Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D.

Background and Aims:The predictive potential of neck circumference (NC) based indices (a measure of upper body fat distribution) for predicting metabolic syndrome (MetS) and its components among Indians is not known. This study aimed to evaluate the role of NC and neck height ratio (NHtR) as independent predictors of MetS and its components as compared to traditional anthropometric indices.Materials and Methods:A total of 451 individuals from 867 screened individuals, 30–80 years age, without any co-morbid state who gave informed written consent underwent clinical, anthropometric, and biochemical assessment.Results:Patients with MetS in both the sexes had significantly higher NC, NHtR, glycated hemoglobin, fasting glucose, and dyslipidemia (higher triglycerides, total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, low-density lipoprotein cholesterol/HDL-C ratio, and lower HDL-C). In both sexes, individuals in the highest tertile of NC had significantly greater central and generalized obesity, lower HDL-C, and significantly higher MetS. Receiver operating characteristic analysis revealed waist circumference (WC) to have the largest area under the curve for predicting MetS in both sexes, followed by NHtR, NC, and body mass index. NC and NHtR of >34.9 cm (sensitivity 78.6%; specificity 59.3%) and >21.17 cm/m (sensitivity 80.7% and specificity 64.6%) respectively for men and >31.25 cm (sensitivity 72.3%; specificity 64.4%) and >20.48 cm/m (sensitivity 80.4% and specificity 60%) respectively for women were the best values for identifying MetS. Increased NC and NHtR had odds ratio of 1.52 (95% confidence interval [CI]: 1.37–1.68; P < 0.001) and 1.96 (95% CI: 1.67–2.29; P < 0.001) respectively in identifying MetS.Conclusion:NC and NHtR are good predictors of MetS and cardiovascular risk factors in Asian Indians. NHtR is reliable and perhaps an even better index than NC with regards to cardiovascular risk prediction.

SummaryParathyroid cysts are rare (0.8–3.41% of all parathyroid lesions) and usually arise secondary to cystic degeneration of parathyroid adenomas. Intrathyroidal parathyroid cysts are extremely rare with only three cases reported till date. We present a 24-year-old female with clinical and biochemical features of primary hyperparathyroidism (PHPT; Ca2 +: 12.1 mg/dl; intact parathyroid hormone (iPTH): 1283 pg/ml) and poor radiotracer uptake with minimal residual uptake in the left thyroid lobe at 2 and 4 h on Tc99m sestamibi imaging. Neck ultrasonography (USG) revealed 0.6×1 cm parathyroid posterior left lobe of thyroid along with 22×18 mm simple thyroid cyst. USG-guided fine-needle aspiration (FNA) and needle tip iPTH estimation (FNA-iPTH) from parathyroid lesion was inconclusive (114 pg/ml), necessitating FNA of thyroid cyst, which revealed high iPTH (3480 pg/ml) from the aspirate. The patient underwent a left hemithyroidectomy. A >50% drop in serum iPTH 20 min after left hemithyroidectomy (29.4 pg/ml) along with histopathology suggestive of intrathyroidal cystic parathyroid adenoma (cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion surrounded by normal thyroid follicles) confirmed that the parathyroid cyst was responsible for PHPT. This report highlights the importance of FNA-iPTH in localizing and differentiating a functional parathyroid lesion from nonfunctional tissue in PHPT.Learning points Fine-needle aspiration from suspected parathyroid lesion and needle tip iPTH (FNA-iPTH) estimation from the saline washing has an important role in localizing primary hyperparathyroidism (PHPT).FNA-iPTH estimation may help in differentiating functional from nonfunctional parathyroid lesion responsible for PHPT.iPTH estimation from aspirate of an intrathyroid cyst is helpful in differentiating intrathyroidal parathyroid cyst from thyroid cyst.

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.

IMPORTANCEWomen with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. OBJECTIVE To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. DESIGN, SETTING, AND PARTICIPANTS This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled

Glucocorticoids are potent immunosuppressive and anti-inflammatory drugs used for various systemic and localized conditions. The use of glucocorticoids needs to be weighed against their adverse effect of aggravating hyperglycemia in persons with diabetes mellitus, unmask undiagnosed diabetes mellitus, or precipitate glucocorticoid-induced diabetes mellitus appearance. Hyperglycemia is associated with poor clinical outcomes, including infection, disability after hospital discharge, prolonged hospital stay, and death. Furthermore, clear guidelines for managing glucocorticoid-induced hyperglycemia are lacking. Therefore, this consensus document aims to develop guidance on the management of glucocorticoid-induced hyperglycemia. Twenty expert endocrinologists, in a virtual meeting, discussed the evidence and practical experience of real-life management of glucocorticoid-induced hyperglycemia. The expert group concluded that we should be proactive in terms of diagnosis, management, and post-steroid care. Since every patient has different severity of underlying disease, clinical stratification would help understand patient profiles and determine the treatment course. Patients at home with pre-existing diabetes who are already on oral or injectable therapy can continue the same as long as they are clinically stable and eating adequately. However, depending on the degree of hyperglycemia, modification of doses may be required. Initiating basal bolus with correction regimen is recommended for patients in non-intensive care unit settings. For patients in intensive care unit, variable rate intravenous insulin infusion could be temporarily used, but under supervision of diabetes inpatient team, and patients can be transitioned to subcutaneous insulin once stable baseline assessment and continual evaluation are crucial for day-to-day decisions concerning insulin doses. Glycemic variability should be carefully monitored, and interventions to treat patients should also aim at achieving and maintaining euglycemia. Rational use of glucose-lowering drugs is recommended and treatment regimen should ensure maximum safety for both patient and provider. Glucovigilance is required as the steroids taper during transition, and insulin dosage should be reduced subsequently. Increased clinical and economic burden resulting from corticosteroid-related adverse events highlights the need for effective management. Therefore, these recommendations would help successfully manage GC-induced hyperglycemia and judiciously allocate resources.

Cross sex hormone therapy (CSHT) is a strongly desired medical intervention for gender incongruent individuals. The goal is to change secondary sex characteristics to facilitate gender presentation that is consistent with the desired sex. When appropriately prescribed CSHT can greatly improve mental health and quality of life for gender incongruent individuals. Appropriate care for gender incongruent individuals in India is almost absent due to lack of country specific guideline and lack of training amongst the medical professionals. This document is intended to assist endocrinologists and physicians whose adult gender incongruent client is seeking gender reaffirmation as female (transfeminine). These individuals require a safe and effective CSHT regimen that will suppress endogenous male hormone secretion and maintain physiologic levels of female sex hormone. In this document, we offer suggestions based on an in-depth review of Guidelines of Endocrine Society, The World Professional Association for Transgender Health guidelines, the Sappho Good Practice Guide of India and collegial meetings with expert Indian clinicians working in this field. Clinicians represented in our expert panel are not gender specialists by training but have developed expertise due to the volume of gender incongruent individuals they manage. This consensus statement on medical management provides protocols for the prescribing clinician relating to diagnosis, baseline evaluation and counselling, prescription planning for feminizing hormone therapy and anti-androgen therapy, targets for monitoring hormone therapy, choice of therapy, clinical and biochemical monitoring, recommending sex reaffirmation surgery and peri-operative hormone therapy. The recommendations made in this document should not be perceived as a rigid set of guidelines and the treating clinicians are encouraged to modify our suggested protocols to address emerging issues.

Ig-G4 related disease (IgG4RD) is a heterogeneous disorder with multi-organ involvement recognised as a separate entity at the start of this century only. It is currently one of the hottest areas of clinical and translational research across specialties. Thyroid involvement in IgG4RD is rare, believed to occur in less than 4% of cases, may be isolated or may be associated with other organ involvement. As of today Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, and few patients of Graves' orbitopathy represent the types of IgG4-related thyroid disease (IgG4RTD). This disorder is frequently confused with malignancy due to the intense sclerosis of thyroid resulting in hard texture on palpation compounded by often-associated compressive symptoms. Diagnosis involves establishing high circulating levels of IgG4 > 135 mg/dL, increased serum IgG4 to IgG ratio of > 8%, immunohistochemistry showing dense lymphoplasmacellular inflammatory infiltrate consisting of IgG4-positive plasma cells with storiform fibrosis and obliterative phlebitis, and increased IgG4 positive plasma cell > 10 cells per high-power field when at least three fields are evaluated. Glucocorticoids are the primary form of therapy in IgG4RD. However, their role in IgG4RTD needs to be evaluated. As of today levothyroxine supplementation for resulting hypothyroidism, appropriate management of Graves' disease, and surgical excision of thyroid in case of compressive symptoms remain the primary treatment options. StreszczenieChoroba związana z Ig-G4 (IgG4RD) jest heterogennym zaburzeniem z zajęciem wielu narządów. Jako osobna jednostka chorobowa została wyodrębniona dopiero na początku tego stulecia. Choroba ta stanowi aktualnie najgorętszy obszar badań klinicznych i translacyjnych w różnych dziedzinach medycyny. Zajęcie tarczycy w IgG4RD jest rzadkie, szacuje się, że występuje w około 4% przypadków, może być izolowane lub związane zajęciem innych narządów. Na chwilę obecną zapalenie tarczycy związane z IgG4 (IgG4RTD) reprezentują: zapalenie tarczycy Riedela, które jest włókniejącą odmianą zapalenia tarczycy w chorobie Hashimoto oraz niektórzy pacjenci z orbitopatią Gravesa. Zapalenie tarczycy związane z IgG4 jest często mylone z chorobą nowotworową ze względu na nasilone stwardnienie tarczycy, które powoduje powstanie twardej struktury wyczuwalnej w badaniu palpacyjnym z towarzyszącymi często objawami uciskowymi. Rozpoznanie choroby obejmuje: stwierdzenie wysokich stężeń krążącej IgG4 > 135 mg/dl, zwiększony stosunek w surowicy IgG4 do IgG > 8%, w badaniu immunohistochemicznym stwierdzenie gęstych nacieków zapalnych złożonych z limfocytów i IgG4 dodatnich plazmocytów , z włóknieniem i zarostowym zapaleniem żył oraz zwiększeniem liczby IgG4 dodatnich plazmocytów > 10 w polu widzenia, jeżeli oceniono minimum 3 pola. Glikokortykosteroidy stanowią leczenie pierwszego wyboru w IgG4RTD. Niemniej ich rola w IgG4RTD wymaga dalszej oceny. Na chwilę obecną podstawowe opcje terapeutyczne obejmują: suplementację lewotyroksyny we wtórnej nied...