Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition characterized by the irreversible destruction of the β cells of the pancreas, which leads to a lifelong dependency on exogenous insulin. Despite the advancements in insulin delivery methods, the suboptimal outcomes of these methods have triggered the search for therapies that may prevent or reverse the disease. Given the autoimmune aetiology of T1DM, therapies counteracting the immune-mediated destruction of the β-cells are the obvious target. Although several treatment strategies have been attempted to target cellular, humoral and innate immunity, very few have had a clinically meaningful impact. Of all the available immunomodulatory agents, cluster of differentiation (CD) 3 antibodies have exhibited the most promising preclinical and clinical results. Muromonab-CD3, which also happened to be a murine CD3 antibody, was the first monoclonal antibody approved for clinical use and was primarily indicated for graft rejection. The adverse effects associated with muromonab-CD3 led to its withdrawal. Teplizumab, a newer CD3 antibody, has a better side-effect profile because of its humanized nature and non-Fc- receptor- binding domain. In November 2022, teplizumab became the first immunomodulatory agent to be licensed by the US Food and Drug Administration for delaying the onset of T1DM in high-risk adults and children over 8 years old. The mechanism seems to be enhancing regulatory T-cell activity and promoting immune tolerance. This article reviews the mechanism of action and the clinical trials of teplizumab in individuals with T1DM or at risk of developing the disease.

Snake envenoming is a neglected, public health problem in tropical and subtropical regions. Local tissue necrosis, neurotoxic, and hemo-vasculotoxic effects are well-recognized features, whereas the endocrine and metabolic derangements are not as well known. In addition to contributing to morbidity, some of these manifestations can be potentially life-threatening if not recognized early. The most prominent endocrine manifestation is hypopituitarism (HP), which can manifest acutely or remain asymptomatic and present years later. Unexplained recurrent hypoglycemia and refractory hypotension are early clinical clues to suspect corticotroph axis involvement in acute settings. Chronic pituitary failure may present, like Sheehan’s syndrome, several years after the bite. The occurrence of acute kidney injury, capillary leak syndrome, and disseminated intravascular coagulation are predictors of HP. Adrenal hemorrhages are documented in autopsy series; however, primary adrenal insufficiency is very rare and confounded by the presence of HP. Hyponatremia, hypokalemia or hyperkalemia, and dysglycemia can occur, but the mechanisms involved are only partially understood. Awareness, a high index of suspicion, correct interpretation of hormonal parameters, and timely treatment of these abnormalities can be lifesaving.

Preexisting diabetes mellitus (DM) should be ruled out early in pregnancy in those at risk. During screening, a significant proportion of women do not reach the threshold for overt DM but fulfill the criteria used for diagnosing conventional gestational DM (cGDM). There is no consensus on the management of pregnancies with intermediate levels of hyperglycemia thus diagnosed. We have used the term early gestational DM (eGDM) for this condition and reviewed the currently available literature. Fasting plasma glucose (FPG), oral glucose tolerance test, and glycated hemoglobin (HbA1c) are the commonly employed screening tools in early pregnancy. Observational studies suggest that early pregnancy FPG and Hba1c correlate with the risk of cGDM and adverse perinatal outcomes. However, specific cut-offs, including those proposed by the International Association of the Diabetes and Pregnancy Study Group, do not reliably predict the development of cGDM. Emerging data, though indicate that FPG ≥ 92 mg/dL (5.1 mmol/L), even in the absence of cGDM, signals the risk for perinatal complication. Elevated HbA1c, especially a level ≥ 5.9%, also correlates with the risk of cGDM and worsened outcome. HbA1c as a diagnostic test is however besieged with the usual caveats that occur in pregnancy. The studies that explored the effects of intervention present conflicting results, including a possibility of fetal malnutrition and small-for-date baby in the early treatment group. Diagnostic thresholds and glycemic targets in eGDM may differ, and large multicenter randomized controlled trials are necessary to define the appropriate strategy.