Bone Metabolism and Endothelial Function in Patients With Type 2 Diabetes Mellitus and Charcot Foot - an Observational Comparative Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
研究概览
简要总结
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.
详细描述
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:
- Control group: 10 healthy volunteers (Hospital staff and spouses/ partners of patients will volunteer as healthy subjects)
- Type 2 diabetic patients without neuropathy: 10
- Type 2 diabetic patients with neuropathy:
- 10 patients with painless neuropathy
- 10 patients with painful neuropathy
- Type 2 diabetic patients with unilateral Charcot foot: 10
Visit Schedule The estimated time for enrollment of patients will be within 3 months. The duration of the study is 5 months.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• Subjects aged between 40-75 years
- •Healthy subjects or non-diabetic subjects for the control group.
- •A diagnosis of type 2 DM based on one of the following criteria (ADA - 2010):
- •Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) or
- •2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT or
- •Classic symptoms of hyperglycaemia or hyperglycaemic crisis with a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).
- •Patients on treatment for type 2 diabetes mellitus
- •Presence of diabetic neuropathy will be confirmed when 2 of the following neurological tests are positive on examination (vibration perception threshold, 10 gm. monofilament, 128 Hz tuning fork, ankle reflex, pin-prick)
- •Painful diabetic neuropathy diagnosed according to LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) scoring
- •For patients with chronic Charcot foot, the diagnosis should be confirmed by clinical judgment and by radiologic examination - X-ray, technetium-labeled bisphosphonate bone scan or MRI)
排除标准
- •• At screening, age below 40 years and above 75 years.
- •Type 1 diabetes mellitus (patients with a history of ketoacidosis, age of onset of DM before 25 years of age, BMI <21 kg/m2 and use of insulin without a concomitant oral hypoglycemic agent)
- •Major cardiovascular complications within 3 months prior to screening
- •Recent history of smoking within the last 6 months
- •Scars, tattoos or rashes over the forearm
- •Recent or current oral steroid therapy or topical steroids applied to the forearm
- •Patients with uncontrolled hypertension (systolic blood pressure [SBP] > 160/90 mmHg) or hypotension (SBP ≤ 100 mm Hg or a diastolic BP of ≤60 mm Hg) at screening.
- •History of general systemic illness including cardiac, hepatic or renal insufficiency
- •Patients with renal insufficiency characterized by a creatinine clearance of less than 60 ml/min or a serum creatinine of more than 130 μmol/l
- •Receiving treatment for inflammatory disease or malignancy
- •Other non-diabetic causes of neuropathy
- •History of chronic alcohol consumption
- •History of metabolic bone disorders (Osteoporosis, Paget's disease, etc.) or treatment for bone disorders (past or current treatment for osteoporosis, bisphosphonate therapy within the last 3 years)
- •History of malignancy
- •History of active foot ulcers
- •History of concomitant therapy that may interfere with bone metabolism e.g. glucocorticoids (within the last 3 months), hormone replacement therapy (in the last 12 months), SERM (selective oestrogen receptor modulator), thiazolidinedione, anticonvulsant use
- •Receiving drugs that fluoresce (e.g., Doxorubicin, Daunomycin, Camptothecin, Protoporphyrin, Fluoroquinolones, Tetracycline, Hydroxychloroquine or Quinidine)
- •History of photosensitivity reactions (e.g., sensitive to ultraviolet light, or taking medication known to cause photosensitivity
- •Simultaneous participation in other clinical trials or involvement in another research trial involving an investigational product in the past 12 weeks.
结局指标
主要结局
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
时间窗: at baseline
Advanced glycation end-products
次要结局
- Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by:(At baseline)