Diabetic late complications

by Kristian F. Hanssen and Tore Julsrud Berg Group

1.30 years prospective study of late complications in type 1 diabetes (The Oslo Study):

  A: Prospective study:
We have studied the progression of vascular changes, especially coronary vascular changes as measured by intravascular ultrasound (IVUS) and coronary angiography in the prospective Oslo Study and identified predictive parameters for this progression, especially AGE parameters.

 B: Cross-sectional study:

Assess both macro and micro vascular status of the patients and associate with skin (measured in Dr. Monnier’s lab Cleveland, USA) and serum AGE. A number of parameters have been followed prospectively over 25 years, and have given valuable data for our cross- sectional study (together with many groups within OUS, especially Dr. Brekke, Department of cardio-vascular radiology and Dr. Fosmark, Department of Ophtalmology).

Specific aims:

  • To study cardiac events; sub endpoints will be the vessel area stenosis, significant plaque (>0.5 mm) progression both on IVUS, and coronary artery stenosis on coronary angiography.
  • Serum and skin AGE, oxidative and inflammatory markers in relationship to complication status.

There are few studies that have examined long term complications and intensive diabetes treatment with such a long duration of the disease, and it is a unique opportunity to study the relationship between complications and biochemical markers of complications.

 

2.Glycation in the arterial wall:

We are studying glycation modification in the arterial wall in atherosclerosis with and without diabetes by western analysis, immunohistochemistry and LC MS/MS (mass spectrometry). We have already discovered some modifications in the wall that might be involved in the increased propensity to atherosclerosis in diabetes.

 

3. Advanced glycation of proteins and vascular complications in childhood diabetes

(together with Dahl-Jørgensens group):

Prospective study of early markers of atherosclerosis in a large group of adolescents with type 1diabetes and controls – its relationship to glycation.

 

4. Coronary and glomerular morphology in kidney transplants – Long term study in two contrasting groups:

PI: Trond G. Jenssen (together with Svein Kolset, Institute of Nutrition)

Study the effect of long-term normoglycaemia vs. hyperglycaemia on changes in the coronary arteries and the renal function and structure in type 1 diabetes patients. Two groups of patients with type 1 diabetes are studied, one group transplanted with a single kidney (HbA1c 8-8.5%), the other who received combined kidney-pancreas grafts and has obtained perfect normoglycaemia over the same period of time (HbA1c 4.5-5.5%). 

  • To investigate proteoglycans and glycosaminoglycans which are important components of the filter network of the basement membrane.
  • To explore proteoglycans (syndecan-1) and macrophage transcription factors (Id-1) in blood samples as markers of early kidney changes.
  • Advanced Glycation Endproducts (AGE, CML,hydroimidazolone) by immuno-histochemistry in the glomerulus and in serum samples to test the hypothesis that glycation markers can predict the development and progression of late complication (specifically early diabetic nephropathy and coronary heart disease).

 

5. DIALONG:

A study of long term survivors with more than 40 years of type 1 diabetes. A large clinical and biochemical study especially on macro-vascular disease and skin and joint complications. . Collaborators within Oslo University Hospital and in Sweden, Denmark and US.

6. Prospective study of pre-eclampsia in pregnant type 1 diabetes.

In collaboration with research groups in Australia and US.