DM Control Research Articles

Systemic RAGE ligands are upregulated in tuberculosis individuals with diabetes co-morbidity and modulated by anti-tuberculosis treatment and metformin therapy

BackgroundLigands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated.MethodsWe examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC).ResultsSystemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens.ConclusionsOur data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.

G protein-coupled receptor kinase-2: A potential biomarker for early diabetic cardiomyopathy.

BackgroundG protein‐coupled receptor kinase‐2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).MethodsC57BL/KS‐db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty‐four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age‐matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E′/A′ < 1 were regarded as LVDD.ResultsCompared to 8‐week‐old diabetic mice and 12‐week‐old control mice, GRK2‐mRNA level and expression in myocardial tissues of 12‐week‐old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen‐3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12‐week‐old diabetic mice elevated as well. The GRK2‐mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.ConclusionsGRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.

Risk factor control and medical therapy of coronary artery disease in Taiwan - Review and Recommendations - Part III: Blood sugar management for patients with coronary artery disease

Cardiovascular disease (CVD) is the leading cause of death in the world and the second important cause of death in Taiwan. Atherosclerosis CVD (ASCVD) especially coronary artery disease (CAD) is the major cause of CVD [1]. Clinically, the presentation of CAD can be divided into acute unstable disease, so-called acute coronary syndrome (ACS) and chronic stable disease. Up to now, the main risk factors for CAD are known as hyperlipidemia, hypertension, hyperglycemia, smoking and family history. The control of the above risk factors and lifestyle modifications can improve the prognosis of CAD patients [1,2]. Here, we described the blood lipid control, blood pressure control, blood glucose control, and lifestyle modifications for CAD in Taiwan. The followings are the part III for blood glucose control. Type 2 Diabetes mellitus (T2DM) has been suggested a CAD equivalent. The risk of CAD may be correlated with the baseline HbA1c. Numerous studies have demonstrated the benefits of controlling modifiable CV risk factors in people with diabetes. Therefore, in patients with documented CAD, DM control is recommended.Because the benefits of intensive glucose control emerge slowly, while the harms can be immediate, people with longer life expectancy have more to gain from intensive glucose control. The 4 randomized clinical trials (RCTs), including UKPDS, ACCORD, ADVANCE, VADT trials, or large meta-analyses, testing intensive glucose control vs. conventional glucose control did not show positive results in reducing major adverse cardiovascular events (MACE) in individual trials. There are also lack of HbA1c target CV outcome trials in patients with CAD. The impact of glucose control on macrovascular complications is less certain. In the consensus, glycemic treatment targets should be individualized based on patient characteristic, including frailty and comorbid conditions, and risk of adverse effects of therapy (e.g., hypoglycemia and weight gain), to balance the benefit and risks of glycemic control, rather than the strengthen the HbA1c target in patients with documented CAD.

2292 A Case Report of Glycogen Hepatopathy: A Reversible, yet Relapsing Cause of Hepatitis in Type 1 Diabetics

INTRODUCTION: Glycogen hepatopathy (GH), a rare glycogen storage disease caused by genetic or acquired overactivation of hepatic glycogen synthesis enzymes, can mimic non-alcoholic fatty liver disease (NAFLD). We describe a case of biopsy proven GH in an adult with Type 1 DM (T1DM). Similar to cases described in the current literature, our case not only portrays the challenges faced by physicians when diagnosing this condition, but also the importance of distinguishing this from NAFLD. CASE DESCRIPTION/METHODS: A 33-year-old Honduran woman with a 25-year history of T1DM complicated by gastroparesis, multiple episodes of DKA and hypoglycemia, and recurrent pancreatitis was referred for abnormal liver enzymes. Family history was negative for liver disease. There was no history of alcohol or recreational drug use. Patients medications included insulin and thyroxine. Physical exam showed hepatomegaly but no stigmata of chronic liver disease. AST and ALT had ranged from 100’s to over 7000 while ALP was elevated to over 400. Albumin, Total bilirubin, platelets, INR, eosinophils, viral hepatitis panel, ANA, smooth muscle AB, LKM Ab, celiac serologies, ceruloplasmin, alpha 1 antitrypsin, iron studies, and acetaminophen levels were all normal. An abdominal ultrasound showed “fatty liver” and an atrophic pancreas. CT abdomen showed hepatomegaly. CBD was found to be normal on EUS and MRCP. A liver biopsy demonstrated glycogenotic hepatocytes. DISCUSSION: GH is frequently misdiagnosed as NAFLD, a more common liver disease that is also associated with diabetes. While GH is known to be reversible with otherwise no known long-term complications, NAFLD has been shown to progress to cirrhosis and cause hepatocellular carcinoma. Definite diagnosis often requires liver biopsy because of overlapping clinical and radiographical pictures. Elevation of both glucose and insulin levels in the setting of fragile DM control is thought to play a role via overstimulation of glycogen synthesis. Recommended treatment is stable “tight” glycemic control; pancreatic transplantation has resulted in sustained GH remission in two case reports. The required degree of stability and tightness of glucose control is not yet known. An increased awareness of GH is needed in an attempt to prevent delay in diagnosis, in a condition with an otherwise unknown incidence.

Saxagliptin attenuates glomerular podocyte injury by increasing the expression of renal nephrin and podocin in type 2 diabetic rats.

To observe the effects of saxagliptin on the expression of mitogen-activated protein kinase 38 (p38MAPK), nephrin and podocin in renal tissue in type 2 diabetic (T2DM) rats, and to explore the possible mechanism of its renal protection. Forty-eight male Sprague-Dawley rats were used for the study and divided into four different groups: normal controls (Group NC), DM controls (Group DM), DM + glibenclamide (Group Su) and DM + saxagliptin (Group Sa). The day drug administration started was defined as week 0. After 12weeks, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), urea nitrogen (BUN) and creatinine (Cr) in serum were detected, simultaneously albumin and creatinine in urine were measured, respectively, and then urinary albumin/creatinine ratio (UACR) was calculated. The pathological morphology of kidney tissue in different groups was observed, and the expression of nephrin and podocin mRNA and protein in kidney tissue were detected. (1) After 12weeks, FBG and HbA1c in Group Su and Group Sa were significantly lower than those in Group DM (both P < 0.05), while there was no significant difference between Group Su and Group Sa. TC, TG and UACR in Group Sa were significantly decreased thanthose in Group DM. (2) When compared with Group DM, the kidney weight/body weight ratios, the average width of glomerular basement membrane and foot process fusion ratio were all improved in Group Sa after 12weeks. (3) The expression of p38MAPK mRNA and protein was significantly decreased, while nephrin and podocin mRNA and protein were significantly higher in Group Sa than those in Group DM after 12weeks. (4) A significant negative correlation was detected between p38MAPK mRNA and nephrin (r = - 0.421, P = 0.009) and podocin mRNA (r = - 0.570, P = 0.000), respectively. Saxagliptin can reduce urinary albumin excretion and exert renal protective effect, especially on podocytes in T2DM rats. The mechanism may be related to its inhibition of renal p38MAPK signaling pathway and the increase in the expression of nephrin and podocin in renal tissue, which is independent of its hypoglycemic effect.

The Effect of Android-based DM Diet Education Program on Eating Behavior and Blood Glucose Level of DM Type 2 Patients in Health Centers in Bandung City

The purpose of this study was to examine the effect of Android-based DM diet education program on changes in eating behavior and blood glucose levels. The study design used in this study was a cluster randomized control trial with a pre-post intervention. The study involved 33 DM patients in the intervention group and 37 patients in the DM control group. The proportion of female subjects was higher than male subjects in the treatment group. Nutrition education intervention, with application media, significantly increased DM disease severity perception score (p = 0.000), expectations of DM treatment (p = 0.000), eating habits practice (p = 0.025), and fasting blood sugar examination (p = 0.414). However, compared to counseling, the increase in perception of the severity of DM disease was significantly different, but for DM treatment expectation perceptions, the practice of eating habits, and fasting blood sugars were not significantly different. Despite increased disease severity perception scores, DM treatment expectations, practice of eating habits, and fasting blood sugar checks in the application group were higher than in the extension group. Thus, the use of both nutritional education intervention methods has a positive impact on increasing perceptions of severity, treatment expectations, practice of eating habits, and fasting blood sugar of DM type 2 patients.

Expression and localization of placental miRNAs in gestational diabetes mellitus pregnancies

Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C > T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C > T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population.This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C > T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results.T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p < 0.0001 by T allele; p = 0.002 by TT and p < 0.0001 by CT genotype).The present study suggests that the functional SNP-1562C > T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.

&lt;i&gt;Schinus molle &lt;/i&gt;Leaves Compost Improves the Growth, Quality and Productivity of Strawberry (&lt;i&gt;Fragaria × Ananassa &lt;/i&gt;Duch) in Potting Culture

Schinus molle leaves, compost (SLC) incorporated with soil at different volume rates contrasted with control (soil alone), intending to improve and stimulating strawberry growth. Anecdotal accounts of SLC for these purposes the experiment has examined the impacts of SLC on strawberry growth and production responses. This research assessed the impacts of a six volume% (v: v) rates of SLC combined with soil at 0, 20, 40, 60, 80 and 100 of growing medium (field soil). The pots RCBD experiment included four replicates designed at the faculty of agriculture, Sana’a University. Plants cultivated in 20% SLC was significantly (p&lt;0.05) greater than control (field soil) in leaf area, yield, fruit weight and crown DM% by about 12.8% 25.8%, 20.4% and 101.6% subsequently. Meanwhile, transplants grown in 80 and 100% SLC developed the highest quantity of crowns and longer of peduncle. Transplants grown in 60% SLC was the poorest of flower number per plant measured with other treatments. Plants in 100% SLC showed the significantly downer of a DM% in the roots and crown parts 65.3% and 82.7% lower than control, respectively, nevertheless, composed the significantly greater 50.4% of fruit TSS than the control treatment. The variation between the SLC rates on the root characters showed that the 100% SLC increased the roots network volume cm3, root length cm2 root surface area cm2, specific root length cm. This study illustrates the benefit of that application SLC.

Developmental exposure to polychlorinated biphenyls (PCBs) in the maternal diet causes host-microbe defects in weanling offspring mice

The gut microbiota is important for maintaining homeostasis of the host. Gut microbes represent the initial site for toxicant processing following dietary exposures to environmental contaminants. The diet is the primary route of exposure to polychlorinated biphenyls (PCBs), which are absorbed via the gut, and subsequently interfere with neurodevelopment and behavior. Developmental exposures to PCBs have been linked to increased risk of neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), which are also associated with a high prevalence of gastrointestinal (GI) distress and intestinal dysbiosis. We hypothesized that developmental PCB exposure impacts colonization of the gut microbiota, resulting in GI pathophysiology, in a genetically susceptible host. Mouse dams expressing two heritable human mutations (double mutants [DM]) that result in abnormal Ca2+ dynamics and produce behavioral deficits (gain of function mutation in the ryanodine receptor 1 [T4826I-RYR1] and a human CGG repeat expansion [170–200 CGG repeats] in the fragile X mental retardation gene 1 [FMR1 premutation]). DM and congenic wild type (WT) controls were exposed to PCBs (0–6 mg/kg/d) in the diet starting 2 weeks before gestation and continuing through postnatal day 21 (P21). Intestinal physiology (Ussing chambers), inflammation (qPCR) and gut microbiome (16S sequencing) studies were performed in offspring mice (P28–P30). Developmental exposure to PCBs in the maternal diet caused significant mucosal barrier defects in ileum and colon (increased secretory state and tight junction permeability) of juvenile DM mice. Furthermore, PCB exposure increased the intestinal inflammatory profile (Il6, Il1β, and Il22), and resulted in dysbiosis of the gut microbiota, including altered β-diversity, in juvenile DM mice developmentally exposed to 1 mg/kg/d PCBs when compared to WT controls. Collectively, these findings demonstrate a novel interaction between PCB exposure and the gut microbiota in a genetically susceptible host that provide novel insight into environmental risk factors for neurodevelopmental disorders.

COMPARATIVE STUDY BETWEEN SINGLE ANASTMOSIS DUODENO-ILEAL BYPASS-SLEEVE AND MINI-GASTRIC BYPASS AFTER FAILED SLEEVE GASTRECTOMY IN MORBIDLY OBESE PATIENTS

Background: About 10-30% of the SG patients are associated with long-term failure, due either to inadequate weight loss or to renewed weight gain. Objective: To compare weight loss as well as the metabolic effects of 2 types of bariatric surgery after failure of primary SG; Single Anastomosis Duodeno-ileal Bypass-Sleeve (SADI-S) and Mini- Gastric bypass (MGB), in the first year postoperative follow up. Patients and Methods: This study is a prospective controlled study which included 30 patients underwent bariatric and metabolic surgeries at Ain-Shams University El-Demerdash Hospital, Cairo,Egypt from July 2017 to July 2018 with one year of postoperative follow up till July 2019. A comprehensive assessment program was carefully structured so that a disciplined routine is followed in each patient. All patients were preoperatively evaluated with provision of extensive information and consented to participate in the study. Results: According to our results, the SADI-S group presented markedly higher percentage of EWL of 91.4% vs 71.6% in MGB afterone year. Control of DM, with HbA1c below 6%, was obtained in 86.6% in both groups with more decrease in mean HbA1c of SADIS being 5.44 vs 5.815% in MGB after one year. Most patients abandoned antidiabetic therapy or at least were controlled by less medications and lower doses. The SADI-S group presented remission of hypertension by 81.8% of patients vs 80% in MGB with far less medications. Lipid profile improvement was noticed in both groups with slightly higher resolution in SADIS group by 93.3% vs 86.6% for total cholesterol, 86.6% vs 80% for T.G, 80% vs 86.6% for LDL, 60% vs 67.6% for HDL in SADIS and MGB patients respectively. Although the nutritional deficiency is still a considerable concern after SADIS, ours study didn’t show intense difference from MGB provided that proper vitamin supplementation and patient compliance are maintained postoperatively. Conclusion: When compared to gastric bypass, SADI-S appearsto be an effective and safe therapeutic technique as a revisional surgery for failed primary SG with excellent short-term results for treating morbid obesity and its associated comorbidities with a low rate of nutritional complications. Proving its safety and efficacy by further studies and long term follow up will grant it more popularity in the future.

Risk Factors of Post PCNL Systemic Inflamatory Response Syndrome (SIRS)

Background: urolithiasis is one of the most common benign urologic diseases, with a nearly 10% of lifetime incidence. In addition, the prevalence of urolithiasis has been rising through the decade worldwide. Objective: To determine the parameters and contributing factors that are associated with SIRS following PCNL. Materials and Methods: an observational retrospective case control study, the medical records of all patients who underwent PCNL for renal stones in-between 10/2017 and 4/2019 (320 patients) at Al-Hussein and Sayed Galal, AlAzhar University Hospitals had been reviewed. The demographic and perioperative data of these patients had been collected. Results: the study comprised 307 patients, the mean age of the studied patients was 40.9±15.8 years (range: 2.5 to 70 years). The mean BMI was 26±3 (range: 18 to 35). There were 193(62.9%) males and 114(37.1%) females. Twenty two patients had bilateral renal stone. In 170(55%) cases the targeted stone was in left side and the rest was in the right one. Forty eight (15.6%) cases developed SIRS post-operative. The age, gender, residual stones, hepatitis and diabetes were found to be independent risk factors for SIRS. Conclusions: good preoperative assessment and strict control of DM and haptic diseases before the procedure, try to render the patient stone free intraoperative as much we can and strict follow up to these categories of patients postoperatively to detect inflammatory response and infectious complications as early as possible.

Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C&gt;T and 1298A&gt;C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is involved in the homocysteine metabolism. Two common variants of MTHFR gene (677C&gt;T and 1298A&gt;C), have been reported to reduce the MTHFR enzyme activity and leading to plasma hyperhomocysteinemia. There are a number of recent case-control studies that investigated the association between the MTHFR polymorphism and diabetic nephropathy (DN), albeit with inconsistent results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of MTHFR with susceptibility to DN. A literature search was conducted on PubMed, Embase and Google scholar from inception till March 18, 2019. For MTHFR 677C&gt;T analysis, a total of 23 studies including DM controls (3095 cases and 3187 DM controls) and 12 studies including non-DM controls (1590 cases and 2052 nonDM controls) were taken. For MTHFR 1298A&gt;C analysis, a total of 7 studies using DM controls (959 cases and 1209 DM controls) and 3 studies using non-DM controls (400 cases and 802 nonDM controls) were taken. Meta-analysis showed that mutant genotypes of the 677C&gt;T (OR: 1.58; 95%CI: 1.16-2.14) and 1298A&gt;C (OR: 1.38; 95%CI: 1.16-1.65) polymorphisms in the MTHFR gene were associated with increased risk of DN (diabetic kidney disease). MTHFR 677C&gt;T and 1298A&gt;C polymorphisms revealed significant heterogeneity between studies. Further, there was no evidence for publication bias for these polymorphisms. In conclusion, this meta-analysis provides strong evidence that MTHFR 677C&gt;T and 1298A&gt;C polymorphisms may be associated with increased risks of DN. However, further studies are still needed to accurately determine whether MTHFR genetic polymorphisms are associated with susceptibility to DN.

460-P: Treatment with Dipeptidyl Peptidase Inhibitors (DPP-4_Rx) Is Associated with Significant Reduction in Macrovascular Events Independent of Glucose Control

We have observed renal protective effects with DPP-4 inhibitor therapy in a prior study done at the VA. Effects of DPP-4_Rx on cardiovascular morbidity and macrovascular events are disputed. Data from a large cohort of veterans diagnosed with type 2 diabetes mellitus (T2DM) were used to identify patients on DPP-4_Rx and without (control). Groups were matched for age (years), sex, BMI, initial renal function, follow-up time (FU, minimum 365 days). Propensity score matching (PSM) was used to adjust groups with a best odds ratio about 1:1. Groups were compared to determine the effect of DPP-4_Rx on the emergence of new macrovascular events identified by ICD-9 and all-cause mortality. Data were extracted using the Veterans Administration Informatics and Computing Infrastructure (VINCI), and analyzed using SAS. Results were compared using t-tests, frequency tables, Kaplan Meier survival curves, hazard ratios (HR) and p values. Results show that subject with DPP-4 (N=24,763) had baseline variables similar to control. DM control improved with DPP-4_Rx but remained worse than control. A significant reduction in new macrovascular events was seen in DPP-4 group (Table). Mortality from all causes was reduced by 78.1%, but time to death was not changed. We conclude that DPP-4_Rx associates with a significant reduction in frequency of all-cause mortality and macrovascular events independent of glucose control. The reduction of macrovascular events explains in part the improved survival and improvements in renal outcomes we have seen before. Disclosure M. Garcia-Touza: None.

1306-P: Cost Effectiveness of Point-of-Care HbA1c in Primary Care Setting in Brazil

Background: Point-of-care (POC) devices allow to assess HbA1c results in a single visit and facilitates the physicians’ decision making for DM control. This study aimed to assess the cost-effectiveness of POC in comparison to standard laboratory (HPLC method) for HbA1c testing in Brazilian primary care. Methods: A Markov model was developed in a 10-year time horizon for the perspective of the public health system. Effectiveness was assessed by the rate of HbA1c control after 6-months follow-up. Data were obtained from an ongoing cohort. Controlled and uncontrolled subjects were included in transition states for negative outcomes (cardiovascular diseases and complications). Probabilities and costs of transition states were extracted from a literature review. Results: Estimated annual cost for patients monitored by HPLC was U.S. $4,884.92 (SD 629.46) for an effectiveness of 0.39. For those monitored by POC, cost and effectiveness were U.S. $5,960.64 (SD 2,514.00) and 0.91, respectively. The evolution of the net monetary benefit is presented in the chart below. Conclusions: HbA1c tested by POC appears to be cost-effective in comparison with laboratory testing to improve glycemic control and prevent DM-related cardiovascular diseases and complications. Disclosure D.S. Medeiros: None. L.S. Rosa: None. S. Mistro: None. C.N. Kochergin: None. D.A. Soares: None. K.O. Silva: None. J.A. Louzado: None. M.L. Cortes: None. V.M. Bezerra: None. W.W. Amorim: None. M.G. Oliveira: None. Funding Medtronic Foundation

Dieta low carb como estratégia de manejo na remissão do diabetes mellitus insulinorresistente: síntese de evidências

Introdução: O DM tipo II está associado à deficiência no funcionamento de determinados mecanismos responsáveis pela regulação da sensibilidade tecidual à ação da insulina, em concomitância à secreção deficiente do hormônio pelas células beta pancreáticas. As dietas LC restringem os carboidratos diários para algo entre 20 e 50g, mostrando associação com uma considerável perda de peso. Todavia, os efeitos da dieta LC no controle do DM II são bastante controversos. Objetivo: Realizar uma revisão da literatura englobando ensaios clínicos que comprovadamente testaram os efeitos da dieta LC na remissão do DM II. Método: Para seleção dos trabalhos foi utilizada a seguinte estratégia de busca: (low-carb OR "low carb" OR “low carbohydrate” OR low-carbohydrate OR ketogenic OR Atkins) AND (diabetes OR diabetics) AND (type-2 OR "type 2" OR type-II OR "type II" OR "insulinresistant") AND "clinical trial", na base de dados PUBMED/MEDLINE. Resultados: Foram revisados 12 artigos que preencheram os critérios de inclusão. Síntese de Evidências: A dieta LC melhora o equilíbrio glicêmico, devendo ser considerada em pacientes portadores de DM tipo II e que necessitam de suporte nutricional. A referida dieta ainda reduz a gordura visceral, melhora a sensibilidade à insulina e aumenta os níveis de HDL. A estabilidade da glicemia diurna e do perfil lipídico podem ser mantidos com a dieta LC, sem efeitos adversos renais, e sem a necessidade de medicamentos hipoglicemiantes. A dieta é bem tolerada e se mostra bastante segura, mesmo quando prescrita em longo prazo.

Predictors of distant metastasis in parotid acinic cell carcinoma

BackgroundDistant metastasis (DM) is a common treatment failure pattern in acinic cell carcinoma (AciCC) of the major salivary glands; therefore, the main goal of this study was to analyse the predictors of DM in parotid AciCC.MethodsConsecutive patients with surgically treated parotid AciCC who were followed for at least 5 years were retrospectively reviewed. Data regarding age, sex, TNM stage, pathologic characteristics, surgical treatment, and follow-up examinations were collected and analysed. The primary end-point was DM control (DMC); the DMC survival was calculated from the date of surgery to the date of event or the latest follow-up examination and analysed by the Kaplan-Meier method. Independent prognostic factors were evaluated by the Cox proportional hazards method.ResultsA total of 144 patients were included. Positive intraparotid nodes (IPNs) were noted in 34 (31.8%) patients. High-grade transformation was noted in 12 (8.3%) patients. A total of 83 (57.6%) patients underwent neck dissection, and neck node metastasis was proven in 37 (44.6%, 37/83) patients. The 10-year DMC rate was 86%. The Cox model analysis confirmed IPN metastasis (1.854 [1.061–4.144], p = 0.011) and high-grade transformation (4.219 [1.948–15.553], p < 0.001) as independent predictive factors of the DMC survival.ConclusionIPN metastasis and high-grade transformation are independent prognostic factors of the DMC survival.

Diabetic Gastroparesis.

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

Arterial stiffness and matrix metalloproteinases: A correlation study in hypertensive type 2 diabetic subjects

Matrix metalloproteinases (MMP’s) and tribbles 3 human homolog (Trb3) are implicated in atherosclerosis. Changes in the concentration of these biomolecules signal the risk of atherosclerosis in type 2 subjects (T2DM), with or without hypertension (HT), at an early stage. Our aim was to assess the relation between noninvasive arterial stiffness indices and circulating levels of MMP2, MMP9 and Trb3. The study included 144 participants divided into 4 groups: T2DM > 5 years + HT, DM + HT (n = 55), T2DM < 2 years, DM (n = 28), HT (n = 31), and healthy controls (HC) (n = 30). Anthropometric measurements and blood biochemistry profiles were established using standard protocols. MMP2, MMP9 and Trb3 were estimated using ELISA. Pulse wave velocities (PWV) and arterial stiffness indices (ASI) were measured using PeriScopeTM. Results were analysed using SPSS 21. MMP2, average Brachial Stiffness Index (ba ASI) (Pearson’s r = 0.235, p = 0.005) and Ankle-Brachial Index (ABI) (Pearson’s r = 0.225, p = 0.007) were positively correlated. Average Ankle ASI (Ank ASI) was positively correlated to Trb3 (Pearson’s r = 0.184, p = 0.028), but negatively to MMP9 (Pearson’s r = − 0.184, p = 0.027). In multiple linear regression, MMP2 influenced ba ASI [adjusted R2 = 0.038; F (3) = 2.862, p = 0.039] and ABI [adjusted R2 = 0.033; F (3) = 2.642, p = 0.052]. MMP9 influenced Ank ASI [adjusted R2 = 0.058; F (3) = 3.912, p = 0.01]. Arterial stiffness indices and matrix metalloproteinases conform early risk of atherosclerosis in diabetic subjects.

GC/MS-based metabolomics strategy to analyze the effect of exercise intervention in diabetic rats.

Metabolomics was used to explore the effect of exercise intervention on type 2 diabetes. The rat model of type 2 diabetes was induced by an injection of streptozocin (30 mg/kg), after fed with 8-week high-fat diet. The rats were divided into three groups: the control group, the diabetic model group (DM) and the diabetes + exercise group (DME). After exercise for 10 weeks, blood samples were collected to test biomedical indexes, and 24-h urine samples were collected for the metabolomics experiment. In the DME group, fasting blood glucose (FBG), both total cholesterol (TC) and total plasma triglycerides (TG), were decreased significantly, compared with those in the DM group. Based on gas chromatography-mass spectrometry (GC/MS), a urinary metabolomics method was used to study the mechanism of exercise intervention on diabetes mellitus. Based on the principal component analysis (PCA), it was found that the DM group and control group were separated into two different clusters. The DME group was located between the DM group and the control group, closer to the control group. Twelve significantly changed metabolites of diabetes mellitus were detected and identified, including glycolate, 4-methyl phenol, benzoic acid, 1H-indole, arabinitol, threitol, ribonic acid, malic acid, 2,3-dihydroxy-butanoic, aminomalonic acid, l-ascorbic acid and 3-hydroxy hexanedioic acid. After exercise, seven metabolites were significantly changed, compared with the control group, the relative contents of benzoic acid, aminomalonic acid, tetrabutyl alcohol and ribonucleic acid in the diabetic exercise group decreased significantly. The relative contents of 2,3-dihydroxybutyric acid, l-ascorbic acid and 3-hydroxy adipic acid increased significantly. l-ascorbic acid and aminomalonic acid which related with the oxidative stress were significantly regulated to normal. The results showed that exercise could display anti-hyperglycemic and anti-hyperlipidemic effects. The exercise had antioxidation function in preventing the occurrence of complications with diabetes mellitus to some extent. The work illustrates that the metabolomics method is a useful tool to study the mechanism of exercise treatment.

SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event

Introduction: Programmed cell death protein 1 (PD-1) inhibitors stimulate the immune system to produce anti-tumor effects and are among a novel drug class of cancer immunotherapy. PD-1 inhibitors are associated with various immune related adverse events (IRAEs) owing to their indiscriminate activation of the immune system. IRAEs involving the endocrine system, particularly affecting the thyroid, pituitary and adrenal glands, are well-established. We however present a case of diabetic ketoacidosis (DKA), an exceedingly rare and life threatening immune-related endocrinopathy, precipitated by the PD-1 inhibitor Pembrolizumab. Clinical case: A 52-year-old female with PMH of T2DM (A1c 8.1%) and metastatic NSCLC (Non-Small Cell Lung Cancer) presented with 1-day history of nausea, vomiting, polyuria, and lethargy. She received an infusion of Pembrolizuab 5 days prior to onset of symptoms. On admission, she was found to have a BG of 617 mg/dL (reference range (RR): 65-99 mg/dL), ketonuria (3+; 80mg/dL; RR: negative), anion gap of 22 mEq/L (RR: 7-15 mEq/L), serum CO2 17 mEq/L (RR: 24-31 mEq/L), and arterial pH 7.29 (RR: 7.35-7.45). Infection work up was negative. She was treated for DKA with IV fluids and IV insulin. After resolution of acidosis, evaluation revealed normal adrenal and thyroid function but undetectable C-Peptide (< 0.9ng/mL; RR: 1.1-4.4 ng/mL) which was previously normal. Diabetes related antibodies were negative. The patient subsequently required insulin to maintain euglycemia, though she was previously treated with oral agents alone, and was discharged on basal bolus insulin. This series of events signifies the abrupt loss β cell function that resulted in profound insulinopenia and DKA. This is recognized to be a rare immune-related endocrinopathy secondary to Pembrolizumab, with DKA occurring in only 0.1% of patients in clinical trials. Pembrolizumab blocks PD-1 receptors on the surface of T cells in order to restore T cell anti-tumor function. This blockade can trigger T cell mediated destruction of various host cells. Pancreatic β cells express PD Ligand-1, which binds to PD-1 receptors as a mode to evade T cell immunity. PD-1 inhibition potentiates inflammation and destruction of pancreatic β cells resulting in worsening control of DM or in rare instances, fulminant β cell failure and DKA. There does not appear to be a dose dependent relationship or serum antibody markers predictive of this adverse event. Conclusion: The expanding use PD-1 inhibitors in cancer treatment has resulted in a host of IRAEs. This case highlights that clinicians and patients alike must be aware of the importance of recognizing DKA as a rare yet potentially lethal adverse event of PD-1 inhibitors. There is currently no clear method to predict which patients are at risk of developing DKA but early and regular screening for glucose intolerance should be standard of care when initiating anti-PD1 therapy.