Effect of pioglitazone on inflammatory response and clinical outcome in T2DM patients with COVID-19: a randomized multicenter double-blind clinical trial.

Background: Coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate-severe COVID-19. Method: We enrolled 350 patients with type 2 diabetes who were admitted to hospitals in Qatar and Kuwait with COVID-19. Patients were randomized to receive, in a double-blind fashion, pioglitazone (n = 189) or a matching placebo (n = 161) for 28 days. The study had two primary outcomes: (1) the incidence of a composite outcome composed of (a) the requirement for mechanical ventilation, (b) death, and (c) myocardial damage; and (2) an increase in C-reactive protein (CRP) levels. Results: The first primary outcome occurred in 28 participants (8%), and the secondary outcome occurred in 17. Treatment with pioglitazone showed a significant reduction in interleukin (IL)-3 levels compared with placebo treatment (mean (SD) 2.73 (± 2.14) [95% CI: 0.02, 1.1], p = 0.043 vs. 2.28 (± 1.67) [95% CI: - 0.23, 0.86], p = 0.3, respectively), with no effect seen in the levels of other inflammatory markers. Even though not significant, a few of the patients on pioglitazone exhibited serum troponin levels > 3 times higher than the normal range seen in patients on placebo. On the other hand, more patients on pioglitazone were admitted to the ICU than those with placebo, and no significant difference in the CRP reduction was observed between the two groups. Conclusion: The results of the present study demonstrate that pioglitazone treatment did not independently provide any additional clinical benefit to patients with type 2 diabetes admitted with a COVID-19 infection. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04604223.

Sodium-glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure.

Background: Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes. Methods: We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes. Results: A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), p = 0.046]. Conclusion: The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.

Qatar Diabetes Mobile Application Trial (QDMAT): an open-label randomised controlled trial to examine the impact of using a mobile application to improve diabetes care in type 2 diabetes mellitus-a study protocol.

BACKGROUND: Mobile health (mHealth) is increasingly advocated for diabetes management. It is unclear if mobile applications are effective in improving glycaemic control, clinical outcomes, quality of life and overall patient satisfaction in patients with type 2 diabetes (T2DM). A new mobile application was specifically built for people with T2DM with the help of the local expertise. The objective of the study was to evaluate the effectiveness of the mobile app. METHODS: The planned study is an ongoing open-label randomised controlled trial in which adults living with T2DM treated with insulin will be randomised 1:1 to the use of this diabetes application versus current standard care. The primary outcome will be the difference in mean HbA1c from baseline to 6 months. Other outcome measures include anthropometric measures, hypoglycaemic events, medication adjustments, number of clinical interactions and missed appointments and patient perceptions of their disease and diabetes self-management. The study will randomise 180 subjects for assessment of the primary outcome. DISCUSSION: We hypothesise that the diabetes-specific mobile application will improve glycaemic control, increase patient empowerment for self-management of diabetes and improve interaction between patients and healthcare providers. If the Qatar Diabetes Mobile Application Trial (QDMAT) demonstrates this, it will inform clinical services for the future self-management of T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03998267 . Registered on 26 June 2019.

Alpelisib-Induced Diabetic Ketoacidosis in a Patient With Metastatic Breast Cancer.

Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor, is a new drug approved for metastatic breast cancer. Hyperglycemia is a known side effect of this medication, however diabetic ketoacidosis is rarely described. We are presenting a 64-year-old female with a known case of Type 2 diabetes mellitus (hemoglobin A1c [HbA1c] 5.6% ) controlled by metformin alone. She was also diagnosed with metastatic breast cancer. She received radiotherapy, trastuzumab and letrozole. Then, she was started on alpelisib as she failed other previous modalities. She presented to the emergency department with a two-week history of polyuria and polydipsia, and laboratory investigation results showed high anion gap metabolic acidosis, ketonemia, and hyperglycemia. She was treated for diabetic ketoacidosis (DKA). After the resolution of DKA, she was kept on daily insulin subcutaneous injections. She was restarted on a reduced dose of alpelisib, but despite this, her blood sugar readings continued to rise, requiring discontinuation of the medication with a resolution of hyperglycemia. The goal of our case report is to emphasize the importance of close glucose monitoring when starting alpelisib to avoid serious complications like DKA.

Corpus callosum hematoma, as a rare complication of COVID-19.

A 46-year-old gentleman had a complicated course of COVID-19 pneumonia. Despite the recovery of the respiratory status, he developed corpus callosum hematoma and critical illness neuropathy/myopathy. The clinical situation became more complicated by developing pulmonary embolism that required anticoagulation. Fortunately, the patient made a good recovery.

COVID-19 Pneumonia Complicated by Seizure Due to Severe Hyponatremia.

Coronavirus disease 2019 (COVID-19) is a widespread disease. Hyponatremia in the setting of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was described with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, seizure as a prominent manifestation of hyponatremia associated with COVID-19 is rare. We present a case of a middle-aged man with mild COVID-19 pneumonia, who developed a seizure due to SIADH-related severe hyponatremia.