Clinical trial NCT00969956: Time To Complications Occurs in Diabetes
Official title: Time to Complications Occurs in Diabetes. Risk Factors Determine When Diabetes Complications Occur
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Retinopathy
Nephropathy
Diabetic Neuropathy
Vascular Disease
Ischemic Heart Disease
Keywords: Diabetes, Complication, Cardio-vascular disease
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2009-09-02
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Typ 1, Typ 2 and LADA Diabetics from the diabetic clinic at Sophiahemmet, Stockholm, Sweden

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.

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:

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

Questionnaires:

1. Are there measurable risk factors that indicate different sensitivity to develop diabetes complications?
2. Are there differences between men and women?
3. 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Time to nephropathy
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Time to autonomous neuropathic ulcers and Amputation
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Time to peripheral neuropathy
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Time to peripheral Macro-Vascular Disease, chronic Foot ulcers and Amputation
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Time to retinopathy
timeFrame: 0, 3-5, 8-10 and 13-15 years
Secondary outcomes:
measure: DNA
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Endothelial markers
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Blood lipids
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: CRP
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Oxidative stress
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Q10
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: IGFBP-1
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: IGF-1
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Inflammatory markers
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Seated blood pressure
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Pulse
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Weight
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: BMI
timeFrame: 0, 3-5, 8-10 and 13-15 years
measure: Waistlines
timeFrame: 0, 3-5, 8-10 and 13-15 years
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Department of Molecular Medicine and Surgery, Rolf Luft Research centre for Diabetes and Endocrinology
Study officials:
affiliation: Karolinska Institutet
name: Kerstin Brismar, Professor
role: PRINCIPAL_INVESTIGATOR
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