Colin A Hardisty

Bio: Colin A Hardisty is an academic researcher from Royal Hallamshire Hospital. The author has contributed to research in topics: Diabetic neuropathy & Diabetes mellitus. The author has an hindex of 5, co-authored 6 publications receiving 555 citations.

Dynamic Foot Pressure and Other Studies as Diagnostic and Management Aids in Diabetic Neuropathy

Abstract: The pressures and loads under the feet during walking have been compared in three groups of 41 patients each, using a microprocessor-controlled optical system. Group A consisted of patients with diabetic neuropathy, group B of non-neuropathic diabetic patients, and group C of nondiabetic controls. Thirteen patients in group A had a history of neuropathic foot ulceration. Other investigations in the diabetic patients included motor conduction velocity (MCV) in the median and peroneal nerves, vibration perception threshold (VPT) in the great toes, the valsalva response (VR), skin resistance (SR), and the ankle pressure index (API). Fifty-one percent of neuropathic feet had abnormally high pressures underneath the metatarsal heads compared with 17% of the diabetic controls and 7% of nondiabetic subjects. All those feet with previous ulceration had abnormally high pressures at the ulcer sites. Of the other investigations, the VPT correlated most significantly with the presence of foot ulceration. In addition, a low median and peroneal nerve MCV, an abnormal VR, a high API, and the absence of sweating all correlated with the presence of foot ulceration. We therefore conclude that simple bedside investigations, such as measurement of the VPT alone, may be useful in identifying those patients at risk of foot ulceration. Foot pressure studies may then be used in such patients as a predictive and management aid by determining specific areas under the foot that are prone to ulceration.

Asymptomatic myocardial ischemia in diabetes and its relationship to diabetic neuropathy: an exercise electrocardiography study in middle-aged diabetic men.

Abstract: The incidence of painless ischemic heart disease is increased in diabetic patients, and it has been suggested that this may be partly due to diabetic neuropathy involving cardiac afferent nerves. We have performed exercise electrocardiography in middle-aged diabetic men without cardiac symptoms to see if silent myocardial ischemia is more common in patients with neuropathy. Thirty patients had diabetic neuropathy (group 1), and 30 did not (group 2). The groups were matched for age and duration of diabetes. The exercise test was abnormal in 14 patients. A positive test was no more common in patients with diabetic neuropathy. During a mean follow-up period of 50 mo, five patients developed clinical heart disease, four of whom had a positive exercise test. An abnormal exercise ECG is common in diabetic men without cardiac symptoms, but our study does not suggest that the high incidence of silent myocardial ischemia in diabetic patients is related to the presence of diabetic neuropathy. In patients with diabetes a positive exercise test is associated with a high risk of developing clinical heart disease in subsequent years.

Early-onset Type 2 diabetes mellitus: an increasing phenomenon of elevated cardiovascular risk

Abstract: The age of onset of Type 2 diabetes mellitus (T2DM) is falling and this condition is not uncommon among those aged less than 30 years, including children and adolescents. Early-onset T2DM has been reported in countries with different ethnic and cultural backgrounds. This phenomenon heralds an important public health issue reflecting the effects of a sedentary lifestyle as part of the globalization and industrialization that is affecting all societies. The pathophysiology of early-onset T2DM is similar to the later onset cohort characterized by beta-cell failure and obesity-induced insulin resistance but the rate of decline in beta-cell function appears to be more rapid. Recent evidence suggests that early-onset T2DM is a more aggressive disease phenotype than the later onset cohort and develops cardiovascular complications, reflected by more adverse cardiovascular risk profile and higher relative risk of myocardial infarction and cardiovascular death. As there is a paucity of clinical trial evidence in this population, clinical judgment is required to initiate treatments to prevent cardiovascular complications guided by assessment of global cardiovascular risk. Future research strategies in this cohort include population-based studies in at-risk populations, exploration of its natural history, development of complications and outcome studies pertaining to the treatment of cardiovascular risk factors.

Genetic and metabolic studies in diabetic neuropathy.

Abstract: Forty-one diabetic patients with symptomatic diabetic neuropathy were studied together with an equal number of matched diabetic subjects without neuropathy. The acetylator status was determined and HLA-A, B, C and DR antigens were investigated. Metabolic control was assessed by measurement of glycosylated haemoglobin and by the mean of multiple random clinic blood glucose values. No significant difference was observed between the two groups in the proportion of fast and slow acetylators. The distribution of HLA frequencies was similar in subjects with and without neuropathy for both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients. When compared with diabetic subjects without neuropathy, the neuropathy group had higher levels of both glycosylated haemoglobin (mean ± SEM: 50.1±1.4 versus 57.5±1.8 mmol hydroxymethylfurfural/mol haemoglobin (10.5±0.3 versus 12.0±0.4% haemoglobin A1, p < 0.01) and mean blood glucose (9.3±0.4 versus 11.3±0.5 mmol/l, p < 0.005). This study provides no evidence that genetic factors increase the susceptibility of diabetic patients to develop neuropathy. In contrast, the elevated glycosylated haemoglobin and blood glucose levels strengthen the association between hyperglycaemia and diabetic neuropathy.

Elevated glycosylated hemoglobin in diabetic neuropathy.

Abstract: Glycosylated hemoglobin (GHb) levels were measured in 36 patients with established symptomatic neuropathy and in an identical number of matched controls. Strict criteria were employed in the selection of subjects and all had neuropathy of at least 12 months’ duration. The diagnosis of neuropathy was supported by estimation of motor conduction velocities and vibration perception threshold. A semi-automated colorimetric technique, employing the reaction between thiobarbituric acid and 5-hydroxy-methyl furfural, was used for the estimation of GHb. Those patients with neuropathy had significantly higher GHb levels (58.2 ± 11.3 mmol HMF/mol Hb) than the controls (50.0 ± 8.9 mmol HMF/mol Hb) (p<0.01). This suggests that hyperglycemia or related metabolic abnormalities are important factors in established symptomatic neuropathy.

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

The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study.

Abstract: Foot ulceration results in substantial morbidity amongst diabetic patients. We have studied prospectively the relationship between high foot pressures and foot ulceration using an optical pedobarograph. A series of 86 diabetic patients, mean age 53.3 (range 17–77) years, mean duration of diabetes 17.1 (range 1–36) years, were followed-up for a mean period of 30 (range 15–34) months. Clinical neuropathy was present in 58 (67%) patients at baseline examination. Mean peak foot pressure was higher at the follow-up compared to baseline (13.5 kg·cm−2±7.1 SD vs 11.2±5.4, p 12.3) being present in 55 patients at follow-up and 43 at the baseline visit (p=NS). Plantar foot ulcers developed in 21 feet of 15 patients (17%), all of whom had abnormally high pressures at baseline; neuropathy was present in 14 patients at baseline. Non-plantar ulcers occurred in 8 (9%) patients. Thus, plantar ulceration occurred in 35% of diabetic patients with high foot pressures but in none of those with normal pressures. We have shown for the first time in a prospective study that high plantar foot pressures in diabetic patients are strongly predictive of subsequent plantar ulceration, especially in the presence of neuropathy.

Assessment and management of foot disease in patients with diabetes

Abstract: Limb- or life-threatening complications in patients with diabetes can be prevented with an integrated, multidisciplinary approach. Most patients seen in clinical practice are in the early stages of the disease process. Glycemic control retards the progression of neuropathy, which is the most important risk factor for ulceration. Early detection of the loss of protective sensation and implementation of strategies to prevent ulceration will reduce the rates of limb-threatening complications. Clinicians should routinely examine the feet of diabetic patients. Education in foot care, proper footwear, and close follow-up are required to prevent or promptly detect neuropathic injury. If ulceration occurs, removal of pressure from the site of the ulcer and careful management of the wound will allow healing in most cases. The failure to heal despite these measures should prompt a search for associated arterial insufficiency. If infection is present, appropriate antimicrobial therapy combined with immediate surgical intervention, including revascularization when necessary, will increase the chances of saving the limb. With this comprehensive approach, it is possible to achieve the goal of a 40 percent decrease in amputation rates among diabetic patients by the year 2000.

Preventive Foot Care in People With Diabetes

Abstract: A number of effective, low-cost strategies are available to identify and treat the person at risk for diabetic foot ulcers and lower-extremity amputation. These strategies must be more widely adopted by all diabetic care providers to maintain the integrity and function of the lower limb, and thus improve the quality of life for people with diabetes.

The Diabetic Foot

Abstract: Diabetic foot problems remain all too common and are likely to increase in prevalence over the next few decades. It has been estimated that an individual with diabetes now has a 25% risk of developing a foot ulcer at some time during their lifespan. A number of controversies are discussed in this chapter starting with the key question of the best screening methods for the “at risk foot” for ulceration. The key message is that simple clinical techniques of examination of the feet and lower limbs are probably the most accurate way to assess for further risk of foot lesions. A foot ulcer will normally heal if the circulation is intact, infection is treated and pressure is taken off the lesion. Physicians find it hard to believe that patients with large plantar foot lesions would actually walk on this lesion, but they forget that sensory loss in the diabetic foot permits walking without discomfort. Thus offloading is frequently neglected and if applied properly, will lead to satisfactory healing in most plantar neuropathic ulcers. In the area of infection, the key question is whether an ulcer is infected or colonized and this is discussed in some detail as is the differential diagnosis between osteomyelitis and Charcot neuroarthropathy. The use and abuse of expensive topical treatments is then discussed and finally the role of footwear in the prevention of recurrent ulcers is described.