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Diabetes mellitus - Top 30 Publications

Potential impact of screening for fatty liver disease by transient elastography with liver stiffness and controlled attenuation parameter measurements: a pilot study.

Background The prevalence of chronic liver diseases is high in developed countries, and the leading causes are amenable to prevention. The German Lebertag is to increase awareness of the burden of chronic liver diseases in the general public. We performed a pilot study using transient elastography with liver stiffness measurement (LSM) and the controlled attenuation parameter (CAP) as a screening tool for previously unrecognized liver diseases. Patients and methods LSM and CAP was performed in 60 individuals, and participants filled in a questionnaire reporting basic characteristics and past medical history. Results Median LSM and CAP values were within the normal range. Participants with self-reported diabetes mellitus had significantly elevated LSM (p = 0.02) and CAP values (p = 0.002). Participants with a BMI > 30 kg/m(2) or dyslipidemia had significantly elevated CAP values (p = 0.007 and p = 0.01, respectively) with normal LSM values. Overall, 35 % of participants had elevated CAP values, indicating a high prevalence of hepatic steatosis. Discussion In a German pilot study, diabetes mellitus was a key risk factor for increased LSM and CAP values. Prevalence of steatosis was high and comparable to other Western countries. Transient elastography is a valuable tool to identify patients with increased risk for metabolic liver diseases. In people without risk factors, LSM and CAP values were within the normal range, indicating that screening for chronic liver injury was not warranted.

Association of matrix γ-carboxyglutamic acid protein levels with insulin resistance and Lp(a) in diabetes: A cross-sectional study.

The risk of cardiovascular disease (CVD) and mortality is increased in patients with chronic kidney disease (CKD), with a background role of vascular calcification in the development of CVD also reported. Studies have demonstrated that high lipoprotein(a) (Lp(a)) levels accelerate the development of atherosclerolsis and are potentially involved in the vascular calcification. Matrix Gla Protein (MGP) seems to play an important role in vascular calcification. The aim of the study was to examine the potential association of MGP concentrations with Lp(a) and insulin resistance.

Diabetes mellitus is associated with late-onset post-stroke depression.

To explore the associated factors of late-onset post-stroke depression (PSD).

Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, A clinical study.

Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls. We recruited 30 participants (12 T2DM and 18 non-diabetic healthy controls). Participants underwent a meal tolerance test during which plasma glucose, insulin and serum C-peptide immunoreactivity were measured. We performed a hyperinsulinemic-euglycemic clamp and measured the glucose-disposal rate (GDR). The fasting serum levels of adiponectin, insulin-like growth factor-1, irisin, autotaxin, FABP4 and interleukin-6 were measured by ELISA. We found a strong negative correlation between FABP4 concentration and GDR in T2DM (r = -0.657, p = 0.020). FABP4 also was positively correlated with insulin secretion during the meal tolerance test in T2DM (IRI (120): r = 0.604, p = 0.038) and was positively related to the insulinogenic index in non-DM subjects (r = 0.536, p = 0.022). Autotaxin was also related to GDR. However, there was no relationship with insulin secretion. We found that serum FABP4 concentration were associated with insulin resistance and secretion in T2DM. This suggests that FABP4 may play an important role in glucose homeostasis.

Using Personalized Medicine in the Management of Diabetes Mellitus.

Diabetes mellitus is a worldwide problem of immense pharmacoeconomic burden. The multifactorial and complex nature of the disease lends itself to personalized pharmacotherapeutic approaches to treatment. Variability in individual risk and subsequent development of diabetes have been reported, in addition to differences in response to the many oral glucose lowering therapies currently available for diabetes pharmacotherapy. Pharmacogenomic studies have attempted to uncover the heritable components of individual variability in risk susceptibility and response to pharmacotherapy. We review the current pharmacogenomics evidence as it relates to common oral glucose lowering therapies and how they can be utilized in the management of polygenic and monogenic forms of diabetes. Evidence supports the use of genetic testing and personalized approaches to the treatment of monogenic diabetes of the young. The data are not as robust for the current application of pharmacogenetic approaches to the treatment of the polygenic type 2 diabetes mellitus, but there are suggestions as to future applications in this regard. We reviewed pertinent primary literature sources as well as current evidence based guidelines on diabetes management. This article is protected by copyright. All rights reserved.

Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging.

Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.

Serum carcinoembryonic antigen is positively associated with leukocyte count in Korean adults.

Emerging evidence shows that serum carcinoembryonic antigen (CEA) levels may modestly be increased in non-neoplastic conditions such as cardiometabolic diseases, which are increasingly being seen as inflammatory diseases. Leukocyte count is widely evaluated marker of inflammation in clinical practice and a useful predictor of cardiometabolic disease. In this study, we aimed to determine the relationship between serum CEA levels and leukocyte counts in Korean adults.

Association between Parkinson's disease and diabetes: Data from NEDICES study.

Despite growing evidence showing an association between Parkinson's disease (PD) and diabetes, epidemiological studies have shown conflicting results.

The Economic Burden of Insulin-Related Hypoglycemia in Spain.

An analysis was conducted to estimate the economic burden of insulin-related hypoglycemia in adults in Spain, derived from a novel concept developed for the UK known as the Local Impact of Hypoglycemia Tool.

Laparoscopic Sleeve Gastrectomy for the Management of Type 1 Diabetes Mellitus.

The prevalence of obesity is on a continuous rise worldwide, with major studies clearly correlating obesity with the development of chronic metabolic disorders including type 2 diabetes. Bariatric surgery has proven to be beneficial in the management of this condition; however, a limited number of studies exist on its effect on type 1 diabetes.

Revealing the potency of Annona muricata leaves extract as FOXO1 inhibitor for diabetes mellitus treatment through computational study.

FOXO1 protein inactivation in the nucleus is one of targets for the treatment of diabetes mellitus. Annona muricata leaves contain flavonoid and phenolic compound alkaloids that were known to be able to increase pancreatic β cell proliferation in animal experiment. This research aimed to predict the active compound ability of the Annona muricata leaves to bind and inhibit FOXO1 protein through in silico study. Analysis of molecular docking was performed by using Autodock Vina PyRx. this research proved that anonaine, rutin, muricatocin a, isolaureline, xylopine, and kaempferol 3-O-rutinoside had an equal or smaller free binding energy compared to the control compound. Rutin and Muricatocin A had the same binding ability toward 66% amino acid residues, compared to control compound with hydrogen bond type, while xylopine, anonaine, isolaureline, kaempferol 3-O-rutinoside had a similar binding ability towards 33% amino acid residues compared to control compound with hydrogen bond type.

Impact of Metabolic Hormones Secreted in Human Breast Milk on Nutritional Programming in Childhood Obesity.

Obesity is the most common metabolic disease whose prevalence is increasing worldwide. This condition is considered a serious public health problem due to associated comorbidities such as diabetes mellitus and hypertension. Perinatal morbidity related to obesity does not end with birth; this continues affecting the mother/infant binomial and could negatively impact on metabolism during early infant nutrition. Nutrition in early stages of growth may be essential in the development of obesity in adulthood, supporting the concept of "nutritional programming". For this reason, breastfeeding may play an important role in this programming. Breast milk is the most recommended feeding for the newborn due to the provided benefits such as protection against obesity and diabetes. Health benefits are based on milk components such as bioactive molecules, specifically hormones involved in the regulation of food intake. Identification of these molecules has increased in recent years but its action has not been fully clarified. Hormones such as leptin, insulin, ghrelin, adiponectin, resistin, obestatin and insulin-like growth factor-1 copeptin, apelin, and nesfatin, among others, have been identified in the milk of normal-weight women and may influence the energy balance because they can activate orexigenic or anorexigenic pathways depending on energy requirements and body stores. It is important to emphasize that, although the number of biomolecules identified in milk involved in regulating food intake has increased considerably, there is a lack of studies aimed at elucidating the effect these hormones may have on metabolism and development of the newborn. Therefore, we present a state-of-the-art review regarding bioactive compounds such as hormones secreted in breast milk and their possible impact on nutritional programming in the infant, analyzing their functions in appetite regulation.

Follow-up of the retinal nerve fiber layer thickness of diabetic patients type 2, as a predisposing factor for glaucoma compared to normal subjects.

To evaluate and follow-up the retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus type 2 compared to a group of healthy individuals with similar demographic characteristics.

Molecular mimicry in Helicobacter pylori infections.

Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.

Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome.

BACKGROUND Neonatal diabetes mellitus is a rare condition and it is important to differentiate it from other causes, such as hyperglycemia in infancy, for better outcomes. We report a case of an infant who presented to our neonatal intensive care unit in ketoacidosis and a comatose state. CASE REPORT Our case was an infant who presented to the neonatal intensive care unit at 38 days of age in ketoacidosis. The female infant, born to consanguineous parents (first cousins), weighing 2,300 grams at birth, presented with extreme dehydration and pale skin. The infant's head was normocephalic and there were no obvious deformities on the rest of her body. Urine examination was positive for ketones and glucose was 4+. Her blood glucose level was 550 mg/dL (30.5 mmol/L). After taking care of electrolytes, insulin was initiated in the form of a continuous drip. After a few days, insulin glargine was initiated, given twice daily via subcutaneous route. A few days later, blood samples were sent from our hospital in India to the UK and genetic testing was performed free of charge by the Department of Molecular Genetics, University of Exeter Medical School, UK, and confirmed a genetic diagnosis of Wolcott-Rallison syndrome. CONCLUSIONS Regardless of whether permanent neonatal diabetes mellitus is associated with Wolcott-Rallison syndrome or other genetic mutations, it is important to initially stabilize the infant and later do a genetic testing to see whether the infant can be given oral sulfonylureas or has to be given insulin therapy.

Tuberculosis and diabetes in Nigerian patients with and without HIV.

Type 2 Diabetes mellitus (DM) and the Human Immunodeficiency Virus (HIV) increase the risk of Tuberculosis (TB). The frequency of DM among patients with TB with and without HIV is poorly documented in many LMIC.

Streptozocin-induced Type-1 diabetes mellitus results in decreased density of cgrp sensory and th sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP(+)) sensory and tyrosine hydroxylase (TH(+)) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP(+) and TH(+) nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP(+) or TH(+) nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP(+)) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP(+) sensory and TH(+) sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis.

Hyperglycemia induced the Alzheimer's proteins and promoted loss of synaptic proteins in advanced-age female Goto-Kakizaki (GK) rats.

Although both type 2 diabetes mellitus (T2DM) and aging are related with Alzheimer's disease (AD), the effects of aging on the Alzheimer's proteins and the synaptic markers in T2DM have not been investigated. This study, we hypothesized that T2DM rats with advanced-age, aggravates the reduction of synaptic proteins and an increase in the Alzheimer's protein markers. Goto-Kakizaki rats (GK) were used as a T2DM group and wild-type rats (WT) were used as a control group. Rats in each group were categorized by age into young-adult (7 months) and advanced-age rats (12.5 months). Blood was collected in all rats to determine plasma glucose and insulin levels. The brains were used for determining the level of Alzheimer's and synaptic proteins. Our data demonstrated that GK rats had a decreased body weight and increased blood glucose levels, compared to their age-matched WT. p-Tau was increased in both advanced-age WT and GK, compared to their young-adult rats. Moreover, amyloid-beta (Aβ) level was higher in advanced-age GK than their age-matched WT. The synaptic proteins were decreased in advanced-age GK, compared to young-adult GK rats. However, no difference in the level of Alzheimer's proteins and synaptic proteins in the brains of young-adult GK compared to age-matched WT was found. Our data suggested that aging contributes to the pathogenesis of AD and the reduction of synaptic proteins to greater extent in a diabetic than in a healthy condition.

IL-6 and IL-18 cytokine gene variants of pulmonary tuberculosis patients with co-morbid diabetes mellitus and their household contacts in Hyderabad.

Association of cytokine genes reflects their susceptibility towards infection and disease in household contacts (HHC) of pulmonary tuberculosis (PTB) patients. Hyperglycemia, a common factor in diabetics might influence their risk towards mycobacterium tuberculosis infection and disease development. This study determines the association of IL-6 and IL-18 cytokine gene variants of TB patients with diabetes mellitus (TBDM) and their HHC in Hyderabad.

Repeated Paradoxical Brain Infarctions in a Patient on Self-Managed Home Hemodialysis Using a Long-Term Indwelling Catheter.

We describe the case of a 51-year-old Japanese man with an end-stage kidney disease caused by a 30-year history of type 1 diabetes mellitus. The patient had suffered repeated bilateral multiple brain infarctions within a short period of time after the initiation of a self-managed daily home hemodialysis regimen using a long-term indwelling catheter inserted into the right atrium. Despite extensive examinations, we could not find any embolic causes except for the catheter and a patent foramen ovale (PFO). The patient had experienced repeated brain infarctions under antiplatelet and anticoagulation therapies, but suffered no further brain infarctions after the removal of the catheter and the alteration of vascular access from the catheter to an arteriovenous fistula in the forearm. We speculate that the indwelling catheter-associated thrombi or air and the right-to-left shunt through the PFO may have caused the repeated paradoxical brain embolisms in this patient.

Differences in Repolarization Heterogeneity Among Heart Failure With Preserved Ejection Fraction Phenotypic Subgroups.

Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome associated with multiple medical comorbidities and pathophysiologic pathways or phenotypes. We recently developed a phenomapping method combining deep phenotyping with machine learning analysis to classify HFpEF patients into 3 clinically distinct phenotypic subgroups (phenogroups) with different clinical outcomes. Phenogroup #1 was younger with lower B-type natriuretic peptide levels, phenogroup #2 had the highest prevalence of obesity and diabetes mellitus, and phenogroup #3 was the oldest with the most factors for chronic kidney disease, the most dysfunctional myocardial mechanics, and the highest adverse outcomes. The pathophysiological differences between these phenogroups, however, remain incompletely described. We sought to evaluate whether these 3 groups differ on the basis of repolarization heterogeneity, which has previously been linked to adverse outcomes in HFpEF. The T-peak to T-end (TpTe) interval, a well-validated index of repolarization heterogeneity, was measured by 2 readers blinded to each other and all other clinical data on the electrocardiograms of 201 HFpEF patients enrolled in a systematic observational study. TpTe duration was associated with higher B-type natriuretic peptide level (p = 0.006), increased QRS-T angle (p = 0.008), and lower septal e' velocity (p = 0.007). TpTe duration was greatest in phenogroup #3 (100.4 ± 24.5 ms) compared with phenogroups #1 (91.2 ± 17.3 ms) and #2 (90.2 ± 17.0 ms) (p = 0.0098). On multivariable analyses, increased TpTe was independently associated with the high-risk phenogroup #3 classification. In conclusion, repolarization heterogeneity is a marker of a specific subset of HFpEF patients identified using unsupervised machine learning analysis and therefore may be a key pathophysiologic marker in this subset of HFpEF patients.

No correlation between body mass index and 30-day prognostic outcome in Asians with acute ST-elevation myocardial infarction undergoing primary coronary intervention.

This study investigated whether body mass index (BMI) was a risk factor predictive of 30-day prognostic outcome in Asians with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Evaluating the short-term cost-effectiveness of liraglutide versus lixisenatide in patients with type 2 diabetes in the United States.

Bringing patients with type 2 diabetes to recommended glycated hemoglobin (HbA1c) treatment targets can reduce the risk of developing diabetes-related complications. The aim of the present analysis was to evaluate the short-term cost-effectiveness of once-daily liraglutide 1.8 mg versus once-daily lixisenatide 20 μg as add on to metformin for treatment of type 2 diabetes in the United States (US) by assessing the cost per patient achieving HbA1c-focused and composite treatment targets.

Determinants of Gestational Diabetes Mellitus, a case-control study.

Gestational diabetes mellitus is glucose intolerance first recognized during pregnancy. The objective of this study was to identify the determinant factors of Gestational Diabetes Mellitus.

Interaction between family history of diabetes and hyperlipidemia on risk of diabetes in population with normotension in Harbin: a cross-sectional study.

Objective: To explore the interaction between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension. Methods: A multistage stratified probability random sampling was conducted to select a representative sample of urban residents aged 20-74 years in Harbin. A total of 376 diabetes patients with normotension and 3 692 residents with normal blood pressure, normal fasting glucose, and normal 2 hours glucose from OGTT were surveyed. The interaction was evaluated by using crossover analysis and additive model. Results: Multivariate logistic regression analysis indicated that there was a possible additive interaction between family history of diabetes and hyperlipidemia on the risk of diabetes. The relative excess risk due to the interaction, the attributable proportion due to the interaction, and the synergy index were 1.97 (95%CI:-0.32-4.26), 0.30 (95%CI: 0.03-0.57), and 1.54 (95%CI: 0.96-2.47), respectively. There were significant combination effects between family history of diabetes and high both total cholesterol and triglyceride, isolated high total cholesterol, and isolated high triglyceride levels; the ORs were 10.55 (95%CI: 5.62-19.80), 7.81 (95%CI: 3.65-16.71) and 5.13 (95%CI: 3.22-8.16), respectively. Conclusion: There might be synergistic effect between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension.

Analysis of dietary pattern and diabetes mellitus influencing factors identified by classification tree model in adults of Fujian.

Objective: To find out the dietary patterns and explore the relationship between environmental factors (especially dietary patterns) and diabetes mellitus in the adults of Fujian. Methods: Multi-stage sampling method were used to survey residents aged ≥18 years by questionnaire, physical examination and laboratory detection in 10 disease surveillance points in Fujian. Factor analysis was used to identify the dietary patterns, while logistic regression model was applied to analyze relationship between dietary patterns and diabetes mellitus, and classification tree model was adopted to identify the influencing factors for diabetes mellitus. Results: There were four dietary patterns in the population, including meat, plant, high-quality protein, and fried food and beverages patterns. The result of logistic analysis showed that plant pattern, which has higher factor loading of fresh fruit-vegetables and cereal-tubers, was a protective factor for non-diabetes mellitus. The risk of diabetes mellitus in the population at T2 and T3 levels of factor score were 0.727 (95%CI:0.561-0.943) times and 0.736 (95%CI: 0.573-0.944) times higher, respectively, than those whose factor score was in lowest quartile. Thirteen influencing factors and eleven group at high-risk for diabetes mellitus were identified by classification tree model. The influencing factors were dyslipidemia, age, family history of diabetes, hypertension, physical activity, career, sex, sedentary time, abdominal adiposity, BMI, marital status, sleep time and high-quality protein pattern. Conclusion: There is a close association between dietary patterns and diabetes mellitus. It is necessary to promote healthy and reasonable diet, strengthen the monitoring and control of blood lipids, blood pressure and body weight, and have good lifestyle for the prevention and control of diabetes mellitus.

Effects of Entecavir and Tenofovir on Renal Function in Patients with Hepatitis B Virus-Related Compensated and Decompensated Cirrhosis.

The renal effects of nucleos(t)ide analogs in patients with chronic hepatitis B are controversial. We aimed to compare the impact of entecavir (ETV) and tenofovir (TDF) on renal function in patients with hepatitis B virus (HBV)-related cirrhosis.

Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway.

Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats.

AR C-106T gene polymorphism and diabetic nephropathy in the Eastern Asians with T2DM: A meta-analysis including 2120 subjects.

Aldose reductase (AR) gene C-106T polymorphism may be associated with diabetic nephropathy (DN) susceptibility, but the results of individual studies remain controversial.

Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus.

We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT). All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the SLC6A4 distal promoter region using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. SLC6A4 mRNA levels were measured by reverse transcription-quantitative PCR (RT-qPCR). Functional SLC6A4 polymorphisms (5HTTLPR, STin2, rs25531) were genotyped using standard PCR-based procedures. Average DNA methylation across the 7 analyzed loci was decreased in the GDM as compared to the NGT group (by 27.1%, p = 0.037) and negatively correlated, before and after adjustment for potential confounder/s, with maternal plasma glucose levels at the 24th to 28th week of gestation (p<0.05). Placental SLC6A4 mRNA levels were inversely correlated with average DNA methylation (p = 0.010) while no statistically significant association was found with the SLC6A4 genotypes (p>0.05). The results suggest that DNA methylation of the fetal SLC6A4 gene is sensitive to the maternal metabolic state in pregnancy. They also indicate a predominant role of epigenetic over genetic mechanisms in the regulation of SLC6A4 expression in the human placenta. Longitudinal studies in larger cohorts are needed to verify these results and determine to which degree placental SLC6A4 changes may contribute to long-term outcomes of infants exposed to GDM.