Clinical Approach to Flash Glucose Monitoring: An Expert Recommendation.

The flash glucose monitoring (FGM) system FreeStyle Libre® is a device that measures interstitial glucose in a very simple way and indicates direction and speed of glucose change. This allows persons with diabetes to prevent hypoglycemic and hyperglycemic events. Scientific evidence indicates that the system can improve glycemic control and quality of life. To obtain the maximum benefit, it is necessary to properly handle glucose values and trends. Due to the generalization of the system use, the purpose of the document is to provide recommendations for the optimal use of the device, not only in the management of glucose values and trends but also in the prevention of hypoglycemia, actuation in exercise, special situations, and retrospective analysis of the glucose data, among others.

Differential effects of HNF-1α mutations associated with familial young-onset diabetes on target gene regulation.

Hepatocyte nuclear factor 1-α (HNF-1α) is a homeodomain transcription factor expressed in a variety of tissues (including liver and pancreas) that regulates a wide range of genes. Heterozygous mutations in the gene encoding HNF-1α (HNF1A) cause familial young-onset diabetes, also known as maturity-onset diabetes of the young, type 3 (MODY3). The variability of the MODY3 clinical phenotype can be due to environmental and genetic factors as well as to the type and position of mutations. Thus, functional characterization of HNF1A mutations might provide insight into the molecular defects explaining the variability of the MODY3 phenotype. We have functionally characterized six HNF1A mutations identified in diabetic patients: two novel ones, p.Glu235Gly and c-57-64delCACGCGGT;c-55G>C; and four previously described, p.Val133Met, p.Thr196Ala, p.Arg271Trp and p.Pro379Arg. The effects of mutations on transcriptional activity have been measured by reporter assays on a subset of HNF-1α target promoters in Cos7 and Min6 cells. Target DNA binding affinities have been quantified by electrophoretic mobility shift assay using bacterially expressed glutathione-S-transferase (GST)-HNF-1α fusion proteins and nuclear extracts of transfected Cos7 cells. Our functional studies revealed that mutation c-57-64delCACGCGGT;c-55G>C reduces HNF1A promoter activity in Min6 cells and that missense mutations have variable effects. Mutation p.Arg271Trp impairs HNF-1α activity in all conditions tested, whereas mutations p.Val133Met, p.Glu235Gly and p.Pro379Arg exert differential effects depending on the target promoter. In contrast, substitution p.Thr196Ala does not appear to alter HNF-1α function. Our results suggest that HNF1A mutations may have differential effects on the regulation of specific target genes, which could contribute to the variability of the MODY3 clinical phenotype.

Cannabinoid CB1 receptors are expressed by parietal cells of the human gastric mucosa.

Experimental data suggest that the endogenous cannabinoid system is involved in gastric function in different animal species. In most of them, CB(1) receptors have been localized on vagal terminals innervating the external wall of the stomach. We aimed at studying the putative presence and distribution of these receptors in the human gastric mucosa. To this end, we first performed Western blotting, RT-PCR, in situ hybridization, and immunohistochemical analysis of CB(1) protein distribution in biopsy samples of healthy individuals. To determine the precise cell populations expressing CB(1) receptors, we performed double immunofluorescence plus confocal microscopy analysis of the same samples. Our results show that CB(1) receptors are present in the gastric epithelium of the mucosa. Specifically, they are expressed by a subpopulation of mucosal cells, the acid-secreting parietal cells, as shown by double immunohistochemical staining and by their differential abundance in subregions of the gastric mucosa. These results reinforce the notion of a prominent role for the endocannabinoid system in the gastric function in humans and postulate the use of cannabinoid CB(1) receptors in parietal cells as new therapeutic targets for the regulation of gastric acid production.

A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age.

BACKGROUND: Mutations in the chloride channel gene, CLCNKB, usually cause classic Bartter syndrome (cBS) or a mixed Bartter-Gitelman phenotype in the first years of life. METHODS: We report an adult woman with atypical BS caused by a homozygous missense mutation, A204T, in the CLCNKB gene, which has previously been described as the apparently unique cause of cBS in Spain. RESULTS: The evaluation of this patient revealed an overlap of phenotypic features ranging from severe biochemical and systemic disturbances typical of cBS to scarce symptoms and diagnosis in the adult age typical of Gitelman syndrome. The tubular disease caused a dramatic effect on mental, growth and puberal development leading to low IQ, final short stature and abnormal ovarian function. Furthermore, low serum PTH concentrations with concomitant nephrocalcinosis and normocalcaemia were observed. Both ovarian function and serum PTH levels were normalized after treatment with cyclooxygenase inhibitors. CONCLUSIONS: The present report confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain. In our country, the genetic diagnosis of adult patients with hereditary hypokalaemic tubulopathies should include a screening of A204T mutation in the CLCNKB gene.

Coincidental diagnosis of an occult hilar steroid cell tumor of the ovary and a cortisol-secreting adrenal adenoma in a 49-year-old woman with severe hyperandrogenism.

OBJECTIVE: To report an exceptional association between an occult ovarian steroid cell tumor and a cortisol-secreting adrenal adenoma. DESIGN: Case report. SETTING: Endocrinology and nutrition unit at a general hospital in Spain. PATIENT(S): A 49-year-old woman who presented with persistence of severe hyperandrogenism after removal of a left adrenal adenoma. INTERVENTION(S): An endocrine study evaluating serum androgens, adrenal function, and tumor markers was ordered. Transvaginal sonography was done to rule out an ovarian tumor. Finally, a selective catheterization of ovarian veins allowed the correct diagnosis. MAIN OUTCOME MEASURE(S): Clinical and endocrine description of the patient and preoperative localization of the source of T secretion. RESULT(S): After adrenal surgery, urinary free cortisol levels decreased to normal values, but serum T remained within the tumoral range (3.04 ng/mL). Selective catheterization of ovarian veins revealed a gradient of T concentration in the right ovary. After bilateral annexectomy, a microscopic steroid cell tumor of hilar type was found in the right ovary. Serum T fell within the normal range, and hirsutism progressively improved. CONCLUSION(S): This unusual association between an occult-virilizing ovarian steroid cell tumor and a cortisol-secreting adrenal adenoma illustrates the value of an accurate preoperative workup in women with severe hyperandrogenism.

Gonadal agenesis 46,XX associated with the atypical form of Rokitansky syndrome.

OBJECTIVE: To describe a patient with bilateral ovarian agenesis associated with the atypical form of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: Case report. SETTING: Unit of Endocrinology, Fundación Hospital Alcorcón. Madrid (Spain). PATIENT: A 17-year-old woman who presented with primary amenorrhea and lack of mammary development. INTERVENTION(S): An endocrine study including pituitary, ovarian, adrenal, and thyroid evaluation was performed. Genetic study was done by karyotype and fluorescence in situ hybridization (FISH) analysis to detect the presence of Y chromosome material. Bone study, intravenous urography, pelvic ultrasound, and laparoscopic study were ordered to evaluate the associated genitourinary and skeletal anomalies. MAIN OUTCOME MEASURE(S): Anatomic, endocrine, and genetic description of the patient. RESULT(S): The gynecologic examination showed a normal vagina ending in a blind pouch. The endocrine evaluation disclosed gonadotropin levels in the menopausal range and nonautoimmune subclinical primary hypothyroidism. The laparoscopic study revealed a single pelvic kidney and an absence of gonads, fallopian tubes, and uterus. The karyotype was 46,XX; no Y chromosome was found in FISH analysis. CONCLUSION(S): To our knowledge, this is the first report of gonadal agenesis 46,XX associated with the atypical form of MRKH syndrome. The primary hypothyroidism may be coincidental.