Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 30% of patients with diabetes mellitus will have disease-related dermatological problems. Dry skin can be associated with autonomic neuropathy and may be fragile, promoting bacterial invasion. Any potentially infected 'diabetic foot' must be taken seriously, and non-painful deep sepsis suspected if there is evidence of sensory loss. Consideration should be given to eliminating nasal carriage of staphylococci if recurrent superficial sepsis occurs in the presence of poor diabetic control. Fungal infections, both of skin and nails, are common but usually not serious in the absence of immunosuppression. Treatment with topical antifungals may need to be combined with systemic therapy for successful eradication. Systemic antifungal therapy should be carefully considered as treatment needs to be prolonged and is potentially toxic, particularly in individuals with diabetes mellitus who often have co-morbidities. Varicose eczema should be treated by physical therapies intended to improve venous return and prevent peripheral edema and tissue injury. Allergic dermatitis is commonly associated with topical treatments and other sensitizers. Many reactions are not apparent from history, and patch testing for sensitivity is recommended. There are several diabetes mellitus-specific conditions that dermatologists must be aware of, including, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic dermopathy (spotted leg syndrome or shin spots), diabetic bullae (bullosis diabeticorum), and limited joint mobility and waxy skin syndrome. Ulceration, due to varying combinations of peripheral vascular disease and sensory neuropathy, is the province of the specialist team dealing with the diabetic foot and should ideally be referred to an appropriate multidisciplinary team.
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PMID:Dermatological care of the diabetic foot. 1218 Aug 94

This study examined NO- and non-NO-, non-prostanoid-dependent pathways of agonist-induced vasodilatation in streptozotocin (STZ)-induced diabetic rats and their age-matched controls at 1-2, 8-10 and 18-20 weeks after induction of diabetes. Using laser Doppler flowmetry, vasodilatory responses to acetylcholine (ACh; 0.1 mM) and morpholino-sydnonimine (SIN-1) were determined in the presence of Ringer solution, during inhibition of NO synthase (NOS) and cyclo-oxygenase (COX) with N(omega)-nitro-L-arginine (L-NNA; 1 mM) + indomethacin (10(-5) M), and during inhibition of K(+) channels, NOS and COX with tetraethylammonium (TEA; 10 mM) + L-NNA + indomethacin. Basal NOS activity and nerve conduction velocity were also determined. In age-matched controls, SIN-1-induced vasodilatation in the presence of TEA + L-NNA + indomethacin, basal NOS activity and the initial vasodilatory response to ACh during NOS and COX inhibition all decreased with maturation. In STZ-induced diabetics, SIN-1-induced vasodilatation in the presence of TEA + L-NNA + indomethacin was impaired immediately after induction of diabetes, but not at 18-20 weeks. NOS activity in STZ-induced diabetics displayed a transient 2-fold increase at 8-10 weeks, decreasing to age-matched control levels at 18-20 weeks. At 18-20 weeks of STZ-induced diabetes, ACh-induced vasodilatation during NOS and COX inhibition was prolonged due to increased K(+) channel activity and experimental diabetic sensory neuropathy (EDN) had developed. Thus, in sciatic nerve microcirculation of STZ-induced diabetic rats: (1) diabetic impairment of vasodilatation in response to exogenous NO was transient; (2) non-NO-, non-prostanoid-dependent vasodilatation and K(+) channel activity were augmented in STZ-induced diabetes; and (3) alterations in NO bioactivity were not related to the development of EDN.
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PMID:NO- and non-NO-, non-prostanoid-dependent vasodilatation in rat sciatic nerve during maturation and developing experimental diabetic neuropathy. 1223 52

Background. Patients with diabetic sensory neuropathy have significant risk of chronic ulcers. Insufficient nerve-derived mediators such as substance P (SP) may contribute to the impaired response to injury. Mutant diabetic mice (db/db), which develop neuropathy and have delayed healing, may provide a model to study the role of nerves in cutaneous injury.Methods. Skin from human chronic nonhealing ulcers and age-matched control skin was immunohistochemically evaluated for nerves. Nerve counts were also compared in murine diabetic (C57BL/KsJ-m+/+ Lepr(db); db/db) and nondiabetic (db/-) skin. Excisional wounds on the backs of db/db and db/- mice were grouped as: (a) untreated db/- mice; (b) untreated db/db mice; (c) db/db mice with polyethylene glycol (PEG); (d) db/db mice with PEG and SP 10(-9) M; or (e) db/db mice with PEG and SP 10(-6) M.Results. We demonstrated fewer nerves in the epidermis and papillary dermis of skin from human subjects with diabetes. Likewise, db/db murine skin had significantly fewer epidermal nerves than nondiabetic littermates. We confirmed increased healing times in db/db mice (51.7 days) compared to db/- littermates (19.8 days; P </= 0.001). SP 10(-6) M (44 days; P = 0.02) and SP 10(-9) M (45 days; P = 0.03) shortened time to closure compared to PEG treatment alone (68 days). Since there was no difference in the percentage contraction in these treatment groups, SP may favorably promote wound epithelization.Conclusions. Our data support the use of db/db murine excisional wounds to evaluate the role of nerves in healing. We have demonstrated that exogenous SP improves wound healing kinetics in an animal model.
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PMID:Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. 1244 24

These studies were intended to explore the relationship between autonomic neuropathy and erectile dysfunction (ED). Sensory thresholds reflecting the integrity of both large diameter, myelinated neurons (ie pressure, touch, vibration) and small diameter axons (ie hot and cold thermal sensation) were determined on the penis and finger. Data were compared across subjects with and without ED, controlling for age, hypertension and diabetes. The correlation of specific thresholds scores and IIEF values were also examined. Seventy-three patients who visited the academic urology clinics at Montefiore hospital were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire: 20 subjects had no complaints of ED and scored within the 'normal' range on the IIEF. Patients were subsequently tested on their index finger and glans penis for vibration (Biothesiometer), pressure (Semmes-Weinstein monofilaments), spatial perception (Tactile Circumferential Discriminator), and warm and cold thermal thresholds (Physitemp NTE-2). Sensation of the glans penis, as defined by the examined sensory thresholds, was significantly diminished in patients with ED and these differences remained significant when controlling for age, diabetes and hypertension. In contrast, thresholds on the index finger were equivalent in the ED and non-ED groups. Threshold and IIEF scores were highly correlated, consistent with an association between diminished sensation and decreasing IIEF score (worse erectile functioning). These relations also remained significant when controlling for age, diabetes and hypertension. The findings demonstrate dysfunction of large and small diameter nerve fibers in patients with ED of all etiologies. Further, the neurophysiologic measures validate the use of the IIEF as an index of ED, as objective findings of sensory neuropathy were highly correlated with worse IIEF scores. The sensory threshold methods utilized represent novel, non-invasive and relatively simple procedures, which can be used in a longitudinal fashion to assess a patient's neurological response to therapies.
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PMID:The neuropathy of erectile dysfunction. 1249 74

We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy.
Diabetes 2003 Jan
PMID:Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. 1250 8

Peripheral sensory neuropathy (PSN) and foot ulcers are disabling and expensive complications of diabetes with few therapeutic options. Knowledge of risk factors for both complications, based on prospective observational studies, permits identification of individuals at high risk and provides options for intervention. Glycemia is the main modifiable risk factor for PSN, whereas PSN and trauma are the principal potentially modifiable risk factors for the development of foot ulceration.
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PMID:Risk factors for diabetic neuropathy and foot ulceration. 1264

Sensory neuropathy is common symptom of the diabetes mellitus and the prevalence of oral lesions is higher in diabetic patients. The distribution of substance P was studied immunohistochemically in streptozotocin induced diabetic rat's tongue. The morphological association of sensory nerves (substance P immunoreactive) with mast cells (nerve fibre-mast cell contact) was monitored. The substance P nerve fibre mast cell contacts were very scanty in control tongue. The number of substance P nerve terminals and mast cells was significantly increased (p < 0.05) in diabetes mellitus after 4 weeks of the treatment compared with the control tongue. The number of mast cell nerve contacts was even more significantly increased (p < 0.001) in diabetes. The distance between nerve fibres and mast cells was about 1 mm and very often less than 200 nm. In some instances, the mast cells were degranulated in the vicinity to nerve fibres. Increased number of mast cell nerve contacts in neurogenic inflammation might cause vasoconstriction and lesions of the oral mucosa, so some disorders such lichen planus, leukoplakia and cancer might frequently develop in diabetes mellitus.
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PMID:Immunohistochemical analysis of substance P containing nerve fibres and their contacts with mast cells in the diabetic rat's tongue. 1471 Oct 32

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). Clinically, 23 patients (60.5%) had signs of small-fibre impairment, and 19 patients (50.0%) had signs of large-fibre impairment. IENF densities were much lower in diabetic patients than in age- and gender-matched controls (1.794 +/- 2.120 versus 9.359 +/- 3.466 fibres/mm, P < 0.0001), and 81.6% (31/38) of diabetic patients had reduced IENF densities. IENF densities were negatively associated with the duration of diabetes (standardized coefficient: -0.422, P = 0.015) by analysis with a multivariate linear regression model. Abnormal results of functional examinations were present in 81.6% (warm threshold), 57.9% (cold threshold), 63.2% (vibratory threshold) and 49% (amplitude of sural sensory action potential) of diabetic patients. Among the three sensory thresholds, the warm threshold temperature had the highest correlation with IENF densities (standardized coefficient: -0.773, P < 0.0001). On nerve conduction studies in lower-limb nerves, there were abnormal responses in 54.1% of sural nerves, and 50.0% of peroneal nerves. Of neurophysiological parameters, the amplitude of the sural sensory action potential had the highest correlation with IENF density (standardized coefficient: 0.739, P < 0.0001). On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.
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PMID:Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments. 1556 91

The radial artery has gained widespread acceptance as a conduit for coronary artery bypass. Advantages include minimal donor site discomfort, ease of handling, excellent early patency rates, and the possibility of freedom from late conduit atherosclerosis. Although most series describe minimal morbidity, a significant incidence of radial sensory neuropathy and isolated instances of hand claudication and ischemia have been reported. We performed an outcome study utilizing the Short Form-36, the Upper Limb-Disabilities of Arm, Shoulder and Hand, and a modified self-administered hand diagram to compare 288 patients undergoing coronary artery bypass utilizing the radial artery with a control group of 174 patients undergoing coronary artery bypass without the radial artery. The data were analyzed by the t test for continuous variables and the chi-square test for categorical variables, and subsequently a multivariate regression model was constructed. No patients developed hand claudication or ischemia. Although there was an incidence of radial sensory neuropathy of 9.9% associated with radial artery harvest, it was not significantly higher than the incidence in the control group (5.2%, p =.16). Intrinsic patient factors such as obesity, age, diabetes, and peripheral vascular disease were the principal determinants of overall health and quality of life issues.
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PMID:Outcome assessment of hand function after radial artery harvesting for coronary artery bypass. 1524 87

We examined the effects of C-peptide replacement on unmyelinated fiber function in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins, and the expression of neurotrophic receptors and content of neuropeptides in dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from onset of diabetes had no effect on hyperglycemia, but it significantly prevented progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and loss. These findings were associated with preventive effects on impaired availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and significant prevention of perturbed expression of insulin, insulin growth factor-1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion cells. These beneficial effects translated into prevention of the decreased content of dorsal root ganglia nociceptive peptides such as substance P and calcitonin gene-related peptide. From these findings we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions.
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PMID:C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes. 1549 55


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