Time To Complications Occurs in Diabetes

Ischemic Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00969956
• Other study ID #: TTCOD
• Status: Terminated
• Start date: April 2012
• Est. completion date: February 2018

Study information

• Verified date: August 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Diabetic Neuropathies
• Diabetic Neuropathy
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Ischemia
• Nephropathy
• Retinopathy
• Vascular Disease
• Vascular Diseases

Locations

Country	Name	City	State
Sweden	Department of Molecular Medicine and Surgery, Rolf Luft Research centre for Diabetes and Endocrinology	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

References & Publications (19)

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Brismar K, Fernqvist-Forbes E, Wahren J, Hall K. Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes. J Clin Endocrinol Metab. 1994 Sep;79(3):872-8. — View Citation

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Fullerton B, Jeitler K, Seitz M, Horvath K, Berghold A, Siebenhofer A. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2014 Feb 14;(2):CD009122. doi: 10.1002/14651858.CD009122.pub2. Review. — View Citation

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Genuth S. Insights from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study on the use of intensive glycemic treatment to reduce the risk of complications of type 1 diabetes. Endocr Pract. 2006 Jan-Feb;12 Suppl 1:34-41. Review. — View Citation

Gomes F, Telo DF, Souza HP, Nicolau JC, Halpern A, Serrano CV Jr. [Obesity and coronary artery disease: role of vascular inflammation]. Arq Bras Cardiol. 2010 Feb;94(2):255-61, 273-9, 260-6. Review. English, Portuguese, Spanish. — View Citation

Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007;3(6):853-76. Review. — View Citation

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King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol. 2008 Aug;79(8 Suppl):1527-34. doi: 10.1902/jop.2008.080246. Review. — View Citation

Kotronen A, Lewitt M, Hall K, Brismar K, Yki-Järvinen H. Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity. J Clin Endocrinol Metab. 2008 Dec;93(12):4867-72. doi: 10.1210/jc.2008-1245. Epub 2008 Sep 16. — View Citation

Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S; Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005 Apr 19;142(8):611-9. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to nephropathy		0, 3-5, 8-10 and 13-15 years
Primary	Time to autonomous neuropathic ulcers and Amputation		0, 3-5, 8-10 and 13-15 years
Primary	Time to peripheral neuropathy		0, 3-5, 8-10 and 13-15 years
Primary	Time to peripheral Macro-Vascular Disease, chronic Foot ulcers and Amputation		0, 3-5, 8-10 and 13-15 years
Primary	Time to retinopathy		0, 3-5, 8-10 and 13-15 years
Secondary	DNA		0, 3-5, 8-10 and 13-15 years
Secondary	Endothelial markers		0, 3-5, 8-10 and 13-15 years
Secondary	Blood lipids		0, 3-5, 8-10 and 13-15 years
Secondary	CRP		0, 3-5, 8-10 and 13-15 years
Secondary	Oxidative stress		0, 3-5, 8-10 and 13-15 years
Secondary	Q10		0, 3-5, 8-10 and 13-15 years
Secondary	IGFBP-1		0, 3-5, 8-10 and 13-15 years
Secondary	IGF-1		0, 3-5, 8-10 and 13-15 years
Secondary	Inflammatory markers		0, 3-5, 8-10 and 13-15 years
Secondary	Seated blood pressure		0, 3-5, 8-10 and 13-15 years
Secondary	Pulse		0, 3-5, 8-10 and 13-15 years
Secondary	Weight		0, 3-5, 8-10 and 13-15 years
Secondary	BMI		0, 3-5, 8-10 and 13-15 years
Secondary	Waistlines		0, 3-5, 8-10 and 13-15 years