Polyagonists in Type 2 Diabetes Management.

PURPOSE OF THE REVIEW: This review summarizes the new developments in polyagonist pharmacotherapy for type 2 diabetes. RECENT FINDINGS: Several dual- and triple-agonists targeting different pathogenic pathways of type 2 diabetes have entered clinical trials and have led to significant improvements in glycaemia, body weight, fatty liver, and cardio-renal risk factors, with variable adverse event profiles but no new serious safety concerns. Combining agents with complementary and synergistic mechanisms of action have enhanced efficacy and safety. Targeting multiple pathogenic pathways simultaneously has led to enhanced benefits which potentially match those of bariatric surgery. Tirzepatide, cotadutide, BI456906, ritatrutide, and CagriSema have entered phase 3 clinical trials. Outcomes from published clinical studies are reviewed. Efficacy-safety profiles are heterogeneous between agents, suggesting the potential application of precision medicine and need for personalized approach in pharmacological management of type 2 diabetes and obesity. Polyagonism has become a key strategy to address the complex pathogenesis of type 2 diabetes and co-morbidities and increasing number of agents are moving through clinical trials. Heterogeneity in efficacy-safety profiles calls for application of precision medicine and need for judicious personalization of care.

Evaluation of socio-demographic and clinical characteristics of PCOS patients attending a tertiary care institute in Colombo.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous aetiology. It is characterized by irregular menses and or oligo/anovulation, hyper-androgenism, and polycystic ovaries. The prevalence and diagnosis of PCOS changes depending on which clinical criteria are utilized to confirm the diagnosis. The prevalence can be high as 8-13% when the Rotterdam criteria are used. However, there is significant inter-individual variation in presentation. We have studied the socio-demographic and clinical characteristics of PCOS patients attending the Endocrinology clinic in a tertiary care institute in Sri Lanka. METHODS: A descriptive cross sectional study was conducted from September 2019 to September 2020 at the Endocrinology Unit of the National Hospital of Sri Lanka. All the patients who met the inclusion and exclusion criteria and who has a diagnosis of PCOS made according to Rotterdam criteria were recruited in to the study. After obtaining informed written consent, the data was collected using an interviewer administered questionnaire. HOMA-IR was calculated using the fasting insulin and blood glucose level. RESULTS: The study enrolled sixty females. The mean age was 26.7 years (range 18-44). The mean weight was 64.8 (SD = 11.9) kg and BMI was 27.1 (SD = 4.8) kg/m-2. According to Asian BMI cut-offs, 1 (1.7%) patient was underweight and 13 (21.7%) had normal weight. Forty six (76.7%) had their weight in the overweight or obese category. Fifty four (90.0%) patients had clinical or biochemical evidence of hyperandrogenism while 24 (40%) had polycystic ovaries on trans-abdominal ultrasound scan and 50 (83.3%) had irregular menstrual cycles. According to the body fat percentage assessed by the whole body DEXA scan 4.1% normal body fat, while 50.0% and 45.8% had overweight and obesity respectively. HOMA-IR detected 61.1% to have high insulin resistance. Out of the patients who had USS of the abdomen 27.5% had co-existent non-alcoholic fatty liver. Fifty four percent of the patients had sub/infertility. CONCLUSIONS: The majority of the population were overweight or obese and had higher prevalence of insulin resistance and non-alcoholic fatty liver. Out of the clinical characteristics used to make the diagnosis of PCOS, the presence of clinical or biochemical evidence of hyperandrogenism and irregular menstrual cycles are more common than the detection of polycystic ovaries on trans-vaginal USS. The higher prevalence of overweight, obesity, insulin resistance and NAFLD associated with PCOS makes the diagnosis and management of the disease crucial to prevent long term consequences of the disease.

A Case of Successful Treatment with Unilateral Oophorectomy in a Patient with Resistant Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous etiology. Typical features consist of oligo/anovulation, polycystic ovaries, and features of hyperandrogenism. Pathogenesis is multifactorial, and positive family history may have a predisposition for disease development. The syndrome is associated with multiple metabolic and nonmetabolic entities. As the disease is involved with multiple adverse outcomes, the successful treatment is pivotal. Among the more advanced options, the unilateral oophorectomy is considered as a last resort to alleviate the symptoms. Case Presentation. A 29-year-old female presented to us with oligomenorrhea, severe hirsutism, androgenic pattern hair loss, acne, increased skin pigmentation, and secondary subfertility. On examination, she was obese with a body mass index (BMI) of 29.6 kg/m2. She had evidence of acanthosis nigricans, androgenic pattern balding, acne, dorsal, supraclavicular fat deposition, and moderate-severe hirsutism. Investigations confirmed excess right ovarian testosterone secretion which led to the ultimate management with right oophorectomy with successful alleviation of clinical features. CONCLUSIONS: The multifaceted medical treatment comprises the first-line therapy in PCOS. Surgery is considered as a second-line option in resistant PCOS following failure of initial therapeutic options. We report a case of resistant polycystic ovary syndrome with secondary subfertility and moderate-to-severe hirsutism who was successfully treated with unilateral oophorectomy with favorable results.

An Adrenocortical Carcinoma Associated with Non-Islet Cell Tumor Hypoglycemia and Aberrant ACTH Production.

Introduction. Adrenocortical carcinomas (ACCs) are infrequently reported to present with severe hypoglycemia syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by tumor cells. Adrenocorticotropic hormone- (ACTH) independent hypercortisolism is the norm of hormonally active ACCs, but aberrant ACTH production by tumor cells can theoretically cause ACTH-dependent hypercortisolism. The purpose of this report was to present a case of an ACC manifested with the co-occurrence of two extremely rare presentations. Case Description. We present a rare case of a 43-year-old male patient admitted with recurrent episodes of severe non-ketotic and non-insulin-mediated hypoglycemia due to IGF-II mediated disease and ACTH-dependent Cushing's syndrome. He was diagnosed with a diffusely disseminated adrenocortical carcinoma with immunohistochemistry of tumor cells showing focal ACTH immunostain positivity. Conclusion. Non-islet cell tumor hypoglycemia and ACTH-dependent Cushing's syndrome are extremely rare presentations of an ACC, and co-occurrence of these entities in a single patient is never reported in the literature.

Five-year results of viscocanalostomy.

PURPOSE: To prospectively study the success rates and complications of viscocanalostomy. METHODS: Prospective nonrandomized case series of 46 eyes (46 patients) with medically uncontrolled primary and secondary open angle glaucoma. All patients in the study underwent viscocanalostomy. Control of intraocular pressure was used to measure success. Pre and postoperative glaucoma medications, visual acuity, complications, and adjunctive procedures were recorded. RESULTS: At 60 months, qualified success (intraocular pressure below 21 mmHg with glaucoma medication) was achieved in 37 (82%) patients and complete success (intraocular pressure below 21 mmHg without medication) in 25 (54%) patients. Nd:YAG laser goniopuncture was performed in 33 (72%) patients with significant post laser reduction of intraocular pressure. No sight threatening complications were observed in this series. Visual acuity remained unchanged in 33 patients (72%). CONCLUSIONS: Viscocanalostomy appears to be a safe and effective intraocular pressure lowering procedure in eyes with primary open angle glaucoma and certain types of secondary open angle glaucoma.

A versatile retarding potential analyzer for nano-satellite platforms.

The design of the first retarding potential analyzer (RPA) built specifically for use on resource-limited cubesat platforms is described. The size, mass, and power consumption are consistent with the limitations of a nano-satellite, but the performance specifications are commensurate with those of RPAs flown on much larger platforms. The instrument is capable of measuring the ion density, temperature, and the ram component of the ion velocity in the spacecraft reference frame, while also providing estimates of the ion composition. The mechanical and electrical designs are described, as are the operating modes, command and data structure, and timing scheme. Test data obtained using an ion source inside a laboratory vacuum chamber are presented to validate the performance of the new design.

Diabetes mellitus among young adults in Sri Lanka--role of GAD antibodies in classification and treatment: the Sri Lanka Young Diabetes study.

AIMS/HYPOTHESIS: Diabetes mellitus is increasing among young adult South Asians. The aim of this study was to determine the prevalence and phenotypic characteristics of diabetes subtypes based on GAD65 autoantibody (GADA) status in those with young adult-onset diabetes in Sri Lanka. METHODS: Clinical, metabolic and GADA data were available for 992 consecutively recruited individuals with diabetes aged < or =45 years (age at diagnosis 16-40 years). Participants were classified according to the following definitions: type 1 diabetes, insulin-dependent <6 months from diagnosis; latent autoimmune diabetes in adults (LADA), GADA-positive, age > or =30 years and insulin-independent > or =6 months from diagnosis; type 2 diabetes, GADA-negative and insulin-independent > or =6 months from diagnosis. RESULTS: The median (interquartile range) age at diagnosis and diabetes duration were 33.0 (29.0-36.1) and 4.0 (1.1-7.1) years, respectively; 42.1% were male. GADA positivity was seen in 5.4% of participants (n = 54) and GADA levels negatively correlated with age at diagnosis (p < 0.0001), BMI (p < 0.0001) and time to insulin requirement (p = 0.006). Type 1 diabetes, type 2 diabetes and LADA were present in 7.0%, 89.7% and 2.6%, respectively. The remaining 0.7% of the participants were GADA-positive, insulin independent > or =6 months from diagnosis and were diagnosed at age <30 years. The metabolic syndrome and homeostasis model assessment of beta cell function (HOMA %B) were lowest in GADA-positive type 1 diabetes and increased progressively in latent autoimmune diabetes, GADA-negative type 1 diabetes and type 2 diabetes. Among those requiring insulin, 69.2% had fasting C-peptide levels in the lowest quartile, whereas only 19.5% were GADA-positive (p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of GADA-positive autoimmune diabetes is low among individuals with young adult-onset diabetes in Sri Lanka. Young-onset diabetic phenotypes appear as a continuum from autoimmune type 1 diabetes to type 2 diabetes.