Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study

Summary The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study – namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA_1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy. [Diabetologia (1996) 39: 1377–1384] Received: 14 December 1995 and in revised form: 27 June 1996     

Factors Related to the Electric Taste Threshold in Type 1 Diabetic Patients

To specify the factors related to taste function in Type 1 diabetes mellitus, 50 diabetic out-patients and 50 control subjects paired for age and sex were screened for taste disorders. None of them consumed significant amounts of alcohol, smoked, or had disease or took drugs capable of altering taste. Taste was studied with electrogustometry, retinopathy was detected by fluorescein angiography, nephropathy by measurement of albuminuria and microalbuminuria, peripheral neuropathy by electroneurography and electromyography, and autonomic neuropathy by cardiovascular function tests. The electrogustometric threshold was, on average, significantly higher in the diabetic group (133 ± 30 μA) than in the control group (29 ± 9 μA; p < 0.001). Electric hypogeusia (electrogustometric threshold > 100 μA) was found among 54% of the diabetic patients vs 2% of the control subjects (p < 0.001). In the diabetic group, the electrogustometric threshold was associated with complications of diabetes, especially with peripheral neuropathy (210 ± 24 vs 90 ± 22 μA; p < 0.001) and microalbuminuria (185 ± 25 vs 86 ± 21 μA; p < 0.01). It was correlated with age (r = 0.37; p < 0.01) and duration of diabetes (r = 0.52; p < 0.001) but not with HbA_1c (r = ?0.04). Using multivariate analysis, duration of diabetes and peripheral neuropathy had the strongest association with taste impairment. These results support previous findings, suggesting that taste impairment is a degenerative complication of diabetes mellitus.     

Autonomic Neuropathy in Type I Diabetes: Influence of Duration and Other Diabetic Complications

ABSTRACT To evaluate the influence of duration on the development of autonomic neuropathy (AN) a group of type I diabetic patients (n=58) who had been diagnosed between the ages of 15 and 25 years was investigated. The duration of diabetes varied from 2 months to 30 years (mean 13 years). AN tests included a deep breathing test (E/I ratio) and an orthostatic test on tilt table (acceleration and brake indices) and the results were corrected for age. A clear correlation between AN test and duration of diabetes was shown only for the En ratio (r= -0.44, p<0.001). On the other hand, deteriorations in the brake index were unrelated to the duration of diabetes and occurred early; 35% of the patients with a duration of 10 years or less showed an abnormal brake index. Autonomic test deviations were related to other diabetic complications. The En ratio and the acceleration index were especially low in patients with retinopathy as well as in patients with symptoms of AN if combined with peripheral neuropathy (PN). The brake index was low in patients with symptoms of AN independent of PN.     

Autonomic Dysfunction and Silent Myocardial Ischaemia on Exercise Testing in Diabetes Mellitus

The incidence and mechanism of painless myocardial ischaemia on exercise testing in diabetic patients is not clear. Therefore, two studies were performed. Retrospectively, all exercise tests carried out in our hospital during the past 5 years were reviewed for silent ischaemia. Prospectively, diabetic patients with known or suspected coronary artery disease underwent autonomic function testing and a second exercise test. Of 1653 exercise tests reviewed, 247 were positive (ST depression > 0.1 mV). Of the 29 diabetic patients with positive tests 20 (69%) had painless ST depression, compared with 77 (35%) of the 218 non-diabetic patients (p < 0.001). The diabetic patients with painful and painless ST depression were comparable for age, sex, therapy, but the 20 with no pain on exercise testing had a longer duration of diabetes and a higher incidence of microvascular complications than the 9 with pain (70 vs 22%, p < 0.05). In the prospective study, 12 of 30 diabetic patients with positive exercise tests had pain in association with ST depression and 18 had no pain. Six patients had mild and 12 severe autonomic neuropathy on formal testing. Twelve had no autonomic dysfunction. Eleven (92%) of 12 patients with severe neuropathy had painless ST depression, compared with 7 (39%) of 18 without severe neuropathy (p < 0.01). Thus, silent myocardial ischaemia on exercise testing is common among patients with diabetes mellitus and is associated with severe autonomic dysfunction.     

Autonomic and Peripheral Nerve Function in Early Diabetic Neuropathy

ABSTRACT. Sundkvist G, Lilja B, Rosén I, Agardh C-D (Departments of Internal Medicine and Clinical Physiology, Malmö General Hospital, and Departments of Clinical Neurophysiology and Internal Medicine, University Hospital, University of Lund, Lund, Sweden). Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function. Acta Med Scand 1987; 221:445–53. Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25–44 years, mean 34; duration of diabetes 10–20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58±0.79 μV vs. 7.34±1.12 μV; p<0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p<0.05) during ARI in AN patients.     

Prevalence of diabetic autonomic neuropathy measured by simple bedside tests

Summary To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beatto-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate response to Valsalva's manoeuvre were applied to 75 male insulindependent diabetics, mean age 40 years, (range 30–49 years). The subjects were subdivided into three groups according to duration of diabetes, which was between 0 and 40 years. Twenty-eight healthy age-matched male controls were also studied. The prevalence of diabetic autonomic neuropathy in the whole diabetic population indicated by abnormal response in beat-to-beat variation during forced respiration was 27%. Diabetic autonomic neuropathy increased in frequency with duration of disease. Patients with nephropathy or proliferative retinopathy had a significantly higher prevalence of diabetic autonomic neuropathy as indicated by abnormal beat-to-beat variation during forced respirations (p<0.01) than patients without these complications.     

Autonomic dysfunction in psoriatic arthritis

Autonomic nervous system (ANS) involvement has been studied in systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, and ankylosing spondylitis but still has not been studied in psoriatic arthritis (PsA). The aim of this study was to investigate the prevalence and the nature of autonomic neuropathy in patients with PsA. Sixteen patients of PsA and 15 age and sex matched control subjects were studied prospectively using a battery of noninvasive tests. Cardiovascular autonomic neuropathy (CAN) was diagnosed by applying four cardiovascular reflex tests, and peripheral sympathetic autonomic function was assessed by Sudoscan. Patients with PsA had significantly higher heart rate response to standing (p?=?0.01), blood pressure response to standing (p?=?0.02), and Sudoscan (p?=?0.01) when compared with healthy controls. Fifty percent (n?=?8) of the patients with PsA had at least two or more abnormal CAN parasympathetic dysfunction; of these, 18.75 % (n?=?3) of the patients had abnormal parasympathetic and sympathetic dysfunction, 68.7 % (n?=?11) and 25 % (n?=?4) of the patients had at least one abnormal parasympathetic and sympathetic parameters, respectively, and 37.5 % (n?=?6) of the patients had moderate sudomotor dysfunction. About 18.7 % (n?=?3) of our parasympathetic dysfunction patients had autonomic symptoms. None of healthy volunteers had abnormal ANS dysfunction. Heart rate response significantly correlated with erythrocyte sedimentation rate (p?<?0.05) and C-reactive protein (p?<?0.05) levels. In conclusion, cardiovascular autonomic and peripheral sympathetic neuropathy occurs in PsA. Parasympathetic function is more commonly found to be abnormal than sympathetic function. There is no correlation of peripheral sympathetic dysfunction with cardiovascular autonomic neuropathy.     

Medial arterial calcification and diabetic neuropathy

Summary The aim of this study was to detect linear arterial calcification (M?nckeberg’s sclerosis) localized in feet, ankles, legs, knees and hands in an attempt to correlate the extent of calcification with the presence and severity of autonomic neuropathy as well as with microangiopathy (proliferative retinopathy, proteinuria >200 mg/die) and peripheral neuropathy. Typical linear calcification were observed in 37 out of 41 (90.2%) patients with autonomic neuropathy and in none of those without autonomic neuropathy (p<0.001). These 37 patients were divided into two subgroups by cluster analysis: Subgroup A, including 18 subjects with calcification length ranging from 8 to 26 cm and moderate autonomic neuropathy, and Subgroup B, including 19 subjects with calcification length between 58 and 126 cm and severe autonomic neuropathy (p<0.0001 by Spearman’s test). No difference in the length of arterial calcification was detected between patients with proteinuria >200 mg/24h and/or proliferative retinopathy and patients without these complications. A possible relationship between arterial calcification and peripheral neuropathy is difficult to evaluate; in fact, the majority of subjects having autonomic neuropathy had peripheral neuropathy, too. Vice versa, around 10% of patients without peripheral neuropathy but with autonomic neuropathy did not have M?nckeberg’s sclerosis. Autonomic neuropathy is the principal factor responsible for calcification of the arterial media, and in addition the severity of the neuropathy, rather than the patient’s age or the known disease duration seems to determine the extent of calcification.     

Prospective Study of Autonomic Nerve Function in Type 1 and Type 2 Diabetic Patients: 24 Hour Heart Rate Variation and Plasma Motilin Levels Disturbed in Parasympathetic Neuropathy

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/I ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/I ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean {interquartile range}]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol I^?1 vs 50 [15] pmol I^?1; p< 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (r_s = 0.65; p<0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.     

Is autonomic neuropathy a risk factor for severe hypoglycaemia? The EURODIAB IDDM Complications Study

Summary The hypothesis that diabetic patients with autonomic neuropathy are at increased risk of severe hypoglycaemia was examined in an epidemiological study of over 3000 IDDM patients in Europe (EURODIAB IDDM Complications Study). Autonomic function was assessed by two standard cardiovascular tests: change in heart rate and systolic blood pressure on standing. Severe hypoglycaemia was defined as an attack serious enough to require the help of another person. Compared to patients (68 %) reporting no attacks in the last year, those reporting one or more attacks were older (34.0 ± 10.7 vs 32.1 ± 9.9 years, mean ± SD, p < 0.0001), had had diabetes for a longer period (16.6 ± 9.5 vs 13.8 ± 9.1 years, p < 0.0001), had better glycaemic control (HbA_1c 6.4 ± 1.8 vs 6.9 ± 1.9 %, p < 0.0001) and were more likely (p = 0.002) to have abnormal responses to both autonomic tests (13.0 vs 7.7 %). A single abnormal autonomic response was not associated with an increased risk of severe hypoglycaemia. The odds ratio for severe hypoglycaemia in people with abnormal responses to both autonomic tests, compared to those with normal responses, was 1.7 (95 % confidence interval 1.3, 2.2) after controlling for age, duration of diabetes, glycaemic control and study centre. In conclusion, a combined autonomic deficit in heart rate and blood pressure responses to standing is associated with only a modest increase in the risk of severe spontaneous hypoglycaemia. Although the increase in risk is not large, severe hypoglycaemia was a frequently reported event in this study. IDDM patients with deficient autonomic responses who strive for tight glycaemic control may therefore be at particular risk of severe hypoglycaemia. [Diabetologia (1996) 39: 1372–1376] Received: 28 December 1995 and in final revised form: 11 June 1996     

Erythropoietin response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure

AimWe aim to investigate erythropoietin (EPO) response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure.MethodsA cross-sectional study was conducted on 211 type 2 diabetes mellitus patients without advanced renal failure [estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m²]. The response of EPO to anemia of type 2 diabetic patients without advanced renal failure was compared with those of nondiabetic control subjects. Autonomic nerve function was assessed using three cardiovascular tests (deep breathing, the Valsalva maneuver, and lying-to-standing). The results of each test were scored as 0 if normal, 1 if borderline, and 2 if abnormal. Autonomic neuropathy was diagnosed when a total score of the tests was 2 or more.ResultsFifty-eight patients were anemic; compared with nonanemic patients, they had a longer duration of diabetes (16.69±10.11 vs. 10.67±8.41 years, P<.001), lower eGFR (66.43±16.30 vs. 81.74±19.49 ml/min/1.73 m², P<.001), and higher cardiovascular autonomic neuropathy score (3.17±1.95 vs. 1.79±1.72, P<.001). Serum EPO level was weakly correlated with hemoglobin (Hb) level (r=?.085, P<.001). However, the slopes of regression lines between EPO and Hb levels differed significantly between type 2 diabetic patients and nondiabetic control subjects (?0.0085 vs. ?0.255, P=.008). Multiple linear regression analysis revealed that cardiovascular autonomic neuropathy score was independently related to Hb (P<.001) or EPO level (P=.052).ConclusionsAutonomic neuropathy is associated with a blunted EPO response to anemia in type 2 diabetic patients without advanced renal failure.     

A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population

Summary A cross-sectional multicentre study of randomly selected diabetic patients was performed using a standardised questionnaire and examination, to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK. Vibration perception threshold was performed in two centres to compare with the clinical scoring systems. A total of 6487 diabetic patients were studied, 53.9% male, median age 59 years (range 18– 90 years), 37.4% Type 1 (insulin-dependent) diabetes mellitus, with a median duration of diabetes 8 years (0–62 years). The overall prevalence of neuropathy was 28.5% (27.4– 29.6 %) (95 % confidence interval) in this population. The prevalence in Type 1 diabetic patients was 22.7% (21.0– 24.4 %) and in Type 2 (non-insulin-dependent) diabetic patients it was 32.1 % (30.6–33.6 %). The prevalence of diabetic peripheral neuropathy increased with age, from 5% (3.1– 6.9 %) in the 20–29 year age group to 44.2 % (41.1–47.3 %) in the 70–79 year age group. Neuropathy was associated with duration of diabetes, and was present in 20.8 % (19.1–22.5 %) of patients with diabetes duration less than 5 years and in 36.8 % (34.9–38.7 %) of those with diabetes duration greater than 10 years. Mean vibration perception threshold measured at the great toe was 21.1±13.5 SD volts and correlated with the neuropathy disability score, r=0.8 p<0.001. In conclusion, diabetic peripheral neuropathy is a common complication associated with diabetes. It increases with both age and duration of diabetes, until it is present in more than 50% of Type 2 diabetic patients aged over 60 years. An increased awareness of the high prevalence of peripheral neuropathy, especially in older patients, should result in improved screening programmes in order to reduce the high incidence of neuropathic diabetic foot ulceration.     

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange

AimsWe aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry.MethodsDAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010–2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed.ResultsOf the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004).ConclusionsDAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.     

Evidence for Diabetic Encephalopathy

Auditory brain stem responses were recorded in 20 normoacoustic long-duration Type 1 diabetic patients (duration of diabetes 26 (range 13–46) years, age 44 (25–66) years) with peripheral neuropathy and retinopathy and in 19 sex-matched normoacoustic short-duration Type 1 diabetic patients (duration of diabetes 2 (0–6) years, age 23 (18–50) years) without clinical signs of neuropathy or microangiopathy. Abnormal brain stem auditory evoked responses were demonstrated in 40% of the long-duration and in 5.3% of the short-duration diabetic patients (p < 0.01). Interpeak latencies J_v—J_I and J_III-J_I were significantly prolonged in both patient groups compared with the non-diabetic control group (p < 0.01). Magnetic resonance imaging was performed in 16 of the long-duration patients and in 40 age-matched healthy volunteers on a whole body MR-scanner. Subcortical and/or brain stem lesions with abnormally high signals were seen in 69% of the long-duration Type 1 patients and in 12% of the healthy volunteers (p < 0.02). Neuropsychological examination including 17 tests for intelligence and cognition were performed in the 20 long-duration Type 1 diabetic patients. The results indicated a performance close to that seen in a control group of healthy age-matched control subjects. Our study demonstrates that a considerable proportion of long-duration Type 1 diabetic patients suffering from retinopathy and peripheral neuropathy additionally have signs but no symptoms of central nervous system affection, diabetic encephalopathy.     

Signal-averaged Electrocardiogram in Patients with Insulin-dependent (Type 1) Diabetes Mellitus With and Without Diabetic Neuropathy

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 ± 23 ms^.5 vs 384 ± 23 ms^.5, p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval. © 1997 by John Wiley & Sons, Ltd.     

The prevalence of diabetic impotence

Summary In a survey of 541 diabetic males, aged 20–59 years, 190 (35%) had erectile impotence. Using linear logistic regression models for analysis the five most significant associations with impotence were age (p<0.001), treatment with either insulin or oral hypoglycaemic agents (p<0.001), retinopathy (p<0.001), symptomatic peripheral neuropathy (p<0.001) and symptomatic autonomic neuropathy (p<0.005). The greatest correlations were found in patients with severe microangiopathy, as demonstrated by proliferative retinopathy and symptomatic autonomic neuropathy. In addition the duration of diabetes and the presence of ischaemic heart disease, nephropathy and poor diabetic control may also be associated with diabetic impotence. It is concluded that diabetic impotence is still a common problem and may have a multifactorial aetiology.     

Urinary Infection and Albumin Excretion in Insulin-dependent Diabetes Mellitus: Implications for the Measurement of Microalbuminuria

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3 %. Over the period of study, 20 of the patients (12 %) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen >10⁷ l⁻¹. Infection was more common in women than men (20 % vs 5 %, p<0.01) and was significantly associated with the presence of peripheral neuropathy (p<0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5 %) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.     

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy

Summary Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p<0.001), fibronectin (p<0.001) and fibrinogen (p<0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p<0.05 at shear-rate of 450 and 225 s⁻¹; p<0.01 at 90 s⁻¹; p<0.001 at 4.5 and 2.25 s⁻¹), plasma viscosity (p<0.001) and lower erythrocyte filtrability (p<0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p<0.01) and nephropathy (p<0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus. This study was presented in part at the 23rd Annual Meeting of the European Association for the Study of Diabetes, Leipzig (GDR), 15–19 September 1987.     

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group

Summary The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16 % in the whole population, 11 % in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA_{1 c} and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation. [Diabetologia (1999) 42: 68–75] Received: 17 April 1998 and in final revised form: 2 September 1998     

Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean type 2 diabetic patients

In addition to chronic hyperglycemia, insulin resistance itself has been proposed to cause a diabetic neuropathy. We evaluated the role of insulin resistance in the pathogenesis of peripheral and autonomic neuropathy in patients with type 2 diabetes. Eighty-six patients with type 2 diabetes were evaluated for the anthropometric and biochemical profiles, and Kitt value was calculated from insulin tolerance test to assess the insulin resistance. Various autonomic function tests, nerve conduction velocity, and quantitative sensory tests were performed to assess autonomic and peripheral neuropathy. In univariate analysis, both autonomic and peripheral neuropathy were significantly associated with glycemic exposure index (GE index), HDL-cholesterol, duration of DM, and Kitt value. In stepwise linear regression analysis, GE index was an independent predictor of autonomic and peripheral neuropathy (β = 0.643, P < 0.001; β = 0.207, P = 0.013, respectively), and Kitt value was also an independent factor for the autonomic and peripheral neuropathy (β = − 0.306, P < 0.001; β = − 0.329, P < 0.001, respectively). Low HDL-cholesterol increased the odds ratio for peripheral neuropathy. Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean Type 2 diabetic patients along with hyperglycemia and HDL-cholesterol.