Matrix Metalloproteinase-2 (MMP-2) and-9 (MMP-9) Gene Variants and Microvascular Complications in Type 2 Diabetes Patients.

Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.

Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

Insulin resistance and ß-cell function in smokers: results from the EGIR-RISC European multicentre study.

AIMS: Tobacco smoking is known to increase the long-term risk of developing Type 2 diabetes mellitus, but the mechanisms involved are poorly understood. This observational, cross-sectional study aims to compare measures of insulin sensitivity and ß-cell function in current, ex- and never-smokers. METHODS: The study population included 1246 people without diabetes (mean age 44 years, 55% women) from the EGIR-RISC population, a large European multicentre cohort. Insulin sensitivity was measured using a hyperinsulinaemic, euglycaemic clamp and the homeostatic model assessment - insulin resistance (HOMA-IR) index. Two ß-cell function parameters were derived from measures during an oral glucose tolerance test: the early insulin response index and ß-cell glucose sensitivity. Additionally, the areas under the curve during the oral glucose tolerance test were calculated for glucose, insulin and C-peptide. RESULTS: According to smoking habits, there were differences in insulin sensitivity, which was lower in women who smoked, and in ß-cell glucose sensitivity, which was lower in men who smoked, but these associations lost significance after adjustment. However, after adjustment, the areas under the glucose and the C-peptide curves during the oral glucose tolerance test were significantly higher in men who smoked. CONCLUSIONS: Smoking habits were not independently associated with insulin sensitivity or ß-cell function in a healthy middle-aged European population. Health-selection bias, methodological shortcomings or a true lack of causal links between smoking and impaired insulin sensitivity/secretion are possible explanations. The mechanisms behind the observed increased glucose and C-peptide areas under the curve during the oral glucose tolerance test in male smokers need to be further evaluated.

Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study.

AIMS: To determine the global extent of hypoglycaemia experienced by patients with diabetes using insulin, as there is a lack of data on the prevalence of hypoglycaemia in developed and developing countries. METHODS: This non-interventional, multicentre, 6-month retrospective and 4-week prospective study using self-assessment questionnaire and patient diaries included 27 585 patients, aged ≥18 years, with type 1 diabetes (T1D; n = 8022) or type 2 diabetes (T2D; n = 19 563) treated with insulin for >12 months, at 2004 sites in 24 countries worldwide. The primary endpoint was the proportion of patients experiencing at least one hypoglycaemic event during the observational period. RESULTS: During the prospective period, 83.0% of patients with T1D and 46.5% of patients with T2D reported hypoglycaemia. Rates of any, nocturnal and severe hypoglycaemia were 73.3 [95% confidence interval (CI) 72.6-74.0], 11.3 (95% CI 11.0-11.6) and 4.9 (95% CI 4.7-5.1) events/patient-year for T1D and 19.3 (95% CI 19.1-19.6), 3.7 (95% CI 3.6-3.8) and 2.5 events/patient-year (95% CI 2.4-2.5) for T2D, respectively. The highest rates of any hypoglycaemia were observed in Latin America for T1D and Russia for T2D. Glycated haemoglobin level was not a significant predictor of hypoglycaemia. CONCLUSIONS: We report hypoglycaemia rates in a global population, including those in countries without previous data. Overall hypoglycaemia rates were high, with large variations between geographical regions. Further investigation into these differences may help to optimize therapy and reduce the risk of hypoglycaemia.

The INTERPRET-DD study of diabetes and depression: a protocol.

AIM: People with diabetes are at an increased risk of developing depression and other psychological disorders. However, little is known about the prevalence, correlates or care pathways in countries other than the UK and the USA. A new study, the International Prevalence and Treatment of Diabetes and Depression Study (INTERPRET-DD) aims to address this dearth of knowledge and identify optimal pathways to care across the globe. METHOD: INTERPRET-DD is a 2-year longitudinal study, taking place in 16 countries' diabetes outpatients' facilities, investigating the recognition and management of depressive disorders in people with Type 2 diabetes. Clinical interviews are used to diagnose depression, with clinical and other data obtained from medical records and through patient interviews. Pathways to care and the impact of treatment for previously unrecognized (undocumented) depression on clinical outcomes and emotional well-being are being investigated. RESULTS: Initial evidence indicates that a range of pathways to care exist, with few of them based on available recommendations for treatment. Pilot data indicates that the instruments we are using to measure both the symptoms and clinical diagnosis of depression are acceptable in our study population and easy to use. CONCLUSIONS: Our study will increase the understanding of the impact of comorbid diabetes and depression and identify the most appropriate (country-specific) pathways via which patients receive their care. It addresses an important public health problem and leads to recommendations for best practice relevant to the different participating centres with regard to the identification and treatment of people with comorbid diabetes and depression.

Stressful life events and type 2 diabetes.

OBJECTIVES: The purpose of this study is to compare cases with type 2 diabetes and their controls for the frequency of stressful life events and social support before the occurrence of the disease. METHODS: The study of cases and their controls was undertaken in Belgrade. A case group comprised 179 subjects in whom type 2 diabetes was for the first time diagnosed in the 'Savski Venac' Medical Center during the period 2005-2007 year. The diagnosis was made by a specialist of internal medicine according to criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. For each case two controls were chosen among patients with trauma (fracture, reposition, internal/external fixation) who were treated at the 'Banjica' Institute for Orthopedic-Surgical Diseases during the same period. Cases and controls were matched by sex, age (±2 years) and place of residence (Belgrade). Data were collected on demographic characteristics, habits, personal history, stressful life events, social support and family medical history. RESULTS: According to multivariate analysis low social support in personal history, such as relatives/friends help and financial assistance in solving problems, and bad management of monthly income were significantly positively related to type 2 diabetes. However, significantly more controls than cases had no financial insurance in case of urgent need CONCLUSION: Examine psychosocial factors play a role in the development of type 2 diabetes.

Relation of the Mediterranean diet with the incidence of gestational diabetes.

BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA_2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4, P<0.001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%, OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.

Taking small steps towards targets - perspectives for clinical practice in diabetes, cardiometabolic disorders and beyond.

Big changes are hard. When trying to achieve guideline targets in diabetes and cardiometabolic disorders, patients can lack commitment or suffer despondency. It is much easier to make small changes in lifestyle or treatment, which are less noticeable and easier to manage long-term. Obesity is central to the cardiometabolic disorders, and even small weight losses of 2-5% can improve the cardiometabolic risk profile and substantially reduce the risk of developing type 2 diabetes. Likewise, small increases in physical activity, such as 15-30 min of brisk walking per day, can cut the risk of heart disease by 10%. Lifestyle or treatment changes that lead to small improvements in metabolic parameters also impact patient outcome - for example, a 5 mmHg decrease in blood pressure can translate into significant reductions in the rates of myocardial infarction and cardiovascular mortality. Benefits of small changes can also be seen in health economic outcome models. Implementing change at an individual versus a population level has different implications for overall benefit and patient motivation. Even very small steps taken in trying to reach guideline targets should represent a positive achievement for patients. Patient engagement is essential - only when patients commit themselves to change can benefits be maintained, and physicians should recognise their influence. Small changes in individual parameters can result in significant beneficial effects; however, a major impact can occur when small changes are made together in multiple parameters. More research is required to elucidate the full impact of small changes on patient outcome.

Diabetic cardiomyopathy: ongoing controversies in 2012.

Diabetic cardiomyopathy is a controversial clinical entity that in its initial state is usually characterized by left ventricular diastolic dysfunction in patients with diabetes mellitus that cannot be explained by coronary artery disease, hypertension, or any other known cardiac disease. It was reported in up to 52-60% of well-controlled type-II diabetic subjects, but more recent studies, using standardized tissue Doppler criteria and more strict patient selection, revealed a much lower prevalence. The pathological substrate is myocardial damage, left ventricular hypertrophy, interstitial fibrosis, structural and functional changes of the small coronary vessels, metabolic disturbance, and autonomic cardiac neuropathy. Hyperglycemia causes myocardial necrosis and fibrosis, as well as the increase of myocardial free radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial function, and induce myocardial inflammation. Insulin resistance with hyperinsulinemia and decreased insulin sensitivity may also contribute to the left ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy may include dyspnea, arrhythmias, atypical chest pain, and dizziness. Currently, there is no specific treatment of diabetic cardiomyopathy that targets its pathophysiological substrate, but various therapeutic options are discussed that include improving diabetic control with both diet and drugs (metformin and thiazolidinediones), the use of ACE inhibitors, beta blockers, and calcium channel blockers. Daily physical activity and a reduction in body mass index may improve glucose homeostasis by reducing the glucose/insulin ratio and the increase of both insulin sensitivity and glucose oxidation by the skeletal and cardiac muscles.

The immunobiology of apotransferrin in type 1 diabetes.

The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.

What are the possible reasons for urethral PSA varieties after radical prostatectomy?

OBJECTIVE: To examine the possible reasons for great varieties in urethral prostate specific antigen (urPSA) levels, in patients after radical prostatectomy (RP). MATERIALS AND METHODS: In 46 patients with pros-tate cancer, PSA, urPSA, total testosterone, body-mass index (BMI) and the stage of androgenic alopecia (AGA) were determined. Forty-five patients underwent retropubic RP, while one underwent cystoprostatectomy with orthotopic bladder construction, due to bladder cancer. RESULTS: Average patients age prior to surgery plus or minus standard deviation was 65.2 +/- 5.8 years. Average urPSA was 20.9 +/- 47.5 ng/ml (0.05 to 212 ng/ml, median 2.24 ng/ml). With urethral PSA cut-off of 2.0 ng/ml, two groups were formed: A (urPSA < 2.0 ng/ml) and B (urPSA = 2.0 ng/ml). Patients in the group A had significantly lower average AGA score, than the patients from the group B (2.4 +/- 1.3 vs. 4.4 +/- 2.2, p = 0.0003). In addition, patients from the group A had significantly lower pos-toperative PSA (0.07+0.08 ng/ml vs. 0.14 +/- 0.06 ng/ml, p = 0.0014). CONCLUSIONS: The patients with higher urPSA have higher AGA scores and higher postoperative PSA. This phenomenon is probably the consequence of higher local dihydrotestosterone activity in the scalp and PSA-secreting urethral glands.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Urinary PSA level and relative tumor volume after prostate biopsy.

OBJECTIVES: To estimate the ratio between urinary prostate specific antigen (uPSA) and tumor volume after prostate biopsy. METHODS: From 2000 to July 2008, uPSA concentration was determined in 60 patients with clinically organ-confined prostate cancer (PCa). All patients underwent six-area transrectal ultrasound (TRUS)--guided biopsy, with at least 12 biopsy cores. Single pathologist determined tumor grade (G), Gleason score (GS), the percentage of tumor infiltration (% TI) and the percentage of positive cores (% PC) in all biopsy cores. Additionally, relative tumor-biopsy volume (RTV) was calculated by multiplying % PC, % TI and prostate ultrasound-derived volume (Vol). Forty-one patients underwent retropubic radical prostatectomy (RRP), while 19 patients underwent radiation therapy. RESULTS: Average uPSA was 308.6 +/- 311.9 ng/ml (range 0.06-988 ng/ml), average PSA was 9.7 +/- 5.5 ng/ml (range 1.2-24.3 ng/ml), tumor grade 1.7 +/- 0.8, Gleason score 5.2 +/- 1.3, the percentage of tumor infiltration 27.6 +/- 21.8%, and the percentage of positive cores, 52.2 +/- 30.7%. Average RTV was 6.3 +/- 8.4 ml (0.29-56 ml). All patients were divided in two groups: I, with RTV 4 ml and II, with RTV = 4 ml. The patients with RTV 4 ml had lower G (1.4 +/- 0.6 vs. 2.1 +/- 0.8, p = 0.0002), lower GS (4.5 +/- 1 vs. 5.8 +/- 1.3, p = 0.003) and higher uPSA (389.4 +/- 340.8 vs. 193.1 +/- 229.7, p = 0.014). There were no differences in serum PSA levels between the groups. CONCLUSION: Relative tumor-biopsy volume (RTV) is useful parameter in the preoperative assessment of tumor volume. Patients with higher RTV had significantly higher G and GS. However, these patients had significantly lower uPSA. This phenomenon could be the consequence of compromised PSA drainage from the peripheral zone of the prostate, caused by the tumor.

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. METHODS: This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times. RESULTS: The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. CONCLUSIONS/INTERPRETATION: Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00331851. FUNDING: The study was funded by Novo Nordisk A/S.

Effect of biphasic insulin aspart on glucose and lipid control in patients with Type 2 diabetes mellitus.

OBJECTIVE: This study examined the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) monotherapy in insulin-naive patients with Type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In this 12-week, open-labelled, uncontrolled, clinical-experience study involving 71 patients with secondary oral antidiabetic agent failure, patients received BIAsp 30 after discontinuing oral antidiabetic drugs (OADs). Glucose and lipid concentrations, hypoglycaemic episodes and adverse events were assessed before and after treatment. Patient data were categorised according to previous OADs into the biguanides (BI) plus sulfonylureas/meglitinides (SU/MEG) and SU-only groups. RESULTS: After treatment, glucose and lipid control was significantly improved in both groups, with a greater improvement in the SU-only group. Mean glycated haemoglobin, fasting blood glucose and postprandial blood glucose excursion improved by 2.15 +/- 1.24%, 3.70 +/- 3.18 mmol/l and 1.26 +/- 2.65 mmol/l in the BI plus SU/MEG group, and by 3.09 +/- 1.62%, 6.11 +/- 5.02 mmol/l and 2.06 +/- 2.33 mmol/l in the SU-only group, respectively. Mean high-density lipoprotein cholesterol and triglycerides improved by 0.09 +/- 0.18 mmol/l and 0.94 +/- 1.17 mmol/l in the BI plus SU/MEG group and by 0.09 +/- 0.18 mmol/l and 1.04 +/- 2.72 mmol/l in the SU-only group, respectively. No major hypoglycaemic episodes or serious treatment-related adverse events were reported. CONCLUSIONS: Our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only. Key limitations were the lack of a comparator group and the short study duration.

Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50.

PURPOSE: To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer. PATIENTS AND METHODS: In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT. RESULTS: Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005). CONCLUSION: The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients.

Human fetal islet transplantation in type 1 diabetics: comparison of immunological effects between multiple implantation regimens.

Previous studies have suggested that the multiple transplants might be equally metabolically efficient to a single regimen for human adult islets. The aim of this study was to compare immunological and metabolic parameters after each of the two regimens of human fetal islets (HFI). Group A single transplants (n = 9) had 180 +/- 20 x 1000 HFI equivalents (IEQs) implanted via a single intramuscular injection. In group B multiple transplants (n = 8) islets were implanted by three consecutive injections of 60 +/- 10 x 1000 IEQs at 7-day intervals. We analyzed the immunological parameters of CD4/CD8 T lymphocyte ratios; islet cell antibodies (ICAs) and insulin antibodies (IAs). We estimated insulin secreting capacity (ISC) as the metabolic parameter. We observed that the CD4+/CD8+ T-cell ratio increased, peaking on day 90, in similar fashion in both groups: day -1: A = 1.18 +/- 0.03 versus B = 1.19 +/- 0.04; on day 90: A = 1.79 +/- 0.09, versus B = 1.75 +/- 0.08 (P = NS) immediately before the decrease in C-peptide levels. Thereafter the ratios rapidly decreased without statistical differences. The levels of ICAs did not change. The levels of IAs, which were increased before transplant, then decreased without statistical differences between the groups. The values of ISC increased after transplant and then decreased similar to the T-cell ratio. Our results demonstrated that regimens of multiple and single HFIs did not show differences in the kinetics of the immunological response presumably mediating graft destruction. The CD4/CD8 ratio increased as the C-peptide level decreased, peaking on day 90 at the time of a decrease in C-peptide. These results may be useful for clinical studies of HFIs for type 1 diabetic patients.