Current Diabetes Reviews - Volume 19, Issue 2, 2023

There is an increasing awareness that in those who develop early-onset (18-39 years) adult type 2 diabetes, an increase in insulin resistance, deterioration in beta-cell, and clustering of cardiovascular risk factors are particularly pronounced. Pregnant women with type 2 diabetes have additional risk factors for serious adverse pregnancy outcomes as well as added barriers regarding healthcare access before, during, and after pregnancy. Compared to pregnant women with type 1 diabetes, those with type 2 diabetes are older, have higher body mass index (BMI), with more metabolic comorbidities and concomitant medications, are more likely to belong to minority ethnic groups, and live in the highest areas of socio-economic deprivation. Approximately, one in seven pregnant women with type 2 diabetes (median age 34 years) are taking ACE-inhibitors, statins (13%), and/or other potentially harmful diabetes therapies (7%). Fewer than one in four are taking a high dose of folic acid before pregnancy, which may suggest that planning for pregnancy is not a priority for women themselves, their healthcare professionals, or the healthcare system. Knowledge of the epidemiology, pathophysiology, and unique management considerations of early-onset type 2 diabetes is essential to providing evidence-based care to pregnant women with type 2 diabetes. This narrative review will discuss contemporary data regarding type 2 diabetes pregnancy outcomes and the increasing recognition that different types of diabetes may require different treatment strategies before, during, and after pregnancy.

Background: Maternal diabetes mellitus during pregnancy is associated with an increased risk of pregnancy complications for both the mother and the fetus. One of the most prevalent complications is pathological fetal growth, and particularly infants are born large for gestational age (LGA), which leads to problematic deliveries, including the need for caesarean section, instrumental delivery, and further perinatal complications. Glucose monitoring during pregnancy is essential for ensuring appropriate glycaemic control and to reduce these associated risks. The current methods of glucose monitoring include measuring glycosylated haemoglobin (HbA1c), selfmonitoring of capillary blood glucose (SMBG), and more recently, continuous glucose monitoring (CGM). Observational studies and randomised controlled trials (RCTs) have assessed the appropriate glycaemic targets for HbA1c, SMBG, and CGM in relation to pregnancy outcomes. Objective: In this review, we have identified current international guidelines on glycaemic targets and reviewed the supporting evidence. Methods: We performed an extensive literature search on glycaemic targets in pregnancies affected by diabetes, and we researched international guidelines from recognised societies. Results and Conclusion: The majority of studies used to define the glucose targets associated with the best pregnancy outcomes, across all modalities, were in women with type 1 diabetes. There were limited studies on women with type 2 diabetes and gestational diabetes. We, therefore, suggest that further research needs be conducted on glucose targets and clinical outcomes, specifically in these populations where CGM technology offers the greatest potential for monitoring glucose and improving pregnancy outcomes.

Monogenic diabetes occurs in up to 3% of people with diabetes. Mutations in over 40 different genes are responsible. The most common genes affected are HNF1A, HNF4A, GCK, and HNF1B. Additionally, other types of diabetes with a genetic aetiology include neonatal diabetes and diabetes plus syndrome. Each of these genetic subtypes has a different phenotype and requires distinctive treatments. Due to the overlap of monogenic diabetes with type 1 and 2 diabetes and even gestational diabetes, they can often be misdiagnosed. During pregnancy, individual subtypes require treatment that is different from standard diabetes care, so recognition and prompt diagnosis of monogenic diabetes are important to avoid inadequate treatment. We describe the management of monogenic diabetes for the most significant subtypes, focussing on the impact on and management in pregnancy. A genetic diagnosis of diabetes can alter long-term treatment in those with diabetes. In pregnancy and the postnatal period, this can involve specific management changes determined by the gene affected and whether there is a fetal inheritance of the gene. Where inheritance of the genotype influences the outcomes, cell-free fetal testing will hopefully soon become a diagnostic tool for early recognition of fetal mutations.

Gestational diabetes mellitus (GDM) is associated with fetal and maternal complications, and the prevalence has been increasing over the past decades. Hence, it is imperative to effectively screen, manage and monitor patients with GDM, but there continues to be a lack of consensus on optimal screening for GDM internationally. In this review, we discuss the current screening methods for GDM, some of which are controversial and vary across several different healthcare systems. We also discuss the changes adapted to these guidelines during the COVID-19 pandemic and review novel approaches to the screening of GDM.

The incidence of metabolic disorders, such as obesity and type two diabetes (T2DM), continues to increase worldwide, and their onset is often attributed to adherence to a western diet and a sedentary lifestyle. However, large variability exists in one's likelihood of developing metabolic dysregulation, illustrating that our understanding of heritability patterns remains poorly understood. Diabetes and obesity are multifactorial diseases, and their onset is influenced by both genetic and environmental factors. Genome-wide association studies report a number of alterations in the coding sequence associated with the onset of T2DM and obesity. However, these genes explain only a fraction of the cases, leaving the majority unaccounted for. The missing heritability question implies that other factors are responsible for the onset and development of the disease. Given that the developing fetus is susceptible to the maternal environment, a growing body of evidence demonstrates that maternal metabolic characteristics as well as disruptions to the prenatal environment may induce long-term genetic, phenotypic, and physiologic adaptations in the developing fetus, which could have a permanent effect on its future health. This phenomenon is known as developmental programming and is mediated through epigenetic modifications, which include modulation of gene expressions that do not alter the original deoxyribonucleic (DNA) sequence. Epigenetic modifications are capable of changing gene expression in metabolism-related genes and are accomplished through DNA methylation, histone acetylation, and ribonucleic acid (RNA) mechanisms. In this review, we discuss maternal metabolic factors, such as obesity, dyslipidemia, and gestational diabetes (GDM) that lead to epigenetic changes in the offspring and predispose future generations to metabolic abnormalities. We will also describe the association between maternal lifestyle factors and exposure to toxins with epigenetic modulations in the offspring. Lastly, we will provide a brief review of the possibility of using epigenetics as potential interventions and therapeutic modalities to help in early diagnosis and prevention of metabolic disorders.

Background and Objective: Diabetes mellitus is the third leading cause of death in Indonesia (6.7 %), followed by stroke (21.1 %) and coronary heart disease (12.9 %). The prevalence of diabetes worldwide continues to increase on a yearly basis, including in Indonesia. Diabetes is a significant burden for many countries due to the high costs of treatment and reduced productivity of diabetes patients. Comprehensive strategies to prevent and treat diabetes are therefore mandatory. Oral hypoglycemic drugs are the first-line therapy for diabetes mellitus patients; however, these oral drugs still have several side effects. Therefore, it is necessary to conduct studies on medicinal plants with hypoglycemic effects to identify substances that have an anti-diabetic potential resembling physiological processes in the body. Indonesian people often use herbal medicines empirically, but the benefits have not been scientifically documented. Melinjo (Gnetum gnemon L.) is a native Indonesian gymnosperm plant, and the seeds are often processed into food. Melinjo seeds extract contains many polyphenols, including trans-resveratrol. Conclusion: Studies on the health benefits of resveratrol are widely available, including antidiabetes and blood sugar control in patients with type 2 diabetes.

The incidence of metabolic syndrome and diabetes mellitus is increasing globally. A diet rich in carbohydrates increases the hyperglycemic state. While considering the lifestyle changes to combat life-threatening diseases, there is an effort to decrease the daily intake of carbohydrates. A low-carbohydrate diet also makes the body rely more on fat for energy, so there is less fat accumulation. A diet is considered to be low-carbohydrate ketogenic if the intake is ≤ 50 g per day. The ‘low -carbohydrate ketogenic diet’ (LCKD) produces ketosis. LCKD contains high-fat, moderateprotein, and low-carbohydrate components. The main objectives of the present review are to discuss insulin resistance in different viscera of the body, describe the role of adipokines in insulin resistance, understand the mechanism of ketogenesis, and determine the impact of LCKD in overcoming insulin resistance in the body. In the present review, we also highlight the beneficial effects of LCKD in metabolic, neurodegenerative, cardiovascular, and lipid disorders and discuss the effect on longevity and aging. LCKD may help in combating the morbidity and mortality arising from the above-mentioned diseases and also help in leading a better quality of life.

Aims: This study aims to determine the prevalence of Type 2 Diabetes Mellitus (T2DM) in primary Brain Tumor (BT) subjects and assess the relationship between serum mutant p53 serum and HbA1c and insulin. Background: T2DM is known to increase the risk of various types of cancer, which are thought to be caused by hyperglycemia, hyperinsulinemia, and inflammation. A cohort study that looked at more than 500,000 subjects with DM over 11 years showed an increased risk of different types of cancer, including brain tumors. However, several recent studies have shown the opposite. One of the important pathways in the pathogenesis of brain tumors is the p53 pathway, in which mutations in the TP53 gene can cause brain cell growth abnormalities. Objective: The first stage involved taking subject data for the period January 2017-November 2020 from the medical records of the RSUPN Dr. Cipto Mangunkusumo Hospital Indonesia to assess the prevalence of T2DM in BT subjects. The second stage was an observational study with a crosssectional design that collected primary data on subjects (n=86) to assess the relationship between serum mutant p53 serum and HbA1c and insulin. Methods: The analysis of serum mutant p53 serum and insulin was made using the ELISA method, while measurement of HbA1c was made using the boronate affinity method. Result: The results show the prevalence of T2DM in BT subjects at Dr. Cipto Mangunkusumo Hospital Indonesia was relatively low (9%). Serum mutant p53 levels in T2DM (1.53 ng/mL ± 0.60) were significantly higher than in BT+T2DM and BT (P < 0.001). The HbA1c value was significantly lower in BT (5.15% ± 0.44) compared to BT+T2DM and T2DM (P < 0.001), while T2DM insulin levels (39.54 IU/mL ± 19.1) were significantly higher than BT+T2DM and BT (P < 0.001). There was no correlation between serum mutant p53 levels and HbA1c and insulin in the three groups. Conclusion: The study concludes that the prevalence of BT with T2DM is relatively low (9%) and that serum levels of mutant p53 in T2DM subjects are higher than in subjects with BT, but there is no correlation between serum mutant p53 levels and HbA1c and insulin values. Further research needs to be conducted by analyzing p53 mutants from other specimens, such as brain tumor tissue.

Background: Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine illnesses among women of reproductive age. PCOS is linked to several issues, including hypothyroidism and metabolic disorders. Hypothyroidism seems to be associated with insulin resistance and other metabolic factors. Objective: The present study aimed to evaluate the incidence of hypothyroidism in PCOS patients and compare it with healthy controls. Moreover, the impact of hypothyroidism on metabolic parameters, particularly insulin resistance, in PCOS patients was also examined. Methods: This study was conducted on 41 women with PCOS and 41 healthy women as controls from March to November, 2018. Participants' demographic information was recorded. Thyroid function tests were compared between the case and control groups. Metabolic parameters were examined between hypothyroid and euthyroid PCOS individuals. Results: Patients with PCOS displayed a greater incidence of hypothyroidism and a higher level of anti-thyroid peroxidase antibodies compared to the control group. High-density lipoprotein (HDL) cholesterol was substantially higher in hypothyroid PCOS patients than in non-hypothyroid individuals, although no significant changes were observed in other metabolic markers. Hypothyroid PCOS patients and those without hypothyroidism did not differ in insulin resistance. Autoimmunity was not found to be linked to a higher risk of metabolic problems. Conclusion: As evidenced by the results of this study, PCOS patients had a higher prevalence of subclinical hypothyroidism than healthy subjects. Metabolic indicators, except for HDL, were not different between PCOS patients with and without hypothyroidism.

Background: The concurrent, recent increase in prevalence of Gestational Diabetes Mellitus (GDM) and twin pregnancy, in combination with the shared risk factors, has led to speculation that multiples are a risk factor for GDM and, GDM may contribute to twin complications. Twin pregnancies have different physiology and greater obstetric risks compared to singletons, including prematurity and growth restriction. However, in twins methods of GDM screening, thresholds for diagnosis and treatment, as well as glycaemic control targets, have been predominantly extrapolated from singletons. Studies investigating the impact of GDM on pregnancy outcomes in twin pregnancies are conflicting. Objective: To provide a comprehensive, critical overview of evidence on GDM in twin pregnancies with an emphasis on prevalence, methods of screening, thresholds for diagnosis, risk of pregnancy complications and the impact of treatment on perinatal outcomes. Methods: Review of retrospective and prospective cohort, case-control, and case-series studies on twin pregnancies with GDM published between 1980 and 2021. Results: Glucose tolerance in twin pregnancies is poorly studied. Specific guidance for screening, diagnosis, and treatment of GDM in twins is lacking. Studies evaluating pregnancy outcomes in twins with GDM are few and heterogeneous. The absolute risk of maternal complications is greater in twins with GDM compared to singletons; conversely, differences in risks between twins with and without GDM may be due to maternal confounders rather than to GDM. Most studies agree on a positive effect of GDM on neonatal outcomes in twins, likely mediated by the hyperglycaemia improving fetal growth. The impact of lifestyle-measures versus medical management on pregnancy outcomes in twins with GDM is unknown. Conclusion: Larger longitudinal studies evaluating glucose tolerance, pregnancy outcomes and the impact of treatment both in mono and di-chorionic twins with GDM are warranted to gain further insight into the pathophysiology of this condition and guide optimal management.