Identifying novel mechanisms that protect some people from diabetic complications

​The PROLONG study: PROtective genetic and non-genetic factors in diabetic complications and LONGevity.

Aim and purpose

The aim of PROLONG is to facilitate discovery of drug targets for diabetes and its complications.

The study has the following goals:

To identify genetic-, metabolic- and life-style factors that are associated with protection from micro-or macro-vascular complications in patients with long-standing type 1 and type 2 diabetes.
To evaluate protective genetic, metabolic and lifestyle factors in the first-degree relatives of diabetic patients.

Design, method and theory

PROLONG  started in Malmö, Sweden, and was expanded nationwide in Sweden, Denmark and Norway (with the project DIALONG - Type 1 diabetes – long term survival) and in the Botnia region of Finland (PROLONG-Botnia).

The Steno Diabetes Center is a unique place for conducting such clinical studies, as it is a highly specialised research and teaching hospital. Every year around 6,000 people with diabetes visit the outpatient clinic.

Patient visits include a questionnaire with information on family history of diabetes, age of parents (living or age at death), smoking, education, physical activity, diet, psychosocial health questions and social status, as well as medication from the electronic patient record. Anthropometric measurements include BMI, waist, hip, height, systolic and diastolic blood pressure. Blood samples are taken for measurements of HbA1c, fasting glucose, C-peptide, lipids (total cholesterol, triglycerides, HDL-cholesterol), GAD ab, albumin, creatinine, glucagon, and other hormones. We collect overnight to measure albumin excretion.

Target groups

There are 1,500 Danish patients with type 1 and type 2 and their 1st-degree relatives intended to be enrolled in the project.

Group 1. Patients with type 1 diabetes:
The case group is defined as Danish patients with type 1 diabetes and more than 30 years'
duration of diabetes without complications (N= 500).

The control group is defined as Danish patients with type 1 diabetes and duration of 5 to 20 years with complications (N=250).

Group 2. Patients with type 2 diabetes:
The case group is defined as Danish patients with type 2 diabetes and early onset (age of onset <40 years) and 25 years' duration of diabetes without complications. N=200
The control group is defined as Danish patients with type 2 diabetes and early onset with duration of 5 to 10 years with complications (N=200).

The first-degree relatives of patients with type 1 or type 2 diabetes will be invited to participate in the project.

Expected outcomes

The project has immense potential to identify novel mechanisms by which some people are protected from diabetic complications. This knowledge could make it possible to develop novel treatments targeted at the underlying molecular mechanisms.


The PROLONG-Steno study is part of a Scandinavian partnership initiative among Sweden, Denmark, Norway and Finland. It is funded by several diabetes foundations, including the Swedish Research Council, the Novo Nordisk foundation, Swedish Diabetesförening, Crafoord foundation, Hjärt-Lung fonden.


Lyssenko V, Nilsson PM. Mapping of protective factors in type 1 diabetes has begun. Some patients appear to be protected against late complications--Several studies are underway]. Lakartidningen. 2012 Apr 4-10;109(14-15):744-5. Swedish.