Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic
Conditions
Keywords
Dietary polyphenols, Protein glycation
Brief summary
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of kidney failure, with high levels of glycohaemoglobin (HbA1c) presenting a sharper decline in renal function and an increase in the risk of mortality and end-stage renal disease (ESRD). Polyphenols may improve renal insufficiency in patients with diabetes with chlorogenic acids (CGA) one of the principle polyphenol groups in the diet - coffee/tea, stone fruits (especially plums/prunes) and some vegetables (artichoke, chicory). CGA (3-4 cups of coffee) has been associated with 25% lower risk of T2DM and a favourable reduction of HbA1c, blood pressure, and oxidative stress levels. This randomised controlled trial, therefore, aims to evaluate the effect of high CGA food on glycation and oxidative stress in T2DM subjects with early renal insufficiency (glomerular filtration rate of 35-60 mL/min) as well as progression of renal insufficiency and the risk of cardiovascular diseases. The study will have two phases - phase I, an interventional study of 3 months followed by phase II, an observational study of 21 months. In phase I, subjects will be randomized into 2 groups: CGA-enriched diet group, or control (habitual) diet group. The treatment group will be provided with a chlorogenic acid-rich food (coffee) with instructions to achieve an intake of 400 mg per day (equivalent to 3-4 coffee cups per day) for 12 weeks. The control group will receive a conventional coffee low in chlorogenic acid. Participants will attend three sessions during phase I; baseline, 6 weeks, and 12 weeks. At baseline, general information, medical history, dietary habits and medication use will be recorded and a Food Frequency Questionnaire completed. Urine and blood samples will be collected and blood pressure, waist circumference, height and weight recorded. Participants' diet over the previous 3 days will be assessed by estimated food diary analysis. In phase II, written dietary recommendations will be provided at three time points (months 6, 12 and 24) - treatment group to achieve a CGA-rich diet (total polyphenol intake of at least 1g per day, and at least 400mg per day of CGA) and standard dietary advice for the control group. Anthropometric/dietary data will be collected as well as blood and urine samples to assess markers of renal function, glycation and oxidative stress, and proteomic markers of cardiovascular disease, coronary artery disease and diabetes.
Interventions
DIETARY_SUPPLEMENTChlorogenic Acid (CGA) enriched coffee
Chlorogenic Acid (CGA) enriched coffee Phase I: CGA-enriched coffee provided with a CGA content of 70-90 mg/100g. Daily CGA intake of 400mg. Phase II: recommendation for achieving a CGA-rich diet of at least 400mg/day (total polyphenol intake of at least 1g/day)
DIETARY_SUPPLEMENTConventional coffee
Phase I: conventional coffee provided (low in CGA) Phase II: standard dietary advice
Sponsors
University of Glasgow
NHS Greater Glasgow and Clyde
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* type 2 Diabetes Mellitus * chronic renal insufficiency with persistent eGFR of 35-60mL/min for at least three months * fluent in English
Exclusion criteria
* dialysis therapy (current or previous) * malignancy * transplant recipient * hyperthyroidism * hypothyroidism * high dose glucocorticoids (≥250 mg) * body mass index (BMI) ≥ 45 kg/m2 * special dietary requirements * take creatine, antioxidants or vitamin supplements * smoker * pregnant * consume \>4 cups of tea/coffee per day * consume \>5 portion of fruits and vegetables per day
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in glycohaemoglobin (HbA1c) | 3 months |
| Change in estimated glomerular filtration rate (eGFR) | 21 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in advanced glycation end product (AGE) | 3 months |
| Change in soluble receptor for AGE (sRAGE) | 3 months |
| Change in F2-isoprostane | 3 months |
| Change in malondialdehyde (MDA) | 3 months |
| Change in Urinary Albumin Excretion | 21 months |
| Change in creatinine | 21 months |
| Change in blood pressure | 21 months |
| Change in fasting glucose | 3 months |
| Change in fibrinogen | 21 months |
| Change in cholesterol | 21 months |
| Change in C-reactive protein | 21 months |
| Change in Interleukin-6 | 21 months |
| Change in thiobarbituric acid reactive substances (TBARS) | 21 months |
| Change in advanced oxidation protein products (AOPP) | 21 months |
| Change in 8hydroxy 2'deoxyguanoside (8OhdG) | 21 months |
| Change in crystatin C | 21 months |
| Change in fructosamine | 3 months |
Countries
United Kingdom
Outcome results
None listed