Time To Complications Occurs in Diabetes

Sponsor

Karolinska Institutet (Other)

Overall Status

Terminated

CT.gov ID

NCT00969956

Collaborator

(none)

Enrollment

Location

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Diabetes causing serious complications is well known. In this study the aim is to follow 950 patients with diabetes for 15 years to study when, in who and how the diabetes complications occurs.

Condition or Disease	Intervention/Treatment	Phase
Retinopathy Nephropathy Diabetic Neuropathy Vascular Disease Ischemic Heart Disease

Detailed Description

Background:

That diabetes cause serious diabetic complications from the eyes, kidneys, nerves and large vessels is known. Good metabolic control during the first 8-10 years has been shown to delay and even alleviate diabetes complications, but not entirely prevent them. When complications occur early after diabetes onset there are also likely genetic causes. If the various diabetes complications have different formation mechanisms or different sensitivity of blood sugar impact is not studied previously.

Hypothesis:

Genetic factors determine increased risk of early onset of complications.
Oxidative stress increases the risk of complications.
Inflammation, hyperlipidemia and hypertension leads to hypoxia and oxidative stress.
Combined hypoxia and hyperglycemia leads to complications.

Questionnaires:

Are there measurable risk factors that indicate different sensitivity to develop diabetes complications?
Are there differences between men and women?
Are there differences between type 1 and type 2 diabetes?

Knowledge achievements:

Being able to anticipate and prevent diabetes complications with specific approaches would mean major benefits for patients and society.

Inclusions criteria:

Diabetes type 1, 2 or LADA: 18-75 years of age. Group A: 150 Type 1 Diabetes, duration 15 years (+/- 2 years) and 150 Type 2 Diabetes 2 years (+/- 2 years) (50% K / M) Group B: 150 Type 1 Diabetes, duration 20 years (+/- 2 years) and 150 Type 2 Diabetes 7 years (+/- 2 years) (50% K / M) Group C: 150 Type 1 Diabetes, duration 25 years (+/- 2 years) and 150 Type 2 Diabetes 12 years (+/- 2 years) (50% K / M) Group D: 50 LADA, onset after 35 years of age, duration of 5-10 years (50% K / M)

Follow-up visits:

Group A: After 3, 8 and 13 years Group B: After 5, 10 and 15 years Group C: After 5, 10 and 15 years Group D: After 3, 8 and 13 years

Definitions:

Type 1 Diabetes: Positive ICA-antibodies and/or GAD-antibodies and/or neg C-peptide. Debut <30 years of age.

Type 2 Diabetes: Negative ICA-antibodies and GAD-antibodies and pos C-peptide (> 0.35 mmol/l).

LADA: Positive ICA-antibodies and/or GAD-antibodies. Debut >35 years of age.

Retinopathy: Level of retinopathy based on fundus photography judged by experienced ophthalmologist and classified according to DRP classification in five steps: 1. No retinopathy, 2. Mild non-proliferative retinopathy, 3. Moderate non-proliferative retinopathy, 4. Severe non-proliferative retinopathy, 5. Proliferative retinopathy

ESRD (end stage renal disease): Dialysis or transplantation demanding, GFR (glomerular filtration rate) <10 ml/min.

Overt nephropathy: Albumin excretion at least two consecutive measurements,≥ 300 mg/L and/or S-Creatinine > 100 women and > 110 mmol/l in men.

Incipient nephropathy: Albuminuria between 30 - 300mg/L or Urine albumin/Creatinine >3.

Hypertension: Measured blood pressure in sitting position after 10 minutes rest, at least two consecutive measurements with at least 4 weeks in between, ≥ 130/80.

Hyperlipidemia: ApoA-1/ApoB: >0.5 and/or Triglycerides >1,7 mmol/L and/or LDL >2.5 mmol/L and/or HDL women <1.3, men <1.1 mmol/L and/or cholesterol >4.5 mmol/L.

Heart disease: History of myocardial infarction, angina pectoris and/or ischemic heart disease (file noted). Pharmacological treatment for ischemic heart disease, heart failure or pathological electrocardiographic changes according to Minnesota code.

Cerebrovascular disease: Deemed to have been: if recorded in the patients file and/or if pathological findings demonstrated on CT/MR.

Peripheral vascular disease: Ankle Index <0.9 (blood pressure arm>ankle) Clinical macroangiopathy, (absence of peripheral pulse) or history typical for claudication intermittens.

Neuropathy: Foot investigation: According to international consensus for the investigation and risk assessment of diabetic feet with a view of peripheral autonomic neuropathy (PAN) and peripheral sensory neuropathy (PSN).

Study Design

Study Type:

Observational

Actual Enrollment :

17 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Time to Complications Occurs in Diabetes. Risk Factors Determine When Diabetes Complications Occur

Actual Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Group A 150 Type 1 Diabetes, duration of 15 years (+/- 2 years) and 150 Type 2 Diabetes, duration of 2 years (+/- 2 years) (50% women / men)
Group B 150 Type 1 Diabetes, duration of 20 years (+/- 2 years) and 150 Type 2 Diabetes, duration of 7 years (+/- 2 years) (50% women / men)
Group C 150 Type 1 Diabetes, duration of 25 years (+/- 2 years) and 150 Type 2 Diabetes duration of 12 years (+/- 2 years) (50% women / men)
Group D 50 LADA (Late Autoimmune Diabetes in Adults), debut after 35 years of age, duration of 5-10 years (50% women / men)

Outcome Measures

Primary Outcome Measures

Time to nephropathy [0, 3-5, 8-10 and 13-15 years]
Time to autonomous neuropathic ulcers and Amputation [0, 3-5, 8-10 and 13-15 years]
Time to peripheral neuropathy [0, 3-5, 8-10 and 13-15 years]
Time to peripheral Macro-Vascular Disease, chronic Foot ulcers and Amputation [0, 3-5, 8-10 and 13-15 years]
Time to retinopathy [0, 3-5, 8-10 and 13-15 years]

Secondary Outcome Measures

DNA [0, 3-5, 8-10 and 13-15 years]
Endothelial markers [0, 3-5, 8-10 and 13-15 years]
Blood lipids [0, 3-5, 8-10 and 13-15 years]
CRP [0, 3-5, 8-10 and 13-15 years]
Oxidative stress [0, 3-5, 8-10 and 13-15 years]
Q10 [0, 3-5, 8-10 and 13-15 years]
IGFBP-1 [0, 3-5, 8-10 and 13-15 years]
IGF-1 [0, 3-5, 8-10 and 13-15 years]
Inflammatory markers [0, 3-5, 8-10 and 13-15 years]
Seated blood pressure [0, 3-5, 8-10 and 13-15 years]
Pulse [0, 3-5, 8-10 and 13-15 years]
Weight [0, 3-5, 8-10 and 13-15 years]
BMI [0, 3-5, 8-10 and 13-15 years]
Waistlines [0, 3-5, 8-10 and 13-15 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diabetes type 1, 2 or LADA: 18-75 years of age.
Group A: 150 Type 1 Diabetes, duration 15 years (+/-2 years) and 150 Type 2
Diabetes 2 years (+/-2 years) (50% F/M)
Group B: 150 Type 1 Diabetes, duration 20 years (+/-2 years) and 150 Type 2
Diabetes 7 years (+/-2 years) (50% F/M)
Group C: 150 Type 1 Diabetes, duration 25 years (+/-2 years) and 150 Type 2
Diabetes 12 years (+/-2 years) (50% F/M)
Group D: 50 LADA, onset after 35 years of age, duration of 5-10 years (50% F/M)
Type 1 Diabetes: Positive ICA antibodies and/or GAD-antibodies and/or neg C-peptide. Debut <30 years of age.
Type 2 Diabetes: Negative ICA-antibodies and GAD-antibodies and pos C-peptide (>0.35 mmol/l).
LADA: Positive ICA-antibodies and/or GAD-antibodies. Debut >35 years of age.