Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is a chronic and progressive illness. Millions of Americans have T2DM and many patients do not achieve the recommended blood glucose levels. Glucagon-like peptide 1 (GLP-1) based therapy is an established treatment for the management of T2DM and is recommended early in the treatment algorithm. GLP-1 therapy is associated with better glycemic control, weight reduction, and favorable cardiovascular outcomes. Tirzepatide (Mounjaro™) is a novel dual glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonist. Evidence from five SURPASS clinical trials has demonstrated that tirzepatide has potent glucose lowering and weight loss with adverse effects comparable to GLP-1 receptor agonists. This paper gives an overview of tirzepatide and SURPASS clinical trials.

Introduction Angiotensin-converting enzyme inhibitors (ACEIs) are first-line pharmaceutical agents in common chronic conditions such as hypertension and heart failure with reduced ejection fraction. When angioedema occurs, if secondary to ACEIs, discontinuation of the ACEI is necessary to mitigate the risk of recurrent angioedema. While angioedema is a well-known adverse effect of ACEIs, it is not well-known that angioedema may recur even after ACEI discontinuation. Additionally, only few reports in the literature describe this phenomenon. This case describes an older man with a history of chronic obstructive pulmonary disease, hypothyroidism, diabetes mellitus, hypertension, and heart failure who presented from an assisted living facility with recurrent angioedema 12 days after an initial episode of angioedema where his ACEI therapy (enalapril) was discontinued. Assessment Empiric methylprednisolone, diphenhydramine, intramuscular epinephrine, intravenous C1 esterase inhibitor Berinert®, and two units of fresh frozen plasma was given in the emergency department. The patient was monitored in the intensive care unit because of mild airway compromise but did not require invasive airway protection. Serum C4 level was normal, ruling out hereditary angioedema. Outcome Patient was discharged after five days in stable condition with resolution of symptoms. Conclusion ACEIs are the most common cause of drug-induced angioedema in the United States. Angioedema is self-limiting swelling that requires close airway monitoring. While health professionals recognize the risk for angioedema with active ACEI use, it is not well known that the risk of angioedema may occur for months following cessation of ACEI therapy. Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important for both providers and pharmacists to provide appropriate diagnosis and monitoring. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence following drug discontinuation.

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus. Therefore, using these two treatments may help treat Parkinson's disease. To further investigate the mechanisms of action of these two compounds, we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin. We found that both exendin-4 and linagliptin reversed motor dysfunction, glial activation, and dopaminergic neuronal death in this model. In addition, both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion. Moreover, in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain- and leucine-rich-repeat- and pyrin-domain-containing 3/caspase-1/interleukin-1β pathway and subsequent pyroptosis by decreasing the production of reactive oxygen species. These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotide-binding oligomerization domain- and leucine-rich-repeat- and pyrin-domain-containing 3/caspase-1/interleukin-1β pathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Therefore, these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

Many individuals with marginally abnormal thyroid function test (TFT) results may be treated and it is unknown if the limits of the TSH and FT4 reference intervals reported alongside the laboratory results are associated with the prevalence of levothyroxine treatment. We obtained information regarding reported TFT reference intervals from UK National Health Service (NHS) laboratories and evaluated its relationship with the prevalence of levothyroxine treatment for corresponding health areas for 2014. The upper limit of serum TSH was significantly, linearly, independently and negatively associated with prevalent levothyroxine treatment: -0.54% (95% confidence intervals -0.68% to -0.40%). The lower limit of serum FT4 was significantly and independently associated with the prevalence of levothyroxine treatment in a non-linear (J-shaped) manner with an increase being noted from a FT4 level of ≈9.5 pmol/L onwards. We conclude that minor changes in the reference range limits for serum TSH and FT4 are associated with levothyroxine treatment.

Phlegmonous duodenitis is an extremely rare condition, and only a few cases have been previously reported. Here, we report a case of phlegmonous duodenitis caused by Streptococcus parasanguinis and Escherichia coli in a 78-year-old immunocompromised patient with diabetes mellitus and immunosuppressive drugs. Abdominal computed tomography showed diffuse thickening of the duodenum and gastric antrum, and esophagogastroduodenoscopy revealed some erosions with purulent discharge and reddish and edematous mucosa in the duodenal bulb. A bacteriological culture test detected the two abovementioned bacteria and established the diagnosis of phlegmonous duodenitis. Following the initiation of antibiotic treatment, his condition rapidly improved. Endoscopists should be aware of this rare entity and pay attention to the endoscopic duodenal findings similar to those of phlegmonous gastritis, particularly in immunocompromised patients who develop abdominal symptoms with severe inflammation.

A 76-year-old lady was found on the floor following a fall at home. She was uninjured, but unable to get up, and had been lying on the floor for roughly 18 hours before her son arrived. She had been unwell for the past 3 days with a cough and shortness of breath. She had a past medical history of diabetes, hypertension, hypercholesterolaemia and atrial fibrillation (AF). On examination, she was alert but distressed, clinically dehydrated, febrile and tachycardic. She was treated for community acquired pneumonia with co-amoxiclav and was fluid resuscitated with Hartmann's solution. Her hyperkalaemia was treated with 50 mL of 50% glucose containing 10 units of rapid-acting insulin. Her creatinine kinase (CK) on admission was 200,000, and she had an acute kidney injury (AKI). Urine dipstick was positive for blood. However, her renal function continued to deteriorate over the succeeding 48 h, when she required renal replacement therapy (RRT) due to fluid overload and anuria.

Background Severe uncontrolled asthma in the pediatric population is a complicated disease and is considered a major challenge for pediatricians. Severe bronchial asthma in the pediatric population is related to significant morbidity and mortality. Children with complicated asthma are at a higher risk for unfavorable outcomes, including medication-associated adverse effects, severe life-threatening exacerbations, and poor quality of life. Methodology A cohort study was conducted at National Guard Health Affairs Hospital in Riyadh, Saudi Arabia. Data were collected using the chart review method utilizing a data collection sheet. A total of 363 charts of children aged one month to 14 years who visited the emergency room (ER) due to asthma exacerbation at NGHA were reviewed, from January 2016 to May 2022, to extract the variables. Variables included demographic data, comorbidities, and asthma-related variables which included the number of asthma exacerbations, hospital admission, ER visit, medication use (non-steroidal anti-inflammatory drugs and steroids), and the presence of allergic rhinitis and eczema. Results A total of 363 patients were analyzed, with 229 (63.1%) males and 134 (36.9%) females. The mean age was 4.9 years (SD = 3.5 years). Overall, 8.5% of patients had congenital heart disease, 4.1% had gastroesophageal reflux disease, 2.2% had diabetes mellitus, 1.9% had obstructive sleep apnea, and 0.6% had hypertension. Most patients presented with a cough at 88.2% (n = 320), followed by shortness of breath at 59% (n = 214) and fever at 46% (n = 167). Male asthmatics visited ER more than females. Forty-four patients were admitted to the hospital. Inhaled steroids were associated with fewer emergency department visits and night symptoms. Most asthmatic patients presented in the winter and fall seasons. Conclusions Asthma is a common pediatric respiratory disease that could be a burden if not controlled well. Unfortunately, the frequency of hospital admissions and pediatric ER visits due to asthma exacerbation is increasing. Comorbidities such as obesity and gastroesophageal reflux disease play a significant role in asthma control.

Type 1 diabetes stands among the most prevalent endocrinological diseases in the pediatric age group. The incidence rate continues to rise globally. Optic neuritis has been described in the literature in association with type 2 diabetes; however, cases of optic neuritis with type 1 diabetes are very few. Here we describe a rare case of a 15-year-old patient with type 1 diabetes mellitus presenting with optic neuritis. Due to the hyperglycemia that steroids can induce in some patients, management with steroids can be difficult. A multidisciplinary team approach is required to ensure that these patients' optic neuritis is properly handled while avoiding steroid side effects.

The polycystic ovarian syndrome affects many women today. Previous research has demonstrated a direct link between it and serious ailments such as type 2 diabetes, heart disease, and infertility. Originally thought to be a reproductive disorder, polycystic ovarian syndrome (PCOS) is now understood to be a metabolic and psychological disorder. Women of reproductive age suffering from PCOS undergo hormonal imbalances in which progesterone, insulin, and testosterone are produced in excess. PCOS exhibits a variety of characteristics as well as a heterogeneity of symptoms, including acne, hirsutism, androgenic alopecia, irregular menstruation, infertility, obesity, and mood disorders like despair and anxiety. Chronic anovulation, hyperandrogenism, type 2 diabetes, dyslipidemia, and an elevated threat of coronary artery disease are some of its defining characteristics. PCOS develops due to interacting genetic and environmental factors. From a gynaecological curiosity, it grew into a multisystem endocrinopathy. It is fascinating to learn how hormonal issues result in gynaecological problems. Insulin resistance, compensatory hyperinsulinism, and an increase in ovarian androgenic hyperresponsiveness to circulating insulin are all directly related to hyperandrogenism and anovulation. Independent of weight, insulin resistance is more common with PCOS and plays a crucial role in the syndrome's metabolic and reproductive complications. Anovulation, polycystic ovaries, and elevated luteinizing hormones, which increase circulating androgen, are all caused by a reduction in follicle-stimulating hormone. High androgen levels cause hyperinsulinemia, which leads cells to become insulin resistant and makes PCOS patients more likely to develop diabetes mellitus. Later research established that women with polycystic ovarian shape and persistent anovulation are the only ones susceptible to insulin resistance. Insulin resistance is thus a distinct characteristic of the condition. The purpose of this review paper is to investigate how PCOS ultimately results in type 2 diabetes mellitus.

Thyroid C-cell hyperplasia (CCH) is divided into physiologic or reactive CCH and neoplastic CCH. Glucagon-like peptide-1 receptor agonists (GLP-1 Ra) is a group of medications used to treat type 2 diabetes that has documented C-cell stimulation effect in rodents, leading to subsequent CCH and medullary thyroid carcinoma (MTC) in rats and/or mice. Currently, there is no sufficient evidence supporting the association between GLP-1 Ra and human thyroid CCH and/or MTC. Here, we present a case of significant hypercalcitoninemia in a 53-year-old diabetic male patient receiving GLP-1 Ra treatment with concurrent multinodular goiter and hyperparathyroidism. Total thyroidectomy and central neck dissection revealed multifocal CCH involving bilateral thyroid lobes and several negative lymph nodes. Subsequent genetic testing did not detect germline mutation of RET gene. However, due to marked hypercalcitoninemia and massive thyromegaly, unsampled medullary thyroid microcarcinoma cannot be completely ruled out. The patient's postsurgical calcitonin level was back to normal. Our case indicates the significant clinical value of monitoring serum calcitonin levels in patients receiving GLP-1 Ra, especially in presence of other thyroid and/or parathyroid pathology that may be associated with increased calcitonin and/or CCH. Literature regarding the association between GLP-1 Ra and CCH is also reviewed.