The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults with and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 microm, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy.

These data suggest that neurogenic nociceptor-mediated vasodilation is impaired in subjects with type 2 diabetes when endothelial and sympathetic function are relatively intact. Heat-induced vasodilation may be a specific test of small heat-sensitive C-fiber peripheral neurons and may be an integral part of the metabolic syndrome.

Aim: To compare the efficacy, safety and tolerability of adding rosiglitazone (RSG) vs. sulphonylurea (SU) dose escalation in older type 2 diabetes mellitus (T2DM) patients inadequately controlled on SU therapy. Methods: A total of 227 T2DM patients from 48 centres in the USA and Canada, aged !60 years, were randomized to receive RSG (4 mg) or placebo once daily in combination with glipizide 10 mg twice daily for 2 years in a doubleblind, parallel-group study. Previous SU monotherapy was ¼ to ½ maximum recommended dose for !2 months prior to screening with fasting plasma glucose (FPG) !7.0 and 13.9 mmol/l. Treatment options were individualized, and escalation of study medication was specifically defined. Results: Disease progression (time to reach confirmed FPG !10 mmol/l while on maximum doses of both glipizide and study medication or placebo) was reported in 28.7% of patients uptitrating SU plus placebo compared with only 2.0% taking RSG and SU combination (p < 0.0001). RSG þ SU significantly decreased HbA 1c , FPG, insulin resistance, plasma free fatty acids and medical care utilization and improved treatment satisfaction compared with uptitrated SU. Conclusions: Addition of RSG to SU in older T2DM patients significantly improved glycaemic control and reduced disease progression compared with uptitrated SU alone but without increasing hypoglycaemia. These benefits were associated with increased patient treatment satisfaction and reduced medical care utilization with regards to emergency room visits and length of hospitalization. Early addition of RSG is an effective treatment option for older T2DM patients inadequately controlled on submaximal SU monotherapy.

Neuropathy is the most common "life-spoiling" complication of diabetes mellitus and the major cause of morbidity. While the primary long-term objective will be to find a cure for diabetes, in the immediate future the major goal is to prevent and reverse the chronic complications of the disease. The heterogeneity of diabetic neuropathy has for years escaped the attention of clinicians and investigators. Attempts have been made to distinguish the different clinical syndromes and the nerve fibre types affected without an in depth understanding of differences in pathogenesis.An improved classification of diabetic neuropathies is required which recognizes more fully the heterogeneity of this disease, as well as the possibility that the pathogenesis and profile of neuropathies encountered in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients may be distinct. Recent human and experimental studies provide an increased understanding of the diversity of underlying pathophysiological and biochemical abnormalities in the IDDM and NIDDM disorders, and how these may relate to the diverse phenotypic expression of diabetic neuropathies. The recommended classification forges closer links between pathology, neurobiology, and immunology and aims to provide a firmer foundation for investigations into the aetiology and rational treatment of diabetic neuropathies. Animal and human data now show or strongly indicate, using end-points specific for participating neuropathies, that diabetic neuropathies may be amenable to immunotherapy and neurotrophic factor treatment. This group was convened to examine the current state of knowledge of the pathogenesis and limited success of past treatments. After considerations of the heterogeneity of neuropathies and their aetiopathogenesis, they have arrived at the following recommendations. Classification of diabetic neuropathiesA wide variety of disturbances of peripheral nerve function are encountered in patients with diabetes. These can be broadly classified into: 1) rapidly reversible neuropathy; 2) persistent neuropathies; 3) focal/multifocal neuropathies. Rapidly reversible: Hyperglycaemic neuropathyPersistent symmetric polyneuropathies: a) distal somatic sensory/motor polyneuropathies (DSPN) involving predominantly large fibres; b) autonomic neuropathies (APN); c) small fibre neuropathies.Focal/multifocal neuropathies: a) cranial neuropathies; b) thoracoabdominal radiculopathies; c) focal limb neuropathies; d) proximal neuropathies; e) compression and entrapment neuropathies.

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