International Journal of Endocrinology and Metabolism
Volume:21 Issue: 3, Jul 2023

Context: 

Global reports have revealed a dramatic rise in the number of patients diagnosed with type 2 diabetes (T2DM) over the past three decades in all age groups, even in children and adolescents. The physiologic phenomenon of insulin resistance during puberty, as well as genetic and epigenetic factors, are implicated in this phenomenon. It seems that patients with early-onset T2DM experience a more aggressive clinical course; however, limited treatments available for these patients pose a challenge. This narrative review intends to scrutinize the micro- and macrovascular complications and treatments of patients with early-onset T2DM.

 The literature search was conducted in the PubMed database to identify all relevant original English articles published from the beginning of 2018 until January 2023.

 Vascular complications, such as albuminuria, hypertension, cardiovascular diseases, and retinopathy, were seen to be more common in early-onset T2DM compared to type 1 diabetes. The odds ratio of vascular complications was higher in early-onset compared to late-onset T2DM. In children and adolescents with T2DM, the only approved medications included metformin, insulin, and glucagon-like peptide-1 agonists. Treatment of early-onset T2DM with metformin monotherapy cannot yield durable glycemic control, and most patients need early combination therapy.

 During the past years, the frequency of early-onset T2DM has been growing at an alarming rate. Vascular complications in these patients seem more aggressive and more challenging to control. Hence, further clinical trials should be conducted to develop novel therapeutic approaches and evaluate their long-term benefits in terms of glycemic control and preventing future complications.

Despite evidence about the relationship between diabetic ketoacidosis (DKA) and infectious diseases, our knowledge of DKA during the coronavirus disease 2019 (COVID-19) pandemic remains unclear.

This study aimed to compare the DKA situation among individuals with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic compared to pre-pandemic.

This retrospective-longitudinal study included individuals with T1DM and T2DM hospitalized with newly diagnosed DKA before (March to August 2018 and 2019) and during (March to August 2020 and 2021) the COVID-19 pandemic. Demographics, the frequency of new-onset diabetes mellitus (DM) and new-onset DKA, days of hospitalization, DKA severity, laboratory tests, and mortality were assessed.

Of 162 patients with DKA, 139 patientswere newly diagnosed. The frequency of individuals withnew-onsetDMhadincreased during the pandemic compared to pre-pandemic (P = 0.047). Moreover, new-onset DKA was higher in 2020 and 2021 versus 2019 and 2018 (P = 0.002). Significantly, there were no T2DM patients with DKA in pre-pandemic, but DKA admissions in people with T2DM increased in 2021 (P < 0.001). The severity of new-onset DKA had increased during the pandemic compared to pre-pandemic (P = 0.000). However, there was no significant difference between pre-and the pandemic regarding mortality (P = 0.981). Additionally, hospitalization length (P = 0.043) and mortality (P = 0.038) were higher in patients with T2DM compared to T1DM.

During the COVID-19 pandemic, the frequency of DKA and its severity was higher than in pre-pandemic, and COVID-19 can be more life-threatening in patients with T2DM. Therefore, healthcare providers should be alert to DKA, especially in patients with T2DM.

The harmful impact of ovariectomy on myocardial ischemia-reperfusion (M/IR) injury has been established in the short term.

In this study, we aimed to investigate the long-term effects of ovariectomy on M/IR injury.

Twomethods involving dorsolateral skin incisions were used to induce the ovariectomized (OVX) rat model. The rats were divided into 2 groups: Control and OVX (n = 6). At the end of the study, the hearts were isolated and subjected to global ischemia using the Langendorff apparatus. Cardiac function indices (CFIs) were recorded, including left ventricular end-diastolic pressure (LVEDP), peak rates of positive (+dp/dt) and negative (-dp/dt) changes in LV pressure, and LV-developed pressure (LVDP). At the end of the reperfusion period, the hearts were used to measure the size of the infarct, levels of nitric oxide metabolites (NOx), andmRNA expression of NO synthase (NOS) enzymes, including endothelial (eNOS), neuronal (nNOS), and inducible (iNOS).

Compared to controls, OVX rats had larger infarct size by 51%, higher LVEDP by 29%, and lower recovery of +dp/dt, –dp/dt, and LVDP by 29%, 22%, and 35%, respectively. Furthermore, in heart tissue, rats that underwent OVX had significantly higher concentrations of nitrate, nitrite, and NOx by 79%, 82%, and 83%, respectively. Additionally, these rats had lower mRNA levels of eNOS by 38% and higher mRNA levels of iNOS by 71%.

The long-term deficiency of estrogen increased the expression of iNOS and decreased the expression of eNOS in the heart tissue of OVX rats. Imbalanced NOS expressions were associated with exacerbated responses to M/IR injury in OVX rats.

It has been reported that sphingosine kinase (SK) 2 plays a role in maintaining metabolism and glucose homeostasis. However, the mechanism remains uncertain.

The present research aimed to further investigate the effect of SK2 knockout on high-fat diet (HFD)-induced obesity and metabolic regulation.

Male SK2-/- and wild-type (WT) control mice were challenged with HFD for 8 weeks. Then, body composition, inguinal white adipose tissue (IWAT) histology, intraperitoneal glucose tolerance tests (IPGTT), and metabolic parameters were examined, and expression levels of uncoupling protein 1 (UCP1), a key molecular marker of thermogenesis, in IWAT were determined.

After 8 weeks of HFD challenge, compared with WT mice, SK2-/- mice displayed decreased whole body, epididymal white adipose tissue (EWAT) and IWAT weights, reduced fat/lean body mass ratios and inguinal adipocytes size; also, SK2-/- mice exhibited improved intraperitoneal glucose tolerance. Next, elevated energy expenditure was observed in SK2-/- mice compared with WT mice; however, neither food intake nor physical activity showed obvious difference between SK2-/- and WT mice. Furthermore, we found that the expressions of UCP1 was markedly increased in IWAT from SK2-/- mice.

SK2-/- mice may resist HFD-induced obesity through increasing energy expenditure by promoting thermogenesis in the beige adipose tissue.

Graves’ disease (GD) is an autoimmune condition affecting the thyroid gland. The aim of treating GD is to control the symptoms of hyperthyroidism and achieve long-term remission. Antithyroid drugs (ATDs) are the medications of choiceamong newly-diagnosed GD patients as they are easy to be delivered and cause remission in more than 50% of patients. However, ATDs increase the risk of hepatotoxicity, especially among patients with liver abnormalities. Patients who cannot tolerate ATDs should receive definitive therapy such as radioactive iodine (RAI) or surgery. In order to minimize the risk of thyroid storm during these procedures, patients should be in euthyroid condition and receive bridging therapy. Therapeutic plasma exchange (TPE), which aims to remove thyroid hormones from plasma, is one of the modalities that can be considered as a bridging therapy during the perioperative period among GD patients who cannot tolerate ATD.

A 35-year-old man with general weakness and thyrotoxicosis symptoms was admitted to the emergency room. Lid retraction, diffuse Goiter, and tremors were evident. Laboratory findings revealed TSH = 0.005 IU/mL, FT4 = 7.77 ng/dL, TRAb = 9.90 IU/L, ALT = 123 U/L, total bilirubin = 23.94 mol/L, and direct bilirubin = 10.26 mol/L. Ultrasonographic examination showed the enlargement of the thyroid gland, and abdomen ultrasonographic evaluation showed mild hepatomegaly with mild fatty infiltration. The patient was diagnosed with GD, suspected thyroid storm, elevated liver transaminases, and fatty liver disease. The patient then received methimazole, propranolol, and glycyrrhizin. During observation, the patient developed drug-induced liver injury (DILI) evidenced by an increase in liver enzymes (ALT up to 1023 U/L) and the elevation of total bilirubin to 258.21 mol/L, so methimazole was stopped. After discontinuing methimazole, liver injury improved. However, thyrotoxicosis symptoms returned, so the patient underwent a total thyroidectomy. In order to achieve a euthyroid status before surgery, five sessions of therapeutic plasma exchange were performed, which improved the signs and symptoms of hyperthyroidism and retained the thyroxine hormone within the normal range. Thyroidectomy was then performed successfully without serious complications (e.g., thyroid storm, etc.).

Therapeutic plasma exchange is a safe and effective bridging therapy for GD patients who require thyroidectomy but cannot tolerate ATDs.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon transient neuroradiological phenomenon that develops vasogenic cerebral edema and could be caused by some pharmacological agents, such as molecular-specific target agents. Lenvatinib belongs to the tyrosine kinase inhibitors and was approved in 2015 for progressive locally advanced or metastatic thyroid cancer refractory to radioactive iodine (I-131) treatment. Herein, we present the case of a 65-year-old woman who, while receiving treatment with lenvatinib for radioiodine-refractory metastatic papillary thyroid carcinoma, developed PRES without hypertension at the initial evaluation. Her clinical and radiological findings improved after withdrawing from the mentioned therapy, and later it was possible to re-incorporate lower doses of the medication, as described in the other three case reports found in the worldwide medical literature. The recognition of this entity is essential to timely suspend the drug and avoid greater comorbidity. This is the first paper reporting this kind of adverse event using lenvatinib in a Hispanic population.