Hepatitis C virus infection in hemodialysis patients is not associated with insulin resistance, inflammation and atherosclerosis.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with increased levels of inflammatory markers and is also a significant risk factor for the development of Type 2 diabetes mellitus (DM) in the general population. In attempt to address this issue in chronic hemodialysis (HD) patients, we evaluated the relation of HCV infection with inflammatory markers, endothelial dysfunction, insulin resistance and atherosclerosis. METHODS: In a cohort of 72 HD patients (36 (50%) had a positive HCV EIA test and 36 (50%) had a negative anti-HCV test), we examined HCV antibody status, insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), serum inflammatory parameters (high sensitive C-reactive protein (CRP), fibrinogen and procalcitonin), and performed echocardiography, high-resolution brachial artery ultrasound and B-mode carotid Doppler examination to assess the vascular functions and atherosclerosis. RESULTS: There were no differences in age, gender, body mass index (BMI), primary disease, duration of dialysis, smoking status, laboratory parameters except glucose, total cholesterol and LDL cholesterol between anti-HCV-positive and anti-HCV-negative groups. The serum concentrations of glucose, total cholesterol and LDL cholesterol were significantly lower in the anti-HCV-positive patients than anti-HCV-negative patients (p = 0.04, p = 0.02, p = 0.01, respectively). There were no significant differences in inflammatory parameters, total insulin secretion (HOMA-beta, p = 0.76) and insulin resistance (HOMA-R, p = 0.91) between anti-HCV-positive and negative patients. The intima media thickness, carotid plaque score and brachial artery endothelium-dependent dilatation did not differ significantly between the two groups (p = 0.44, 0.45, and 0.17, respectively). CONCLUSION: HCV infection was not related to atherosclerosis and insulin resistance in hemodialysis patients. Since hemodialysis patients had a large number of uremia-related cardiovascular risk factors, the effect of HCV infection could disappear in this group of patients.

Symptoms of depression and diabetes-specific emotional distress are associated with a negative appraisal of insulin therapy in insulin-naïve patients with Type 2 diabetes mellitus. A study from the European Depression in Diabetes [EDID] Research Consortium.

AIMS: A meta-analysis concluded that depression is associated with poor glycaemic control in Type 2 diabetes (DM2). In DM2 patients with deteriorating glycaemic control, the initiation of insulin therapy is often postponed. The aim of the present study was to determine whether symptoms of depression and diabetes-specific emotional distress are associated with a more negative appraisal of insulin therapy. METHODS: We collected cross-sectional data in two outpatient university clinics in Istanbul, Turkey. The study sample consisted of 154 insulin-naïve patients with DM2. A self-report questionnaire was used to obtain demographic and clinical data. Main instruments were the Centre for Epidemiologic Studies Depression Scale, (CES-D), the Problem Areas In Diabetes scale (PAID) and the Insulin Treatment Appraisal Scale (ITAS). RESULTS: Analysis of variance revealed that patients with a higher depression score rated insulin therapy significantly more negative then patients with lower depression scores. Moreover, 47% of patients with a high depression score had a negative appraisal of insulin therapy on 7 or more of the 20 ITAS-items, compared to 25 to 29% of those with low-moderate depression scores. Multiple regression analyses showed that a negative appraisal of insulin therapy was significantly associated with higher depression and diabetes-distress scores and low education, but not with sex, age or duration of diabetes. CONCLUSIONS: Our results suggest that in insulin-naïve Type 2 diabetes patients, higher levels of depression and diabetes-distress tend to be associated with more negative beliefs about insulin. Whether these negative attitudes translate into postponing initiation of insulin therapy needs to be tested in longitudinal research.

The electrophysiological findings of subclinical neuropathy in patients with recently diagnosed type 1 diabetes mellitus.

To assess the prevalence of subclinical neuropathy within the first year of type 1 diabetes mellitus, 30 patients and 14 healthy subjects have been studied prospectively. The patients whose diabetes duration was longer than 1 year have been excluded from the study. Control group consisted of healthy volunteers. Subjective neuropathy symptoms, neurological examination, and electrophysiological findings were evaluated. All patients were clinically asymptomatic. At least two abnormal independent neurophysiological nerve parameters, which were required as the criterion of the peripheral nervous system subclinical involvement, were found as in 96.6% of diabetic patients in the first years. The percentages of abnormal electrophysiological parameters in different motor and sensory nerves were 86.7% in sural nerve, 83.3% in peroneal motor nerve, 73.3% in posterior tibial motor nerve, 66.7% in median motor nerve, 63.3% in ulnar motor nerve, 60% in median sensory nerve, and 46.7% in ulnar sensory nerve. While distal motor latency, F conduction time, and minimum F latency were the most frequent abnormal parameters in the upper extremity electrophysiological study; conduction velocity, minimum and mean F latencies, F conduction time were the most frequent abnormal parameters in the lower extremity. In all sensory nerve conduction studies, the most frequent abnormal parameter was the onset latency. In the autonomic sympathetic nerve electrophysiological study, plantar SSR latency was found significantly longer than the control group. In the lower extremity generally somatic motor fibres, sensory large fibres and sympathetic autonomic nerve fibres were found to be more affected. There is a correlation between HbA1c levels and nerve conduction velocity in posterior tibial and peroneal nerves. However, upper extremity nerve conduction dysfunction was not correlated with HbA1c value. Neither the duration of disease nor the age of the subject correlated with the nerve dysfunction.

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.

Doxazosin, but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective, randomized-controlled study.

Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this randomized-controlled study, we aimed to compare the effect of doxazosin and amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female: 5/10, mean age: 46 +/- 13 years) and 9 controls (male/female: 3/6, mean age: 35 +/- 8 years) were included. Patients and controls had no family history of diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker of IR. Patients were grouped randomly to doxazosin (n = 8; 2-4 mg/day) and amlodipine (n = 7; 5-10 mg/day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C peptide, HOMA) were similar between amlodipine and doxazosin groups. There was no difference in age, gender and body mass index among study groups. The follow-up time was 12 weeks. Patients with CRF had higher HOMA (1.83 +/- 0.55 vs 1.00 +/- 0.36, p = 0.001), fasting insulin (8.06 +/- 1.98 vs 4.46 +/- 1.31 IU/l, p < 0.001) and serum triglyceride levels (197 +/- 136 vs 112 +/- 67 mg/dl, p = 0.04) as compared to controls. Serum HDL cholesterol levels were significantly lower in patients with CRF than controls (40 +/- 10 vs 57 +/- 14 mg/dl, p = 0.02). HOMA significantly decreased after doxazosin (1.91 +/- 0.45 vs 1.41 +/- 0.21, p = 0.02), however, no difference was found after amlodipine. Also, fasting insulin levels were decreased after a 12-week doxazosin therapy from 8.17 +/- 1.22 vs 6.58 +/- 0.84 IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did not significantly change during the study period in 2 groups. No adverse effect requiring drug discontinuation was observed during the 12-week period in the study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas amlodipine has no effect. This may be of advantage in the treatment of hypertension in this group of patients for preventing some long-term complication of IR.

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.

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.

Influence of insulin resistance on total renin level in normotensive women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of insulin resistance on the plasma total renin level in normotensive women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Twenty-five normotensive women with PCOS were compared with 11 normotensive control women with regular cycles and no features of PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Insulin resistance was estimated by continuous infusion of glucose with model assessment in the early follicular phase. MAIN OUTCOME MEASURE(S): Plasma levels of total renin and angiotensin II and serum levels of gonadotropins, DHEAS, total T, free T, 17 alpha-hydroxyprogesterone, and PRL were determined. RESULT(S): Plasma concentrations of angiotensin II were similar in the PCOS group and the control group. The concentration of total renin in plasma was higher in women with PCOS than in healthy women independent of insulin resistance. The sensitivity and specificity of the plasma total renin level to diagnose women with PCOS were calculated as 80% and 71.4%, respectively. CONCLUSION(S): The plasma total renin level is higher in normotensive women with PCOS than in healthy women independent of insulin resistance.

Safety and efficacy of [Lys(B28), Pro(B29)]-human insulin in patients with diabetes mellitus.

The primary objectives of this study were to assess the efficacy and safety of Lys(B28), Pro(B29) in the treatment of patients with diabetes mellitus and to compare Lys(B28), Pro(B29) to currently available regular insulin with respect to quality of life. This study was designed as an open-label, non-comparative one. The number of patients enrolled in the trial was 39. At Visit 1 (week 0), blood samples for fasting, 1- and 2-hour postprandial blood glucose, and HbA1c were taken. At Visit 2 (week 6) and Visit 3 (week 12), fasting, 1- and 2-hour postprandial blood glucose, and HbA1c levels were measured again. There was no significant change in HbA1c, fasting blood glucose and 1- and 2-hour postprandial blood glucose levels. The 1- and 2-hour postprandial blood glucose excursions decreased significantly from Visit 1 to Visit 3. There were no serious adverse events during the study. Half of the patients had less hypoglycemia with LysPro insulin, while 25% had an increase in episodes. Thirty percent of patients were more satisfied with LysPro insulin than with the short-acting insulin that they had previously used. In conclusion, LysPro therapy can be regarded as safe, since there were no unexpected adverse events and no changes in the usual physical parameters.

Effects of methylprednisolone pulse therapy on insulin injections in patients with insulin-dependent diabetes mellitus.

In this study we evaluated 31 insulin-dependent diabetes mellitus (IDDM) patients (ages 12.1 +/- 3.4 years, 18 males/13 females) who started on multiple subcutaneous insulin injections (MSII) within six weeks of diagnosis and achieved either complete (CR: no insulin requirement and near-normoglycemia for at least two weeks) or incomplete (ICR: minimum 50% decline in insulin requirement while maintaining near-normoglycemia for two weeks or more) remissions within the first 12 weeks of the MSII trial. Methylprednisolone pulse therapy (MP) was administered four times per day by i.v. bolus at a dose of 30 mg/kg (max. 1000 mg) on alternative days. Eleven patients did not accept "MP-pulse" therapy; therefore, we followed these cases (7 males/4 females) as the control group. During the first year of follow-up, 13 patients from the "MP pulse" group achieved CR (3 males/1 female) or ICR (5 males/4 females) in 3.5 to 14 months. Remission occurred in only two of the control group cases (1 male CR for 17 days and 1 female CR for 7 months). Of those with CR in the "MP-pulse" and control groups, all were greater than 12 years of age, and all but one in the "MP-pulse" group were males. The stimulation capacity of beta cells (as defined by percentage increase in serum C-peptide levels after glucagon injection) among CR cases was found to be higher than that of non-remitted (NR) cases (p < 0.05 at onset, p < 0.001 during MSII-induced remission and p < 0.05 at the end of the first year of follow-up). Although patients with CR or ICR had higher beta cell reserves than NR cases at onset, only CR cases could sustain this capacity during the MSII-induced remission phase and one year after "MP-pulse" therapy. From this preliminary study, we conclude that "MP-pulse" therapy, may lead to prolonged near-normal beta cell function or partly preserved residual beta cell reserve during the MSII-induced remission phase of IDDM, The beneficial effects of MP could be seen clearly in patients diagnosed during the late childhood years.

Relationship of leukoaraiosis to vascular risk factors and lesion type in stroke patients.

Nonspecific periventricular white matter lucencies on computed tomograms (leukoaraiosis) were found in 49 (55%) of 89 stroke patients. We compared the vascular risk factors and the types of stroke with and without leukoaraiosis. Patients with leukoaraiosis were significantly older than those without it. The duration of hypertension was longer than those without leukoaraiosis. Mean diastolic blood pressure was associated with leukoaraiosis. No association was found with systolic blood pressure, diabetes mellitus, angina pectoris, myocardial infarction, heart failure, valvular disease and intermittent claudication. Patients with leukoaraiosis were significantly more likely to have lacunar infarcts on computed tomograms but were less likely to have cortical infarcts, subcortical infarcts or cerebral hemorrhage.

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.

The effects of diabetes on penile somato-afferent system.

The direct evaluation of the autonomic nervous system to detect the neurogenic component of erectile dysfunction in men is not possible. Biothesiometry, a vibration perception test, is a simple method for the assessment of the penile somato-afferent system. A nomogram for the evaluation of somato-afferent system has been developed utilizing the biothesiometer in healthy men. This nomogram was used to compare the biothesiometric values of potent and impotent diabetic patients. According to our data, the radix penis is selectively damaged by diabetes mellitus in the first stage of the disease, whereas the glans penis is damaged later on when the disease reaches the stage of impotence.

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.