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A combined PIXE and optical microscopy approach was applied to examine the dental calculus of patients with periodontal disease. PIXE was performed with the Bucharest 3 MV Tandetron with 3 MeV protons and a HPGe detector, using hydroxyapatite (HA) and other standards. Sections 30 µm thick were prepared and observed using polarization microscopy and histochemical techniques. Both methods revealed the heterogeneous nature of dental calculus. Two main types (I and II) were postulated based on Ca/P ratios (p

Over 170 million people worldwide are diagnosed with diabetes and it’s estimated that the number will reach 370 million cases by 2030. Diabetes represents a major risk factor for all cardiovascular diseases with a high mortality rate. Furthermore, diabetes represents a risk factor for peripheral artery disease (PAD) cases and its association leads to significant increase in risk for vascular and cardiac events at foot and leg level thus impacting the quality of life of the patient. The atherosclerosis which is found at the base of PAD pathogenesis results from accumulation of lipids and fibrous material between the tunica intima and tunica media vascular walls resulting in progressive constriction of the vessel’s flux. This phenomenon can lead to complications such as thrombosis or rupture of the atheroma plaque which results in occlusion of downstream vessels. Reducing the risk factors which contribute to the atherosclerosis pathogenesis such as endothelial dysfunction, increase in platelets activity, dyslipidemia, immunological and inflammatory factors as well as tobacco contributes to the reduction of atherothrombotic episodes with impact on the patient’s quality of life.

It is unanimously accepted that patients with diabetes have a higher likelihood for infections. The metabolic imbalance associated with diabetes suppresses the immunity system of the cutaneous organ. Hyperglycemia causes an increase of the activity of the sorbitol route with consumption of NADPH. Furthermore, the sorbitol from the cells leads to increase of osmolality in cells as well as reduction of intracellular myo-inositol. These strains on the cellular metabolism expose the cells to oxidative stress. An additional factor is the reduced chemotaxis and phagocytosis impact on the bacterial activity of leukocytes which leads to further predisposition of infection for diabetes patients. Hence the poor control of glycemic levels leads to immunity changes which affects the local immune response against the aggression of pathogenic agents.

Since diabetes is considered to be both a chronic pathology and an inflammatory disease involving interleukins, the present paper proposes the molecular recognition of interleukins 1β, 6, 1...

Diabetic foot infections are a common complication in people with diabetes. This article will discuss the foot-related complications that can happen in people with diabetes, as well as guidelines for good foot care. Patient education is a central component in the self management of diabetes infections in both prevention and treatment. Poor knowledge of foot care practices is an important risk factor for foot problems among diabetics. Studies have demonstrated deficiencies in knowledge and practices regarding foot care, particularly among rural populations with diabetes. Patients should be informed about the risk factors and their complications that could lead to amputation. The mainstay therapy for intervention of diabetic lower limb complications is prevention.

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns develop and have a major impact on cardiovascular risk. To address these patterns, weight-loss programmes under medical supervision for overweight and obese adolescents are developed. It was observed that those who control the quality and quantity of their carbohydrates, by consuming more fruits and vegetables, associated with increased physical activity reduce their CVR. Some limited studies have shown that low carbohydrate diet (LCD) is safe and effective, but one should take into consideration the limited duration and the structure of the LCD. If there is a proper adherence to this type of nutritional intervention, it results in weight loss, improvement in insulin resistance, lipid profile and subclinical hypothyroidism reversal. We reviewed the literature starting from 2009 by searching all the observational, randomised clinical trials and meta-analyses on MEDLINE and SCOPUS databases regarding obesity and related metabolic diseases (dyslipidemia, type 2 diabetes, hypertension, hypothyroidism, LCD) in adolescents and synthesized the nutritional interventions for this population that could decrease CVR.

Here we describe a novel prototype method for parallel sampling of electrical signals from 200 sensors. The amplified signal from each sensor was remotely converted into a luminous signal on a LED matrix. A digital camera supported by a duralumin skeleton, was installed at 15 cm above an LED matrix inside an opaque box. Images were sampled at discrete time intervals of 5 s. A total of 25,920 images of the LED matrix have been recorded. Thus, 5.2 million measurements have been recorded as light intensities from the LED matrix. Light intensities of individual LEDs from the images were converted into 1 pixel value/LED. Each pixel value was then converted into percentages for evaluation. We used this methodology to measure the temporal variation of the electrical current on the skin of the torso on human volunteers, to assess the presence of a correlation between the electrical activity and diabetes (Ionescu-Tirgoviste et al., 2018). This method also allowed us to compile the first high resolution map of the electrical activity generated by the human skin (Ionescu-Tirgoviste et al., 2018). • A novel method for a parallel acquisition of electrical signals which can be applied in any related field. • It provides the ability to retrieve a large number of electrical channels simultaneously. • It provides for an inexpensive and reliable way to digitize hundreds to thousands of channels at video rate frequencies. Method name: Photon-pixel coupling, Keywords: Parallel, Signal, Acquisition, Electrical activity, Darlington, Sensors

Here, we describe a general-purpose prediction model. Our approach requires three matrices of equal size and uses two equations to determine the behavior against two possible outcomes. We use an example based on photon-pixel coupling data to show that in humans, this solution can indicate the predisposition to disease. An implementation of this model is made available in the supplementary material.

Here, data related to the electrical activity of the human skin are presented in detail. The 3D electrical activity maps in normal and diabetic individuals are shown and described using raw data obtained with Photon-Pixel coupling. Average electrical activity matrices are shown by subject, gender and group. Distributions of the electrical activity data are shown in connection with the ventral and dorsal side of the human torso. For a better understanding of the electrical activity data, critical parameters of the individuals that participated in the study are also presented., Graphical abstract fx1

Aims: To study the age and sex-dependent mortality rates and causes of death in a large Romanian diabetes cohort as compared with the general population.Methods: All adult patients aged 20–64 years...

Diabetes Mellitus is a huge syndrome which can be detected from the first day of life until the last year of life of a centenarian. In the current classification of diabetes among the so-called “idiopathic phenotypes”, apart Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) has been included provisionally term “Latent Autoimmune Diabetes in Adults” (LADA). This has unclear characterization regarding the age at onset, the presence of anti-β-cell antibodies and the level of insulin secretory function, in conformity with C-peptide levels. According to several recent publications, there are no specific biochemical or genetic markers for Latent Autoimmune Diabetes in Adults (LADA), but only a gradual transition from T1D to T2D. In addition, the word “latent” in the construction of “LADA” term is inaccurate because in this phenotype nothing is latent: both the autoimmunity and diabetes are present and are even parts of the diagnosis. So that, the best term should be what in reality this sub-phenotype is: an Intermediary Diabetes Mellitus (IDM). Some recent genetic data strongly support this designation.

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years.METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

The purpose of this article is to describe the research of Nicolae Constantin Paulescu and to emphasize his role in the discovery of insulin. Methods: We made a thorough review of the literature and research in the Romanian Academy Archive in order to find adequate references. Results: In 1912 N.C. Paulescu analysed the clinical and biochemical alterations in diabetic patients and in dogs after performing a pancreatectomy, that apart hyperglycemia and glycosuria (carbohydrate metabolism), had noted also changes in lipid and protein metabolism. In 1916 he started the experiments with a pancreas extract obtained by his original method, that was injected intravenously to the diabetic dogs. The results of his first experiments showed: “The pancreatic extract injected into a peripheral vein produce: 1) A diminution and even a temporary suppression of diabetic hyperglycemia, which may be replaced by hypoglycemia; 2) A diminution or even temporary suppression of glycosuria; 3) A diminution of blood urea; 4) A diminution of urinary urea. In other words, the intravenous injection of the pancreatic extract has as effect the disappearance of diabetic symptoms. The attenuation of the diabetic syndrome begins immediately after the injection. It reaches a maximum after 2 hours,- and it lasts for about 12 hours”. He concluded as such: “This discovery,- which sheds a bright light over the pathogenesis of diabetes gives us also the key for the treatment of this syndrome”. In 1921, Paulescu had published extensively his data in two outstanding French journals 8 months before the first publication of Banting and Best from February 1922. It is clear that insulin has been discovered in Europe. Conclusion: Paulescu thought that a new hormone – Pancreine, that he discovered is the key element in the treatment of diabetes, but his outstanding research was unfairly neglected., Svrha je ovog članka opisati istraživanje Nicolaea Constantina Paulescua i istaknuti njegovu ulogu u otkriću inzulina. Metode: Temeljito smo pregledali literaturu i istraživanja u rumunjskoj akademskoj arhivi kako bismo pronašli odgovarajuće reference. Rezultati: N. C. Paulescu je 1912. analizirao kliničke i biokemijske promjene kod pacijenata s dijabetesom i kod pasa nakon izvođenja pankreatektomije, koji su osim hiperglikemije i glikozurije (metabolizam ugljikohidrata) zabilježili i promjene u metabolizmu lipida i proteina. Godine 1916. Paulescu je započeo eksperiment s ekstraktom gušterače dobivenim njegovom izvornom metodom, koji je intravenski ubrizgan u pse koji su bolovali od dijabetesa. Rezultati njegovih prvih eksperimenata pokazali su: “Ekstrakt gušterače ubrizgan u perifernu venu proizvodi: 1. smanjenje, pa čak i privremenu supresiju dijabetičke hiperglikemije, koja može biti zamijenjena hipoglikemijom; 2. smanjenje ili čak privremenu supresiju glikozurije; 3. smanjenje uree u krvi; 4. smanjenje uree urina. Drugim riječima, intravenozna injekcija ekstrakta gušterače ima za posljedicu nestanak simptoma dijabetesa. Smanjenje dijabetičkog sindroma počinje odmah nakon ubrizgavanja, a maksimum doseže nakon dva sata – i traje oko 12 sati.” Zaključio je: “Ovo otkriće, koje baca novo svjetlo na patogenezu dijabetesa, daje nam i ključ za liječenje ovog sindroma.” Paulescu je 1921. objavio svoje podatke u dva izvanredna francuska časopisa i to osam mjeseci prije prve publikacije Bantinga i Besta u veljači 1922. Jasno je da je inzulin otkriven u Europi. Zaključak: Paulescu je smatrao da je novootkriveni hormon, nazvan pancrein, ključni element u liječenju dijabetesa, ali njegovo izvanredno istraživanje nepravedno je zanemareno.

Background and Aims. Diabetes mellitus and obesity modify the resting metabolic rate (RMR) in opposite directions. This study aimed to evaluate the relationship between RMR, insulin activity and adipocytokines in type 2 diabetes patients with associated obesity. Material and Method. Anthropometric and biochemical measurements, bioimpedance body composition, C peptide, insulin, proinsulin, adiponectin, leptin, indirect calorimetry measured RMR were determined in 306 (53% male, 54.9% obese) diabetic patients. Results. RMR, C peptide, insulin, proinsulin, Homeostasis Model Assessment (HOMA) IR, HOMA %B, leptin increased and adiponectin decreased with body mass index (BMI). BMI had a statistical significant higher effect size on fat mass (FM), leptin (0.652-0.339 eta squared), moderate positive effect size on fat-free mass (FFM), insulin, C peptide, RMR, HOMA %B (0.228 - 0.155 eta squared) and lower effect size on HOMA-IR, adiponectin, proinsulin-to-adiponectin ratio, proinsulin (0.098-0.062 eta squared). RMR had positive correlations with FFM (r=0.633), BMI (r=0.300), proinsulin-to-adiponectin ratio (r=0.218), HOMA1-IR (r=0.176), proinsulin (r=0.151), insulin (r=0.144), fasting plasma glucose (r=0.132), fat mass (r= 0.131), triglycerides (r = 0.119), proinsulin-to-insulin ratio (r= 0.117) and negative with age (r=-0.368), HDL cholesterol (r=-0.284), adiponectin(r=-0.282) and leptin (r=-0.178). Conclusions RMR was correlated with HOMA IR and insulin resistance biomarkers, but not with HOMA %B and C peptide.

Prevention of diabetes mellitus is done by increasing medical knowledge about a healthy lifestyle, early identification and reduction of risk factors. The present study is a review of national projects and studies of medical education, appreciates the involvement of experts, authorities and the media in informing the public on diabetes and shows the impact on the population. Although efforts are made to increase the level of medical education, patient compliance with diabetes remains low on lifestyle changes, compliance with treatment, and regular medical visits.

Background The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania) study is the first national study analyzing the prevalence of diabetes mellitus (DM) and prediabetes, and their association with cardiometabolic, sociodemographic, and lifestyle risk factors in the Romanian population aged 20–79 years. Methods This was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Sociodemographic, lifestyle, and anamnestic data were collected through self- and interviewer-administered questionnaires, and biochemical assays and oral glucose tolerance tests were performed. Results In all, 2728 participants from 101 clinics of general practitioners were randomly selected, with a probability proportional to population size according to the 2002 Romanian Census. The participation rate was 99.6%. Impaired glucose regulation (prediabetes, known and unknown DM) was found in 28.1% of the study population. The overall age- and sex-adjusted prevalence of DM was 11.6% (95%CI 9.6%–13.6%), of which 2.4% (95%CI 1.7%–3.1%) had unknown DM. The prevalence of DM increased with age and was higher in men than in women. The age- and sex-adjusted prevalence of prediabetes was 16.5% (95%CI 14.8%–18.2%), with the highest percentage in the 60–79 year age group and in women. Obesity, abdominal obesity, dyslipidemia, low education level, and a family history of diabetes were associated with glucose metabolism disorders. Conclusions The PREDATORR study shows a high prevalence of impaired glucose regulation in the adult Romanian population, providing data on the prevalence of DM and prediabetes and their association with several risk factors.

The human skin is not only the largest organ, but also the most important candidate for novel non-invasive methods of investigation. Here we describe a large-scale prototype for determining the real-time distribution of the electrical activity from the surface of the human skin. A collection of 200 sensors have been placed across the entire trunk surface. The output of each sensor was remotely inserted into a 20 × 10 LED matrix for a parallel capture of the signals. Continuous observations of the electrical activity pattern were made above the LED matrix by a digital camera in an obscure environment. A total of 5.2 million measurements (25,920 maps) have been recorded as light intensities from the LED matrix and converted into percentages for evaluation. A total of 36 individuals were divided equally into two groups and subjected to a short glucose tolerance test for 1 h; one group with established Type 2 Diabetes (T2D) and the other group without diabetes. The electrical activity pattern and the average signal intensity of normal individuals (37% ± 8.1) and diabetic individuals (58% ± 7.8), showed a significant difference of 21%. The average signal intensity on the ventral side (VS) and dorsal side (DS) of the torso exhibited different behaviors in diabetics and non-diabetics. On average, diabetic individuals have shown an electrical activity of higher intensity on DS (DS = 60%, VS = 55%), while the normal group has shown a higher intensity on VS (DS = 36%, VS = 39%).

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The aim of this study was to correlate anthropometric, biochemical and oxidative stress parameters in newly diagnosed (ND) T2DM patients and to investigate the role of oxidative stress in T2DM associated with obesity. A group of 115 ND- T2DM patients was compared to a group of 32 healthy subjects in terms of clinical, anthropometric, biochemical and oxidative stress parameters. ND-T2DM patients had significantly lower adiponectin, glutathione (GSH) and gluthatione peroxidase (GPx) and elevated insulin, proinsulin, HOMA-IR index, proinsulin/insulin (P/I) and proinsulin/adiponectin (P/A) ratio, fructosamine, and total oxidant status (TOS). The total body fat mass was positively correlated with total oxidant status (TOS). Positive correlations were found between TOS and glycated hemoglobin (HbA1c), and between TOS and glycaemia. Negative correlations were identified between: GPx and glycaemia, GPx and HbA1c, and also between GSH and fructosamine. The total antioxidant status was negatively correlated with the respiratory burst. The identified correlations suggest the existence of a complex interplay between diabetes, obesity and oxidative stress.

Background and Aims: Resting metabolic rate (RMR) is important to estimate energy requirements. Our aim was to investigate the RMR in newly diagnosed type 2 diabetic (T2DM) patients with metabolic syndrome (MS) in relation with obesity, gender, some adipokines and insulin resistance parameters. Material and Methods: 138 newly diagnosed T2DM adults were evaluated for anthropometric, clinical, biochemical parameters, and RMR. The group was subdivided according to body mass index and MS presence. Results: Determined RMR (RMRd), predicted RMR (RMRp), oxygen consumption and carbon dioxide production at rest were significantly lower for subjects with BMI < 30 kg/m2 compared to subjects with BMI ≥ 30 kg/m2 (pConclusions: Subjects with T2DM and MS have significantly lower than predicted RMR, compared to those without MS, indicating that they may have an energy sparing metabolism. Gender influences the energy metabolism and may play a particular role in energy the metabolism of people with T2DM and MS.

Background and aims. The aim of this paper was to make a comparison between the main clinical characteristics (especially age at onset and body mass index - BMI) of newly diagnosed diabetic patients based on the analysis of our current data, our previous data and data from international literature. Materials and method. We analyzed a cohort of 1463 (757 males and 706 females) recorded between 2010-2012 and compared it with the previous cohorts of diabetic patients belonging to the same “Ion Pavel” Diabetes Centre, Bucharest and whose characteristics were published along the years. We divided patients according to age, sex and type of diabetes. Results. Our data showed that the main clinical characteristics (the decrease of the age at onset and the increase in BMI) in the recent cohort of diabetic patients can be related to the lifestyle changes and the increased prevalence of overweight and obesity in the general population. Conclusions. The pathogenesis of type 2 diabetes is closely related with a negative effect of overweight on the β-cell function, suggesting that prevention of diabetes must be based on a decrease in BMI induced by an appropriate change in the modern pathogenic lifestyle.

I don’t know who did use for the first time the terms of diabetologist and diabetology. Diabetologia, the most famous European journal in this field has already 53 years and those who created it were, of course diabetologists. “The antidiabetic center” from Bucharest was established 72 years ago, thus the author of this success becoming the first Romanian diabetologist. The “CI Parhon” National Institute of Endocrinology in Bucharest was established in 1946. Fortunately, the relationships between Constantin I. Parhon (President of the Great National Assembly in 1947) and Ion Pavel (a close of the Romanian Royal House) were of mutual respect. This is why in Romania endocrinology never included diabetes and the Romanian diabetology could develop progressively and independent, without barriers but also without the backup it would have deserved. C.I. Parhon (1874-1967) lived for 93 years while I. Pavel (1897-1991) lived for 94 years. Each of them left behind a medical specialty in its own.

Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases

Obesity is an epidemic disease, increasingly addressed through surgical options for weight loss. Benefits of these surgical procedures, such as weight loss and improvement of obesity-related co-morbidities, are well established. However, postoperative complications do occur. Deficiencies in micronutrients, which include water and fat-soluble vitamins and minerals, are common after bariatric surgery. Recognition of the clinical signs and symptoms of micronutrient deficiencies is important to minimize long-term adverse effects.

a b s t r a c t Aim: To investigate the historical changes in survival with diabetes in elderly people with diabetes. Research design and methods: We analyzed 6504 deaths (44.5% males) registered in a large urban population, aged � 65 years, and deceased between 1943 and 2009. We split the analysis into three time periods according to year of death: 1943‐1965, 1966‐1988 and 1989‐ 2009. The parallel changes in the corresponding general population were available. Results: The mean age at diabetes onset was 70.8 � 4.7 years, with mean disease duration at death 7.5 � 5 years, and mean age at death 78.3 � 5.9 years. The mean survival loss due to diabetes (expected minus observed survival) was 4.5 � 5.1 years (4.9 � 5.1 years for females versus 4.1 � 5.2 years for males, p < 0.001). The mean disease duration at death was 6.4 � 5.7 years in the period 1943‐1965, followed by a significant ( p = 0.019) rise to 7 � 5 years in 1966‐ 1988, and 8.3 � 4.9 years ( p < 0.001) in 1989‐2009. There was a significant increase in coronary heart disease and stroke, and a significant decrease in infections and end-stage renal disease as causes of death. Conclusions: We found a significant increase in age at onset and survival with diabetes leading to a significant increase in age at death. Females had a higher survival loss due to diabetes compared with males.

The prevalence of type 2 diabetes mellitus (T2DM) and obesity is steadily increasingworldwide. To fight the twin pandemics of obesity and T2DM, clinicians need everytool they can get. Major, durable weight loss is uncommon with medical andbehavioral approaches; many diabetes drugs promote weight gain, while using themto obtain better blood glucose profiles increases the risk of hypoglycemia. Bariatricsurgery seems to be the most effective method for promoting major and durableweight loss in obese subjects, leading also to ameliorations of obesity-associated comorbidities,especially T2DM. Currently, indications for bariatric surgery includemorbidly obese patients or patients with a body mass index (BMI) >35 withsignificant co-morbidities. Currently, bariatric surgery (also referred to as“metabolic surgery”) is advocated for the treatment of T2DM even in overweightsubjects who do not meet the current BMI criteria. This review examines the currentevidence regarding the mechanisms of T2DM resolution following bariatric surgery.

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I2 = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

To investigate the historical changes in survival with diabetes in adult type 2 diabetes patients.We analyzed 9066 deaths, 54.2% males, registered at "I. Pavel" Bucharest Diabetes Centre, aged 40-64 years and deceased between 1943 and 2009. We split the analysis in three time periods according to year of death: 1943-1965, 1966-1988 and 1989-2009.The mean age at diabetes onset was 55.5 ± 6.2 years, with mean disease duration at death 12.7 ± 8.2 years and mean age at death 68.2 ± 8.7 years. The mean disease duration at death was 9.9 ± 7.3 years in 1943-1965 period, followed by a significant (p0.001) rise to 12.2 ± 8.2 years in 1966-1988, and 14 ± 8.1 years (p0.001) in 1989-2009. There was a significant increase for coronary heart diseases and cancer and a significant decrease for infections and end-stage renal disease as causes of death.We found a significant increase in age at onset and survival with diabetes leading to a significant increase in age at death.

Resistin is a cytokine which plays an important role in cardiovascular disease by influencing systemic inflammation and endothelial activation. In human endothelial cells (HEC) it increases the expression of P-selectin and fractalkine, and enhances monocyte adhesion by antioxidant mechanisms. This study investigated whether the natural antioxidants curcumin (CC) and an extract of Morus alba leaves (MA) have protective effects in resistin-activated HEC. HEC were exposed to 100 ng/mL resistin for 6 and 18 h in the absence or presence of MA or CC and the expression of fractalkine and P-selectin was determined by RT-PCR and western blot. Intracellular accumulation of reactive oxygen species (ROS) was monitored by fluorimetry and NADPH oxidase activity by a lucigenin-enhanced chemiluminescence assay. In addition, adhesion assays using the monocytic U937 cells were performed. The results showed that treatment of HEC exposed to resistin with MA and CC: (1) inhibited significantly P-selectin and fractalkine expression, (2) inhibited the increase in the intracellular ROS level, (3) reduced NADPH activation and (4) reduced monocytes adhesion to HEC. The results indicate that MA and curcumin target resistin-induced human endothelial activation partly via antioxidant mechanisms and suggest that they may represent therapeutic agents in vascular disease mediated by resistin. Copyright © 2011 John Wiley & Sons, Ltd.

Diabetes mellitus is a complex disorder of the energy metabolism of the human body. In the last WHO/ADA classification, the main forms of this disease are Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus. According to the same classification, the pathogenesis of T2DM is considered to include a progressive insulin secretory defect on the background of insulin resistance. Recently, controversies surround the concept of peripheral insulin resistance emerging in the 70's as an attempt to explain the differences from the T1DM phenotype whose autoimmune nature was as that time revealed. The insulin resistance hypothesis was based on the supposition that high plasma insulin levels are the result of a primary molecular defect against which the normal beta cells will react with an increased insulin secretion. This hypothesis has been used to explain both the pathogenesis of T2DM and the metabolic syndrome, named also for a short period of time "the insulin resistance syndrome". We will try to argue that what it is attributed to peripheral insulin resistance belongs in fact to obesity. Special emphasis is put on the role of the adipocytes, including the secretion of different adipokines with the secondary lipotoxicity, oxidative stress and pro-inflammatory reaction, explaining the complex relationship between obesity and diabetes.

Background: The aim of this study was to investigate the occurrence of subclinical atherosclerosis, evaluated by carotid artery intima-media thickness (CIMT) in subjects with newly diagnosed type 2 diabetes. Methods: A total of 167 subjects, 50 newly diagnosed type 2 diabetic subjects and 117 non-diabetic subjects were included in the study. Obese and overweight newly diagnosed type 2 diabetic patients were matched for age and BMI with obese and overweight non-diabetic subjects. Only postmenopausal women were selected. The following biomarkers were analyzed: fasting glucose, HbA1c, fasting insulin, fasting proinsulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, adiponectin, leptin, hs-CRP, urine albumin/creatinine ratio. 75 g oral glucose tolerance test was performed in all subjects. Ultrasound imaging was used to evaluate IMT of the common carotid artery. Results: CIMT was greater in newly diagnosed type 2 patients compared to non-diabetic subjects. When analyzed by BMI, the difference regarding CIMT between diabetic and non-diabetic subjects was significant only in overweight subjects, in both sexes. In univariate analysis in men with newly diagnosed type 2 diabetes, CIMT was positively correlated with age, SBP, triglycerides, leptin and negatively correlated with HDL-cholesterol and in women CIMT was positively correlated with SBP and leptin. Independent determinants of CIMT in patients with newly diagnosed type 2 diabetes were in men age (β = 0.556, p = 0.0028) and log leptin (β = 0.393, p = 0.049) and in women systolic blood pressure (β = 0.48, p = 0.026). Conclusions: Subclinical atherosclerosis is present in newly diagnosed type 2 diabetic subjects. Body fat accumulation in men and hypertension in postmenopausal women have a primary role in increase carotid intima-media thickness.

Microvascular complications associated with type 1 diabetes mellitus (T1DM) are caused in part by endothelial dysfunction. We aimed to determine the association between polymorphisms in endothelial nitric oxide synthase (eNOS) gene (894G>T, 4ab) and T1DM-associated microvascular disorders, and the roles of nitrite/nitrate products (NOx) and low molecular weight-AGEs (LMW-AGEs) levels in this relationship. We carried out a case-control study (328 subjects) and determined genotypes by PCR. The rare-type TT of eNOS 894G>T was significantly overrepresented in patients without microvascular disorders as compared with control (OR=3.64; 95% C.I.=1.02–12.73; P=0.039). The prevalence of neuropathy was high among 894GG homozygotes (OR=0.5; 95% C.I.=0.29–0.86; P=0.012) who had high levels of triglycerides, elevated systolic BP, increased NOx, and LMW-AGEs. Decreased NOx levels were associated with 894TT genotype (beta=−0.65; P=0.043) in diabetic patients prone to microvascular complications. Multiple regression analysis indicated a negative correlation between eNOS 894G>T and diabetic neuropathy (P=0.025). The distribution of eNOS 4aa genotype was high (P=0.042) in patients with T1DM; however, it does not represent a risk factor for neuropathy. The overrepresentation of eNOS 894TT genotype in diabetic patients is associated with low risk for neuropathy. Decreased NOx and LMW-AGEs levels and lower lipid profile are the main features of patients carrying the eNOS 894T allele. These data suggest that the eNOS 894TT genotype may play a protective role by preventing microvascular disorders.

To investigate the survival with diabetes in patients treated with insulin from diagnosis.We analyzed 845 subjects, 55.9% males, registered at "I. Pavel" Bucharest Diabetes Centre, insulin-treated from diagnosis, aged40 years and deceased between 1946 and 2005. We divided the subjects in two groups by age at diagnosis: group A18 years and group B 18-39.99 years. We used 20 years time periods for year of death: 1946-1965, 1966-1985 and 1986-2005.The mean age at diabetes onset was 30.36+/-8.04 years, disease duration at death 20.98+/-11.62 years and age at death 51.34+/-14.37 years. The mean increase in survival with diabetes was 19.3 years for group A and 15.9 years for group B. There was a significant decrease in infections in both groups. The increase in coronary heart diseases and stroke is evident only in group B.We found no changes in age at onset, which combined with an increase in survival with diabetes lead to a significant increase in age at death over the six decades analyzed.

Advanced glycation end products (AGEs) are involved in the occurrence of vascular complications in diabetes. The present study was undertaken to investigate the level of low-molecular weight products of AGEs (LMW-AGEs) in relation to microvascular complications in type 1 diabetes, and the possible relationship with nitric oxide (NO) as a marker of endothelial function. Patients with normal renal function (NRF) were classified into two groups: (1) without, and (2) with diabetic neuropathy; and patients with renal impairment also into two groups: (3) diabetic renal disease, and (4) end-stage renal disease. The fluorescence of LMW-AGEs and measurement of NO metabolites was assessed in 277 serum samples. In addition, multiple regression analysis was performed. In group 1, LMW-AGEs level (9.3±1.1 AF%) was higher than in the control group (2.4±0.3 AF%). A trend in the increase of LMW-AGEs with neuropathy (29.7±5.5 AF%, group 2), and further with renal impairment (47.0±8.0, group 3 and 137.8±25.5 AF%, group 4), was observed. In multivariate regression analysis LMW-AGEs were associated with NO metabolites in group 2. In NRF patients, diabetic neuropathy was significantly correlated with LMW-AGEs and NO metabolites, independently of serum creatinine and duration of diabetes. This relationship suggests that the NO and LMW-AGEs’ actions (possibly synergistic) in endothelial activation possess a role in the initiation and development of diabetic microvascular complications.

Background: Blood pressure control is the main influential variable in reducing microalbuminuria in patients with type 2 diabetes. In this subanalysis of the Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide sustained release (SR) and enalapril in reducing blood pressure and microalbuminuria in patients ≥65 years of age. Methods: Of the 570 hypertensive patients with type 2 diabetes and persistent microalbuminuria in the NESTOR study, 187 (33%) individuals ≥65 years of age were included in this analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine and/or atenolol was added if required. Results: The urinary albumin-to-creatinine ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group. Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35% limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the enalapril groups, respectively (P = .1136). The effects of both treatments seen in these elderly patients were similar to those observed in the main population, although the extent of the reduction in microalbuminuria was slightly higher. Both treatments were well tolerated, and no difference between groups was observed regarding glucose or lipid profiles. Conclusion: Indapamide SR is not less effective than enalapril in reducing microalbuminuria and blood pressure in patients aged >65 years of age with type 2 diabetes and hypertension. Am J Hypertens 2007;20: 90-97

Genome-wide association studies (GWAS) published in the last decade raised the number of loci associated with type 1 (T1D) and type 2 diabetes (T2D) to more than 50 for each of these diabetes phenotypes. The environmental factors seem to play an important role in the expression of these genes, acting through transcription factors that bind to promoters. Using the available databases we examined the promoters of various genes classically associated with the two main diabetes phenotypes. Our comparative analyses have revealed significant architectural differences between promoters of genes classically associated with T1D and T2D. Nevertheless, five gene promoters (about 16%) belonging to T1D and six gene promoters (over 19%) belonging to T2D have shown some intermediary structural properties, suggesting a direct relationship to either LADA (Latent Autoimmune Diabetes in Adults) phenotype or to non-autoimmune type 1 phenotype. The distribution of these promoters in at least three separate classes seems to indicate specific pathogenic pathways. The image-based patterns (DNA patterns) generated by promoters of genes associated with these three phenotypes support the clinical observation of a smooth link between specific cases of typical T1D and T2D. In addition, a global distribution of these DNA patterns suggests that promoters of genes associated with T1D appear to be evolutionary more conserved than those associated with T2D. Though, the image based patterns obtained by our method might be a new useful parameter for understanding the pathogenetic mechanism and the diabetogenic gene networks.