Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin.

Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. Methods: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. Results: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, p ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. Conclusions: Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin's mechanisms of action.

Metabolomic profile of patients on levothyroxine treatment for hypothyroidism.

Background: Hypothyroidism is clinically characterized by a decrease in levels of the circulating thyroid hormones namely thyroxine and triiodothyronine. The main treatment for hypothyroidism is thyroid hormone replacement using levothyroxine to normalize serum thyroid hormone levels. Objectives: In this study, we explored the metabolic changes in the plasma of patients with hypothyroidism after reaching a euthyroid state with levothyroxine treatment. Methods: Plasma samples from 18 patients diagnosed as overt hypothyroidism were collected before and after levothyroxine treatment upon reaching a euthyroid state and were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate and univariate analyses evaluated data to highlight potential metabolic biomarkers. Results: Liquid chromatography-mass spectrometry-based metabolomics revealed a significant decrease in the levels of ceramide, phosphatidylcholine, triglycerides, acylcarnitine, and peptides after levothyroxine treatment; this could indicate a change in the fatty acid transportation system and an enhanced ß-oxidation, compared with a hypothyroid state. At the same time, the decrease in the peptides suggested a shift in protein synthesis. In addition, there was a considerable rise in glycocholic acid following therapy, suggesting the involvement of thyroid hormones in stimulating bile acid production and secretion. Conclusions: A metabolomic analysis of patients with hypothyroidism revealed significant changes in several metabolites and lipids after treatment. This study showed the value of the metabolomics technique in providing a complementary understanding of the pathophysiology of hypothyroidism and as a crucial tool for examining the molecular impact of levothyroxine treatment on hypothyroidism. It was an important tool for investigating the therapeutic effects of levothyroxine on hypothyroidism at the molecular level.

Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment.

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide.

The metabolomics approach revealed a distinctive metabolomics pattern associated with hyperthyroidism treatment.

Background: Hyperthyroidism is characterized by increased thyroid hormone production, which impacts various processes, including metabolism and energy expenditure. Yet, the underlying mechanism and subsequent influence of these changes are unknown. Metabolomics is a broad analytical method that enables qualitative and quantitative examination of metabolite level changes in biological systems in response to various stimuli, pathologies, or treatments. Objectives: This study uses untargeted metabolomics to explore the potential pathways and metabolic patterns associated with hyperthyroidism treatment. Methods: The study consisted of 20 patients newly diagnosed with hyperthyroidism who were assessed at baseline and followed up after starting antithyroid treatment. Two blood samples were taken from each patient, pre (hyperthyroid state) and post-treatment (euthyroid state). Hyperthyroid and euthyroid states were identified based on thyroxine and thyroid-stimulating hormone levels. The metabolic alteration associated with antithyroid therapy was investigated using liquid chromatography- high-resolution mass spectrometry. The untargeted metabolomics data was analyzed using both univariate and multivariate analyses using MetaboAnalyst v5.0. The significant metabolic pattern was identified using the lab standard pipeline, which included molecular annotation in the Human Metabolome Database, LipidMap, LipidBlast, and METLIN. The identified metabolites were examined using pathway and network analyses and linked to cellular metabolism. Results: The results revealed a strong group separation between the pre- and post-hyperthyroidism treatment (Q2 = 0.573, R2 = 0.995), indicating significant differences in the plasma metabolome after treatment. Eighty-three mass ions were significantly dysregulated, of which 53 and 30 characteristics were up and down-regulated in the post-treatment compared to the pre-treatment group, respectively. The medium-chain acylcarnitines, octanoylcarnitine, and decanoylcarnitine, previously found to rise in hyperthyroid patients, were among the down-regulated metabolites, suggesting that their reduction could be a possible biomarker for monitoring euthyroid restoration. Kynurenine is a downregulated tryptophan metabolite, indicating that the enzyme kynurenine 3-hydroxylase, inhibited in hyperthyroidism, is back functioning. L-cystine, a cysteine dimer produced from cysteine oxidation, was among the down-regulated metabolites, and its accumulation is considered a sign of oxidative stress, which was reported to accompany hyperthyroidism; L-cystine levels dropped, this suggests that the plasma level of L-cystine can be used to monitor the progress of euthyroid state restoration. Conclusion: The plasma metabolome of patients with hyperthyroidism before and after treatments revealed differences in the abundance of several small metabolites. Our findings add to our understanding of hyperthyroidism's altered metabolome and associated metabolic processes and shed light on acylcarnitines as a new biomarker for treatment monitoring in conjunction with thyroxine and thyroid-stimulating hormone.

Proteomic profiling of thyroid tissue in patients with obesity and benign diffuse goiter.

Goiter is a term to describe the enlargement of the thyroid gland. The pathophysiology and molecular changes behind development of diffuse benign goiter remains unclear. The present study targeted to identify and describe the alterations in the thyroid tissue proteome from patients (obese euthyroid) with benign diffuse goiter (BDG) using proteomics approach. Thyroid tissue samples, from 7 age and sex matched, patients with BDG and 7 controls were obtained at the time of surgery. An untargeted proteomic analysis of the thyroid tissue was performed out utilizing two-dimensional difference (2D-DIGE) in gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for identification of the proteins. Progenesis software was used to identify changes in expression of tissue proteins and found statistically significant differences in abundance in a total of 90 proteins, 46 up and 44 down (1.5-fold change, ANOVA, p ≤ 0.05) in BDG compared to the control group. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of signalling pathways linked to ERK1/2, Glutathione peroxidase and NADPH oxidase associated to organismal injury and abnormalities, endocrine system disorders and cancer. The thyroid tissue proteome in patients with BDG revealed a significant decrease in thyroglobulin along with dysregulation of glycolysis and an increase in prooxidant peroxidase enzymes. Dysregulation of metabolic pathways related to glycolysis, redox proteins, and the proteins associated with maintaining the cytoskeletal structure of the thyrocytes was also identified.

Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer.

Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46-75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.

Plasma proteomics reveals an improved cardio-metabolic profile in patients with type 2 diabetes post-liraglutide treatment.

BACKGROUND: Diabetes mellitus is a chronic multisystem disease with a high global prevalence, including in Saudi Arabia. The Glucagon-like Peptide (GLP-1) receptor agonist liraglutide is known to lower glucose levels, reduce weight and improve cardiovascular outcome. However, mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. METHODS: In the present study, a 2D-DIGE MALDI-TOF mass spectrometric approach combined with bioinformatics and network pathway analysis explore the plasma proteomic profile. The study involved 20 patients with T2DM with mean age of 54.4 ± 9.5 years and Hemoglobin A1c (HbA1c) between 8% and 11% (inclusive). RESULTS: A statistically significant change (p < .006) was observed in HbA1c with no significant changes in body weight, renal function, or markers of dyslipidemia post-treatment with liraglutide. 2 D-DIGE gel analysis identified significant changes (⩾1.5-fold change, Analysis of variance (ANOVA), p ⩽ 0.05) in 72 proteins, (62 down and 10 up) in liraglutide pre-treatment compared to the post-treatment state. Proteins identified in our study were found to regulate metabolic processes including acute phase response proteins, enzymes, apolipoproteins with involvement of the inflammatory signaling pathways, NF-κB, AKT, and p38 MAPK. CONCLUSION: Liraglutide treatment decreased levels of acute phase response that to reduce the systemic chronic inflammatory state and oxidative stress, and eventually improve the cardio-metabolic profile in these patients.

Proteomic Analysis of Endometrial Cancer Tissues from Patients with Type 2 Diabetes Mellitus.

Endometrial cancer (EC) is the most common form of gynecological cancer. Type 2 diabetes mellitus is associated with an increased risk of EC. Currently, no proteomic studies have investigated the role of diabetes in endometrial cancers from clinical samples. The present study aims to elucidate the molecular link between diabetes and EC using a proteomic approach. Endometrial tissue samples were obtained from age-matched patients (EC Diabetic and EC Non-Diabetic) during surgery. Untargeted proteomic analysis of the endometrial tissues was carried out using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF). A total of 53 proteins were identified, with a significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two groups, among which 30 were upregulated and 23 downregulated in the EC Diabetic group compared to EC Non-Diabetic. The significantly upregulated proteins included peroxiredoxin-1, vinculin, endoplasmin, annexin A5, calreticulin, and serotransferrin. The significantly downregulated proteins were myosin regulatory light polypeptide 9, Retinol dehydrogenase 12, protein WWC3, intraflagellar transport protein 88 homolog, superoxide dismutase [Cu-Zn], and retinal dehydrogenase 1. The network pathway was related to connective tissue disorder, developmental disorder, and hereditary disorder, with the identified proteins centered around dysregulation of ERK1/2 and F Actin signaling pathways. Cancer-associated protein alterations such as upregulation of peroxiredoxin-1, annexin 5, and iNOS, and downregulation of RDH12, retinaldehyde dehydrogenase 1, SOD1, and MYL 9, were found in the EC tissues of the diabetic group. Differential expression of proteins linked to cancer metastasis, such as the upregulation of vinculin and endoplasmin and downregulation of WWC3 and IFT88, was seen in the patients with diabetes. Calreticulin and alpha-enolase, which might have a role in the interplay between diabetes and EC, need further investigation.

Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis.

CONTEXT: There is renewed interest in using very low-carbohydrate ketogenic (VLCK) diets to manage diabetes. Many clinical trials have been published, often with mixed results. OBJECTIVE: This meta-analysis compares the effect of a VLCK diet on glycemic control, body weight, lipid profile, medication use, and dropouts with that of recommended diets for 12 weeks or longer in people with type 2 diabetes. DATA SOURCES: Ovid MEDLINE, Ovid Embase, CENTRAL, and CINAHL databases were searched (January 1980 through September 2019). STUDY SELECTION: Two authors independently reviewed search results to select randomized controlled trials (RCTs) comparing a VLCK diet (carbohydrate intake < 50 g/d or < 10% of total energy) with any recommended diet for type 2 diabetes in adults. Discrepancies were resolved after consulting with the third author. DATA EXTRACTION: Eight RCTs with 648 participants were identified. RESULTS: Compared with control diets, the VLCK diet resulted in a greater decrease in hemoglobin A1c after 3 months (weighted mean difference[WMD]: -6.7 mmol/mol; 95%CI, -9.0 to -4.4) (WMD: -0.61%; 95%CI, -0.82 to -0.40; P < 0.001; moderate-certainty evidence) and after 6 months (WMD: -6.3 mmol/mol; 95%CI, -9.3 to -3.5) (WMD: -0.58%; 95%CI, -0.85 to -0.32; low-certainty evidence). There was a significantly greater weight loss with the VLCK diet after 3 months (WMD: -2.91 kg; 95%CI, -4.88 to -0.95; low-certainty evidence) and after 6 months (WMD: -2.84 kg; 95%CI, -5.29 to -0.39; low-certainty evidence). The VLCK diet was not better than a control diet after 12 months. It was superior in decreasing triglyceride levels, increasing high-density lipoprotein cholesterol levels, and reducing the use of antidiabetic medications for up to 12 months. CONCLUSION: The VLCK diet appears to control glycemia and decrease body weight for up to 6 months in people with obesity and diabetes. Beneficial changes in serum triglycerides and high-density lipoprotein cholesterol, along with reductions in antidiabetic medications, continued in the VLCK group until 12 months. However, the quality of currently available evidence is not sufficient to recommend VLCK diets. A major limitation of the VLCK diet is patients' lack of adherence to carbohydrate restriction. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020154700.

Serum Proteomic Analysis of Cannabis Use Disorder in Male Patients.

Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.

Serum proteomic profiling of patients with amphetamine use disorder.

BACKGROUND: Amphetamine use disorder has been recently classified as an epidemic condition. Amphetamine use/abuse has been associated with several neurological and inflammatory effects. However, the exact mechanism involved in these effects warrants further investigation. The aim of this study was to determine any alterations in the serum proteome of individuals classified as patients with amphetamine use disorder compared to that of control subjects. METHODS: An untargeted proteomic approach employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was used to identify the patterns of differentially expressed proteins. Serum samples were collected from 20 individuals (males) including 10 subjects with amphetamine use disorder and 10 healthy controls for the present study. RESULTS: The analysis revealed 78 proteins with a significant difference in protein abundance between the amphetamine-addicted subjects and controls. Among them, 71 proteins were upregulated while 7 proteins remained downregulated in the amphetamine-addicted group. These proteins were further analyzed by ingenuity pathway analysis (IPA) to investigate their correlation with other biomarkers. IPA revealed the correlation of altered proteins with mitogen-activated protein kinase (MAP2K1/K2), p38MAPK, protein kinase-B (PKB; Akt), extracellular signal-regulated kinase (ERK1/2), and nuclear factor-κB signaling pathways. Importantly, these pathways are highly involved in neurological diseases, inflammatory responses, and cellular compromise. CONCLUSIONS: Our data suggest that the changes in the levels of serum proteins between amphetamine and control groups might affect cellular compromise, inflammatory response, and neurological diseases.

Primary Hypertriglyceridemia: A Look Back on the Clinical Classification and Genetics of the Disease.

INTRODUCTION: Hypertriglyceridemia (HTG) is one of the most common metabolic disorders leading to pancreatitis and cardiovascular disease. HTG develops mostly due to impaired metabolism of triglyceride-rich lipoproteins. Although monogenic types of HTG exist, most reported cases are polygenic in nature. AIM: This review article is focused on the classification of Primary HTG and the genetic factors behind its development with the aim of providing clinicians a useful tool for early detection of the disease in order to administer proper and effective treatment. DISCUSSION: HTG is often characterized by a complex phenotype resulting from interactions between genetic and environmental factors. In many instances, the complexity, perplexing causes, and classification of HTG make it difficult for clinicians to properly diagnose and manage the disorder. Better availability of information on its pathophysiology, genetic factors involved, environmental causes, and their interactions could help in understanding such complex disorders and could support its effective diagnosis and treatment. CONCLUSION: The current review has summarized the case definition, epidemiology, pathophysiology, clinical presentation, classification, associated genetic factors, and scope of genetic screening in the diagnosis of primary HTG.

Genetics and genomics studies in type 2 diabetes: A brief review of the current scenario in the Arab region.

BACKGROUND: Type 2 diabetes (T2D) is a polygenic and multi-factorial complex disease, the challenge to find genetic markers that could explain the risk of development of this disease still remains unresolved. The Arab region is one among the populations with a high prevalence of T2D and a large number of studies have been carried out in exploring the genetic factors associated with T2D risk. AIM: To summarize the recent developments in the Arab world based on the recent studies that had looked into genetic factors associated with the development of T2D in the Arab populations. METHODS: A systematic literature search was conducted to identify studies published between 2015 and 2018 reporting genetic factors or polymorphisms associated with the risk of T2D in the Arab world. The online databases PubMed and Web of Science were used to perform the literature search. CONCLUSION: The present study has evaluated 14 studies published during the year 2015-2018. Studies from Egypt, Iraq, Jordan, Oman, Qatar, Saudi Arabia, Tunisia, and United Arab Emirates had been explored studying the associations of GIPR, ADIPOQ, FTO, (GRCh38.p12), MLXIP, AKNAD1, KCNJ11 CDKAL1, CDKN2A/2B, TCF7L2, ACE, SNAP25, ELMO1, VDR, KCTD8, GABRA4 and PRKD1 genes with T2D development.

Design of Arab Diabetes Gene-Centric Array (ADGCA) in population with an epidemic of Type 2 Diabetes: A population specific SNP evaluation.

In the case of diabetes and other complex diseases, the challenge has always been to find genetic markers that explain the excess risk associated with development of the disease. In the last 12 years, advances in genotyping technology provided substantial development in the discovery of loci contributing to Type 2 diabetes (T2D) susceptibility. Therefore, the aim of this study is to custom design, for the first time in Arab world, an "Arab Diabetes Gene Centric Array" (ADGCA) that assays 643, 745 SNP markers including 50,617 diabetes associated SNPs. The array content was designed after comprehensive literature search prioritizing Diabetes associated SNPs. PCA was performed to evaluate the relationship between world populations and the Saudi population in building the backbone for the array. A genotype data matrix for PCA analysis was produced by including the genotypes of the 270 HapMap samples including JPT, CHB, YRI and CEU to genotypes of the 1457 Saudi samples. Imputation was executed using IMPUTE2 software and the 1000GP Phase III reference panel. All markers incorporated to ADGCA were validated. Quality checks and evaluation of its capacity and performance as a platform for genetic screening for T2D was performed using the latest stastical tools available. We were successful in designing ADGCA as a custom made chip array designed with a motive to capture genetic variation in loci known or reported to be associated with the development of T2D. However, implementation of ADGCA is currently being performed by our research group using 2000 DNA samples respectively from diabetic and non diabetic individuals which could further validate the use of ADGSA in genetic screening of T2D.

Pulmonary artery aneurysm and thrombosis in active tuberculous consolidation.

Tuberculosis continues to remain challenging with a variety of complications. We report the case of a 58-year-old female who developed pulmonary artery aneurysm with intra-arterial thrombus as a complication of active tuberculosis. Even though there are reports of pulmonary artery aneurysm in tuberculous cavity, pulmonary artery aneurysm and intra-arterial thrombus in active tuberculosis are very rare.

Native Valve Candida Endocarditis Complicating Pregnancy after Abdominal Surgery.

Candida endocarditis is an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial morbidity and mortality. A 28-year-old primigravida at 32 weeks of gestation was admitted with low-grade fever and lower abdominal pain for 2 weeks. She had undergone open appendicectomy 2 months before admission. Echocardiogram showed a pedunculated 24 mm × 21 mm mass attached to the undersurface of anterior mitral leaflet near the tip and moderate mitral regurgitation. Repeated blood cultures showed growth of nonalbicans candida. She was immediately started on liposomal amphotericin and was taken up for surgery, but despite all efforts she succumbed to her illness.

Maturity onset diabetes of the young (MODY)--history, first case reports and recent advances.

The world is seemingly facing a global increase in people suffering from diabetes especially in developing countries. The worldwide occurrence of diabetes for all age groups in year 2000 was estimated to be 2.8% and this number is most certainly expected to rise to 4.4% by 2030. Maturity-onset of diabetes of the young, or MODY, is a form of monogenic diabetes that is caused by mutations occurring in a number of different genes. Mutations in different genes tend to cause a slightly different variant of diabetes. MODY is typically diagnosed during late childhood, adolescence, or early adulthood and is usually observed to develop in adults during their late 50's. One of the main drawbacks in its diagnosis is that many people with MODY are misdiagnosed as having type 1 or type 2 diabetes. However, a molecular and genetic diagnosis can result in a better treatment and could also help in identifying other family members with MODY. This article explores the historical prospect and the genetic background of MODY, a brief summary of the first case reported and the significant factors that differentiate it from type 1 and type 2 diabetes.