Diabetic peripheral neuropathy in type 2 diabetes mellitus in Korea

Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.     

Diabetic autonomic neuropathy

Summary This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasingly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-respiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years.     

Diabetic autonomic neuropathy

Summary One of the earliest manifestations of diabetic neuropathy is denervation of the cardiovascular system; loss of heart rate variability may have a prevalence as high as 21.5% in diabetic patients, and declines at 1 beat/min/year, which is 3 times faster than in normal subjects. The cause of this neuropathy is unknown: attempts at decreasing the excess quantities of sorbitol, glucose and fructose in nerve tissue have lead to little functional improvement in man. Nerve ischaemia and immunological damage have stimulated increased interest lately, the latter particularly because of the structural homology of nerve growth factor and insulin. Symptoms from autonomic neuropathy are rare. When present they may well be intermittent, but never remit; they rarely progress or become disabling. One uncommon consequence of loss of sympathetic vascular tone is postural hypotension. This may result from failure of splanchnic vasoconstriction on standing. Food and insulin can greatly exacerbate the postural blood pressure fall. Reduced vascular tone in the neuropathic foot leads to increased arterio-venous shunt flow. The local reflex control of this shunt flow is also abnormal: paradoxical vasoconstriction occurs in response to local skin heating and postural reflexes are reduced. This high shunt flow together with its abnormal vascular control may be important in the pathogenesis of neuroarthropathy and foot ulceration. The prognosis of patients with autonomic neuropathy is better than previously reported. Abnormal heart rate variability alone is of no prognostic value. The presence of symptoms, in particular postural hypotension, significantly reduces survival. The majority of deaths however, result from concurrent renal disease and macrovessel atheroma.     

Diabetic autonomic neuropathy

Summary The use of heart rate monitoring in the diagnosis of diabetic autonomic neuropathy, and its value in observing the natural history of this disorder, has been assessed. Two tests were used: measurement of heart rate variation during deep breathing and of heart rate change on standing up. Two hundred and eighty seven diabetics aged between 20 and 49 years were studied, and 21 of them were observed repeatedly over 3 to 5 years. Heart rate variation (HRV) on deep breathing proved to be the more sensitive diagnostic index of autonomic neuropathy and was abnormal or borderline in 62 of 64 patients with established autonomic symptoms. Autonomic abnormalities were also detected in some diabetics without autonomic symptoms especially in those with peripheral neuropathy, 30% of whom had abnormal HRV on deep breathing. Abnormal tests appeared to represent permanent autonomic damage and may be present for years without the development of autonomic symptoms, occasionally (7%) preceding any other manifestation of diabetic neuropathy. Serial observations of HRV on deep breathing over 3 to 5 years showed little change, although overall there was a small deterioration of autonomic function, with a decrease of HRV score of 1.0 per year. The tests used are simple, and provide quantitative bedside measurements of autonomic function. When heart rate variation is normal, autonomic neuropathy is virtually excluded.     

Diabetic autonomic neuropathy

The incidence of autonomic dysfunction as a complication of diabetes mellitus is reported to be as high as 20% to 40%. Symptoms of diabetic autonomic neuropathy (DAN) are often vague, and signs difficult to detect on routine physical examination. The early diagnosis of DAN is possible by utilizing several simple noninvasive tests, which may also be helpful in localizing the lesion(s) to specific autonomic pathways. DAN may affect multiple organ systems, to include cardiovascular, gastrointestinal, genitourinary and/or neuroendocrine, and may, in fact, be life-threatening. The same metabolic disturbances of somatic peripheral nerve may also be responsible for DAN. Like somatosensory neuropathy, definitive therapy for DAN is not yet satisfactory, although multiple chemotherapeutic agents have been tried and warrant further investigation.     

Diabetic peripheral neuropathy in ankles and feet: muscle strength and plantar pressure

This study aims to evaluate and correlate the vascular, sensory and motor components related to the plantar surface in individuals with diabetic peripheral neuropathy. 68 patients were categorized into two groups: 28 in the neuropathic group and 40 in the control group. In each patient, we assessed: circulation and peripheral perfusion of the lower limbs; somatosensory sensitivity; ankle muscle strength; and pressure on the plantar surface in static, dynamic and gait states. We used the Mann–Whitney test and analysis of variance (ANOVA and MANOVA) for comparison between groups, and performed Pearson and Spearman linear correlations amongst the variables (P?<?0.05). The somatosensory sensitivity, peripheral circulation and ankle muscle strength were reduced in the neuropathic group. In full peak plantar pressures, no differences were seen between groups, but differences did appear when the foot surface was divided into regions (forefoot, midfoot and hindfoot). In the static condition, the plantar surface area was greater in the neuropathic group. In the dynamic state, peak pressures in the neuropathic group, were higher in the forefoot and lower in the hindfoot, as well as lower in the hindfoot during gait. There were positive or negative correlations between the sensitivity deficit, dorsal ankle flexor strength, plantar surface area, and peak pressure by plantar region. The sensitivity deficit contributed to the increased plantar surface area.     

Diabetic neuropathy and microcirculation

The microcirculation in diabetic and neuropathic feet is subject to the same changes found in other end organs of diabetic patients, such as the retina or the kidney. Complications such as foot ulceration lead to further morbidity and hospitalizations. Research into the causes of microcirculatory dysfunction has revealed an interplay of numerous factors. The most prominent findings are impaired endothelium-dependent and -independent vasodilation and reduced or absent nerve-axon reflex-related vasodilation. This renders the diabetic foot unable to mount a vasodilatory response under conditions of stress, such as injury, and makes it functionally ischemic even in the presence of satisfactory blood flow under normal conditions.     

Diabetic peripheral neuropathy in people with type 2 diabetes: too little too late

Diabetic peripheral neuropathy in people with type 2 diabetes is poorly managed because of its insidious onset, delayed diagnosis and more complex aetiology resulting from the contribution of not only hyperglycaemia, but also ageing, hyperlipidaemia, hypertension and obesity. Because there is no US Food and Drug Adminstration-approved disease-modifying therapy for diabetic peripheral neuropathy, the key to ameliorating it in type 2 diabetes has to be through earlier diagnosis and timely multi-factorial risk factor reduction. The management of painful diabetic peripheral neuropathy also requires a detailed appraisal of the choice of therapy, taking into account efficacy, patient wishes, comorbidities, side effect profile and potential for abuse.