PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs

• Status: Completed
• Trial end date: 2017-12-01
• Target enrollment: 0
• Participant gender: All

Summary

There is evidence of the association between diabetic microangiopathy and elevated serum concentrations of advanced glycation end-products (AGEs). AGEs levels are associated with ingestion of specific foods (baked meats and milk powder); reducing their dietary intake lowers AGEs concentrations, with beneficial metabolic effects; however threre is still no evidence of whether this has an impact on microvascular complications of DM. We recently applied for funding to compare in a RCT the effects of Cholestyramine versus placebo, on visual electrophysiology. This drug is similar to Sevelamer in structure, both act as chelators of bile salts, and reduce absorption of dietary AGE, lowering serum levels. However it is essential to carry out preliminary tests to assess aspects that may imply adjustments to the proposed protocol, such as: 1) tolerance to the drug 2) short term effect of the drug versus placebo on serum levels of AGEs 3) effects of the drug versus placebo in levels of fat soluble vitamins (D and K specifically) 4) intra and interindividual variability of electrophysiological measurements of vision (ERGMF and optic nerve conduction velocity) 5) drug versus placebo in electrophysiological measurements of vision (neuroconduction ERGMF and optic nerve). Objective: The present project is planned as a pilot study, which will clarify points 1 to 5. Methodology: patients (6 DM2, 25 -50 y) will be assessed through anthropometry, clinical laboratory tests (creatinine, chemistry profile, lipid profile, microalbuminuria glycosylated hemoglobin, vitamin B12, 25OH vitamin D and prothrombin), dietary recalls specifically designed to analyze the regular consumption of AGEs, serum CML and neuro-ophthalmological study (fundus, ERGMF and optic nerve conduction). Subsequently each patient will be assigned to treatment with placebo for 3 months and then Cholestyramine 6 g / day for 12 weeks and at the end of each period will be reassessed using the same methodology. If patients cannot tolerate the drug, they will be assigned to a reduced AGE diet.

Expected results: Cholestyramine will have side effect similar to placebo (mainly digestive). The active drug and not placebo will reduce serum levels of AGEs and electrophysiological parameters of vision at 12 weeks. It is expected that a low AGEs diet in patients who do not tolerate the drug will also reduce serum CML although to a lesser degree and will also induce electrophysiologic changes.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Chile
• Collaborator: Clinica Alemana de Santiago
• Treatments: Cholestyramine Resin

Criteria

Inclusion Criteria:

• TYPE 2 DIABETES

• More than 5 and less than 10 years of disease

• Adherent to treatment with oral hypoglycemic agents or insulin

• Agree to participate in the study through a written informed consent.

• High habitual intake of AGEs according the food recall .

Exclusion Criteria:

• Severe Obesity (BMI> 35 kg / m2)

• Glycosylated hemoglobin> 9%, anemia, renal failure (creatinine> 1.5 mg / dL or calculated creatinine clearance <60 ml / min), fasting plasma glucose> 250 mg / dL

• History of acute hyperglycemic complications requiring hospitalization in the past 2 years

• Severe diabetic dyslipidemia (LDL> 130, TG> 350 mg / dL)

• Vitamin B12 deficiency

• History of heart, liver, lung cancer or chronic diseases

• Clinical diagnosis of diabetic neiropathy and eye conditions that could hinder electroretinogram, such as uncorrected refractive defects, cataracts and severe diabetic retinopathy or macular edema.

• Poorly controlled hypertension or acute vascular event in the past 2 years

• Pregnancy.