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Pathophysiology of Diabetes
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Gestational diabetes mellitus (GDM) develops during pregnancy, characterized by a reduced ability to metabolize carbohydrates. This is usually due to a deficiency of insulin or insulin resistance. The condition disappears after the infant is delivered. However, in a large number of cases, it returns years afterward, as type 2 diabetes mellitus. Placental lactogen and extensive destruction of insulin by the placenta appear to play roles in precipitating GDM. Usually, pregnant women are screened for GDM between 24 and 28 weeks of gestation, via the 50 g, 1-hour glucose tolerance test. If the patient has risk factors for GDM, she will be screened in the first trimester. Risk factors include any previous pregnancy that involved GDM or a neonate heavier than 4,500 g at birth, unexplained fetal death, family history of diabetes in close relatives, previous persistent glycosuria, and a body mass index (BMI) over 30 kg/square meter (m2). With gestational diabetes, results are most accurately obtained via a glucose tolerance test. If the result is 140–199 mg/dL, a full glucose tolerance test is done. If the glucose is 200 mg/dL or higher, insulin is given. When 2 or more results are abnormal, the patient is placed on a controlled diet for the remainder of the pregnancy. If needed, insulin or oral hypoglycemics are administered. Rigid control of plasma glucose during pregnancy eliminates risks of adverse outcomes almost completely.
Oncology
Published in Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss, Understanding Medical Terms, 2020
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss
A number of general symptoms are associated with the oncologic disorders. Anemia is present in over half of patients with disseminated cancer and may be the first symptom of malignant disease. Hemorrhage occurs as a result of tumor invasion of blood vessels, causing intravascular coagulation and thrombocytopenia. Fever occurs In many patients with cancer, usually due to infections. Malnutrition, or the cachexia of malignancy, is often the most debilitating aspect, resulting from a combination of anorexia, loss of adipose tissue and protein stores, and abnormal glucose tolerance effects. Other manifestations may include neurological disorders, effusions, obstruction of the superior vena cava, hypercalcemia, and psychological effects. Most patients experience pain.
Biochemistry
Published in Michael McGhee, A Guide to Laboratory Investigations, 2019
A glucose tolerance test is indicated if: the random plasma glucose concentration is >6 but <11 mmol/lthere is a strong clinical indication of the possibility of gestational diabetes mellitus (GDM).Interpretation
Design of novel therapeutics targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss
Published in Expert Opinion on Drug Discovery, 2023
Despite a large body of evidence that would suggest that GIPR signaling promotes body weight gain, in the last decade a number of studies began to report that GIPR agonism is able to impart protection from obesity. Kim et al showed that transgenic mice overexpressing GIP, contrary to expectation, were significantly lighter than WT mice when fed a HFD [39]. Development of GIPR agonists began, with disappointing results at first as low doses of DPP-IV resistant analogs of GIP administered chronically did not result in reduced body weight or food intake in HFD-induced obese mice [40]. However, a paper published by investigators at Novo Nordisk in 2017 showed that various acylated analogues of both murine and human GIP, given daily at high doses ranging from 20 to 100 nmol kg−1 day−1, could produce significant reductions in body weight in the region of 10% over 14–28 days [41]. Reductions in body weight were driven through food intake reductions as energy expenditure remained unchanged. As expected, acute improvements in glucose tolerance were also observed. The structure of selected GIPR agonists is summarized in Figure 1.
Evaluation of the effects of bredemolic acid on selected markers of glucose homeostasis in diet-induced prediabetic rats
Published in Archives of Physiology and Biochemistry, 2022
Akinjide Moses Akinnuga, Angezwa Siboto, Bongiwe Khumalo, Ntethelelo Hopewell Sibiya, Phikelelani Ngubane, Andile Khathi
While abnormal glucose metabolism is often associated with overt T2DM, studies have shown that these abnormalities begin in the PD state (Brannick et al. 2016, Luvuno et al. 2016). In the PD condition, hyperinsulinaemia results as a compensatory mechanism to regulate insulin resistance and impaired glucose tolerance (Tabák et al. 2012). Impaired glucose tolerance is associated with decreased insulin sensitivity and sustained intermediate hyperglycaemia (Brannick et al. 2016). Subsequently, glucose uptake decreases gradually and the insulin-dependent peripheral tissues such as skeletal muscles are gradually starved of glucose, thus causing a decrease in glycogen level in the muscles (Brannick et al. 2016). Supposedly, due to decreased glucose uptake, the peripheral cells are depleted of energy. Therefore, a compensatory mechanism of ghrelin hormone release is initiated to stimulate the hypothalamus via the orexigenic signalling pathway and increase food intake (hyperphagia) to circumvent hypoglycaemia (Chabot et al. 2014).
Investigating the root cause of N-nitrosodimethylamine formation in metformin pharmaceutical products
Published in Expert Opinion on Drug Safety, 2021
Nasr Eldin Hussein Nasr, Metwaly Gamel Metwaly, Eman Osama Ahmed, Ahmed Roshdy Fares, Aliaa Nabil ElMeshad
The International Diabetes Federation in 2019 has reported that 463 million, of the world’s population aged 20 to 79 years have diabetes and this is expected to increase to 578 million by 2030 and to 700 million by 2045 [19]. Metformin (MET) is generally accepted as the first-line treatment of type 2 diabetes and is currently the most commonly used oral agent for this condition [20]. MET is effective as monotherapy and in combination with other glucose-lowering medications [21]. MET has superior or equivalent efficacy of glucose-lowering compared to other oral antidiabetic agents and reduces microvascular complications in patients with type 2 diabetes; more limited data support a beneficial effect to reduce macrovascular disease as well. MET does not typically cause weight gain and in some cases causes mild weight reduction. In patients with impaired glucose tolerance, treatment with MET delays the progression to diabetes. Prescriptions of MET raised from 51.6 million in 2008 to 61.6 million in 2012 [22]. In 2013, MET was prescribed for 83.6% of patients with type 2 diabetes in UK [23]. MET is the sixth prescribed product in the United States. IQVIA report of medicines spending and affordability in the United States for 2020 stated that the number of MET prescriptions in 2019 was 80 million [24]. Also, MET is the third most prescribed drug in India [25,26].