Anne L. Carrington

Bio: Anne L. Carrington is an academic researcher from Manchester Royal Infirmary. The author has contributed to research in topics: Peripheral neuropathy & Foot (unit). The author has an hindex of 13, co-authored 14 publications receiving 2273 citations. Previous affiliations of Anne L. Carrington include Biochemical Society.

The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort.

Abstract: Aims To determine the incidence of, and clinically relevant risk factors for, new foot ulceration in a large cohort of diabetic patients in the community healthcare setting. Methods Diabetic patients (n = 9710) underwent foot screening in six districts of North-west England in various healthcare settings. All were assessed at baseline for demographic information, medical and social history, neuropathy symptom score, neuropathy disability score, cutaneous pressure perception (insensitivity to the 10 g monofilament), foot deformities, and peripheral pulses. Two years later, patients were followed up via postal questionnaire to determine the incidence of new foot ulcers. Cox’s proportional hazards regression analysis was used to determine the independent, relative risk of baseline variables for new foot ulceration. Results New foot ulcers occurred in 291/6613 patients who completed and returned their 2-year follow-up questionnaire (2.2% average annual incidence). The following factors were independently related to new foot ulcer risk: ulcer present at baseline (relative risk (95% confidence interval)) 5.32 (3.71–7.64), past history of ulcer 3.05 (2.16–4.31), abnormal neuropathy disability score (≥ 6/10) 2.32 (1.61–3.35), any previous podiatry attendance 2.19 (1.50–3.20), insensitivity to the 10 g monofilament 1.80 (1.36–2.39), reduced pulses 1.80 (1.40–2.32), foot deformities 1.57 (1.22–2.02), abnormal ankle reflexes 1.55 (1.01–2.36) and age 0.99 (0.98–1.00). Conclusions More than 2% of community-based diabetic patients develop new foot ulcers each year. The neuropathy disability score, 10 g monofilament and palpation of foot pulses are recommended as screening tools in general practice.

Multicenter Study of the Incidence of and Predictive Risk Factors for Diabetic Neuropathic Foot Ulceration

Abstract: OBJECTIVE To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy. RESEARCH DESIGN AND METHODS A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with N1DDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe ≥25 V in at least one foot and ≤50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits. RESULTS After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration ( P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%. CONCLUSIONS Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.

Foot ulcer risk is lower in South-Asian and African-Caribbean compared with European diabetic patients in the U.K : the north-west diabetes foot care study

Abstract: OBJECTIVE —To determine 1 ) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K and 2 ) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups. RESEARCH DESIGN AND METHODS —In this U.K. population–based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%). RESULTS —The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively ( P < 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans ( P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20–0.41) ( P < 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35–0.76) ( P < 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation. CONCLUSIONS —South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation.

Can Motor Nerve Conduction Velocity Predict Foot Problems in Diabetic Subjects Over a 6-Year Outcome Period?

Abstract: OBJECTIVE —This study examined motor nerve conduction velocity (MNCV) and other peripheral nerve and vascular tests as predictors for foot ulceration, amputation, and mortality in diabetes over a 6-year follow-up period. RESEARCH DESIGN AND METHODS —We recruited 169 diabetic subjects (without significant peripheral vascular disease with an ankle brachial pressure index [ABPI] ≥0.75) for the study and separated them into groups (to ensure diversity of nerve function). The control group consisted of 22 nondiabetic people. At baseline, all subjects underwent assessment of MNCV; vibration, pressure, and temperature perception thresholds; peripheral vascular function; and other diabetes assessments. RESULTS —Over the 6-year outcome period, 37.3% of the diabetic subjects developed at least one new ulcer, 11.2% had a lower-limb amputation (LLA) (minor or major), and 18.3% died. Using multivariate Cox’s regression analysis (RR [95% CI] and removing previous ulcers as a confounding variable, MNCV was found to be the best predictor of new ulceration (0.90 [0.84–0.96], P = 0.001) and the best predictors of amputation were pressure perception threshold (PPT) (5.18 [1.96–13.68], P = 0.001) and medial arterial calcification (2.88 [1.13–7.35], P = 0.027). Creatinine (1.01 [1.00–1.01], P < 0.001), MNCV (0.84 [0.73–0.97], P = 0.016), and skin oxygen levels (14.32 [3.04–67.52], P = 0.001) were the best predictors of mortality. CONCLUSIONS —This study shows that MNCV, which is often assessed in clinical trials of neuropathy, can predict foot ulceration and death in diabetes. In addition, tests of PPT and medial arterial calcification can be used in the clinic to predict LLA in diabetic subjects.

Diabetic Foot Ulcers and Their Recurrence

Abstract: Foot ulceration is the most common lower-extremity complication in patients with diabetes mellitus. This review considers the pathogenesis, treatment, and management of diabetic foot ulcers, including prevention of recurrence.

Diabetic Autonomic Neuropathy

Abstract: Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastro- paresis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brit- tle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal (GI), genitourinary, and cardiovascular). GI distur- bances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal inconti- nence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to con- sideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunc- tion should be performed for individuals with diabetes who have recurrent urinary tract infec- tions, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; mea- surement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve func- tion; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an in- creased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of auto- nomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing) be used for longitudi- nal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing re- quires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recom- mended tests for assessing CAN is readily per- formed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of au- tonomic dysfunction earlier) serves to estab- lish a baseline, with which 1-year interval tests can be compared. Regular HRV testing pro- vides early detection and thereby promotes timely diagnostic and therapeutic interven- tions. HRV testing may also facilitate differen- tial diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and diz- ziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to im- prove metabolic control and to use therapies such as ACE inhibitors and -blockers, proven to be effective for patients with CAN. Diabetes Care 26:1553-1579, 2003

Microvascular and Macrovascular Complications of Diabetes

Abstract: Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia. The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding. ### Diabetic retinopathy Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …

Diabetic neuropathies: a statement by the American Diabetes Association.

Abstract: The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. This statement is based on two recent technical reviews (1,2), to which the reader is referred for detailed discussion and relevant references to the literature. An internationally agreed simple definition of DPN for clinical practice is “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (3). However, the diagnosis cannot be made without a careful clinical examination of the lower limbs, as absence of symptoms should never be assumed to indicate an absence of signs. This definition conveys the important message that not all patients with peripheral nerve dysfunction have a neuropathy caused by diabetes. Confirmation can be established with …