Nodule size as predictive factor of efficacy of radiofrequency ablation in treating autonomously functioning thyroid nodules.

CONTEXT: No defined pre-treatment factors are able to predict the response to radiofrequency ablation (RFA) of an autonomously functioning thyroid nodule (AFTN). OBJECTIVE: Primary endpoint was to evaluate the success rate of RFA to restore euthyroidism in a cohort of adult patients with small solitary AFTN compared with medium-sized nodules. Secondary endpoints included nodule volume reduction and rate of conversion from hot nodules to cold using scintiscan. METHODS: This was a 24-month prospective monocentric open parallel-group trial. Twenty-nine patients with AFTN were divided into two groups based on thyroid volume: 15 patients with small nodules (<12 mL) in group A and 14 patients with medium nodules (>12 mL) in group B. All patients underwent a single session of RFA and were clinically, biochemically, and morphologically evaluated at baseline and at 1, 6, 12 and 24 months after treatment. RESULTS: After RFA, there was greater nodule volume reduction in group A compared with group B (p < 0.001 for each follow-up point). In group A, there was a greater increase in TSH levels than in group B at 6 (p = 0.01), 12 (p = 0.005), and 24 months (p < 0.001). At 24 months, the rate of responders was greater in group A than in group B (86 vs. 45%; p < 0.001). In group A, 86% of nodules converted from hot to cold compared with 18% in group B (p < 0.001). CONCLUSIONS: A single session of RFA was effective in restoring euthyroidism in patients with small AFTNs. Nodule volume seems to be a significant predictive factor of the efficacy of RFA in treating AFTN.

Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition.

Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014.

Serum chitotriosidase in postmenopausal women with severe osteoporosis.

UNLABELLED: Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis. INTRODUCTION: Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis. METHODS: In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum ß-CrossLaps (CTX) were measured in the whole population. RESULTS: Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p < 0.001, respectively) even after adjustment for age (p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = -0.38, p = 0.001, femoral neck: r = -0.35, p = 0.001, total femur: r = -0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit (p < 0.001), beta-CTX (p = 0.013), and age (p < 0.001) was observed. CONCLUSION: This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis.

Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism.

UNLABELLED: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. METHODS: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. RESULTS: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. CONCLUSION: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium.

In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes.

AIMS: To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes. METHODS: Thirty-six people with Type 1 diabetes and 20 age- and sex-matched healthy control subjects were enrolled. Tests to determine heart rate response to deep-breathing (expiratory-to-inspiratory ratio), heart rate response to lying-to-stand test (30:15 ratio) and blood pressure response to standing were performed to detect cardiac autonomic neuropathy. Corneal confocal microscopy was performed to assess: corneal nerve density and corneal nerve beadings; branching pattern; and nerve fibre tortuosity. RESULTS: Compared with control participants, participants with Type 1 diabetes had fewer (mean ± SD 45.4 ± 20.2 vs 92.0 ± 22.7 fibres/mm²; P < 0.001) and more tortuous corneal nerve fibres (20 participants with Type 1 diabetes vs four control participants had nerve tortuosity grade 2/3; P = 0.022) and fewer beadings (mean ± SD 15.1 ± 3.5 vs 20.6 ± 5.0; P < 0.001). Of the participants with Type 1 diabetes, 11 met the criteria for the diagnosis of cardiac autonomic neuropathy. Corneal nerve density was significantly lower in participants with cardiac autonomic neuropathy than in those without (mean ± SD 32.8 ± 16.4 vs 51.7 ± 18.9 fibres/mm²; P = 0.008). This difference remained significant after adjustment for age (P = 0.02), gender (P = 0.04), disease duration (P = 0.005), insulin requirement (P = 0.02) and neuropathy disability score (P = 0.04). CONCLUSION: This study suggests that corneal confocal microscopy could represent a new and non-invasive tool to investigate cardiac autonomic neuropathy in people with Type 1 diabetes. Larger studies are required to define the role of corneal confocal microscopy in the assessment of cardiac autonomic neuropathy.

Buccal spray insulin in subjects with impaired glucose tolerance: the prevoral study.

AIM: Postprandial hyperglycaemia is a consequence of reduced first phase insulin response and is associated with increased cardiovascular risk and mortality. The aim of this proof-of-concept study was to investigate the safety and efficacy of treatment with buccal spray insulin (Oral-lyn™, Generex Biotechnology Corporation, Toronto, Ontario, Canada) on postprandial plasma glucose and insulin levels in subjects with impaired glucose tolerance (IGT). METHODS: A total of 19 female and 12 male Caucasian subjects, 52.2 ± 13.5 (SD) years old, having a body mass index of 33.1 ± 6 (SD) kg/m² with confirmed IGT were included in the study. Subjects were randomized to take 4, 6 or 12 Oral-lyn puffs (1 puff = 1 s.c. rapid insulin UI) split into two equal doses each, one before and the second 30 min after a standard 75 g oral glucose tolerance test (OGTT). Glucose and insulin levels were measured at baseline and 30, 60, 90, 120 and 180 min afterwards. RESULTS: Glucose fluctuations during OGTT were not modified by 4 or 6 Oral-lyn puffs. Treatment with 12 puffs was followed by 29.6% decrease in plasma glucose at 2 h and 26.8% decrease at 3 h, altogether p = 0.01. Considering all time points of the OGTT, there was a mean reduction of 15.8% in glucose levels. With 6 of the total 12 puffs used in group C there was a significant increase in the insulin levels during OGTT at 30 min (p < 0.04) but not at 2 or 3 h. No hypoglycaemic episodes were observed at any time points of the OGTT. CONCLUSIONS: This proof-of-concept study demonstrates that treatment with buccal spray insulin is a simple and valuable therapy for reducing postprandial hyperglycaemia in obese subjects with IGT. Importantly, this treatment is safe and none of the study subjects experienced hypoglycaemia.

Differences between ATA, AACE/ACE/AME and ACR TI-RADS ultrasound classifications performance in identifying cytological high-risk thyroid nodules.

OBJECTIVE: Thyroid ultrasound is crucial for clinical decision in the management of thyroid nodules. In this study, we aimed to estimate and compare the performance of ATA, AACE/ACE/AME and ACR TI-RADS ultrasound classifications in discriminating nodules with high-risk cytology. DESIGN: Cross-sectional study. METHODS: 1077 thyroid nodules undergoing fine-needle aspiration were classified according to ATA, AACE/ACE/AME and ACR TI-RADS ultrasound classifications by an automated algorithm. Odds ratios (ORs) and receiver operating characteristic (ROC) curves for high-risk cytology categories (TIR3b, TIR4 and TIR5) were calculated for the different US categories and compared. RESULTS: Cytological categories of risk increased together with all US classifications' sonographic patterns (P < 0.001). The diagnostic performance (C-index) of ACR TI-RADS and AACE/ACE/AME significantly improved when adding clinical data as gender and age in the regression model (P < 0.001). A significant difference in the final model C-index between the three US classification systems was found (P < 0.029), with the ACR TI-RADS showing the highest nominal C-index value, significantly superior to ATA (P = 0.008), but similar to AACE/ACE/AME (P = 0.287). ATA classification was not able to classify 54 nodules, which showed a significant 7 times higher risk of high-risk cytology than the 'very low suspicion' nodules (OR: 7.20 (95% confidence interval: 2.44-21.24), P < 0.001). CONCLUSIONS: The ACR TI-RADS classification system has the highest area under the ROC curve for the identification of cytological high-risk nodules. ATA classification leaves 'unclassified' nodules at relatively high risk of malignancy.

A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes.

BACKGROUND: In the MADIAB trial (a 21-day randomized, controlled trial in patients with type 2 diabetes (T2D)), intervention with the Ma-Pi 2 macrobiotic diet resulted in significantly greater improvements in metabolic control compared with a standard recommended diet for patients with T2D. We report on a 6-month follow-up study, which investigated, whether these benefits extended beyond the 21-day intensive dietary intervention, in real-world conditions. SUBJECTS: At the end of the MADIAB trial (baseline of this follow-up study), all participants continued their assigned diet (Ma-Pi or control) for 6 months. The Ma-Pi 2 group followed the Ma-Pi 4 diet during this follow-up study. Forty of the original 51 subjects (78.4%) participated in the follow-up (body mass index, 27-45 kg m(-2); age, 40-75 years). Primary outcome was percentage change from baseline in HbA1c; secondary outcomes were anthropometric data and lipid panel. RESULTS: A significantly greater median percentage reduction was observed for HbA1c in the Ma-Pi group (-11.27% (95% confidence interval (CI): -10.17; -12.36)) compared with the control group (-5.88% (95% CI: -3.79; -7.98)) (P < 0.001). Total and low-density lipoprotein (LDL) cholesterol increased in both groups with no differences between groups (P=0.331 and P=0.082, respectively). After correcting for age and gender, the Ma-Pi diet was associated with a higher percentage reduction in HbA1c (95% CI: 2.56; 7.61) and body weight (95% CI: 0.40; 3.99), and a higher percentage increase in LDL cholesterol (95% CI: -1.52; -33.16). However, all participants' total and LDL cholesterol levels remained within recommended ranges (<200 mg dl(-1) and <100 mg dl(-1), respectively). The Ma-Pi diet group achieved the target median HbA1c value (<5.7% (39 mmol mol(-1))) at 6 months. CONCLUSIONS: Both the Ma-Pi and control diets maintained their benefits beyond the 21-day intensive monitored intervention over a 6-month follow-up in real-world conditions. The Ma-Pi diet resulted in greater improvement in glycemic control.

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

BACKGROUND AND AIMS: A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. PATIENTS AND METHODS: We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. RESULTS: In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. CONCLUSION: Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX).

OBJECTIVE: Various adjuvant therapies have been introduced along with intensive insulin therapy in patients with recent onset type 1 diabetes. Nicotinamide (NA), administered at diagnosis of the disease, can have beneficial effects on the clinical remission rate, improve metabolic control and preserve or slightly increase beta-cell function, probably by reducing toxicity due to free oxygen radicals. Vitamin E, a known antioxidant, inhibits lipid peroxidation; this can lead to protection of islet beta cells from the combined effects of interleukin 1, tumor necrosis factor and gamma interferon. The aim of the present study was to investigate whether the addition of vitamin E to NA could improve metabolic control and the residual beta-cell function, as measured by C-peptide secretion, in children and adolescents with recent onset type 1 diabetes; patients were followed-up for 2 years after diagnosis. PATIENTS AND STUDY DESIGN: Recent onset type 1 diabetes patients (n=64, mean age 8.8 years) were recruited by participating centres of the IMDIAB group. Thirty-two patients were randomized to NA (25 mg/kg body weight) plus vitamin E (15 mg/kg body weight); 32 patients acted as controls and received NA only at the same dose as above. Intensive insulin therapy was applied to both treatment groups. RESULTS: There were three drop outs during the 2-year follow-up period. Overall, patients assigned to the NA+vitamin E group or the NA group did not significantly differ in terms of glycated hemoglobin (HbA1c) levels, insulin requirement or baseline C-peptide secretion. Patients diagnosed at an age of less than 9 years showed significantly reduced C-peptide levels compared with those aged over 9 years at diagnosis and at the 2-year follow-up but there were no differences between the NA and NA+vitamin E treated groups. However at 6 months, patients over 9 years of age treated with NA+vitamin E showed significantly higher C-peptide compared with the NA group (P<0.003). In both age groups and in the different treatment groups, C-peptide levels found at diagnosis were preserved 2 years later. CONCLUSIONS: The use of NA alone, or in combination with vitamin E, along with intensive insulin therapy is able to preserve baseline C-peptide secretion for up to 2 years after diagnosis. This finding is of particular interest for pre-pubertal children with type 1 diabetes and has never been reported before.

Is metformin safe enough for ageing type 2 diabetic patients?

We assessed the effect of adding low doses of metformin to sulfonylurea therapy in 76 elderly Type 2 diabetic patients by monitoring glycaemic control and blood lactate for one year. Metformin markedly improved glycaemic control. Fasting lactate concentrations were not affected and post-meal lactate peaks were minimally increased. Additional benefits included an improvement in some lipid parameters, a reduction in serum uric acid and a significant weight loss in overweight patients. Metformin was clinically well-tolerated. Instead of advanced age alone, renal function and/or any other age-related factor likely to contribute to lactate overproduction should be the basis for deciding on metformin therapy. No evidence indicated that metformin should be denied "a priori" to ageing Type 2 diabetic patients.

Meformin, plasma glucose and free fatty acids in type II diabetic out-patients: results of a clinical study.

Abnormalities in free fatty acid (FFA) metabolism are an intrinsic feature of type II diabetes mellitus and may even play a role in the development of glycaemic imbalance. This study investigated whether the anti-diabetic drug metformin can reduce FFA levels in clinical practice and whether this correlates with its anti-diabetic effect. For 6 months metformin was added to sulfonylurea therapy in 68 type II diabetic outpatients with poor glycaemic control, being administered before meals and at bed-time. Basal and daily area-under-the-curve (AUC) glucose levels dropped (both P < 0.0005) like basal and daily AUC FFA levels (P < 0.004 and P < 0.001 respectively) reductions were all correlated (P < 0.001 and P < 0.003 respectively). Reductions in fasting and daily AUC glucose correlated more closely with body fat distribution, expressed by waist-hip ratio (WHR) (P < 0.006 and P < 0.004 respectively), than with the body mass index (BMI) (P < 0.02 and P < 0.04 respectively). Similarly fasting and daily AUC FFA correlated with WHR (P < 0.007 and P < 0.01 respectively) but not with BMI (both P = ns). Subdividing male and female diabetic patients into groups with low and high WHRs, fasting and daily AUC glucose were reduced in men (P < 0.01 and P < 0.02) and in women (P < 0.02 and P < 0.04 respectively) with low WHRs less than in men and in women with higher WHRs (for each gender P < 0.0001 and P < 0.0002, respectively). Decreases in fasting and daily AUC FFA, which did not reach significance in either men or women with low WHRs, were statistically significant in men (P < 0.03 and P < 0.01 respectively) and in women (P < 0.02 and P < 0.005 respectively) with high WHRs. These findings suggest that an improvement in FFA plasma levels might contribute to metformin's anti-diabetic activity which appears to be more marked in patients with high WHRs. Moreover adding a bed-time dosage to the standard administration at meal times seems to be an effective therapeutical strategy.

Relationship between plasminogen activator inhibitor type-1 plasma levels and the lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus.

The first part of the paper deals with the relationship between two inhibiting factors of the complex enzyme cascade regulating fibrinolysis, namely plasminogen activator inhibitor type-1 (PAI-1) and lipoprotein(a) (Lp(a)). Blood concentrations of Lp(a), PAI-1 antigen (PAI-1 AG) and activity (PAI-1 AT), and the main parameters of lipo- and glyco-metabolic balance were studied in 80 type II diabetic patients. Roughly hyperbolic patterns have been found between PAI-1 and Lp(a). Negative statistically significant linear correlation can be elicited when Log PAI-1 AG and Log PAI-1 AT values are plotted versus Lp(a) values, the first one being particularly tight. These findings suggest a nearly on/off control of the two parameters, limiting the risk of hypofibrinolysis. The second part of the paper was aimed at verifying this hypothesis. A group of 30 diabetic patients were treated for 3 months with metformin, an antidiabetic biguanide compound which has been reported to reduce PAI-1 levels both in diabetic and in non-diabetic patients. Metformin significantly reduced PAI-1 AG and PAI-1 AT but did not influence plasma Lp(a) levels. A clear linear correlation between the basal Lp(a) values and the changes in PAI-1 AG levels was found. An even tighter correlation was elicited between the decrease in PAI-1, and PAI-1 pretreatment values.

Glycosylated hemoglobin and fructosamines: does their determination really reflect the glycemic control in diabetic patients?

The present experiment was designed to determine whether scavenging capacity of serum, in addition to glucose level, influences hemoglobin and serum protein glycosylation in non-insulin dependent diabetic patients. For this purpose forty-seven patients homogeneous for age, disease duration, therapy and glyco-metabolic control were selected. Fasting and post-prandial glycemia and insulinemia as well as glycosuria were weekly analysed during the sixty days preceding glycosylated hemoglobin (HbA1c), fructosamines and serum scavenging capacity determination. This last parameter has been evaluated by a method based on the property of beta-phycoerythrin (beta-PE) to loss its fluorescence when damaged by oxygen radicals, that were produced by Cu++ and H2O2. The oxygen radical absorbance capacity (ORACOH) of serum was assayed as the ability of serum to delay the loss of beta-PE fluorescence. As expected, a statistically significant positive correlation was found comparing both fructosamines and HbA1c levels with mean fasting glycemia measured over twenty and sixty days, respectively. The key result of this study is represented by the finding that both HbAlc and fructosamines levels show a statistically significant negative correlation with ORACOH values. This correlation can explain a large percent of the data dispersion occurring when ORACOH is not taken into account. In order to better describe the role of ORACOH, patients were separated into two sub-groups with an ORACOH lower (L-ORACOH) and greater (H-ORACOH) than 100 U/ml. Examining the correlation between mean fasting glycemia and the two glycosylated proteins considered in these two sub-groups, curves with different slopes were obtained, supporting that the rate of glycosylation of both proteins was higher in L-ORACOH patients as compared to those with H-ORACOH. Present data suggest that for a proper interpretation of the HbA1c and fructosamines data in diabetic patients, the scavenging capacity level of serum should be taken into account.

Diabetes mellitus and malignant external otitis: a case study.

Malignant external otitis (MEO) is an infection of the external auditory meatus, that affects elderly diabetic patients. As this disease results in a high percentage of deaths, especially if the diagnosis is delayed, we thought that it would be useful to cite a recent case study that was resolved in a positive way, in spite of the extent of the disease.

Metformin treatment in elderly type II diabetic patients.

Pharmacological treatment in elderly patients with type II, non-insulin dependent diabetes mellitus (NIDDM) is becoming a growing and complex problem in the clinical practice, since longevity in almost every population is increasing, and the prevalence of NIDDM also rises with age. It is generally indicated that age over 65-70 years represents a specific contraindication against the administration of the biguanides since the risk of the drug-associated lactic acidosis increases with age. However very few data exist in literature about the effect of biguanides, particularly metformin, in aging patients. Therefore, we aimed to evaluate the effects of adding metformin to poorly controlled sulfonylurea-treated elderly diabetic subjects for a one year period. Eighty-four type II diabetic patients aged more than 70 years and with a poor glycemic control were recruited after an informed consent. All diabetic patients were treated with various sulfonylureas at medium doses and presented renal and liver biochemical function tests within normal ranges and were free of severe macroangiopathy and respiratory or congestive heart failure. Metformin treatment was added to the previous sulfonylurea dosages in order to achieve a satisfactory glycemic control. All patients showed a marked improvement in the glycemic control with no significant modification in fasting blood lactate and a mild increase in the post-prandial lactate peak which, however, always felt largely within the normal ranges. Metformin also improved some metabolic vascular risk factors such as plasma cholesterol levels that were reduced, circulating HDL-cholesterol levels that mildly but significantly increased and uric acid that was lowered. In conclusion our data further support the opinion that metformin has not to be denied to diabetic patients on the sole basis of their age.

Biochemical markers of type 1 diabetes: clinical use.

In type 1 diabetes, a number of specific and non-specific antigens have been identified. The major autoantigens involved in the destructive process of beta-cells leading to the development of type 1 diabetes are proinsulin/insulin, glutamic acid decarboxylase (GAD) and the transmembrane protein tyrosine phosphatase (IA-2). These are the only autoantigens that partially satisfy the criteria by which an autoantigen or cross-reactive nonself antigen could be evaluated for a pathogenic role in autoimmune diseases. Antigens by definition induce antibody production and in type 1 diabetes, such (auto) antibodies are accepted as biochemical markers for the disease. Here we describe the main features and usefulness of these markers for disease prediction.

[A 61-year-old woman with abdominal pain and urination disorders]. / Donna di 61 anni con dolore addominale e disturbi della minzione.

The case of a 61 yo diabetic woman presenting with dysuria and lower abdominal pain is described. The incomplete resolution of the clinical picture after short antibiotic treatment and a strong suspect of autonomic neuropathy oriented to an anamnestic reevaluation that evidenced the presence of pneumaturia. The last was the key-symptom that guided to diagnostic imaging showing emphysematous cystitis while a gastroscopy confirmed the presence of autonomic neuropathy manifested by gastroparesis. Emphisematous cystitis is a characteristic infectious complication of diabetic patients induced by a persistent incomplete bladder emptying and bacterial glucose fermentation. The complete eradication of the infectious agent requires a long term antibiotic course and a prompt identification of this pathology.