Centre For Diabetes And Endocrinology

Hypothyroidism is typically associated with bradyarrhythmias, but can rarely precipitate life-threatening ventricular arrhythmias. We present a case of severe hypothyroidism manifesting as polymorphic ventricular tachycardia (VT). A previously healthy woman in her early 50s presented with an acute onset of breathlessness and on examination had hypotension and tachycardia. ECG revealed polymorphic VT, promptly terminated by defibrillation using 200J biphasic shock. Investigations uncovered severe primary hypothyroidism (thyroid-stimulating hormone: 142 mIU/l) and left ventricular (LV) dysfunction with ejection fraction (EF) of 35%. Coronary angiogram was normal. Treatment with levothyroxine and standard heart failure therapy was initiated. In conclusion, at 3- and 6-month follow-ups, the patient remained asymptomatic and had no episodes of tachyarrhythmias without antiarrhythmic drugs, and her LV function normalized (EF: 55%). This case highlights the importance of considering hypothyroidism in patients presenting with unexplained ventricular arrhythmias.

The glucagon receptor antagonist (GRA) volagidemab is the first‐in‐class fully human monoclonal antibody that inhibits glucagon receptor. GRA can improve glycemia by reducing endogenous glucose production and reduce risks of diabetic ketoacidosis by suppressing ketogenesis. This systematic review and meta‐analysis analyzed the efficacy and safety of volagidemab in type‐1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) involving T1D patients receiving volagidemab. The primary outcome was to evaluate changes in total daily dose (TDD) of insulin. The secondary outcomes were to evaluate changes in measures of glycemia, hypoglycemia, and adverse events. Data from 3 RCTs (98 patients) were analyzed. Volagidemab (70 mg/week) was associated with a significant reduction in TDD of insulin requirement (mean difference [MD]: −8.45 units/day (95% confidence interval [CI]: [−12.09, −4.81]); I² = 83%; p < 0.01) and average blood glucose (MD: −21.42 mg/dL (95% CI: [−37.10, −5.74]); I² = 88%; p < 0.01), compared to placebo. Volagidemab use was associated with a significant increase in time in range (blood glucose: 70–180 mg/dL) (MD: 10.93% (95% CI: [6.69, 15.17]); I² = 55%; p < 0.01) and significant reduction in time above range (blood glucose >180 mg/dL) (MD: −11.93% (95% CI: [−14.71, −9.15]); I² = 6%; p < 0.01) without any impact on time below range (blood glucose <70 mg/dL) (MD: 0.14% (95% CI: [−0.56, 0.84]); I² = 0%; p = 0.70), compared to placebo. Occurrence of treatment‐emergent adverse events (odds ratio [OR]: 0.96 (95% CI: [0.36, 2.56]); I² = 8%; p = 0.94) and hypoglycemia (OR: 0.56 (95% CI: [0.11, 2.89]); I² = 0%; p = 0.49) were similar among volagidemab users as compared to placebo. Short‐term volagidemab use was associated with significant reduction in insulin requirement along with improvement in glycemia.

Acne and rosacea are common inflammatory skin conditions that are associated with systemic inflammation and metabolic abnormalities. Here, we review the evidence for a connection between diabetes, acne, and rosacea. Acne has been linked to type 2 diabetes and insulin resistance. The pathophysiologic basis of this connection involves hyperandrogenism and activation of the mTORC1/FoxO1 pathway. However, rosacea has a less clear link to insulin resistance. While available evidence is insufficient to recommend routine screening of all acne and rosacea patients for diabetes, management of glucose intolerance shows promise in improving the severity of skin disease. Nevertheless, future studies involving larger cohorts and randomized controlled trials need to be conducted to clarify the role of diabetes in acne and rosacea.

Introduction The MiniMed™ 780G system is an advanced insulin pump system incorporating an AHCL (Advanced Hybrid Close Loop) algorithm that automatically adjusts insulin delivery based on glucose levels. All guidelines recommend the use of Automated Insulin Delivery therapy for people with type 1 diabetes (PWT1D) and they highlight that a specifically trained and expert team should provide training on HCL systems for PWT1D, but none of the publications detail the curriculum profile that diabetes educators should have. This paper aims to establish a consensus on the optimal educational pathway for diabetes educators on the MiniMed™ 780G system. Methods An Expert Panel (EP) of 11 key opinion educators in diabetes technology in the EMEA area was assembled. Using the Delphi method, a consensus questionnaire based on the literature research was created, discussed and validated by the EP members. An agreement level of ≥ 75% was considered a strong consensus. Results EP members had on average 16.3 years of clinical experience and followed at least 50 PWT1D using the MiniMed™ 780G system. All EP members agreed that a structured educational pathway to train diabetes educators in the use of the MiniMed™ 780G system is needed. 100% of the EP members agreed that the pathway should include a mentorship programme and in-field training; 90% agreed on using face-to-face training with the support of e-learning modules. The EP members believed that minimum competency standards for diabetes educators around the principles of diabetes care and education are needed. Conclusion The educational pathway created by the EP showed that skills are needed at an advanced level and that mentorship in developing these skills is critical. This pathway is vital for supporting the implementation of diabetes technology into everyday life and can remove barriers and increase access to PWT1D.

Background The increasing global prevalence of type 2 diabetes necessitates innovative treatment strategies to mitigate not only hyperglycemia but also its associated cardiovascular risks. Oral semaglutide, a glucagon-like peptide-1 receptor agonist, has shown high efficacy in lowering glucose and inducing weight loss in randomized trials. However, evidence of its beneficial effects in daily clinical practice is limited. In this study we determined the real-world effectiveness of oral semaglutide and investigated whether it impacts metabolic parameters beyond glucose and weight control in patients with moderate to high cardiovascular risk. Methods In a single-center outpatient setting, 53 patients with type 2 diabetes treated with oral semaglutide were retrospectively analyzed. Changes in anthropometric measurements and laboratory parameters over a follow-up period of 3–9 months were assessed. Results Oral semaglutide significantly improved glycemic control and facilitated weight loss, with 50% of patients achieving a body weight loss of ≥5% in a real-world setting. Moreover, oral semaglutide treatment reduced alanine aminotransferase and hepatic steatosis index significantly. In patients on stable lipid-lowering therapy, we observed a significant reduction in total cholesterol and low-density lipoprotein cholesterol levels following treatment with oral semaglutide. Effects on liver inflammation were associated with glucose and weight control, whereas lipid-lowering effects were associated only with glucose control. Conclusion This real-world study demonstrates oral semaglutide efficacy beyond glucose and weight control suggesting its potential in comprehensive cardiovascular risk management in individuals with type 2 diabetes. Research to optimize the clinical use of oral semaglutide in diabetes care and cardiovascular risk reduction may further increase its beneficial effects.

Objective To evaluate the usage pattern of glimepiride and metformin fixed-dose combinations (FDC) and to determine its efficacy and tolerability in Type 2 diabetes mellitus (T2DM) patients with established complications in Indian settings. Methods This was a retrospective multi-centric ( n = 156), cross-sectional study. Patients of either sex, age above 18 years, who had developed microvascular and/or macrovascular complications receiving any strength of glimepiride and metformin FDC for the treatment of T2DM were included. Demographics, clinical characteristics, laboratory assessments, and adverse event profiles were retrieved from medical records. Results A total of 470 patients with a mean age of 53.6 years were included. The majority of patients was obese (68.1%). Hypertension (58.7%) was the most common comorbidity, followed by dyslipidemia (36.0%). Macrovascular and microvascular complications were observed in 21.5% and 86.8% of patients, respectively. Among the available strengths, glimepiride 2 mg and metformin 500 mg FDC was most widely used in 30.2% of patients. Dosage up-titration was observed in 44.3% of patients. A significant improvement in glycemic parameters was observed posttreatment with glimepiride and metformin FDC ( P < 0.001). Physicians’ global evaluation of efficacy and tolerability showed a majority of patients on a good to excellent scale (96.0% and 93.1%). Conclusion Glimepiride and metformin FDCs have been extensively studied and found to be safe and effective in improving glycemic control with minimal risk of hypoglycemic events and weight gain in T2DM patients with established complications in Indian settings.

Introduction Hypothyroidism (HypoT) is a common condition whose prevalence varies according to regional and ethnic factors, dietary iodine, gender, and age. The symptoms of HypoT are generally nonspecific, with considerable overlap with other conditions. These symptoms are not useful for diagnosing HypoT, and a thyroid function test is required for a final diagnosis. Materials and methods We aimed to provide an overview of the recent global literature on HypoT in older adults. A narrative, nonsystematic review of the international literature from a single major medical online database (PubMed) for the past 5 years was performed. The relevant literature was narrated in a concise thematic account. Results Most studies and expert opinions reiterated the benefit of replacement therapy in younger and middle-aged individuals. A good volume of literature also considered the interplay between thyroid hormones and (1) cardiovascular function and risk factors, (2) cognitive function, (3) mental health, and (4) quality of life. Most workers are cognizant of the important difference in normal ranges of thyroid-stimulating hormone (TSH) and the consequent TSH targets in older adults compared to younger age groups. Extra care is recommended for the initiation and titration of thyroid hormone replacement therapy to avoid cardiovascular and skeletal adverse effects of relative overtreatment. Conclusion While clinical benefit is evident in patients under age 65 with overt and subclinical HypoT who are treated with levothyroxine, treatment may be harmful in older adults with subclinical HypoT. The 97th percentile of TSH distribution is 7.5 mIU/L for patients over age 80. Hence, TSH goals should be individualized in older adults to achieve any possible benefit and avoid unnecessary harm.

Background Managing diabetes during Ramadan fasting is a challenge due lifestyle changes. We describe the characteristics and patterns of care for type 2 diabetes mellitus (T2DM) during Ramadan 2020 and 2022. Methods Our study included multinational Muslims with T2DM who were during routine consultation. We collected data on demographics, fasting characteristics, and complications. Descriptive statistics, Chi square test and multiple testing were performed. Results 12,529 patients participated. Mean age was 55.2 ± 11.8 years; 52.4% were females. Mean diabetes duration was 9.9 ± 7.4 years; 27.7% were with HbA1c > 9% (75 mmol/mol) and 70% with complications. Metformin was the most used followed by insulin. 85.1% fasted ≥ 1 day; fasting mean duration was 27.6 ± 5.6 days. Hypoglycemia occurred in 15.5% of whom 11.7% attended emergency department or were hospitalized; this was significantly associated with age and/or duration of diabetes. Hyperglycemia occurred in 14.9% and was also associated with age or diabetes duration. 6.1% attended emergency department or were hospitalized. 74.2% performed SMBG during fasting. 59.2% were educated on Ramadan fasting, with 89.7% receiving it during routine consultation. Conclusions Ramadan fasting in T2DM is high. Multidisciplinary approach is required to mitigate complications. Our findings support current recommendations for safe fasting

Background There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. Objective This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. Methods In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. Results The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54–2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. Conclusion This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Viral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal infection restricts systemic glucose availability, which promotes the antiviral type I interferon (IFN-I) response. Following viral infection, we find that IFNγ produced by γδ T cells stimulates pancreatic β cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune–endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral infection.

Context Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child. Objective To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly. Design & methods Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry. Results 87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications. Conclusion Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.

Introduction Lipodystrophies are a group of disorders characterized by selective and variable loss of adipose tissue, which can result in an increased risk of insulin resistance and its associated complications. Women with lipodystrophy often have a high frequency of polycystic ovary syndrome (PCOS) and may experience gynecological and obstetric complications. The objective of this study was to describe the gestational outcomes of patients with familial partial lipodystrophy type 2 (FPLD2) at a reference center with the aim of improving the understanding and management of pregnant women affected by this condition. Methods This was a retrospective analysis of data obtained from questionnaires regarding past pregnancies and a review of medical records from the beginning of follow-up in outpatient clinics. Results All women diagnosed with FPLD2 who had previously become pregnant were included in this study (n=8). The women in the study experienced pregnancies between the ages of 14 and 38 years, with an average of 1.75 children per woman. The pregnancies in question were either the result of successful conception within 12 months of attempting to conceive or unplanned pregnancies. During pregnancy, two women (25%) were diagnosed with gestational diabetes mellitus (GDM), one (12.5%) with gestational hypothyroidism, and one (12.5%) with preeclampsia. Among the 17 pregnancies, two miscarriages (11.8%) occurred, and five cases (29.4%) of macrosomia were observed. Four instances of premature birth and an equal number of neonatal hypoglycemia cases were recorded. The reported neonatal complications included an unspecified malformation, respiratory infection, and two neonatal deaths related to heart malformation and respiratory distress syndrome. Conclusion Our data showed a high frequency of fetal complications in women with FPLD2. However, no instances of infertility or prolonged attempts to conceive have been reported, highlighting the significance of employing effective contraception strategies to plan pregnancies at optimal times for managing metabolic comorbidities.

Functioning gonadotroph adenomas with clinical manifestations are extremely rare and the majority of these are FSH-secreting macroadenomas. Clinical symptoms are due to excess gonadotrophins and sex hormones, and these may be present for a long time before the diagnosis of pituitary adenoma is made. We present the case of a 37-year-old Caucasian male with clinical manifestations of an FSH-secreting pituitary macroadenoma. He had sexual dysfunction for a year followed by bilateral testicular pain and enlargement which was initially treated as suspected recurrent epididymitis, but his symptoms did not resolve. He presented a year later with headaches and bilateral superior temporal visual field defects. Brain imaging confirmed a pituitary macroadenoma with optic chiasm compression. Pituitary profile demonstrated an unusually high FSH with high normal LH and normal testosterone level. The patient successfully underwent transsphenoidal hypophysectomy and histology confirmed gonadotroph differentiation and immunoreactivity predominantly with FSH. Gonadotrophin levels and testosterone dropped significantly after surgery, and he was started on testosterone replacement. MR imaging, 2 years post surgery, showed no recurrence of pituitary adenoma. In conclusion, testicular enlargement and hypogonadal symptoms associated with low testosterone levels are recognised features in FSH-secreting pituitary adenomas. Our patient had hypogonadal symptoms but consistently high normal testosterone levels prior to surgery. The reason for low libido despite high testosterone is unclear. Our case highlights the need to suspect such rare underlying pituitary pathology when dealing with unusual combinations of hypogonadal symptoms, testicular enlargement with low or normal testosterone levels. Learning points Functioning pituitary adenomas that secrete excess follicle-stimulating hormone (FSH) are very rare and often present with symptoms related to pituitary mass effect. Testicular enlargement alongside sexual dysfunction are commonly reported symptoms amongst male patients. Pituitary profile results demonstrate a raised FSH level with either a low, normal, or even high testosterone level which may not always correlate to clinical symptoms. Pituitary pathology should be considered in males presenting with unusual combinations of testicular enlargement and hypogonadal symptoms even with normal testosterone levels.

Background: Diabetes mellitus is a serious public health concern. It is associated with many psychological problems, such as depression, anxiety, and eating disorders. These co-morbidities are associated with improper adherence to treatment, self-care, poor glycemic control, more complications, and worse outcomes. Methods: This study aimed to measure the level of medication adherence among type 2 diabetics in Jazan, Saudi Arabia, and to find its association with their psychological status (specifically, depression and anxiety). A cross-sectional descriptive design was used among adults with type 2 diabetes at the Diabetes and Endocrinology Center in Jazan, Saudi Arabia. The estimated sample size was 480 patients. The General Medication Adherence Scale and Patient Health Questionnaire-4 (PHQ-4) were used as tools to achieve the study objectives. Results: A total of 449 diabetic patients completed the survey (93.5% response rate). Patients with poor, low, and partial adherence account for 337 (75%) of patients and only 112 (25%) have good and high medication adherence. Employment and duration of illness were highly significant with a positive relationship to treatment adherence (p = 0.010 and 0.000, respectively). On the other hand, age and disease duration had a significant relationship with psychological disorders (p = 0.029 and 0.002, respectively). Of the patients, 64 (14.3%) had high scores on the PHQ-4, with depressive symptoms in 46 (10.24%) and anxiety symptoms in 75 (16.7%). Correlation analysis reveals that there is a highly significant negative correlation between psychological disorders and adherence to medications (r = -0.288, p = 0.000). Conclusion: A negative correlation between psychological disorders and adherence to medications was found. The findings indicate the importance of psychological support for diabetic patients for better treatment adherence.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005–2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm² (0.0038–0.17)) and total hip (0.094g/cm² (0.013–0.19)), compared to the lumbar spine (0.049g/cm² (− 0.0032–0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2–15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.