete outcome data was available on all other patients, recorded in centralized registries and national electronic health records, where hospitals mandatorily report diagnoses and procedures for all admissions and outpatient treatments. Roughly half the patients in each group completed 24-hour urine collections for albuminuria and GFR assessment at the end of the follow-up period.

At the end of follow up, 24 patients remained in the conventional group (55 deaths) and 42 remained in the intensive group (38 deaths), a 45% reduction in mortality3. The median time to first cardiovascular event was 8.1 years longer in the intensive group, and it was calculated that the intensive treatment protocol was associated with a median of 7.9 years of life gained3.

The effect of the intervention on progression of CKD was similarly dramatic. There were higher rates of regression to normoalbuminuria and significantly delayed progression to macroalbuminuria. The yearly rate of GFR decline was 28% lower in the intensive group as compared to control4. Significantly reduced progression to ESRD was also seen; five patients in the intensive group compared with ten in the conventional group developed ESRD, equating to a hazard ratio of 0.364.

Finally, the incidence of a composite end-point of GFR <45mls/min, ESRD or death occurred in 79% of patients in the conventional arm, compared to 56% in the intensive arm4.

These are results from a small, single-center study. Enrollees would appear to be very compliant as judged by their adherence to follow-up and the significant number that submitted 24-hour urine collections, even at 21 years follow-up. All of these factors may limit the generalizability of these findings. However, despite these limitations, the magnitude of effects argue strongly that considerable long-term benefits could be gained if this type of approach were adopted more widely.

References:

  1. Ji L, Hu D, Pan C, et al. Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients. The American Journal of Medicine 2013;126:925 e11-22.
  2. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999;353:617-22.
  3. Gaede P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59:2298-307.
  4. Oellgaard J, Gaede P, Rossing P, Persson F, Parving HH, Pedersen O. Intensified multifactorial intervention in type 2 diabetics with microalbuminuria leads to long-term renal benefits. Kidney International 2017;91:982-8.

Headshot of Dr. McGrathDr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.

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