Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study.

Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing's disease (CD). Hyperglycemia during treatment can occur because of the drug's mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 µg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.

Bone Mineral Density and Bone Turnover Marker in a Subclinical Thyrotoxic State in Young Premenopausal Women.

BACKGROUND: Subclinical thyrotoxicosis (SCH) is characterized by normal serum thyroid hormone levels and low thyrotropin levels. The impact of this condition on the skeletal system may vary depending on its cause, yet the relationship is not fully comprehended in premenopausal women. Studies are scarce about its effects on bone health in our population. OBJECTIVES: This study aims to evaluate the bone mineral density (BMD) and bone turnover markers in premenopausal women with SCH and determine if any differences exist based on the condition's etiology. METHODS: A cross-sectional study was conducted at Ramaiah Medical College involving 36 participants for one year and six months after approval from the Ethics Committee. The carboxy-terminal telopeptide of type I collagen in blood and BMD were measured at the lumbar vertebrae (L1-L4) and femoral neck by dual-energy x-ray absorptiometry (Hologic v 2.0, Hologic, Massachusetts, U.S.). Statistical analysis was done using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States).  Results: The mean age of the study population was 35.2 ± 7.2 years. The etiology was Graves' disease [n=11 (33.3%)], iatrogenic [n=14(38.8%)], toxic adenoma [n=6 (15.1%)], and multi-nodular goiter [n=5 (15.1%)]. The mean BMI was 23.5 ± 3.8 kg/m2, and the mean levels of corrected calcium, phosphorus, and 25 hydroxy-vitamin D were 9.12 ± 0.25 mg/dl, 2.95 ± 0.34 mg/dl, and 29.4 ± 6.4 ng/ml, respectively. The mean BMD at hip and spine was 0.81 ±0.16 g/cm2 and 0.92±0.08 g/cm2 respectively. The mean Z-score was (-0.02 ± 0.8) and (-0.92± 0.08) at the hip and spine. No significant difference was observed in the BMD at the hip (p = 0.14) or spine (p = 0.44) between the endogenous and exogenous subclinical thyrotoxic subgroups. At the same time, the carboxy-terminal telopeptide of type I collagen was significantly different between the two groups (p<0.05). CONCLUSION: In our cross-sectional study of premenopausal women with SCH, BMD at the hip or spine as measured by dual-energy X-ray absorptiometry did not reveal any significant reduction. The subclinical thyrotoxic state may not have an adverse effect on bone health in premenopausal females with sufficient levels of serum 25-hydroxy-vitamin D in the short term.

Thyroid Eye Disease and Its Association With Diabetes Mellitus: A Major Review.

PURPOSE: Thyroid eye disease (TED) associated with diabetes mellitus (DM) presents unique challenges. DM is a risk factor for TED. Standard management of TED with glucocorticoids (GC), orbital radiation, or teprotumumab can cause adverse events in poor glycemic control. The authors reviewed the literature on the relationship between TED and DM and the management of co-existing diseases. METHODS: The authors searched PubMed with keywords "thyroid eye disease," "diabetes mellitus," and similar terms from 2013 to 2022. The authors included relevant studies after screening the abstracts. Additional references to the selected studies were included where applicable. Data were extracted from the final articles according to the preplanned outline of the review. RESULTS: The initial search yielded 279 abstracts. The final review included 93 articles. TED and DM interact at multiple levels-genetic, immunologic, cellular, nutritional, and metabolic. Both DM and thyroid dysfunction exacerbate the morbidity caused by the other. Metabolic factors also affect the inflammatory pathway for TED. Patients with DM develop TED with greater frequency and severity, necessitating interventions for vision salvage. Agents (GC, teprotumumab, or radiation) used for TED are often unsuitable for treatment with DM, especially if there is poor glycemic control or diabetic retinopathy. There were no studies on using steroid-sparing agents in TED with DM. CONCLUSION: TED and DM co-exist because of multiple intersections in the pathophysiology. Challenges in the treatment include increased TED severity and risk of hyperglycemia and retinopathy. Multidisciplinary teams best undertake treatment of TED with DM.

Real-World Observational Study on Vildagliptin With Insulin (VIL-INS) or Vildagliptin and Metformin With Insulin (VIL-MET-INS) Therapy in Indian Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE:  The therapeutic use of vildagliptin and insulin (VIL-INS) or vildagliptin and metformin in combination with insulin (VIL-MET-INS) in the Indian scenario has yet to be explored by generating real-world evidence. Therefore, the present study aimed to evaluate the demographic, clinical characteristics, and treatment patterns of patients with type 2 diabetes mellitus (T2DM) in Indian settings in the above context. METHODOLOGY:  This observational study conducted at 600 healthcare centers in India retrospectively analyzed data of adult patients with T2DM who had been treated with either vildagliptin with insulin or a combination of vildagliptin and metformin with insulin. Data were collected from medical records and analyzed by appropriate statistical tests. RESULTS:  A total of 12,603 patients with T2DM were included with a mean age of 53.4 years of which 63.8% were males. The majority of patients (n=6511; 51.7%) received a combination of vildagliptin and metformin on top of insulin. A significantly high proportion of patients in the age group of 18-40 years received this treatment compared to patients who were initiated on insulin treatment after vildagliptin and metformin combination (11.6% vs. 9.7%; P<0.001). Of all the patients, 70.0% were able to achieve target glycemic control with either VIS-INS or VIL-MET-INS. After treatment with VIL-INS or VIL-MET-INS, the mean glycated hemoglobin (HbA1c) levels significantly decreased with a mean change of 1.46%. Out of all patients, 13.5% experienced weight changes during treatment, with 67.4% of them showing weight loss. A total of 68 patients reported hypoglycemic events and among them, 49 patients had mild hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a majority of patients rated their experience as good to excellent (86.3% and 86.0%, respectively). CONCLUSION:  Both treatment regimens were effective in terms of reduced HbA1c to achieve glycemic control. Furthermore, it is well tolerated without an increase in the risk of hypoglycemia or weight gain. Hence, this therapy has favorable outcomes for T2DM management in Indian clinical settings.

Study of FGF21 Levels in Transgender People and its Association with Metabolic Parameters.

Background: Fibroblast growth factor (FGF21) is a metabolic regulator whose role in humans is unidentified. FGF21 has generated a lot of potential of becoming a therapeutic agent for the management of type 2 diabetes mellitus and dyslipidaemia. The role of FGF21 in gender dysphoria individuals has not been studied. Objective: Primary objective was to assess FGF21 levels in transgender individuals and compare with controls and secondary objective was to compare FGF21 levels with lipid and glucose parameters in transgender people. Results: Twenty-three transfemales and 21 transmales were included in the study and compared with 44 controls. Height and fasting blood glucose of transfemales was statistically greater than transmales, with no other differences in baseline characteristics. Although FGF21 levels were numerically greater in transfemales (183.50 ± 97.39), it was not statistically significant. FGF21 levels did not vary statistically when compared to controls although it was numerically higher. Univariate analysis was done in transgender patients and FGF21 levels were positively correlated with serum total cholesterol and serum LDL cholesterol in transfemales but not in transmales. Multivariate analysis was also done taking 50th centile and 75th centile of FGF21 levels of controls and was found that only serum total cholesterol and serum LDL positively correlated with FGF21 levels in transfemales with 75th centile as cutoff. Conclusion: FGF21 levels correlated positively with serum triglycerides and serum LDL cholesterol in transfemales but not in transmales. Hence, FGF21 levels can be used as a marker for the development of metabolic syndrome in transfemales.

Healthcare Practitioners' Perspective of Prevailing Awareness on Diabetes Complications: A Questionnaire-Based Pan-India Study.

The increasing prevalence rate of diabetes mellitus (DM) and the associated long-term complications warrant a need to improve awareness of DM-related complications in the Indian population. Our questionnaire-based pan-India study (April 2021-March 2022) aims to capture the observations of healthcare practitioners (HCPs) on the prevailing level of knowledge and awareness regarding diabetes among their patients. We refer to this as the 90:90:90 program. It aims to achieve 90% awareness, 90% screening and detection of diabetes and prediabetes, and 90% achievement of effective treatment and control. A structured questionnaire was circulated to 1800 HCPs using Google Forms (Google, Mountain View, CA) and Zoom poll questions (Zoom Video Communications, Inc., San Jose, CA) during 125 symposiums. About half (48.6%) of the HCPs observe that less than 40% of their patients are aware of the risk factors of diabetes, and less than 60% of the patients were aware of its cardiovascular complications. About 92-95% of the HCPs recommend screening for diabetes in adults over 30 years of age and suggest the inclusion of a blood glucose estimate as a fifth vital to be tested during doctor visits. Less than 40% of patients fail to achieve the treatment goal, possibly due to lack of adherence, access to medicines, and financial constraints. Therefore, spreading awareness of DM complications and early screening for DM among adults (>30 years) could help achieve better management and treatment outcomes.

Pheochromocytoma: Clinical Experience From a Single Tertiary Care Center in India.

INTRODUCTION: Pheochromocytoma is a catecholamine-secreting tumor arising from adrenomedullary chromaffin cells that has a varied clinical presentation. Identification of this tumor, which has episodic symptoms, is a diagnostic challenge for clinicians. Diagnosis at an appropriate time is important because it is associated with significant morbidity and mortality. This study aims to mitigate the limited availability of data in our geographical area. AIMS AND OBJECTIVES: To assess the clinical, biochemical, and radiological features and outcomes of patients diagnosed with pheochromocytoma at our center. MATERIALS AND METHODS: This is a retrospective study. Patients diagnosed with pheochromocytoma during 2015-2023 were included in the study. Clinical, biochemical, and radiological data were collected at presentation, post-surgery, discharge, and until the last follow-up; data were retrieved from hospital records. Statistical analysis was done using IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. RESULTS: This study included 19 patients, of whom 10 (52.6%) were female. The most common clinical presentation was a hypertensive crisis in patients with pre-existing hypertension (63.1%), followed by headache (47.3%). The classical triad of headache, palpitation, and sweating was seen in only three patients (15.7%). The mean tumor size was 5.01±2.06 cm, with a range of 2.5 to 12 cm. All patients underwent adrenalectomy; six patients (31.5%) had perioperative complications, with post-operative hypotension being the most common at 21% (n = 4), followed by an acute coronary event during alpha blockade in one patient (0.05%) and an intra-operative hypertensive crisis in one patient (5%). A biochemical remission rate post-surgery was achieved in 17 (89.47%) patients. CONCLUSIONS: Hypertensive crisis in patients with pre-existing hypertension was the predominant presenting feature in most of our patients. Female predominance was noted (52.3%) compared to males. Perioperative complications were observed in 31.5% of patients, with post-operative hypotension being the most common complication.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

IDEA Group Consensus Statement on Medical Management of Adult Gender Incongruent Individuals Seeking Gender Affirmation as Male.

Gender-affirming hormone therapy (GAHT) is the most frequent treatment offered to gender-incongruent individuals, which reduces dysphoria. The goal of therapy among gender-incongruent individuals seeking gender affirmation as male is to change their secondary sex characteristics to affect masculine physical appearances. GAHT greatly improves mental health and quality of life among gender incongruent individuals. India-specific guideline for appropriate care for gender-incongruent individuals is almost absent. This document is intended to assist endocrinologists and other healthcare professionals interested in gender incongruity for individuals seeking gender affirmation as male. A safe and effective GAHT regimen aims to effect masculinising physical features without adverse effects. In this document, we offer suggestions based on an in-depth review of national and international guidelines, recently available evidence and collegial meetings with expert Indian clinicians working in this field. Clinicians represented in our expert panel have developed expertise due to the volume of gender incongruent individuals they manage. This consensus statement provides protocols for the hormone prescribing physicians relating to diagnosis, baseline evaluation and counselling, prescription planning for masculinising hormone therapy, choice of therapy, targets for monitoring masculinising hormone therapy, clinical and biochemical monitoring, recommending sex affirmation surgery and peri-operative hormone therapy. The recommendations made in this document are not rigid guidelines, and the hormone-prescribing physicians are encouraged to modify the suggested protocol to address emerging issues.

Study of Effects of Gender-Affirming Hormone Therapy on Bone Mineral Density in Individuals with Gender Dysphoria.

Introduction: Gender affirming hormone therapy (GAHT) is the mainstay treatment in transitioning individuals and has positive physical and psychological effects. Among the things to monitor in transgender patients on long-term hormones, bone health is an essential consideration. As the calcium intake in the Indian population is less, and many gender-incongruent individuals may not take adequate calcium in their diet, we needed data on the bone health of Indians with gender dysphoria as the information available globally may not apply to our population. Materials and Methods: The study was performed to assess bone mineral density in individuals with gender dysphoria who were on gender-affirming hormonal therapy for at least 6 months. It was a hospital-based cross-sectional study of bone mineral density measured at two sites - hip and spine in individuals with gender dysphoria on GAHT for at least six months. Results: A total of 30 individuals were included in this study. The mean age of individuals with Gender dysphoria was found to be 28.17 ± 6.15 years, and the age range was 19-42 years. Out of the 30 individuals, 14 were transgender males, and the remaining 16 were transgender females. Bone mineral density at the hip and spine in transgender males was 1.047 ± 0.124 g/cm2 and 1.065 ± 0.115 g/cm2, which was better compared to transgender females in whom the bone mineral density at hip and spine was 0.899 ± 0.873 g/cm2 and 0.854 ± 0.099 g/cm2 (P = 0.001 for hip; P = 0.000 for spine). The Z score at hip and spine were better in transgender males as compared to transgender females (P < 0.001 for hip; P < 0.001 for spine) when compared to genetic sex and at the spine (P = 0.001) when compared to affirmed sex. In this study, we observed that the transgender females who underwent orchidectomy had a lower mean Z score at spine compared to individuals who did not undergo the procedure. Conclusions: The current study results indicate that GAHT does have positive effects on bone health in transmen.

Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study.

PURPOSE: Pasireotide is an effective treatment for acromegaly and Cushing's disease, although treatment-emergent hyperglycemia can occur. The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin/other permitted oral antidiabetic drugs. METHODS: Multicenter, randomized, open-label, Phase IV study comprising a core phase (≤ 16-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n = 190) or Cushing's disease (n = 59) received long-acting (starting 40 mg IM/28 days) or subcutaneous pasireotide (starting 600 µg bid), respectively. Patients with increased fasting plasma glucose (≥ 126 mg/dL on three consecutive days) during the 16-week pre-randomization period despite metformin/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followed by liraglutide) or insulin for another 16 weeks. The primary objective was to evaluate the difference in mean change in HbA1c from randomization to end of core phase between incretin-based therapy and insulin treatment arms. RESULTS: Eighty-one (32.5%) patients were randomized to incretin-based therapy (n = 38 received sitagliptin, n = 28 subsequently switched to liraglutide; n = 12 received insulin as rescue therapy) or insulin (n = 43). Adjusted mean change in HbA1c between treatment arms was - 0.28% (95% CI - 0.63, 0.08) in favor of incretin-based therapy. The most common AE other than hyperglycemia was diarrhea (incretin-based therapy, 28.9%; insulin, 30.2%). Forty-six (18.5%) patients were managed on metformin (n = 43)/other OAD (n = 3), 103 (41.4%) patients did not require any oral antidiabetic drugs and 19 patients (7.6%) were receiving insulin at baseline and were not randomized. CONCLUSION: Many patients receiving pasireotide do not develop hyperglycemia requiring oral antidiabetic drugs. Metformin is an effective initial treatment, followed by incretin-based therapy if needed. ClinicalTrials.gov ID: NCT02060383.

Basal Insulin Titration: Moving Towards a More Patient-Centric Approach with Gla-100 in India.

Owing to the progressive nature of the disease, patients with type 2 diabetes mellitus (T2DM) eventually require adjustment or titration of insulin doses to achieve the desired glycemic control. Titration inertia, or the inability to dose-titrate, is one of the key barriers to optimized insulin therapy and is common in Asian countries such as India. Simple and effective titration algorithms involving the use of basal insulin, which has the lowest hypoglycemia risk, that can be individualized by physicians and easily followed by patients aid in tackling titration inertia. In this context, insulin glargine 100 U/mL (Gla-100) appears to be the ideal insulin to overcome titration inertia, owing to its low risk of hypoglycemia and effective glycemic control. Different guidelines recommend the use of basal insulin, such as Gla-100, and encourage a patient-centric approach for dose titration. Although the effective implementation of the patient-centric approach in India is challenging, it is nevertheless achievable.

Perioperative Glycemic Control in Patients who Underwent Cardiac Transplantation and Effect on the Outcome at Discharge in a Tertiary Care Centre.

OBJECTIVES: To study the glycemic status and insulin requirements in patients who underwent cardiac transplantation and to compare it among patients with and without diabetes mellitus. To compare preoperative glycemic status and perioperative insulin requirements with the outcome. METHODS AND MATERIALS: The retrospective data of the glycemic status of patients before and after cardiac transplantation were collected and analyzed. Different variables like HbA1c, creatinine, age, BMI, and glycemic status were compared with the outcome. RESULTS: A total of 18 patients with a mean age of 46.72 ± 16.94 years (mean ± SD) and a median age of 48.5 years underwent cardiac transplantation. The mean preoperative glycosylated hemoglobin (HbA1c) was 8.75 ± 2.15% (72 ± 2.36 mmol/mol) and 5.82 ± 0.45% (40 ± 4.89 mmol/mol) in patients with and without diabetes mellitus, respectively. The mean insulin requirement of insulin on postoperative days 0, 1, 2, and 3 was 1.396, 0.503, 0.490, and 0.537 (IU/kg/day) in patients with diabetes, whereas in patients without diabetes mellitus it was 1.955, 0.561, 1.19, and 0.61 (IU/kg/day), respectively. The mean insulin requirement at the time of discharge was 0.698 ± 0.43 IU/kg/day (mean ± SD) and 1.285 ± 1 IU/kg/day (mean ± SD) (p = 0.36) in patients with and without diabetes mellitus, respectively (p = 0.53, 0.11, 0.41, and 0.32, respectively). There was no association with the outcome when analyzed with different variables like HbA1c, creatinine, BMI, age, hemoglobin, insulin requirements, and glycemic status. CONCLUSIONS: Perioperative glycemic control is crucial for successful cardiac transplantation irrespective of diabetic status.

Serum CCL 18 Levels in Women with Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common metabolic disorders seen in women of the reproductive age group, with the majority of them having insulin resistance. There is a need to identify sensitive markers of insulin resistance. CC chemokine ligand 18 (CCL 18) secreted from white adipose tissue is upregulated in individuals with insulin resistance. OBJECTIVES: To study the correlation between serum CCL 18 levels and insulin resistance in PCOS. MATERIALS AND METHODS: This case-control study included 45 PCOS women and an equal number of age and body mass index (BMI) matched controls. Estimation of serum CCL 18, serum testosterone, fasting plasma glucose, fasting insulin, HbA1c, and ultrasonography of abdomen and pelvis was done and HOMA IR was calculated. RESULTS: Serum CCL 18 level was higher in women with PCOS when compared to controls. The mean level of serum CCL 18 (ng/mL) in the PCOS group and control group was 28.32 ± 4.17 and 11.90 ± 4.91, respectively (P < 0.001). Blood pressure, waist circumference, waist-hip ratio, modified Ferriman Gallway score (FG) score serum total testosterone, fasting serum insulin, and HOMA IR showed a relationship with serum CCL 18 levels. Serum CCL 18 was an independent predictor of PCOS (P < 0.05). A serum CCL 18 cutoff level of 18.84 ng/mL showed 93.3% sensitivity and 91.7% specificity in distinguishing PCOS subjects from healthy individuals. CONCLUSION: There is a significant correlation of serum CCL 18 level with insulin resistance in PCOS subjects and serum CCL levels can be considered as a marker of PCOS.

IDEA Group Consensus Statement on Medical Management of Adult Gender Incongruent Individuals Seeking Gender Reaffirmation as Female.

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.

Best Practices and Tools for Titrating Basal Insulins: Expert Opinion from an Indian Panel via the Modified Delphi Consensus Method.

AIM: To develop an evidence-based expert group consensus document on the best practices and simple tools for titrating basal insulins in persons with type 2 diabetes mellitus (T2DM). BACKGROUND: Glycemic control is suboptimal in a large proportion of persons with T2DM, despite insulin therapy, thereby increasing the risk of potentially severe complications. Early initiation of insulin therapy and appropriate dose titration are crucial to achieving glycemic targets. Attitudes and practices among healthcare professionals (HCPs) and perceptions about insulin therapy among persons with diabetes contribute largely to suboptimal glycemic control. Improving HCP-patient communication, encouraging the use of additional educational tools, and providing support for the titration process to increase confidence, both at the initiation visit and at home, facilitate the optimization of dose titration. In Indian settings, specific guidelines and a consensus statement are lacking on the optimal insulin initiation dose, frequency of dose titration, and basal insulin profile needed to achieve optimal titration. In clinical practice, physicians and persons with diabetes often do not adhere to the titration algorithms that currently exist for the purpose of achieving optimal titration as they perceive these to be very cumbersome. In this context, a group of experts met at an advisory board meeting and arrived at a consensus on best practices for the titration of basal insulin in persons withT2DM in India, using the modified Delphi methodology. REVIEW RESULTS: After a review of evidence and further discussions, the expert group provided recommendations on insulin initiation dose, ideal period for titration in practice, titration regimen for use in practice, basal insulin profile for titration, and choosing a self-monitoring blood glucose schedule for titration. CONCLUSIONS: In the management of T2DM, insulin can be effectively titrated by following a few simple recommendations. The use of second-generation basal insulin aids in mitigating the risk of hypoglycemic events. The implementation of a simplified titration regimen is crucial to achieving glycemic targets and long-term treatment goals.

Neuropsychological Impairments in Young Patients With Subclinical Hypothyroidism: A Case Control Study.

BACKGROUND: There is a lack of clarity about the cognitive dysfunction in young patients with subclinical hypothyroidism (SCH). This study was done to explore the neuropsychological impairments in young patients with SCH and compare them with euthyroid controls. METHODS: Patients between 18 and 45 years of age and diagnosed with SCH were recruited. Controls were euthyroid age, gender, and education matched. All the cases and controls underwent a detailed neuropsychological assessment with a battery of tests validated for use in the age groups of 18 to 65 years. RESULTS: Thirty-nine patients with a mean age of 30.3 ± 7.7 years (female:male ratio 12:1) and 23 controls (female:male ratio 21:2) with a mean age of 33.4 ± 7.1 years (P = .24) were included in the study. The mean TSH value was 6.36 ± 1.3 mIU/L and 2.49 ± 1.03 mIU/L in cases and controls, respectively (P < .001). The visual memory delayed recall was impaired, in 48.71% (n = 19) and 21.7% (n = 5) cases and controls, respectively (P = .03). The category fluency test showed impairment in a greater number of cases (35.9%, n = 14) as compared to controls (13%, n = 3; P = .04). CONCLUSION: This study shows that younger patients with SCH have delayed visual memory recall and category fluency deficits, which are suggestive of dysfunction of the prefrontal cortex and temporal lobe in young SCH patients. These impairments may justify the treatment of young SCH patients with replacement therapy.

Serum Fibroblast Growth Factor 21 Levels in Patients with Hyperthyroidism and its Association with Body Fat Percentage.

BACKGROUND: Most of the actions of thyroid hormone (TH) on body metabolisms like maintenance of basal metabolic rate (BMR) and body fat are similar to that of fibroblast growth factor 21 (FGF21). We hypothesized that in patients with hyperthyroidism, the pathological changes in the BMR, body fat are mediated by TH through FGF21. OBJECTIVES: To study the association of serum FGF21 levels with hyperthyroidism and correlate body fat percentage with serum FGF21 levels in hyperthyroid patients. STUDY DESIGN: Case-control prospective follow-up study. METHODOLOGY: A total of 68 hyperthyroid patients and age, sex-matched healthy controls who fulfilled the inclusion and exclusion criteria were studied. Among them, 45 cases were followed up at 3 to 6 months after the achievement of euthyroidism. Body fat percentage was calculated from Jackson and Pollock 3 site equation and Siri equation. BMR percentage was calculated by the Gale formula. RESULTS: The mean age in years in the cases was similar to that of controls (36.14 ± 10.01 vs. 36.57 ± 10.53, P = 0.81). The serum FGF21 levels at baseline were significantly elevated in patients with hyperthyroidism compared to controls [median 406.6 pg/ml (interquartile range, 262.9-655.6) vs. 252.3 (125.1-341) P < 0.001] and declined dramatically following treatment with anti-thyroid drugs [405 (275.5-680.4) vs. 203.6 (154.6-230.6) P < 0.001]. Serum FGF21 levels negatively correlated with body fat percentage (r = -0.268, P = 0.002). After adjusting to various confounding factors, serum FGF21 was independently associated with hyperthyroidism and was significant. (OR [95%CI] 3.78 (1.046-13.666) P = 0.043). CONCLUSION: Serum FGF21 levels were elevated in hyperthyroid patients and decreased following treatment with anti-thyroid drugs. It was independently associated with hyperthyroidism. There may be a future therapeutic role of FGF21 inhibition in the reversal of these changes in addition to anti-thyroid drugs in patients with hyperthyroidism.

Relationship between Salivary Alpha-2 Macroglobulin and HbA1c among Patients with Type-2 Diabetes Mellitus: A Cross-sectional Study.

CONTEXT: Type-2 diabetes mellitus (DM2) requires an adequate glycemic control to avoid diabetic complications. The best parameter available is glycosylated hemoglobin (HbA1c), as it gives us an overview of an individuals' glycemic control of the previous 4 months. Salivary biomarkers used as a diagnostic tool can indicate the control or degree of progression of diseases. Studies indicate that salivary alpha-2-macroglobulin (A2MG) levels are elevated in diabetes patients. AIMS: To study the relationship of salivary A2MG with glycosylated Hba1c among patients with DM2. SETTINGS AND DESIGN: A total of 87 patients of DM2, age 35-65 years were recruited. MATERIALS AND METHODS: The routine oral cavity examination and dental check-up was done to rule out any dental disease. The patients with hepatic diseases and inflammatory diseases of oral cavity and body were excluded. The values of HbA1c were collected from the records of patients. Salivary A2MG levels were estimated by enzyme-linked immunosorbent assay. Levels of fasting and postprandial blood sugar, serum creatinine, and A2MG were compared with the HbA1c groups (<7 and ≥ 7). STATISTICAL ANALYSIS USED: Descriptive statistics (Software SPSS version 20.0). Nonparametric Pearson correlation test was used to assess the correlation between HbA1c and A2MG. RESULTS: A positive correlation between salivary levels of A2MG and blood levels of HbA1c in blood was observed in this study. Results showed that there was also a significant correlation in mean values of fasting and postprandial blood sugar, serum creatinine, and salivary A2MG in diabetic subjects. CONCLUSION: Measurement of A2MG in saliva represents a promising noninvasive alternative method to evaluate glycemic index and consequently avoiding comorbidities.