Diabetes: From Research to Clinical Practice.

The number of people living with diabetes, the number of deaths attributable to it, and the cost of treating the disease and its complications are increasing exponentially. Centuries of research led to the discovery of insulin and other drugs based on pathophysiology from "the triumvirate to ominous octet". The agonists of the glucagon-like peptide-1 (GLP-1) receptor, and the inhibitors of the sodium-glucose transport protein 2 (SGLT2) are the new drugs that improve cardiovascular outcomes and provide renal protection, and they are being used increasingly for evidence-based treatment of type 2 diabetes. Bariatric surgery, when indicated, results in excellent weight- and metabolic-control, and in many instances even remission of diabetes. Technological advances like Flash glucose monitoring, continuous subcutaneous insulin infusion (CSII), and continuous glucose monitoring (CGM) have improved glycemic control, reduced episodes of severe hypoglycemia, and improved quality of life. For the treatment of diabetic macular edema intravitreal injection of several anti-VEGF agents are being used. Numerous people living in the middle- and low-income countries cannot afford the costs of care of diabetes. Institutions like the World Health Organization, the World Bank and the International Monetary Fund should roll out plans to convince the politicians to invest more in improving the diabetes care facilities.

Hyperlactatemia in diabetic ketoacidosis is common and can be prolonged: lactate time-series from 25 intensive care admissions.

Hyperlactatemia is a documented complication of diabetic ketoacidosis (DKA). Lactate responses during DKA treatment have not been studied and were the focus of this investigation. Blood gas and electrolyte data from 25 DKA admissions to ICU were sequenced over 24 h from the first Emergency Department sample. Hyperlactatemia (> 2 mmol/L) was present in 22 of 25 DKA presentations [mean concentration = 3.2 mmol/L]. In 18 time-series (72%), all concentrations normalized in ≤ 2.6 h (aggregate decay t1/2 = 2.29 h). In the remaining 7 (28%), hyperlactatemia persisted > 12 h. These were females (P = 0.04) with relative anemia (hemoglobin concentrations 131 v 155 g/L; P = 0.004) and lower nadir glucose concentrations (5.2 v 8.0 mmol/L, P = 0.003). Their aggregate glucose decay curve commenced higher (42 mmol/L v 29 mmol/L), descending towards a lower asymptote (8 mmol/L v 11 mmol/L). Tonicity decay showed similar disparities. There was equivalent resolution of metabolic acidosis and similar lengths of stay in both groups. Hyperlactatemia is common in DKA. Resolution is often rapid, but high lactates can persist. Females with high glucose concentrations corrected aggressively are more at risk. Limiting initial hyperglycemia correction to ≥ 11 mmol/L may benefit.

Timeliness of referral of children with new onset type 1 diabetes.

INTRODUCTION: Type 1 diabetes (T1D) is characterised by autoimmune destruction of pancreatic ß cells leading to insulin deficiency. Prompt referral to a specialist paediatric diabetes team (PDT) for insulin initiation and further management is important to prevent diabetic ketoacidosis (DKA), which remains the most common cause of death in this condition. OBJECTIVE: The aim was to study the timeliness of referrals from general practitioners (GPs) to PDT, of children suspected of having TID. METHOD: We carried out a survey of the practice of GPs when they suspect TID in a young person, to investigate whether they recognised the need for urgent referral to PDT. In addition, we carried out retrospective case notes review of children diagnosed with diabetes mellitus between January 2005 and December 2014. RESULTS: 111/300 (37%) of GPs replied to survey. Of these, 73/111 (65.8%) would have referred promptly to the PDT in accordance with National Guidelines. However, 34.2% would have taken an action that would have led to delay in referral to PDT. 96 children were diagnosed with TID during the audit period. There was a delay in referral in 35 (36.5%) children. 19/35 (54.3%) of these children presented with DKA. Mean duration of delay in presentation to the PDT was 1.8 days. In both survey and audit, the most common reason for delayed referral was GP attempting to confirm the diagnosis by undertaking further diagnostic tests. CONCLUSIONS: Our study has identified a modifiable reason for delayed referrals of children with TID.

The Development of Diabetes and Diabetic Ketoacidosis Following Immunotherapy Treatment: A Systematic Review of Case Reports.

As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available that target tumor cells in innovative ways. Immunotherapies (e.g., immune checkpoint inhibitors (ICI)) ramp up the immune system to target cancer cells, providing patients with more personalized and tumor cell-specific treatment options. This new age oncological treatment option has been found to provide a more meaningful and stronger alternative to traditional chemotherapy, resulting in longer periods of remission and milder side effects. However, because ICI heightens the immune system, resultant autoimmune conditions can occur. One of the most recently shown adverse effects of ICI are extreme hyperglycemia (i.e., type 1 diabetes) and diabetic ketoacidosis (DKA). To determine the incidence of immunotherapy-induced diabetes, a systematic literature review was performed using CINHAL, EBSCO, MEDLINE, and Web of Science. A total of 403 articles were initially screened, with a final 28 case reports included. The results show that checkpoint inhibitors were found to be most commonly associated with new-onset diabetes as opposed to traditional chemotherapy. Additionally, 41% of patients developed autoimmune diabetes and DKA after being placed on a single therapy of pembrolizumab (targets PD-1: programmed cell death protein 1). However, the pathological process underlying the development of endocrinopathies after treatment with ICI continues to be under investigation.

A Curious Case of Diabetic Ketoacidosis Secondary to Avelumab.

Immune checkpoint inhibitors (ICIs) have completely changed cancer treatment in the last decade and are now widely used in several cancers. In the era of immunotherapy, oncologists have changed not only the way they evaluate treatment efficacy but also the management of treatment-related adverse events. This new profile of immune adverse events has resulted in an urgent need for a more holistic view of cancer patients and for more collaborations with other organ specialists to optimize patient treatment and support. The anti-programmed death-ligand 1 antibody, avelumab, has been widely used as a maintenance treatment in stage IV urothelial carcinoma since the results from the Javelin 100 bladder trial were published. We report a case of a 75-year-old man with stage IV urothelial carcinoma submitted to first-line platinum-based chemotherapy followed by maintenance avelumab. He achieved a complete bone and pulmonary response 10 months after stopping avelumab, which was suspended due to a serious immune adverse event, an ICI-induced type 1 diabetes mellitus. At present, the patient has an overall survival of 24 months and shows no evidence of disease with a good quality of life 16 months after avelumab suspension. We hypothesized that a late response to avelumab could explain this unexpected outcome.

A Case of Diabetic Ketoacidosis Complicated With Necrotizing Esophagitis.

Acute necrotizing esophagitis (ANE) is known as the "black esophagus." We present a case of ANE in a patient with slowly progressive type 1 diabetes mellitus. A 49-year-old man presented with vomiting, characterized by coffee residue-like emesis, and was diagnosed with diabetic ketoacidosis. Upper gastrointestinal endoscopy revealed black mucosa extending from the middle of the esophagus to the gastric junction, leading to a diagnosis of ANE. The patient was treated with proton pump inhibitors and showed marked improvement. The patient was discharged on the 20th day of illness.

From Hyperglycemia to Broken Heart Syndrome: A Case of Diabetic Ketoacidosis-Induced Takotsubo Cardiomyopathy.

Diabetic ketoacidosis (DKA) is one of the hyperglycemic emergencies seen in patients with poorly controlled diabetes mellitus. One of the potential cardiovascular complications of this hyperglycemic crisis, not that well documented in the literature, is takotsubo cardiomyopathy (TCM) also known as stress-induced cardiomyopathy or "broken heart syndrome". It is a reversible condition where the heart muscle becomes suddenly weakened and stunned, which is mostly known to develop in patients who have suffered a stressful life event or are undergoing an acute illness. We present an interesting case of a 45-year-old female with a history of poorly controlled diabetes mellitus who presented with significant hyperglycemia and laboratory results concerning DKA. The patient was also complaining of new-onset chest pain on arrival. Further workup revealed elevated troponin, severely reduced ejection fraction, and echocardiographic findings concerning TCM.  The coexistence of DKA and TCM is rare but clinically significant. This case emphasizes the value of clinical vigilance in patients with this hyperglycemic crisis and encourages us to always consider stress-induced cardiomyopathy as a potential complication. Further research is needed to better elucidate the exact mechanisms linking DKA and stress-induced cardiomyopathy. This will help improve outcomes and prevent recurrence in this vulnerable patient population.

Diabetic Ketoacidosis Presenting as Abdominal Pain in a Two-Year-Old Female: A Case Report.

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes and can sometimes be the first indication of undiagnosed type 1 diabetes mellitus (T1DM). Our case presents a unique scenario in which a two-year-old female presented to her pediatrician with persistent abdominal pain, along with fatigue and tachypnea. On physical examination, she was mildly distressed, tachypneic, and utilized accessory muscles during respiration. Subsequent urinalysis indicated elevated glucose levels of 500 milligrams/deciliter (mg/dL). She was promptly referred to the emergency department to be treated for DKA. Upon arrival, the patient's glucose level was elevated at 533 mg/dL, with an anion gap of 25. She was stabilized and admitted to the pediatric intensive care unit (PICU) with a new diagnosis of T1DM with ketoacidosis. Given the emergent nature of DKA and the need for immediate treatment, physicians should consider DKA as a potential diagnosis for any pediatric patient presenting with abdominal pain.

Anchoring on Hyperglycemia and Sepsis in the Presence of an Unforeseen Thyroid Storm.

Thyroid storm (TS) is a relatively rare but life-threatening complication of an overactive thyroid that can manifest in a myriad of ways due to its multisystem involvement. Due to its relatively high mortality rate, it is essential that TS is recognized and treated promptly. TS can occur due to trauma, drugs, and sepsis. Identifying TS as a diagnosis is challenging to pinpoint due to its similar presentation to more common pathologies like sepsis and diabetic ketoacidosis (DKA). Here, we present a case of a 31-year-old African-American woman with type 2 diabetes mellitus following sepsis secondary to Escherichia coli pyelonephritis and DKA. Despite standard sepsis treatment, which included appropriate intravenous fluids and antibiotics, the patient did not improve. Further workup, utilizing the Burch-Wartofsky score, helped identify TS as the underlying cause of the patient's hospitalization, despite no history of underlying thyroid disease. The inclusion of thyroid pathology as part of the differential diagnosis and workup of a patient with a sepsis-like presentation to avoid anchoring bias warrants further investigation.

A Devastating Floating Aortic Thrombus and Ketosis-Prone Diabetes.

This article reports a case study of a middle-aged patient diagnosed with Ketosis-Prone Diabetes (KPD) and diabetic ketoacidosis who had a mobile thrombus in the distal aortic arch with catastrophic complications from thrombus embolization. The pathogenesis of the mobile aortic thrombus is currently under investigation, with many risk factors having been found. Based on the patient's limited manifestation of atherosclerosis and the absence of any indications of thrombophilia, KPD and inflammation from uncontrolled hyperglycemia likely played a significant role in the formation of the thrombus. KPD is a subtype of diabetes characterized by the abrupt onset of severe hyperglycemia and ketoacidosis. The inflammation caused by uncontrolled hyperglycemia in KPD patients can lead to endothelial dysfunction and the activation of prothrombotic pathways. There is a lack of consensus regarding the optimal approach for managing a mobile aortic thrombus. The main strategies under consideration are conservative care, including anticoagulation alone, invasive removal of the thrombus, or endovascular intervention.