Utility of DN4 questionnaire in assessment of neuropathic pain and its clinical correlations in Turkish patients with diabetes mellitus.

AIM: We aimed to assess the utility of DN4 questionnaire (Douleur Neuropathique en 4 questions) to define the frequency and severity of neuropathic pain (NP) and also its clinical correlation to daily clinical practice. METHODS: We included 1357 patients with diabetes (56.5% women, 90.4% type 2 diabetes) who were followed up in our diabetes outpatient clinic. Presence of NP was evaluated by performing simultaneous DN4 questionnaires and physical examination. Those who had a DN4 score ≥4 were considered to have NP. RESULTS: The mean age was 58.2±12.1 years, mean duration was 12.5±7.5; (min-max: 1-45) years, mean HbA1c level was 7.8±1.6% (min-max: 5-16.2%), (61.7±6.0mmol/mol; min-max: 31.1-153.6mmol/mol). Three hundred thirteen patients (23%) were diagnosed with NP using the DN4 tool. Male gender (p=0.01), receiving antihypertensive treatment (p=0.01), presence of retinopathy (p<0.001), cardiovascular disease (CVD) (p=0.01) and previously diagnosed neuropathy (p<0.001) were significantly associated with higher NP scores. Those who had increased DN4 scores were more likely to be on oral hypoglycemic agents (OHA)+insulin combinations (p<0.001), had longer diabetes duration (p<0.001) and higher HbA1c levels (p=0.001). Logistic regression model revealed that diabetes duration (OR: 1.02, 95% CI: 1.00-1.04, p=0.007), elevated HbA1c levels (1.11, 1.02-1.21, 0.015), presence of retinopathy (1.41, 1.20-1.64, <0.001), management with at least one OHA (1.47; 1.12-1.92; 0.004) or any insulin regimen (1.62; 1.16-2.27; 0.005) (compared with diet only-regimens) were significantly associated with NP. CONCLUSION: Utilization of DN4 questionnaire in daily clinical practice is an effective tool in the identification of pain related with peripheral diabetic polyneuropathy.

The effect of nephropathy on plasma sphingosine 1-phosphate concentrations in patients with type 2 diabetes.

OBJECTIVES: Sphingosine 1-phosphate (S1P) is carried in plasma by the HDL particles and albumin. It mediates several protective functions of HDL. Because of its barrier-enhancing effect, it has attracted attention in diseases associated with endothelial dysfunction. We examined the impact of circulating levels of S1P in diabetic nephropathy together with apoprotein M, a S1P-binding protein in HDL. Plasma levels of dimethylarginines were evaluated in this context. DESIGN AND METHODS: Patients with type 2 diabetes mellitus were divided into three groups according to daily albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria (n=30 in each). In addition to routine analysis, S1P and apo M in plasma were measured using the enzyme-linked immunosorbent assays. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and l-arginine were determined by HPLC. Tukey's or Mann-Whitney U-test was used for the statistics. RESULTS: Plasma S1P levels showed a significant decline in parallel to kidney dysfunction. The highest significance was detected in the macroalbuminuric group. Although a significant increase in plasma SDMA in albuminuric groups was observed, apo M, l-arginine and ADMA levels were similar between the groups. CONCLUSION: Low plasma levels of S1P seemed to be associated with diabetic nephropathy. The main reason for the decreased S1P levels in our patients seems to be severe urinary albumin loss due to nephropathy. Low levels of S1P in patients with nephropathy may adversely affect the endothelial integrity and barrier function, thus causing a vicious circle.

Effect of acute maximal exercise on lymphocyte subgroups in type 1 diabetes.

The essential therapy of diabetes mellitus includes medical nutrition therapy (MNT), exercise and medical therapy. Exercise, besides its metabolic effects, has positive influence on the immune system, but some forms of exercise may cause trauma for muscle and skeletal systems, they may also support negative effects on the immune system. Nineteen type 1 diabetic patients (mean age 22.1 +/- 2.8 yrs), followed by Diabetes Outpatient Clinic and twenty age matched male control subjects were included into the study, to demonstrate the effects of maximal, acute exercise on the immune system. The exercise test was performed according to Bruce protocol on treadmill. In diabetic subjects, increased CD19 and CD23 expressions were observed before exercise. In both groups (diabetic/control) CD3, CD4 expressions and CD4/CD8 ratio were decreased following the exercise, however expression of natural killer (NK) cells increased. Compared to type 1 diabetic patients healthy subjects had longer acute exercise that caused the increased level of CD8 expression, however type 1 diabetic patients did not show any difference. These results indicate that submaximal aerobic exercise might be recommended for type 1 diabetics without any complications because of its positive reflection on metabolic control and no negative effects on the immune system.

Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.

BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition. METHODS: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00095654. FINDINGS: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01). INTERPRETATION: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.

Evaluation of insulin resistant diabetes mellitus in Alström syndrome: a long-term prospective follow-up of three siblings.

Alström syndrome is a rare cause of diabetes mellitus. We studied two generations of a Turkish family in whom four members were affected by Alström syndrome. The natural course of the syndrome in three sisters was followed for 13 yr. The three sisters had short stature and truncal obesity, and developed complete blindness due to retinitis pigmentosa at 10, 5 and 13 yr of age. Two had sensorineural hearing loss and mild mental retardation, while the other developed diabetic ketoacidosis (DKA) at 14 yr and was treated with insulin from onset of diabetes. In the second case, diagnosis of diabetes was made by an OGTT at age 20 yr, and controlled with diet alone for 11 yr, then with a sulphonylurea for 2.5 yr, then with insulin. The third case developed acute hyperglycaemia at 20 yr, and required insulin from onset. Moreover, transitional features of impaired carbohydrate and fat metabolism (severe hyperinsulinaemia and insulin resistance progressing to islet beta cell failure, and hypertriglyceridaemia with fatty liver) were demonstrated, in accord with the literature. Previously unreported findings characteristic of nephro-uropathy with early-onset hypertension were also detected, and included in all cases proteinuria, glomerulopathy, and abnormal locations of the kidneys, narrowed uretero-renal junctions and dilated ureters.

Alstrom syndrome: a case report.

Alstrom syndrome is a rare disorder characterized by early obesity, loss of central vision, diabetes mellitus, hearing loss and short stature. Previous studies, have reported no information regarding oral findings. This article describes oral findings in two cases of Alstrom syndrome. In both cases, gingivitis was present and also light yellow-brown discolored enamel bands were observed on the anterior teeth. This staining may have resulted from discoloration of the preexisting slight band-like enamel hypoplasia. The gingiva was examined histologically by light and transmission electron microscopy. Irregular thickness of the basal lamina and delamination of the myelin sheath were detected by transmission electron microscopy. There is no information about pathological odontogenesis in Alstrom syndrome in previous reports. Oral present findings may contribute further information about the clinical manifestations of Alstrom syndrome.

F wave parameters and F tacheodispersion in mild diabetic neuropathy.

F tacheodispersion and some F wave parameters have previously been suggested to be useful in the detection of peripheral nerve involvement in diabetic patients with normal nerve conduction studies. In this study, ulnar and tibial F wave parameters of diabetic cases with normal motor and sensory nerve conduction studies (Group 1) were calculated, F tacheodispersion histograms were constructed and compared with the same parameters obtained from the normal controls (Control group) and diabetic cases with abnormal motor and sensory nerve conduction examinations (Group 2). There was a tendency towards lower conduction velocities in ulnar and tibial tacheodispersion histograms of Group 1 and Group 2, as compared to Control group. Most of the F wave values were significantly abnormal in Group 2 in comparison to other two groups, whereas statistically significant differences between Group 1 cases and Control group were found in minimum ulnar F wave conduction velocity (FCVmin), mean ulnar FCV (FCVmean), tibial FCVmin and tibial FCVmean values. Unlike other methods, F waves give information about the entire length of the motor nerve fiber. In mild neuropathies, in which nerve fibers are damaged uniformly, testing the whole length of a nerve with this method may be beneficial in detection of a mild conduction abnormality.

Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes.

AIM: To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT). METHODS: Seventy-two patients (age 35-70 years, BMI < or = 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40-80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1c and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed. RESULTS: Both drugs were effective in reducing of HbA1c, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode. CONCLUSIONS: The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a first-line drug, particularly in the treatment of overweight type 2 diabetic patients.

Salivary peroxidase activity in whole saliva of patients with insulin-dependent (type-1) diabetes mellitus.

In this study, salivary peroxidase activity was measured in a group of 10 patients with insulin-dependent (type I) diabetes mellitus (IDDM) who had a tendency towards periodontitis. In healthy subjects (N : 10), mean salivary peroxidase activity was 0.0025 +/- 0.001 IU/ml, while in this group of type I diabetic patients it was 0.051 +/- 0.015 IU/ml, a significantly higher level (p < 0.001). Approximal plaque index (API), modified sulcus bleeding index (mod SBI) and pocket depths were assessed clinically. The values for mod SBI and API were 60% and 68% respectively for the diabetic patients while for the control group mod SBI was measured 0.0% and the value for API was 10.67% (p < 0.001). The administration of this simple and practical test may provide an early marker of a tendency towards periodontitis in IDDM patients.

Alteration of visual function in impaired glucose tolerance.

People with impaired glucose tolerance are considered to be prone to diabetes. To evaluate their visual function we investigated colour vision with the Farnsworth-Munsell 100 Hue test and contrast sensitivity with Arden's grating cards in people with imparied glucose tolerance (IGT), people with normal glucose tolerance (NGT) and others with type II diabetes (NIDDM). Eyes with low vision or any anterior or posterior segment abnormalities were excluded. Contrast sensitivity and color vision differed significantly between the groups (p < 0.01). It thus appears that patients with IGT but without clinical diabetes could be followed up to see whether these alterations have any predictive value for the development of diabetes and diabetic retinopathy.

Diabetic sclerodactyly.

Sclerodactyly is a chronic skin disorder seen together with long-term degenerative microvascular complications of diabetes mellitus. In this study, the relationship between sclerodactyly and various clinical and laboratory characteristics of diabetes mellitus have been investigated. One hundred and forty-two diabetic patients (63 type 1 and 79 type 2) and 72 healthy controls were evaluated clinically. Among the 142 diabetic patients, skin biopsies were taken from 21; 38 underwent soft tissue X-ray examination and 78 underwent periungual capillaroscopy. Among the healthy controls those with sclerodactyly were on the average 12 years older than those without (T: 3.38; P < 0.01). On the other hand, among the patients with either type 1 or type 2 diabetes mellitus the ages were similar between those with and without sclerodactyly. There were no statistically significant differences in the prevalence of diabetic complications. The presence of complications, increased proximal nail fold capillarity, HbA1c levels, radiological and histopathological findings were not different among those patients who had or did not have sclerodactyly.

Evaluation of penile arterial system with color Doppler ultrasonography in nondiabetic and diabetic males.

The parameters of the functional evaluation of the penile arterial system in sexually active males are based on a minimal number of volunteers and impotent patients of neurogenic origin who are expected to have a normal vascular system. In order to investigate these parameters in 23 sexually active diabetic and nondiabetic males, penile arterial systems were evaluated by color Doppler ultrasonography. Parameters obtained from the cavernous arteries were arterial diameter (pre- and postpapaverine), diameter increase rate and systolic peak blood flow velocity. Systolic peak blood flow velocities in papaverine-induced erection were 36.75 (+/- 9.99) and 37.50 (+/- 13.18) cm/s for right and left cavernosal arteries, respectively, in nondiabetic 16 men. The mean cavernosal artery diameter changes were 89.23 and 77.93% for right and left cavernosal arteries. Systolic peak blood flow velocities were 24.57 (+/- 7.44) and 25.42 (+/- 9.45) cm/s and diameter increase rates were 78.57 and 37.50% for right and left cavernosal arteries in diabetic sexually active men. Sexually active diabetics have a significantly lower cavernosal artery peak blood flow velocity and diameter increase rate than nondiabetics (p < 0.01). Thus a subclinic dysfunction of erection might be introduced in diabetic males. In conclusion, each investigator should determine his own standards on sexually active subjects and on those with different etiologies such as diabetics mellitus, hypertension and hypercholesterolemia, contributing to erectile dysfunction.

Immunoprotection in spontaneous remission of type 1 diabetes: long-term follow-up results.

This prospective pilot study was undertaken to test the efficacy of oral methyl-prednisolone (MP) therapy at spontaneous remission phase of type 1 diabetes in intervening the course of the disease. Twenty-five type 1 diabetic patients who were classified as having a spontaneous remission (honeymoon) were divided into treatment and non-treatment groups on voluntary basis. Fifteen patients thus making up the treatment group (13 males and 2 females, mean age 23.8 +/- 6.2 years) received 0.7-1.0 mg/kg/day of MP p.o. for 2 weeks. The dose of the drug was then gradually diminished every week until 5 mg/day (approx. 0.1 mg/kg/day) and discontinued at 10 +/- 2 weeks. In case of hyperglycemia occurring in 12 of 15 patients due to the administration of steroid, insulin was used to normalize blood glucose levels (average 0.47 +/- 0.21 IU/kg/day). The non-treatment group (8 males and 2 females, mean age 21.8 +/- 8.9) did not receive any special medication or placebo except for insulin whenever necessary to regulate glycemia. Upon completion of protocol, all patients in treatment group displayed clinical remission with 10 still in non-insulin requiring remission for follow-up periods ranging between 16 and 91 months. The remaining 5 patients relapsed within 3-15 months of therapy. Other metabolic (including basal and stimulated C-peptide levels) and immunological indices that have spontaneously ameliorated with the occurrence of honeymoon were also maintained within normal range in the NIR patients. Meanwhile, natural remission in the non-MP-treated group terminated at 3.4 +/- 0.6 months with deterioration of all metabolic and immunological markers as well as increasing requirements for insulin. In conclusion, the spontaneous remission of the patients could be prolonged significantly by MP therapy as opposed to no therapy (P < 0.001). These results suggest that the spontaneous remission phase may be a crucial point of intervention in immunotherapy of type 1 diabetes and that randomized trials with MP at this particular phase would be worthwhile.