ABSTRACT
Aim: Validation of epigenome-wide association studies is sparse. Therefore, we evaluated the methylation markers cg06500161 (ABCG1) and cg11024682 (SREBF1) as classifiers for diabetes stratification. Patients & methods: DNA methylation was measured in blood (n = 167), liver (n = 99) and visceral adipose tissue (n = 99) of nondiabetic or Type 2 diabetic subjects by bisulfite pyrosequencing. Results: DNA methylation at cg11024682 in blood and liver correlated with BMI. Methylation at cg06500161 was influenced by the adjacent SNP rs9982016. Insulin-resistant and sensitive subjects could be stratified by DNA methylation status in blood or visceral adipose tissue. Conclusion: DNA methylation at both loci in blood presents a promising approach for risk group stratification and could be valuable for personalized Type 2 diabetes risk prediction in the future.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics , Diabetes Mellitus, Type 2/genetics , Sterol Regulatory Element Binding Protein 1/genetics , DNA Methylation , Diabetes Mellitus, Type 2/blood , Genetic Markers/genetics , Humans , Insulin/metabolismABSTRACT
CONTEXT: Posterior pituitary function in patients with suspected diabetes insipidus is usually assessed by a water deprivation test. Alternatively, a nonosmotic stimulus such as hypoglycemia may be used to stimulate vasopressin [arginine vasopressin (AVP)] secretion. Plasma AVP measurement may aid in the diagnosis and, especially, differential diagnosis of diabetes insipidus and polydipsia. However, AVP measurement is cumbersome. Copeptin, the stable C-terminal glycopeptide of the AVP prohormone, is stoichiometrically secreted from the posterior pituitary. OBJECTIVE: The aim was to study the value of copeptin levels in the diagnosis of diabetes insipidus during insulin-induced hypoglycemia. PATIENTS AND METHODS: A total of 38 patients were studied during insulin-induced hypoglycemia as part of a combined pituitary function test for possible anterior pituitary disease. There were 29 patients who had normal posterior pituitary function, and nine had central diabetes insipidus. Blood sampling was done before and 30, 45, and 90 min after iv insulin injection. Copeptin was measured with a new sandwich immunoassay. RESULTS: Patients with intact posterior pituitary function had basal copeptin levels of 3.7 +/- 1.5 pm, with a maximal increase to 11.1 +/- 4.6 pm 45 min after insulin injection. Copeptin levels in patients with diabetes insipidus were 2.4 +/- 0.5 pm before insulin injection, with a maximum increase to 3.7 +/- 0.7 pm. Both basal and stimulated copeptin levels were lower in patients with diabetes insipidus as compared with patients with intact posterior pituitary function. A stimulated copeptin level 45 min after insulin injection of less than 4.75 pm had an optimal diagnostic accuracy to detect diabetes insipidus. CONCLUSION: Copeptin measurement may be used to assess posterior together with anterior pituitary function during insulin-induced hypoglycemia.
Subject(s)
Biomarkers/blood , Glycopeptides/blood , Insulin , Pituitary Diseases/diagnosis , Diabetes Insipidus, Neurogenic/diagnosis , Diabetes Insipidus, Neurogenic/metabolism , Diagnosis, Differential , Glycopeptides/metabolism , Humans , Hypoglycemia/metabolism , Pituitary Diseases/metabolism , Pituitary Gland, Anterior/physiology , Pituitary Gland, Posterior/physiology , Sensitivity and SpecificityABSTRACT
The long-term consequences of neonatal lipopolysaccharide (LPS) exposure on adult behavioral and neuroendocrine stress responsiveness as well as on the clinical course of periodontal disease were assessed in male Lewis rats. At 3 and 5 days of age, pups were administered either saline (SHAM) or LPS or were left undisturbed. After postnatal treatment, mothers licked LPS-treated pups significantly more. In adult LPS rats of 3-5 months of age, home cage activity indicated changes of the diurnal rhythmicity. Furthermore, SHAM- and LPS-treated animals displayed treatment-specific signs of increased anxiety in social interaction, elevated plus maze, holeboard, and open field tests. At 7 months of age, a dramatic increase of periodontal fiber loss in LPS rats was associated with increased plasma interleukin-6 levels. In contrast, SHAM treatment caused high plasma interferon-gamma cytokine levels and protective effects in periodontal disease. Parameters of the response to novelty were significantly correlated with later disease susceptibility. Thus, LPS-induced early postnatal illness modulates the adult behavioral responsiveness to stress and predisposes to periodontal disease.
