Untreated Diabetes Research Articles

Rhino-orbital mucormycosis in a patient with diabetes

A man aged 70 years who had diabetes for 12 years presented with an ulcer that had been on his right cheek for 5 days and had prevented him from opening his right eye for the past 3 days. He was from an impoverished family and came from a very remote area of Puducherry, India. Since being diagnosed with type 2 diabetes, he had received only irregular treatment because he was unable to aff ord the necessary drugs; his HbA1c was 11% (96·7 mmol/mol). He had a 3·2 cm long, slough-covered ulcer on his right cheek and had completely lost vision in his right eye. The histopathological examination revealed broad wide-angled aseptate hyphae with thrombosis of blood vessels and necrosis—typical of mucormycosis. The patient was treated with surgical debridement of the necrotic tissue and given intravenous amphotericin B. However, 5 days after admission, his conscious level deteriorated, suggestive of intracranial extension, and he died 2 days later. Many people in India are not aware of the risk factors, symptoms, and treatment of diabetes, so many patients seek treatment only when complications develop. Mucormycosis is a rare complication seen in patients with untreated diabetes. The morbidity and mortality associated with this complication are further magnifi ed by the scarcity of skilled doctors in many areas.

Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders.

PurposeThe severity of untreated or refractory diabetes mellitus has been functionally linked to elevated concentrations of free plasma glucose, clinically defined as hyperglycemia. Operationally, the pathophysiological presentations of prolonged hyperglycemia may be categorized within insulin-dependent and insulin-independent, type 1 and type 2 diabetic phenotypes, respectively. Accordingly, major areas of empirical biomedical research have focused on the elucidation of underlying mechanisms driving key cellular signaling systems that are significantly altered in patients presenting with diabetes-associated chronic hyperglycemia.MethodsPresently, we provide a translationally oriented review of key studies evaluating the aberrant effects of hyperglycemia on two major signaling pathways linked to debilitating cellular and systemic effects via targeted disruption of mitochondrial bioenergetics: (1) advanced glycation end-products (AGEs)/and their cognate receptor for advanced glycation end-products (RAGEs), and (2) the hexosamine biosynthetic pathway (HBP).ResultsIn preclinical models, cultured vascular endothelial cells exposed to hyperglycemic glucose concentrations were observed to produce enhanced levels of reactive oxygen species (ROS) functionally linked to increased formation of AGEs and expression of their cognate RAGEs. Importantly, inhibitors of AGEs formation, mitochondrial complex II, or un-couplers of oxidative phosphorylation, were observed to significantly reduce the effects of hyperglycemia on ROS production and cellular damage, thereby establishing a critical linkage to multiple levels of mitochondrial functioning. Hyperglycemia-mediated enhancement of mitochondrial ROS/superoxide production in vascular endothelial cells has been functionally linked to the shunting of glucose into the HBP with resultant long-term activation of pro-inflammatory signaling processes. Additionally, exposure of cultured cells to hyperglycemic conditions resulted in enhanced HBP-mediated inhibition of protein subunits of mitochondrial respiratory complexes I, III, and IV, intimately associated with normative cellular bioenergetics and ATP production.ConclusionsConvergent lines of evidence link chronic hyperglycemic conditions to aberrant expression of AGEs/RAGEs and HBP signaling pathways in relation to the pathophysiological formation of ROS and pro-inflammatory processes on the functional dysregulation of mitochondrial bioenergetics.

Effects of Crabapple (Malus sylvestris) on Blood Glucose and Lipid Levels in Diabetic Rats

We aimed to investigate the impact of crabapple on blood glucose and lipids levels in the streptozotocin (STZ)-induced diabetic rats. Rats were divided into 3 groups. The first group was control; the second group was diabetic rats while the third group was diabetic rats fed with crabapple (2 g/day). Diabetes was induced by STZ. After 6 weeks of experimental period blood samples were collected from the abdominal aorta under anaesthesia and lipid parameters were measured with auto-analyzer. However, there was significant increase both in blood glucose and lipid levels of untreated diabetes group. Likewise, blood triglyceride levels were found to be significantly reduced in the diabetic group fed with crabapple compared with untreated diabetic animals. This is the first study that approves blood glucose and triglyceride lowering effects of crabapple after six weeks supplementation. However, the underlying mechanisms of this action remain to be investigated later.

Transdermal Detection of Low Concentrations of Hydrogen Sulfide

We report here a novel approach to measure circulating hydrogen sulfide (H2S) non‐invasively as a potential way to diagnose and monitor endothelial dysfunction and peripheral artery disease (PAD). PAD is a life‐threatening condition caused by arterial constriction and obstruction of blood flow leading to limb ischemia. Current methods to diagnose and monitor PAD lack sensitivity, result in frequent false‐negatives, and require specialized technicians. Recent studies indicate that decreased H2S production is an underlying cause of PAD. In addition, reduced plasma H2S correlates with endothelial dysfunction in untreated hypertension, diabetes, sleep apnea and other cardiovascular diseases. Conversely, excess H2S is cytotoxic causing irreversible damage to mitochondrial function. Therefore, careful monitoring of plasma H2S levels is essential to diagnose and treat vascular disease and to prevent H2S toxicity. This device was designed to measure H2S at the surface of the skin to test the hypothesis that the diffusion rate (and therefore gas phase concentration) of H2S is directly proportional to the concentration of H2S in the blood. Our results demonstrate that the device is sensitive enough to detect H2S at 10 part per billion (ppb) or lower in gas standards and in the headspace of a 3 nM solution of Na2S (H2S donor). In vitro studies used excised rat skin superfused on the subcutaneous surface with a H2S solution. H2S was detected in a stream of N2 gas flowing through a sealed chamber on the epidermal side both by GC/MS measurement and with the sensor only when the superfusing solution contained an H2S donor demonstrating that H2S diffuses through the skin. The diffusion rate of H2S through excised abdominal skin from a male Sprague‐Dawley rat is approximately 1.42×10−9 μmol/s/cm2/μM. The device also detected increases in H2S on the skin surface in anesthetized rats within seconds of intra‐venous injection of Na2S at doses that caused a fall in arterial pressure, with an estimated average diffusion rate of 4×10−8 μmol/s/cm2/μM. Therefore, this noninvasive, highly‐sensitive and portable device has the potential to transform diagnosis and monitoring of early stage PAD and to monitor H2S biosynthesis or exposure in vivo.

Type 2 diabetes and the risk of non-Hodgkin's lymphoma: a report from two population-based cohort studies in China.

Coinciding with the increased incidence of non-Hodgkin's lymphoma (NHL) during the past decades, there has been a significant increase in the prevalence of diabetes mellitus in mainland China. We therefore evaluated whether type 2 diabetes (T2D) is associated with the risk of NHL using data from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). The SMHS and SWHS are two on-going, prospective, population-based cohorts of more than 130 000 Chinese adults in urban Shanghai. Self-reported diabetes was recorded on the baseline questionnaire and updated in follow-up surveys. Cox regression models with T2D as a time-varying exposure were used to estimate hazard ratios and 95% confidence intervals, adjusting for covariates. After a median follow-up of 12.9 years for SWHS and 7.4 years for SMHS, 172 NHL cases were identified. Patients with T2D have a higher risk of incident NHL with a hazard ratio of 2.00 (95% confidence interval: 1.32-3.03) compared with those without diabetes. This positive association remained when the analysis was restricted to untreated diabetes or after excluding NHL cases that occurred within 3 years after the onset of diabetes. No interaction effect was found in the development of NHL between T2D and other potential risk factors. A linear inverse association was found between T2D duration and the risk of NHL in both men and women (Pfor linearity<0.01), with a highest risk of incident NHL in the first 5 years after the diagnosis of diabetes. Our study suggested that T2D might be associated with an increased risk of NHL.

Antidiabetic and Plasma Endogenous Antioxidant Activity of &lt;i&gt;alstonia boonei&lt;/i&gt; in Alloxan-Induced Male Diabetic Rabbits

Alstonia boonei is a well-known plant of medicinal value but its effect on endogenous plasma antioxidant in diabetes remains unknown. Thus, need to investigate the effects of the methanolic extract of the plant on plasma bilirubin and uric acid level in alloxan induced diabetes rabbits. Twenty five rabbits divided into five groups of four rabbits each were used. There was a significant change in the levels of total bilirubin and uric acid in the plasma of treated groups as compared with both non diabetes and untreated diabetes group, while conjugated bilirubin level was relatively unchanged in the treated group. This work clearly indicates that methanolic extract of Alstonia boonei stem bark is effective in the management of diabetes as well as restoration of lost endogenous plasma antioxidants experienced in diabetes mellitus.

Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes

Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60mgkg−1, i.p.). Animals from exercised groups swam (5 days/week, 90min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-α, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM.

Single muscle fiber contractile properties in diabetic RAT muscle.

Diabetes is associated with accelerated loss of muscle mass and function. We compared the contractile properties of single muscle fibers in young rat soleus muscle of uncontrolled streptozotocin-induced diabetic animals (n = 10) and nondiabetic controls (n = 10). Single fiber maximal force, shortening velocity, and power were assessed during maximal activation with calcium using the slack test 4 weeks after induction. Myosin heavy chain expression was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Oxidized myosin levels were detected by analyzing protein carbonyls in muscle homogenates. All fibers expressed the type I myosin heavy chain isoform. Diabetic rats had higher blood glucose (537 vs. 175 mg/dl; P < 0.001) and lower body weight (171 vs. 356 g; P < 0.001) than controls. Muscle fibers from diabetic rats showed smaller cross-sectional area (1128 vs. 1812 μm(2) ), lower maximal force (258 vs. 492 μN), and reduced absolute power (182 vs. 388 μN FL/s) (all P < 0.0001). No differences were seen in shortening velocity, specific force or specific power. Myosin carbonylation was higher (P < 0.01) in diabetic rats. After 4 weeks of untreated diabetes, there are significant alterations in muscle at the level of isolated single fibers and myosin protein, although some contractile properties seem to be protected. Muscle Nerve, 2015 Muscle Nerve 53: 958-964, 2016.

Congenital heart disease and its journey from dental plaque to arterial plaque

Congenital heart disease is mostly found in children, approximately around 7–10% from overall heart diseases. The etiology is multifactorial but reported associations include untreated maternal diabetes, phenylketonuria, intake of retinoic acid last but not least is oral pathogens present in periodontopathic bacteria. The main objective of this article is to explain about different mechanisms by which it is associated with dental, periodontal manifestations. It also explains about two patients who reported to our hospital with congenital heart disease and their dental and periodontal management.

Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus.

In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood–brain barrier and tight junction markers in the rat hippocampus. Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood–brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood–brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction.

Electronic health record phenotyping improves detection and screening of type 2 diabetes in the general United States population: A cross-sectional, unselected, retrospective study

ObjectivesAn estimated 25% of type two diabetes mellitus (DM2) patients in the United States are undiagnosed due to inadequate screening, because it is prohibitive to administer laboratory tests to everyone. We assess whether electronic health record (EHR) phenotyping could improve DM2 screening compared to conventional models, even when records are incomplete and not recorded systematically across patients and practice locations, as is typically seen in practice. MethodsIn this cross-sectional, retrospective study, EHR data from 9948 US patients were used to develop a pre-screening tool to predict current DM2, using multivariate logistic regression and a random-forests probabilistic model for out-of-sample validation. We compared (1) a full EHR model containing commonly prescribed medications, diagnoses (as ICD9 categories), and conventional predictors, (2) a restricted EHR DX model which excluded medications, and (3) a conventional model containing basic predictors and their interactions (BMI, age, sex, smoking status, hypertension). ResultsUsing a patient’s full EHR or restricted EHR was superior to using basic covariates alone for detecting individuals with diabetes (hierarchical X2 test, p<0.001). Migraines, depot medroxyprogesterone acetate, and cardiac dysrhythmias were associated negatively with DM2, while sexual and gender identity disorder diagnosis, viral and chlamydial infections, and herpes zoster were associated positively. Adding EHR phenotypes improved classification; the AUC for the full EHR Model, EHR DX model, and conventional model using logistic regression, were 84.9%, 83.2%, and 75.0% respectively. For random forest machine learning out-of-sample prediction, accuracy also was improved when using EHR phenotypes; the AUC values were 81.3%, 79.6%, and 74.8%, respectively. Improved AUCs reflect better performance for most thresholds that balance sensitivity and specificity. ConclusionsEHR phenotyping resulted in markedly superior detection of DM2, even in the face of missing and unsystematically recorded data, based on the ROC curves. EHR phenotypes could more efficiently identify which patients do require, and don’t require, further laboratory screening. When applied to the current number of undiagnosed individuals in the United States, we predict that incorporating EHR phenotype screening would identify an additional 400,000 patients with active, untreated diabetes compared to the conventional pre-screening models.

Untreated diabetes mellitus, but not impaired fasting glucose, is associated with increased left ventricular mass and concentric hypertrophy in an elderly, healthy, Swedish population

Background/objectivesTo examine whether higher fasting plasma glucose (FPG) levels were independently associated with left ventricular (LV) mass and/or geometry in elderly, otherwise healthy subjects. MethodsWe tested cross-sectional associations between echocardiographically determined LV mass/geometric patterns, cardiovascular risk factors, and FPG categorized as normal fasting glucose (NFG), impaired fasting glucose (IFG), and untreated diabetes mellitus (DM), in 486 men and 207 women aged 56–79years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. ResultsUnadjusted mean LV mass index (LVMI) was significantly greater among subjects with DM than those without (90+/−26g/m2 vs. 85+/−20g/m2, p=0.01), as were both relative wall thickness (RWT) (0.43+/−0.09 vs. 0.40+/−0.08, p=0.01) and prevalence of concentric LV hypertrophy (LVH) (11% vs. 6%, p=0.03). However, only RWT remained significantly associated with the presence of DM after multivariable adjustment (p=0.04). Interaction analyses revealed that greater LVMI/LVH was predominantly associated with higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among subjects with IFG or DM, but not NFG. ConclusionsSubjects with untreated DM had higher values of LVMI and a greater prevalence of concentric LVH, but the associations were not independent of other risk factors. NT-proBNP was primarily associated with greater LV size in subjects with IFG or DM.

Inverse association of HbA1c with faecal elastase 1 in people without diabetes.

Faecal elastase 1 (FE1) was inversely correlated with diabetes duration and HbA1c in type 2 diabetes. The association of FE1 and HbA1c has not been investigated in people without diabetes. Type 2 diabetes patients (oral antidiabetic drugs or insulin: n = 391; medically untreated: n = 145) and matched (age, sex, practice) people without diabetes (n = 529) from general practices in Cambridgeshire (UK) were included. FE1 measurements (μg/g stool) were performed centrally (ScheBo-Tech Institute, Wettenberg, Germany). Linear regression models were fitted using FE1 as dependent variable and HbA1c, diabetes (no, untreated diabetes, treated diabetes) and interactions as independent variables. Potential confounders were sex, age, BMI, current alcohol consumption, smoking, triglycerides, and amylase. In univariate linear regression models, HbA1c was significantly inversely related to FE1 in controls (β-coefficient: -108.74, p < 0.0001), whereas no significant associations were found for the diabetes groups. The inverse relationship of HbA1c with FE1 concentrations in people without diabetes persisted after adjusting for potential confounders in multivariate regression (β-coefficient: -109.18, p < 0.0001). In people without diabetes, there were lower FE1 concentrations among those with increased diabetes risk (HbA1c 5.7%-6.4% [38.8-46.4 mmol/mol]: 395 ± 204 μg/g vs. HbA1c ≤ 5.6% [≤37.7 mmol/mol]: 476 ± 219 μg/g; p < 0.0001). The prevalence of FE1<100 μg/g was significantly increased among persons with an HbA1c of 5.7%-6.4% (38.8-46.4 mmol/mol) compared with those with a normal HbA1c ≤ 5.6% (≤37.7 mmol/mol) (6.1% vs. 1.4%; p = 0.004). The present study suggests that pancreatic exocrine dysfunction might be an early disturbance that develops in parallel with hyperglycemia.

Vitamins C and E (ascorbate/α-tocopherol) provide synergistic neuroprotection in the jejunum in experimental diabetes

The present study evaluated the synergistic effects of the association of ascorbic acid and α-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons (p<0.05). The association of ascorbic acid and α-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons.

Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease

This study evaluated the contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes. One-hundred and sixty cirrhotic patients with normal fasting plasma glucose (FPG), three with impaired fasting glucose and seven with untreated diabetes mellitus (DM) underwent an extended oral glucose tolerance test (OGTT). The OGTT data were analyzed with a Minimal Model to estimate dynamic (derivative) control (DC) and static (proportional) control (PC) of β-cell function, and with the Oral Glucose Insulin Sensitivity (OGIS)-2h index to estimate insulin sensitivity. Twenty-six patients (15.6%) had normal glucose tolerance (NGT), 60 (35.8%) had impaired glucose tolerance (IGT), and 84 (48.6%) had DM. DC was significantly reduced in DM vs. NGT and IGT patients. PC was significantly impaired in DM and IGT vs. NGT patients and in DM vs. IGT subjects. The OGIS-2h index was significantly reduced to a similar extent in DM and IGT vs. NGT patients. Patients with Child-Pugh class B and C cirrhosis had reduced DC and PC, but not OGIS-2h values, as compared with subjects in class A. Moreover, Child-Pugh class/score was an independent predictor of β-cell function even after adjustment for glucose tolerance. Abnormalities of glucose tolerance occur frequently in cirrhosis even in patients with normal FPG, thereby supporting the importance of performing an OGTT. Transition from IGT to DM is driven primarily by β-cell dysfunction. Insulin secretion worsens in parallel with the severity of liver disease, thus suggesting a detrimental effect of liver failure on pancreatic islets on its own.

Arsenic exposure and type 2 diabetes: results from the 2007-2009 Canadian Health Measures Survey.

Inorganic arsenic and its metabolites are considered dangerous to human health. Although several studies have reported associations between low-level arsenic exposure and diabetes mellitus in the United States and Mexico, this association has not been studied in the Canadian population. We evaluated the association between arsenic exposure, as measured by total arsenic concentration in urine, and the prevalence of type 2 diabetes (T2D) in 3151 adult participants in Cycle 1 (2007-2009) of the Canadian Health Measures Survey (CHMS). All participants were tested to determine blood glucose and glycated hemoglobin. Urine analysis was also performed to measure total arsenic. In addition, participants answered a detailed questionnaire about their lifestyle and medical history. We assessed the association between urinary arsenic levels and T2D and prediabetes using multivariate logistic regression while adjusting for potential confounders. Total urinary arsenic concentration was positively associated with the prevalence of T2D and prediabetes: adjusted odds ratios were 1.81 (95% CI: 1.12-2.95) and 2.04 (95% CI: 1.03-4.05), respectively, when comparing the highest (fourth) urinary arsenic concentration quartile with the lowest (first) quartile. Total urinary arsenic was also associated with glycated hemoglobin levels in people with untreated diabetes. We found significant associations between arsenic exposure and the prevalence of T2D and prediabetes in the Canadian population. Causal inference is limited due to the cross-sectional design of the study and the absence of long-term exposure assessment.

Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet

Endothelial dysfunction develops as a result of oxidative stress and is responsible for diabetic vascular complications. We investigated the effects of selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats. Male Wistar rats were divided into five groups: controls, untreated diabetics, and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was induced by a single intraperitoneal injection of low dose streptozotocin to rats fed a high fat diet. Endothelium-dependent and -independent relaxations were measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase levels were measured in liver samples. RT-PCR showed that selenium reversed increased NADPH oxidase expression and decreased eNOS expression to control levels. Selenium also improved the impairment of endothelium-dependent vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant status in diabetic rats. Our findings suggest that selenium restores a normal metabolic profile and ameliorates vascular responses and endothelial dysfunction in diabetes by regulating antioxidant enzyme and nitric oxide release.

Altered activities of kininase II, an angiotensin converting enzyme, prekallikrein, and nitric oxide in Kuwaiti patients with type 2 diabetes.

The current investigation was conducted to examine kininase II or angiotensin converting enzyme (ACE), plasma prekallikrein (PK), and nitric oxide (NO) concentrations in healthy Kuwaiti subjects and newly diagnosed Kuwaiti type 2 diabetic patients before and after treatment for 6 weeks with metformin hydrochloride 500 mg twice daily after meal. With the consent of volunteers, blood and urine samples were collected after an overnight fasting. Samples were collected from the diabetic patients before and after treatment for 6 weeks. Enzyme linked immunosorbent assay (ELISA) was carried out on the aliquoted samples to measure the concentration of kininase II. NO was detected via colorimetry. Plasma Kininase II or ACE levels were significantly (P <0.01) increased by 18% in untreated diabetics when compared with healthy volunteers. However, after treatment there was a significant decrease of 20% in their ACE levels. Plasma prekallikrein levels were raised significantly (P <0.01) by 28% in diabetic patients in contrast with the control subjects and the levels were significantly reduced (P <0.0001) by 44% after treatment with metformin hydrochloride. NO levels were found to be significantly decreased in plasma by 56% and in urine by 62% in untreated diabetic patients as compared with the healthy subjects. However, when the treated diabetic patients were compared with untreated diabetics, there was an increase of 50% in plasma and 37% in urine samples. The high levels of kininase II, prekallikrein, and reduced NO may be partly responsible for the induction of renal, cardiac, and hypertensive complications associated with type 2 diabetes. Reduced NO level is an indication of endothelial dysfunction resulting in increased blood pressure. Oral anti-diabetic treatment is associated with protective effects through the reduction of kininase II (ACE), prekallikrein, and elevation of NO levels.

TCTAP C-011 Stent Thrombosis That Long Inflation Using Perfusion Balloon Was Effective to Manage the Large Amount of Thrombus

### Patient initials or identifier number K.H. ### Relevant clinical history and physical exam A 58-year-old man was admitted to our hospital due to chest pain. His coronary risk factor was untreated diabetes. ECG showed ST elevation at II III aVF and Troponin I level was mildly elevated. He was

Java project on periodontal diseases: periodontal bone loss in relation to environmental and systemic conditions.

To assess in a population deprived from regular dental care the relationship between alveolar bone loss (ABL) and environmental/systemic conditions. The study population consisted of subjects from the Purbasari tea estate on West Java, Indonesia. A full set of dental radiographs was obtained of each subject and amount of ABL was assessed. In addition, the following parameters were evaluated: plasma vitamin C, vitamin D3 , HbA1c and CRP, the haptoglobin phenotype, presence of putative periodontopathic bacteria and viruses, dietary habits, smoking and anthropometrics. In this population 45% showed vitamin C depletion/deficiency, 82% had vitamin D3 insufficiency/deficiency, 70% were in a pre-diabetic state, 6% had untreated diabetes, 21% had elevated CRP values ranging from 3.1 to 16.1mg/l. Results of the regression analysis, including all above mentioned parameters, showed four significant predictors, explaining 19.8% of the variance of ABL. Number of Porphyromonas gingivalis cells and CRP values showed a positive relationship with ABL, whereas BMI and number of guava fruit servings were negatively related. Results confirm previous findings that elevated levels of P.gingivalis may be indicative for periodontitis progression. A new finding is that guava fruit consumption may play a protective role in periodontitis in a malnourished population.