An observational study in Diabetic Angiopathies and Bone Diseases, Metabolic, sponsored by Tameside General Hospital. Completed at 1 site in United Kingdom. Open to participants aged 40 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-16.
Sponsored by Tameside General Hospital · Observational
This study is part of a research project for a University MD Program. This is an observational study aimed at comparing the differences in bone metabolism and microcirculation in patients with type 2 diabetes mellitus (with and without diabetic neuropathy and Charcot foot) with healthy subjects.
Diabetes is gradually becoming a global epidemic along with its associated complications. Diabetes can affect several systems in our body particularly the eyes, nerves and the kidneys. The damaging effects occur at the level of the small blood vessels (microcirculation) that supply these vital structures. Normally, the inner lining of these blood vessels (endothelium) plays a very important role in maintaining adequate blood flow. The endothelium releases a chemical substance called nitric oxide, which relaxes these small blood vessels thereby ensuring sufficient blood supply to these key structures. Nitric oxide also prevents blockage of these vessels. Any form of metabolic stress like hyperglycaemia (raised blood sugar as seen in diabetes) can cause abnormal changes in the normal behaviour of the endothelium (endothelial dysfunction). Therefore hyperglycaemia promotes endothelial dysfunction by lowering nitric oxide levels, which may lead to diabetic complications like diabetic retinopathy (eye damage), nephropathy (kidney damage) or neuropathy (nerve damage).
In addition, patients with diabetes also suffer from osteoporosis (thinning of bones). Osteoporosis is a bone disorder characterised by a reduction in bone mineral content leading to an increased risk of developing fractures. The increased risk of fractures in patients with type 2 diabetes is attributed to poor bone quality resulting from the harmful effects of high blood glucose. Studies have also shown that nitric oxide has a bone protective effect as demonstrated by its ability to prevent bone fragmentation and improve bone strength.
Study of markers of endothelial function and bone metabolism will facilitate a better understanding about the origin of diabetic complications. This will aid in the development of novel therapeutic agents that target the harmful triggers in diabetes and eventually may prevent and retard the onset of the debilitating diabetic complications.
This is an observational study aimed at observing and comparing differences in bone metabolism and microcirculation in patients with type 2 diabetes and healthy controls.
In this study, 50 participants will be recruited and then categorised into the following groups:
Type 2 diabetic patients with neuropathy:
Visit Schedule The estimated time for enrollment of patients will be within 3 months. The duration of the study is 5 months.
Screening (-2 Weeks): To assess for eligibility. This will include informed consent process, medical history and physical examination, screening for neuropathy and routine bloods. Laboratory work-up done at screening will be considered for data analysis.
Visit 1 - Baseline visit
Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
Clinical Procedures
Assessment of the microcirculation with Laser Doppler Iontophoresis:
A standard measurement of microcirculation is laser Doppler iontophoresis, which is used by several research institutes. In this trial the skin microcirculation will be measured on the dorsum of the foot using a Perimed Laser Doppler imager and iontophoresis system.
Endothelial-mediated vasodilation will be measured by the iontophoresis of acetylcholine, while sodium nitroprusside will be used to measure endothelium-independent vasodilation. The iontophoresis system consists of an ION chamber (iontophoresis delivery vehicle device) that sticks firmly to the skin and a reference electrode. The response in blood flow will be imaged and quantified using the Perimed Laser Doppler Imager (PeriScan PIMII; Perimed, Sweden).
Analysis of AGE:
An AGE reader, which utilizes the principle of skin autofluorescence, will measure the accumulation of AGE in the skin. This validated device provides a real-time, non-invasive assessment of cardiovascular risk for chronic diseases like Diabetes, renal failure, cardiovascular disease, etc. AGE-modified proteins have autofluorescent properties and when excited by ultraviolet (UV) light they emit fluorescence in particular wavelengths. The levels of AGE in skin correlate with AGE levels in blood.
The volar aspect of the forearm will be placed on the AGE reader, which is equipped with a UV light source. The UV light triggers AGE in skin, after penetrating 1mm of the dermis, to emit autofluorescence that is then detected by the AGE reader. The intensity of fluorescence correlates with the quantity of AGE in the skin.
Assessment of calcaneal BMD:
This is a simple and convenient method to assess peripheral BMD and assess fracture risk. The device used is a quantitative ultrasound called Sahara Clinical Bone Sonometer (Sahara Clinical Bone Sonometer; Hologic, Waltham, MA). The calcaneus is the preferred peripheral site to assess fracture risk. This device uses ultrasound waves to determine the BMD of the calcaneus. In this procedure, once the bare heel is placed in the device, the BMD is calculated within 30 seconds and the results are then generated on paper by the device.
40 patients with type 2 diabetes mellitus will be considered eligible for the study. Patients with a previous diagnosis of type 2 diabetes mellitus and newly diagnosed type 2 DM seen at Tameside Hospital will be recruited into the study. In addition, eligible patients will be identified and referred from University Hospital of South Manchester (UHSM) and appropriate GP practices (from Oldham, Tameside and Wythenshawe).
Source of healthy controls: Hospital staff and spouses/ partners of patients will volunteer as healthy subjects.
Subjects aged between 40-75 years
Classic symptoms of hyperglycaemia or hyperglycaemic crisis with a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).
Exclusion Criteria:
At screening, age below 40 years and above 75 years.
10 healthy volunteers * Anthropometric measures: Height, weight, BMI, waist circumference * Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature * Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism. * Assessment of skin microcirculation with Laser Doppler Iontophoresis * Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound) * Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
10 patients * Anthropometric measures: Height, weight, BMI, waist circumference * Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature * Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism. * Assessment of skin microcirculation with Laser Doppler Iontophoresis * Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound) * Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
10 patients * Anthropometric measures: Height, weight, BMI, waist circumference * Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature * Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism. * Assessment of skin microcirculation with Laser Doppler Iontophoresis * Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound) * Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
10 patients * Anthropometric measures: Height, weight, BMI, waist circumference * Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature * Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism. * Assessment of skin microcirculation with Laser Doppler Iontophoresis * Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound) * Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
10 patients * Anthropometric measures: Height, weight, BMI, waist circumference * Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature * Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism. * Assessment of skin microcirculation with Laser Doppler Iontophoresis * Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound) * Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Endothelial-dependent and independent vasodilatations
Time frame: At baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Markers of endothelial activation, which include adhesion molecules like ICAM, VCAM and inflammatory molecules.
Time frame: at baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Serum Nitric oxide
Time frame: at baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Advanced glycation end-products
Time frame: at baseline
Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by:
Bone turnover markers like P1NP, CTX, Sclerostin, RANKL, OPG, OPN, OCN, BMP4 and TGF-1β.
Time frame: At baseline
Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by:
Calcaneal bone mineral density (BMD)
Time frame: At baseline
This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.
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Tameside General Hospital