Increased Insulin Resistance Research Articles

The Impact of Macronutrient and Dietary Patterns on Gestational Diabetes Mellitus

Pregnancy is a physiological condition that increases insulin resistance (IR) due to hormonal changes, including elevated levels of estrogen, progesterone, and human placental lactogen (HPL). Such IR, especially in the later stages of pregnancy, can cause gestational diabetes mellitus (GDM), characterized by glucose intolerance first detected during pregnancy. GDM poses significant health risks for both the mother and the fetus, including the potential for pre-eclampsia, emergency C-sections, and type 2 diabetes (T2D) for the mother, as well as preterm birth, hypoglycemia, and being large for gestational age (LGA) for the baby. Proper dietary modifications can help regulate blood sugar levels, improve insulin sensitivity, and ensure healthy gestational weight gain (GWG), thereby reducing the possibility of undesirable outcomes. This paper discusses the role of energy, carbohydrate, fat, and protein, and compares the effects of the Mediterranean diet (MD) and Western diet (WD) on the risk of GDM. The main objective of this paper is to identify the most effective dietary strategies for preventing and managing GDM. The finding indicates that a MD rich in nutrient-dense foods, complex carbohydrates/lower GI, unsaturated fatty acids (FAs), and balanced protein has beneficial effects on GDM. In contrast, the WD with empty calories, simple carbohydrates/higher glycemic index (GI), saturated FAs (SFA), and animal-based protein increases the risk of GDM. Future studies should continue to explore the long-term effects of dietary interventions, integrate other lifestyle factors, and consider genetic differences to provide comprehensive management strategies for GDM.

Lack of glycemic control in type two diabetes mellitus patients is associated with reduced serum epidermal growth factor level and increased insulin resistance

Lack of glycemic control in type two diabetes mellitus patients is associated with reduced serum epidermal growth factor level and increased insulin resistance

The Induction of Diabetes by High-Sugar and High-Fat Diets and Potential Applications of Healthy Eating

The rising prevalence of diabetes has intensified research in this field. Among the various causes of diabetes, insulin resistance plays a crucial role. High-sugar, high-fat diets are known to induce hyperglycemia and obesity, which significantly affect the progression of insulin resistance. It should be noted that obesity can significantly increase insulin resistance, thereby inducing prediabetes and aggravating diabetic symptoms. Additionally, such diets disturb the balance of intestinal flora. Controlling carbohydrate intake through low-carb or ketogenic diets can effectively improve glucose and lipid metabolism, improving insulin sensitivity, reducing insulin resistance, and lowering insulin levels. Adjustments to diet can also help shape a healthy gut flora composition. Furthermore, consuming natural products like flavonoids can also contribute to the improvement of diabetic symptoms. This article summarizes the impact of high-sugar, high-fat diets on the progression of diabetes, their effects on insulin resistance and intestinal flora, and the regulatory benefits of a healthy diet in managing diabetes.

Fat mass mediating effect on the association of worsening insulin resistance with increased left ventricular mass in 1595 adolescents: a 7-Year Longitudinal and Mediation Study

Abstract Background Fat mass-insulin resistance vicious cycle has been established in the young population and late adolescence has been identified as the critical time when the pathologic cycle begins. However, the independent and synergistic effect of fat mass in the relationship of insulin resistance with cardiac structure remains unexamined in a large cohort of adolescents, possibly due to the scarcity of repeated echocardiography measures. Mounting effective prevention strategies relies on strong evidence of the timing of the earliest cardiovascular alteration induced by insulin resistance. Purpose To investigate the longitudinal association of insulin resistance with left ventricular mass (LVM) and the mediating effect of fat mass in adolescents. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting glucose and insulin measured at 17- and 24-year clinic visits were included. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated from fasting insulin x fasting glucose/22.5 at ages 17 and 24 years. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7) was available at baseline and follow-up. Fat mass was repeatedly measured with dual-energy Xray absorptiometry at both time points. Multivariable adjusted association was examined using generalized linear mixed-effect models and adjusted for sex, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, and time-varying covariates measured at both baseline and follow-up such as age, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol. Mediation analysis was conducted with a structural equation model adjusting for same covariates, except fat mass. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median insulin resistance increased from 1.46 to 1.74, median fat mass increased from 15.6kg to 19.2kg and the mean LVMI increased from 35.4g/m2.7 to 38.1g/m2.7, over 7 years. In a fully adjusted model, increased insulin resistance from adolescence through young adulthood was significantly associated with increased LVMI (effect estimate 1.01g/m2.7 [95% CI, 0.63 – 1.57], p<0.001) across the 7-year observation period. Increased fat mass mediated (62.3% mediation effect) the longitudinal association between insulin resistance and LVMI from ages 17 – 24 years. Conclusion Worsening insulin resistance from adolescence through young adulthood was associated with increased cardiac mass, contributing 37% to the total increase in LVMI between ages 17 to 24 years but increased fat mass explained two-thirds of the relationship.

Correlation between portal hypertension and somatic constitution: rationale behind the concept

This review summarizes recent data on the correlation of somatic constitution and portal hypertension.Somatotype reflects the constitutional composition of the human body. Excess endomorphic component (i.e. obesity) increases the risk of portal hypertension (PH - elevated pressure in the portal system above 12 mmHg) development. Among the prehepatic and posthepatic PH causes only congestive hepatopathy, a consequence of heart failure, is connected with obesity. A number of pathways connect the hepatic PH causes with obesity. Firstly, the action of proinflammatory cytokines produced by adipose tissue in greater amount in obesity promotes fatty acid uptake and storage by hepatocytes, leading to elevated oxidative stress and metabolic dysfunctions, activation of stellate cells, that differentiate into myofibroblasts and produce components of the intercellular matrix such as collagen into the perisinusoidal space resulting in fibrosis. Secondly, insulin resistance associated with obesity promotes dysfunction of the hepatic microcirculatory blood vessels, hyperlipidemia and liver steatosis. Thirdly, AMISS (Absence of Meal-induced Insulin Sensitization Syndrome), caused by regular high-carbohydrate and low-protein food consumption, manifested in decreased postprandial secretion of hepatic hormone hepatalin, which increases glucose uptake by skeletal and cardiac muscle, results in prolonged postprandial hyperglycemia, compensatory hyperinsulinemia and hyperlipidemia, leading to increased insulin resistance and a prediabetic state, associated with steatohepatosis. Thus, excess endomorphic component is to be regarded as a prognostic factor for portal hypertension.

Impact of physical activity levels on the association between air pollution exposures and glycemic indicators in older individuals

BackgroundAir pollution may exacerbate diabetes-related indicators; however, the longitudinal associations between air pollutant concentrations and glycemic markers remain unclear. In this prospective cohort study, we examined the longitudinal associations between air pollution and glycemic indicators among older individuals with normoglycemia at baseline and determined whether these associations differed according to changes in physical activity levels.MethodsOverall, 1,856 participants (mean age, 70.9 years) underwent baseline and 4-year follow-up surveys. We used linear mixed-effect models to examine the associations between previous 1-year exposures to air pollutants and glycemic indicators. We further investigated associations between previous 5-year exposures to air pollutants and glycemic indicators after the inverse probability of treatment weighting (IPTW). We explored effect modifications by the level of physical activity maintenance and changes in metabolic equivalent of task (METs) for physical activity.ResultsLevels of particulate matter with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm, and nitrogen dioxide (NO2) were significantly associated with increased fasting blood glucose, Hemoglobin A1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) values. After IPTW, the associations remained significant for PM10 and NO2. The positive associations of NO2 with insulin and HOMA-IR remained significant in the maintained inactive group, but not in the maintained moderate-to-vigorous active group. The positive associations of PM10 or NO2 with insulin and HOMA-IR remained significant in the group with increased METs, but not in those with decreased METs. In the post-hoc analysis of non-linear relationships between an increase in METs and glycemic indicators, insulin and HOMA-IR remarkably increased in the higher PM10 and NO2 exposure group from the point of 12,000 and 13,500 METs-min/week increase, respectively.ConclusionsWe demonstrated longitudinal associations between air pollution exposures and increased insulin resistance in older individuals. Maintaining moderate-to-vigorous physical activity may mitigate the adverse effects of air pollution on insulin resistance. In older individuals dwelling in highly polluted areas, an increase of less than 12,000 METs-min/week may be beneficial for insulin resistance.

Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes.

The gut microbiota, a complex ecosystem of microorganisms in the human gastrointestinal tract (GI), plays a crucial role in maintaining metabolic health and influencing disease susceptibility. Dysbiosis, or an imbalance in gut microbiota, has been linked to the development of type 2 diabetes mellitus (T2DM) through mechanisms such as reduced glucose tolerance and increased insulin resistance. A balanced gut microbiota, or eubiosis, is associated with improved glucose metabolism and insulin sensitivity, potentially reducing the risk of diabetes-related complications. Various strategies, including the use of prebiotics like inulin, fructooligosaccharides, galactooligosaccharides, resistant starch, pectic oligosaccharides, polyphenols, β-glucan, and Dendrobium officinale have been shown to improve gut microbial composition and support glycemic control in T2DM patients. These prebiotics can directly impact blood sugar levels while promoting the growth of beneficial bacteria, thus enhancing glycemic control. Studies have shown that T2DM patients often exhibit a decrease in beneficial butyrate-producing bacteria, like Roseburia and Faecalibacterium, and an increase in harmful bacteria, such as Escherichia and Prevotella. This review aims to explore the effects of different prebiotics on T2DM, their impact on gut microbiota composition, and the potential for personalized dietary interventions to optimize diabetes management and improve overall health outcomes.

Hexokinase Domain Containing 1 (HKDC1) Gene Variants and Their Association With Gestational Diabetes Mellitus: A Mini-Review

Abstract Gestational diabetes mellitus (GDM) is the most common metabolic disorder during the gestational period. Maternal glucose metabolism differs significantly from nonpregnant levels during pregnancy, with increased insulin resistance being the main physiological response. Maternal glucose levels during pregnancy, have a significant impact on the development of early and long-term metabolic health of the offspring. Therefore, a better understanding of the GDM pathophysiology is needed. Hexokinase domain containing 1 (HKDC1) gene was discovered as a gene related to glucose metabolism during pregnancy compared with nongravid state. HKDC1 plays a critical role in glucose homeostasis during pregnancy. Haplotypes of HKDC1 genetic variants associated with 2-h plasma glucose (2hPG) in pregnancy, disrupt regulatory element activity, thereby reducing HKDC1 expression in different tissues. The association of HKDC1 variants with gestational diabetes and 2hPG was investigated in several ethnic groups. These studies suggested that HKDC1 plays a more important role in glucose metabolism during pregnancy than outside of it and also demonstrated that while GDM and type 2 diabetes mellitus have many similarities, there are differences in at least one underlying pathway. This review focuses on the findings of the genetic studies on HKDC1 and GDM.

The High Estradiol Environment after IVF Causes the Increased Risk of Glucose Metabolic Dysfunction in Offspring.

Assisted reproductive technology (ART) is associated with increased metabolic risks in offspring. The effect of high maternal estradiol (E2) levels during early pregnancy on the glucose metabolism of offspring remains unclear. To evaluate glucose metabolism in in vitro fertilization (IVF)-conceived children and assess whether high E2 exposure during early pregnancy is associated with metabolic alterations. This retrospective analysis included 500 singletons aged 3-10 years born after fresh embryo transfer (ET) (n=200), frozen ET (n=100), and natural conception (NC) (n=200) from a university hospital. Children underwent anthropometric measurements and examinations for fasting glucose, insulin, and lipid levels. A mouse model of high E2 exposure during early pregnancy was established to study glucose and insulin tolerance, and insulin secretion. Compared with NC, children born after fresh ET showed higher fasting glucose/insulin levels, increased insulin resistance, and higher incidence of impaired fasting glucose, which might be associated with a higher maternal E2 levels. Frozen ET showed intermediate results. In mice, offspring exposed to high E2 levels during gestation exhibited impaired glucose/insulin tolerance and defects in insulin secretion. High maternal E2 levels in early pregnancy are associated with altered glucose metabolism and increased metabolic risks in IVF-conceived children. Further studies are needed to elucidate the underlying mechanisms.

12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus

Abstract Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None. Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances. Presentation: 6/1/2024

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c >15.5% (<5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (<5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was <7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

8538 Pancreatic Islet Adaptations to Hyperglycemia Are Prevented by Glycolytic Inhibition and Amplified by Inhibiting Membrane Depolarization

Abstract Disclosure: N.B. Whitticar: None. B.P. List: None. N. Bruce: None. R. Bertram: None. C.S. Nunemaker: None. Long before type 2 diabetes ensues, pancreatic islets undergo functional changes to compensate for increasing insulin resistance. Primarily, the islets increase their ability to secrete insulin by augmenting the glucose-stimulated insulin secretion (GSIS) pathway. As metabolic syndrome worsens, islets become functionally exhausted, leading to cellular dysfunction and apoptosis. To avoid the negative consequences of this compensatory response, various steps of the GSIS pathway can be attenuated to restore normal functional levels before the islets fail. Determining which inhibitors can prevent the earliest adaptations to hyperglycemia may reveal the processes that play a causal role in islet failure. The chemicals mannoheptulose (MH), diazoxide (DZ), and nifedipine (NP) were chosen to inhibit the glucokinase enzyme, KATP-channel closure, and voltage-gated calcium channels, respectively. CD-1 mouse islets were placed in 20 mM glucose to simulate hyperglycemia along with a concentration of each inhibitory drug that reduced insulin secretion by 30-40%. After 48-hour treatment, glucose-stimulated calcium tests were performed to determine if the treatments could prevent the negative adaptation to hyperglycemia. Only islets treated with MH to reduce glycolytic activity maintained a normal calcium response. Islets in the MH group also retained a strong insulin response to glucose and were not depleted of insulin content. Unexpectedly, inhibition of calcium influx and insulin secretion with DZ or NF caused a substantial increase in basal insulin secretion compared to islets in standard culture (P<0.01, n=6; P=0.06, n=6, respectively). These results indicate that the signaling pathway that causes the adaptation to hyperglycemia lies upstream of KATP channels and downstream of glucokinase. Mathematical modeling using the Integrated Oscillator Model was able to replicate our results and suggests that high rates of glycolytic and mitochondrial metabolism are associated with the signal that adapts islets to hyperglycemia, and that reducing intracellular calcium in the face of high glucose further increases basal insulin secretion. Ongoing studies will determine if metabolic acceleration or altered membrane conductance are responsible for the earliest islet adaptations to hyperglycemia. Our results suggest that reducing metabolic activity, but not calcium influx, prevents adaptations to hyperglycemia in mouse islets. These findings can be applied to potentially prevent the progression of obesity and hyperinsulinemia into type 2 diabetes. Presentation: 6/2/2024

Metabolic Syndrome, Thyroid Dysfunction, and Cardiovascular Risk: The Triptych of Evil

The triad formed by thyroid dysfunction, metabolic syndrome (MetS), and cardiovascular (CV) risk forms a network with many connections that aggravates health outcomes. Thyroid hormones (THs) play an important role in glucose and lipid metabolism and hemodynamic regulation at the molecular level. It is noteworthy that a bidirectional association between THs and MetS and their components likely exists as MetS leads to thyroid dysfunction, whereas thyroid alterations may cause a higher incidence of MetS. Thyroid dysfunction increases insulin resistance, the circulating levels of lipids, in particular LDL-C, VLDL-C, and triglycerides, and induces endothelial dysfunction. Furthermore, THs are important regulators of both white and brown adipose tissue. Moreover, the pathophysiological relationship between MetS and TH dysfunction is made even tighter considering that these conditions are usually associated with inflammatory activation and increased oxidative stress. Therefore, the role of THs takes place starting from the molecular level, then manifesting itself at the clinical level, through an increased risk of CV events in the general population as well as in patients with heart failure or acute myocardial infarction. Thus, MetS is frequently associated with thyroid dysfunction, which supports the need to assess thyroid function in this group, and when clinically indicated, to correct it to maintain euthyroidism. However, there are still several critical points to be further investigated both at the molecular and clinical level, in particular considering the need to treat subclinical dysthyroidism in MetS patients.

Childhood adversity, accelerated GrimAge, and associated health consequences.

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

The Role of Arginase and some Parameters in Diabetic Type 2 Patients with and without Retinopathy

Background: Oxidative stress plays a major role in the pathogenesis of diabetes mellitus by damaging cellular organelles and enzymes in blood such as arginase1, insulin and glutathione s-transferase; increasing lipid peroxidation such as malondialdehyde and increasing insulin resistance which can lead to diabetic complications such as diabetic retinopathy. Objectives: To explore the relationship of oxidative stress to the development of diabetic retinopathy by measuring the levels of Arginase1, the activity of glutathione s-transferase enzyme, and the levels of malondialdehyde as a secondary product of lipid peroxidation (biomarker for oxidative stress). Patients and MethodsThis study was conducted from November 2022 to January 2023 at the Ibn Al-Haitham Teaching Eye Hospital in Baghdad, the University of Baghdad / Department of Chemistry and the National Diabetes Centre for Treatment and Research at Al-Mustansyrriah University. This study was conducted on 120 subjects distributed as follows: 40 non-diabetic obese controls, 40 type 2 diabetics with no retinopathy, and 40 type 2 diabetic retinopathy patients, between 30 and 65 years of age. All groups were subjected to tests: measuring fasting blood glucose (FBG), HbA1c, lipid profile (cholesterol, triglycerides, HDL- cholesterol, LDL- cholesterol, and VLDL cholesterol), serum total arginase1, malondialdehyde glutathione s -transferase, body mass index (BMI), and waist-to-hip ratio. Results: Mean arginase1 levels were significantly higher in diabetic patients than in diabetic retinopathy and control groups (p ≤ 0.05). The mean xidative stress marker malondialdehyde concentration was significantly higher in diabetic retinopathy patients than in type 2 diabetics and the control group (P ≤ 0.05). The mean glutathione s-transferase activity in diabetic retinopathy patients was significantly higher than in the control group and type 2 diabetics (P ≤ 0.05). Conclusion: There is a relationship between oxidative stress and the development of diabetic retinopathy, where the levels of arginase1 and malondialdehyde increased and the activity of glutathione s –transferase enzyme increased as a result of oxidative stress and inflammation associated with complications of type 2 diabetes.

Interplay of Adiponectin With Glycemic and Metabolic Risk Metrics in Patients With Diabetes.

Background Type 2 diabetes mellitus (T2DM) is characterized by low insulin production or resistance. Adiponectin, a hormone produced by adipocytes, is essential for regulating glucose metabolism and is correlated with insulin decrease. Aim The aim of this study is to estimate the levels of adiponectin in T2DM patients and their relationship with various metabolic markers (glycated hemoglobin (HbA1c), fasting blood sugar (FBS), fasting insulin, lipid profile, and anthropometric variables in an Indian cohort. Methods This study was conducted at King George's Medical University (KGMU), India, from October 2022 to October 2024. The study (case-control)included 234 subjects: T2DM patients and age-sex-matched healthy controls. Diagnosis of T2DM followedAmerican Diabetes Association criteria. Data collection involved medical history, anthropometric measurements, blood pressure, and biochemical assessments including FBS, HbA1c, lipid profiles, insulin levels, and insulin resistance. Serum adiponectin levels were estimated using an ELISA kit. Results T2DM patients had a significantly higher HbA1c value (7.82±0.96%) compared to controls (5.31±0.39%, p<0.001). Insulin resistance was also significantly higher in T2DM patients (4.31±0.95) than in controls (3.62±0.82, p=0.002). Adiponectin levels were significantly lower in T2DM patients (6.87±3.73 µg/mL) compared to controls (10.18±5.16 µg/mL, p<0.001). Low levels of adiponectin were correlated with HbA1c (r=-0.58, p<0.001), FBS (r=-0.51, p<0.001), and total cholesterol (r=0.38, p<0.001). Adiponectin levels also were correlated with BMI (r=-0.33, p<0.001). Conclusion Lower adiponectin levels in T2DM patients correlate with HbA1c and increased insulin resistance, suggesting that adiponectin may be a biomarker for diabetes management and risk assessment.

Association Between Mycobacterium tuberculosis Sensitization and Insulin Resistance Among US Adults Screened for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure. Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics. We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance.

The role of magnesium in pancreatic beta-cell function and homeostasis.

Magnesium plays an essential role in glucose utilization and insulin signaling. Recent advances have revealed a greater prevalence of hypomagnesemia in general, and low intracellular magnesium levels in individuals with diabetes contribute to β-cell dysfunction and insulin resistance. This article describes the documented effects of magnesium on various aspects of β-cells and glucose homeostasis. Studies have demonstrated that magnesium deficiency is associated with reduced pancreatic β-cell activity and increased insulin resistance in patients with type 2 diabetes. Additionally, magnesium is involved in many cellular events, including energy homeostasis, protein synthesis, and DNA stability. Furthermore, magnesium is critical for proper glucose utilization and insulin signaling, and magnesium deficiency can lead to the dysregulation of ATP-sensitive potassium (KATP) channels in pancreatic β-cells, impairing insulin secretion. Therefore, maintaining adequate magnesium levels is crucial for maintaining overall health and preventing of metabolic disorders such as type 2 diabetes.

The Interplay between COVID-19 and Diabetes: Understanding Hyperglycemia, Complications, and Management Challenges in Diabetic Patients

The COVID-19 pandemic has significantly impacted individuals with diabetes, revealing a complex interplay between the virus and pre-existing hyperglycemia. This review explores how COVID-19 exacerbates hyperglycemia in diabetic patients, primarily through mechanisms such as stress response, cytokine storms, and increased insulin resistance. Diabetic individuals are particularly susceptible to severe COVID-19 outcomes, including heightened mortality rates, due to compromised immune responses and coexisting conditions like cardiovascular and renal complications. The review also addresses the unique challenges of managing diabetes during COVID-19, including the need for adjustments in insulin therapy and the impact of COVID-19 treatments, such as corticosteroids, on glucose control. Additionally, it highlights the potential long-term effects of COVID-19 on diabetic patients, including the onset of new diabetes and persistent metabolic issues. The review emphasizes the importance of glycemic control, vaccination, and holistic care approaches to mitigate the severity of COVID-19 in diabetic patients. Furthermore, it examines the psychological and socioeconomic impacts of the pandemic on this vulnerable population. As ongoing research continues to investigate the interaction between COVID-19 and diabetes, this review provides a comprehensive understanding of the challenges and future directions in managing diabetic patients during and after the pandemic. Keywords: COVID-19, Diabetes, Hyperglycemia, Complications, Management Challenges, Diabetic Patients