Diabetes mellitus (DM) is one of the most common endocrine diseases, characterized by an increase in plasma glucose. The most prevalent form of diabetes is type 2 diabetes (T2D), currently affecting more than 300 million people worldwide¹ Furthermore, DM is not only a disease complicating human health worldwide, but also a substantial burden to health care systems, especially in developing countries. Acral ischemic gangrene is a common and serious complication of type 2 DM and is one of the main causes of mortality and disability associated with DM². Its pathological basis is a vascular defect caused by DM. The pathogenesis of this vascular defect involves vascular endothelial cell damage, accumulation of glycation end products (Advanced Glycation End products, AGEs), and proliferation of smooth muscle cell or matrix due to chronically elevated levels of glucose, cholesterol, and insulin. All these factors lead to arterial reconstruction. Furthermore, extensive micro-thrombosis develops as a result of hypercoagulability, and nonsymmetric stenosis or occlusion of peripheral vessels emerge at terminal stages. Early vascular lesions occur early on and usually impact arterioles without any clinical symptoms. Importantly, these early arteriolar lesions occur prior to clinical manifestations of DM, and are potentially reversible at this stage. When disease progresses, pathological changes in arterioles become irreversible due to persistent metabolic disorders, and result in serious complications such as acral ischemic gangrene³, diabetic nephropathy⁴ etc. An early intervention can prevent or delay progressive development of arteriolar vascular disease^{5, 6} .Therefore, early and proper assessment of acral microcirculation is crucial for reducing the likelihood of severe complications. Unfortunately, evaluation of microcirculation disturbance in the acra, particularly in patients with DM, has been hampered by the lack of proper imaging parameters.  It is likely that microcirculatory disturbances of varying degree occur in early stages of the disease. Microcirculatory disturbances include alteration of the microvascular flow and metabolic changes of tissues and cells due to pathological change of microvessels, remodeling of arterioles, and high blood coagulation. Common methods of clinical detection include a nail fold microcirculation analysis, fluorescence microscopic technique, and hemorheologic test⁷ The blood supply in the nail bed reflects not only the physiologic and pathological condition of the nail bed itself, but is also closely associated with the general pathological condition. For this reason, the nail bed is often used to assess the microcirculation of the body. A study demonstrates that abnormal microcirculation of digital arterioles exists in most patients with DM prior to ischemic acral gangrene. The abnormal microcirculation manifested early with hemodynamic changes, decreased blood flow, and increased resistance of arterioles in finger and toe. It was further observed that arterioles of fingers and toes in patients with DM were abnormally distributed, twisted, discontinued, and disarranged⁸. As disease progresses, the number of arterioles further diminishes. The hemodynamic changes of the finger and toe arterioles in patients with complicated DM (hypertension and/or hyperlipemia) are even more pronounced. This also explains how the metabolic disorder aggravates the disturbance of digital microcirculation. Decreased blood flow and increased blood flow resistance in the diastolic phase were the earliest hemodynamic changes observed in a study⁸. These changes indicate that arteriolar damage in the early stage of type 2 DM is mainly in the form of decreased vascular elasticity, and that Resistance Index (RI) is a relatively sensitive marker to detect these changes. Furthermore, vascular abnormalities of nail bed arterioles appeared prior to those in pulp arterioles, and this was true for both finger and toe. Therefore, examination of the nail bed arterioles is likely a more sensitive technique to detect early vascular abnormalities and there has been a paucity of studies in this issue and hence we plan a study directly correlating acral vascular changes with microvascular complications.

AIMS & OBJECTIVES

The aim of this study is

1.      To compare the changes in vascularity in nail bed and digital arterioles in diabetic patients with microvascular complications, with diabetic patients without microvascular complications and also compared with age and sex matched controls without diabetes.

2.      To assess whether these vascular changes can be used as a marker of microvascular complications.

MATERIAL & METHODS

Patients attending diabetic clinic or endocrine out patient department (OPD) services of SSKM Hospital and IPGME& R will be considered. Patients >30 years and <60 years of age will be considered. Study subjects will be divided into 3 groups. Each group will comprise of 30 study subjects. Group 1 would include diabetic patients with at least one of the microvascular complications, group 2 to include diabetic patients without microvascular complications and group 3 involve non diabetic age and sex matched controls.  Duration of diabetes will be noted for all the patients. Exclusion criteria include patients with clinical signs of acral ischemic gangrene, Takayasu’s arteritis, autoimmune disorders, clubbing and skin infections including fungal paronychia. Patients with pregnancy would be excluded. The initially considered patients would be screened for microvascular complications, dilated fundus examination for retinopathy, spot urine albumin creatinine ratio(ACR) for nephropathy and vibration pressure threshold (VPT) and monofilament(MFT) for neuropathy and all patients would undergo detailed clinical examination. Lipid profile, serum creatinine, HbA1c, uric acid, electrolytes, and hemogram would be estimated in all patients.

The patients would be explained about the study and only those who give informed written consent would be included in the final study. Clearance from the Institutional Ethics committee will be obtained before the study initiation. In the finally included patients in the study ultrasound Doppler of the nail bed arterioles and digital arterioles of the middle finger of the non dominant hand will be done using a 18 MHz linear transducer,⁹ With the use of colour and power colour Doppler blood flow will be studied and Peak systolic velocity (PSV), End diastolic velocity (EDV), Resistance Index (RI), percentage area of vascularity will be calculated in all the study subjects. A temperature of 20 to 25 degree Celsius will be maintained at Doppler site and patients will be there for at least 30 minutes to negate temperature bias. A master chart depicting all the values will be made for the final statistical analysis.

Statistical Analysis

ANOVA unpaired t- test will be used for analysis of continuous variables and all results of continuous variables will be expressed as mean ± SD.

References:

1. IDF diabetes atlas. 4th edition. International Diabetes Federation; 2009. Available at: http://www.diabetesatlas.org/.

2. King H, Keuky L, Seng S, Khun T, Roglic G, Pinget M. Diabetes and associated disorders in Cambodia: Two epidemiological surveys. Lancet: 2005:366:1633–1639

3. Alnaeb M.E, Crabtree V.P, Boutin A, Mikhailidis D.P, Seifalian A. M, Hamilton G. Prospective assessment of lower-extremity peripheral arterial disease in diabetic patients using a novel automated optical device. Angiology: 2007: 58: 579–585

4. Wolf G, Ritz E Diabetic nephropathy in type 2 diabetes prevention and patient management. Journal of the American Society of Nephrology: 2003: 14: 1396–1405.

5. Sachidanandam K, Hutchinson J.R, Elgebaly M. M, et al.  Glycemic control prevents microvascular remodeling and increased tone in type 2 diabetes: Link to endothelin-1. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology: 2009: 296: R952–R959.

6. Vinik A.I, Vinik E. Prevention of the complications of diabetes. American Journal of Managed Care: 2003: 9: S63–S80.

7. Vigilance J. E, Reid H. L Segmental blood flow and rheological determinants in diabetic patients with peripheral occlusive arterial disease. Journal of Diabetes and Its Complications; 2008: 22: 210–216.

8. Fang Ma Baozhen Zhao Huiping Zhang Wei-Ping Li Yuan-Yuan Liu Yuan-Yuan Dang etal, Usefulness of Enhanced Power Doppler Imaging in Monitoring Acral Microcirculation in Type 2 Diabetes Mellitus and its Complications Cell Biochem Biophys ;2011: 61:435–441 

9. Cecchini A, Montella A, Ena P, Meloni GB, Mazzarello V. Ultrasound anatomy of normal nails unit with 18 mhz linear transducer.Ital J Anat Embryol.;2009:114(4):137-44.