Journal of Clinical Endocrinology and Metabolism

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OBJECTIVE: Impaired follicular regulatory T (Tfr) cells enhance T follicular helper (Tfh) cells activity, resulting in the expansion of autoreactive B cells and autoantibody production. However, the role of Tfr cells in the pathogenesis of type 1 diabetes (T1D) is unclear. METHODS: We evaluated the expression and changes in function of circulating Tfr cells by studying patients with T1D alongside those with type 2 diabetes(T2D), first-degree relatives of T1D patients (T1D-FRs) and healthy controls...

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CONTEXT: Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear. OBJECTIVE: To assess associations between early pregnancy plasma zinc, selenium, copper and molybdenum and blood glucose levels later in the 2nd trimester. DESIGN: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies - Singleton cohort, a prospective cohort study between July 2009 and January 2013...

CONTEXT AND OBJECTIVE: We describe clinical features and biochemical characteristics of a unique population of severely affected untreated patients with congenital adrenal hyperplasia (CAH) from an Indonesian population, with proven cortisol deficiency but without clinical signs of cortisol deficiency. We evaluated the in vitro glucocorticoid activity of all relevant adrenal steroid precursors occurring in CAH patients. DESIGN: Cross sectional cohort study and translational research...

PURPOSE: Changes in blood glucose levels have been shown to influence eating in healthy individuals; however, less is known about glucose's effects on food intake in obese (OB) individuals. The goal of this study was to determine the predictive effect of circulating glucose levels on eating in free-living OB and normal weight (NW) individuals. METHODS: Interstitial glucose levels, measured with a continuous glucose monitor (CGM) system, were obtained from 15 OB and 16 NW volunteers (age: 40±14, 37±12 yr; weight: 91±13, 68±12 kg; HbA1c: 5...

CONTEXT: We previously developed and validated an inexpensive and parsimonious prediction model of 2-year all-cause mortality in real-life type 2 diabetic patients. OBJECTIVE: This model, now named ENFORCE, was now investigated in terms of i) prediction performance at 6 years, a more clinically useful time-horizon; ii) further validation in an independent sample; iii) performance comparison in real-life versus clinical trial setting. DESIGN: Observational prospective...

CONTEXT: mTORC1 activity is often increased in the adrenal cortex of patients with primary aldosteronism and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a possible target for treatment of primary aldosteronism. OBJECTIVE: To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with primary aldosteronism. DESIGN: (i) Plasma aldosterone, corticosterone and angiotensin II were measured in mice treated for 24 hours with vehicle or rapamycin...

CONTEXT: In patients with Cushing's disease (CD) and a typical image of adenoma at MRI, transsphenoidal surgery is consensual. However, when MRI is inconclusive or normal, some authors now advocate medical treatment instead. The implicit assumption is that modern MRI should miss only very small microadenomas, too difficult to visualize at surgery. OBJECTIVE: To analyze the evolution with time of the performances of MRI and the outcomes of surgery in CD patients with a typical image of adenoma vs...

CONTEXT: Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown. OBJECTIVE: To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men. DESIGN: Two open-labeled crossover studies were performed in human subjects...

CONTEXT: Although the role of iron in the development of type 2 Diabetes (T2D) has long been concerned, prospective studies directly linking body iron stores to T2D risk in sex-dependent context still inconsistent. OBJECTIVE: A systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk among men and women. DATA SOURCES: We searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018...

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CONTEXT: Evidence indicates that there is a significant impairment/loss of β-cell function/mass even before the stage of prediabetes. Elevated plasma proinsulin is a sign of β-cell dysfunction in the patients with diabetes/prediabetes. However, the dynamic changes of glucose stimulated proinsulin secretion (GSPS) among non-diabetic individuals remain obscure. OBJECTIVE: To examine GSPS and glucose-stimulated insulin secretion (GSIS) among individuals with normal glucose tolerance (NGT) and IGT, and to evaluate whether impaired GSPS is an early biomarker of β-cell impairment in the NGT individuals with subthreshold postprandial plasma glucose (PPG)...

CONTEXT: In the human adrenal, serotonin (5-HT), released by mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R). In primary pigmented nodular adrenocortical disease (PPNAD) cells, activation of the cAMP/protein kinase A (PKA) pathway by PRKAR1A mutations triggers upregulation of the 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and the 5-HT4, 5-HT6 and 5-HT7 receptors. Because ACTH stimulates cortisol secretion through activation of PKA, adrenocortical tissues exposed to sustained stimulation by ACTH may harbor increased expression of TPH and 5-HT4/6/7 receptors...

PURPOSE: Diabetes mellitus is a risk factor for the development and progression of chronic kidney disease (CKD). However, the association of prediabetes with adverse kidney outcomes is uncertain. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), including 9,361 participants without diabetes at baseline. We categorized participants according to fasting glucose as having impaired fasting glucose (≥100 mg/dL [(≥5...

CONTEXT: The incidence of Type 1 Diabetes (T1D) is increasing worldwide. The quest to understand T1D etiology as well as how to predict diabetes is ongoing and, in many ways, those goals intertwine. While genetic components associate with T1D, not all T1D individuals have those components and not all subjects with those components develop disease. OBJECTIVE: More robust methods for prediction of T1D are needed. Can high CD4+CD40+ T cell (Th40) levels be used as a biomarker in addition to other markers? METHODS: Th40 levels were assessed along with other parameters in blood collected from prediabetic TrialNet subjects...

CONTEXT: Chronic inflammation increases diabetes risk and may be exacerbated by excess adipose tissue. Whether cardiovascular fitness can offset chronic inflammation associated with excess adipose tissue in older adults is unclear. OBJECTIVE: The study aimed to examine the influence of cardiorespiratory fitness on links between adiposity and pro- and anti-inflammatory biomarkers related to metabolic risk in physically active older women. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study comprising older community-dwelling women (n = 109; age, 65-70 yr)...

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CONTEXT: It is unclear how adolescent glycemic status relates to brain health in adulthood. OBJECTIVE: To assess the association between adolescent fasting plasma glucose (FPG) and MRI-based brain measures in midlife. DESIGN: Between 1973 and 1992, the Bogalusa Heart Study (BHS) collected FPG from children 3 to 18 years old, and followed up between 1992 and 2018. Cognitive tests and brain MRI were collected in 2013-2016 and 2018. SETTING: Observational longitudinal cohort study...

CONTEXT: Underlying mechanisms leading to Gestational Diabetes Mellitus (GDM) are still under investigation and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating microRNAs are involved in placental development and function and are encapsulated in Extracellular Vesicles (EVs). OBJECTIVE: to compare differential expression of microRNAs in circulating EVs in pregnancies complicated by GDM versus controls...