Persistent Hyperglycemia Research Articles

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.

Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.

Flavonoid-Rich Trianthema decandra Ameliorates Cognitive Dysfunction in the Hyperglycemic Rats.

The present study was aimed at the evaluation of neuroprotective ability of methanolic extract of Trianthema decandra (METD) against hyperglycemia-related cognitive impairment in rats. The extract of T. decandra was standardized by TLC and HPTLC methods. To verify the identity and purity of isolated compounds, they were segregated and characterized using various techniques, including UV-visible spectrophotometry, FT-IR, H-NMR, and Mass spectroscopy. α-Amylase and α-glucosidase inhibition property of the extracts were assessed in-vitro. The screening of the neuroprotective effects of METD in hyperglycemic rats was done utilizing Morri's water (MWM) and elevated plus maze (EPM) model, as well as acetylcholinesterase (AChE) activity. The extracts of Trianthema decandra and its chemical constituents, namely quercetin and phytol, demonstrated a significant protective effect on enzymes like α-amylase and α-glucosidase. Methanol and hydroalcoholic extracts have shown the strongest inhibitory activity followed by chloroform extract. Quercetin and phytol were associated with the methanolic and chloroform extracts which were identified using TLC and HPTLC techniques. During the thirty days of the study, the induction of diabetes in the rats exhibited persistent hyperglycemia, hyperlipidemia, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Regimen of METD (200 and 400 mg/kg) in the diabetic rats reduced the glucose levels in blood, lipid, and liver profile and showed positive results on Morri's water and elevated plus maze tasks. During the investigation, it was determined that Trianthema decandra extracts and the chemical constituent's quercetin and phytol in it had anti-diabetic and neuroprotective activities.

Important aspects of carbohydrate metabolism disorders development in hematology/oncology patients during therapy with glucocorticosteroids: a review of the literature

Glucocorticosteroids are highly effective anti-inflammatory and immunosuppressive agents. The drugs were introduced into therapeutic practice from the mid-20th century and are still widely used in the treatment of various diseases. They are an integral part of the treatment of patients with hematological malignancies. One of the clinically significant complications of glucocorticosteroid therapy is steroid-induced carbohydrate metabolism disorders. Diabetes mellitus is one of the main risk factors for the development of cardiovascular diseases, which are the main non-oncological cause of death in the population and a significant treatment complication in patients with malignant neoplasms. Early detection of the disease and improved treatment efficiency increase the survival rate of patients with various types of neoplasms. It is also important to pay attention to quality of life improving in cancer patients after treatment.The aim of this review is to analyze the pathogenesis features, as well as predictors of early detection and prevention of possible complications of persistent hyperglycemia in patients with hematological malignancies.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.

Anti-Inflammatory Phytochemicals for the Treatment of Diabetic Nephropathy

Background: Diabetes is a metabolic disease characterized by hyperglycemia. Persistent hyperglycemia can cause Diabetic nephropathy (DN). It is a major microvascular complication that leads to chronic kidney disease (CKD) that progressively develops into end-stage renal disease (ESRD). It is the most debilitating condition that affects 15-25% of patients with type I diabetes and approximately 30-40% with type II diabetes worldwide. Purpose: In this review, we aim at various inflammatory mediators and different inflammatory path-ways involved in the progression of DN with special emphasis on phytoconstituents which gives pro-tection against DN by acting on these mediators and pathways. Methods: The literature was searched for the key words: inflammation, anti-inflamatory, phytoconsti-tutents/ phytochemicals, diabetic nephropathy, clinical and preclinical studies. Results: The various epidemiological, preclinical, and clinical evidence showed a close relationship between inflammatory response and progression of DN, as such, there is no effective treatment for DN, therefore, there is an unmet need for novel therapeutic approaches to treat them. From ancient times, phytochemicals, also known as phytonutrients, are the bioactive nutrients found in plants and foods, which have proven potentially useful for human well-being. Phytochemicals have demonstrat-ed a promising therapeutic role in nephropathy, principally through the regulation of oxidative stress and inflammation.

Efficacy of Integrated Ayurveda Treatment in Type 2 Diabetes mellitus with special reference to Prameha: A Randomised controlled Trial

Background: Diabetes mellitus (DM) is marked by persistent hyperglycemia, often due to insulin resistance. Type 2 diabetes mellitus (T2DM) constitutes 90% of cases and shares similarities with Prameha, a disorder characterized by frequent urination. Aims and objectives: This study aimed to compare Integrated Ayurveda Treatment (IAT) with standard diabetic treatment for Prameha. Materials and methods: A randomized, controlled open-label trial involved 200 T2DM subjects with HbA1C above 7%, taking metformin (≥1g /day). They were assigned to Standard Dietary Treatment (SDT) or IAT. SDT comprised metformin, dietary, and lifestyle modifications, while IAT included metformin with Ayurvedic medicine, specific Ayurveda diet, and yoga. Observation and result: Observations favoured Ayurveda treatment over standard diabetes treatment for most Prameha preliminary symptoms (purvarupa). Regarding Prameha rupa (symptoms), IAT significantly outperformed than SDT. Also, Ayurveda treatment group, led to improvements in HbA1C, fasting and postprandial blood sugar, and insulin resistance parameters compared to standard treatment group. Conclusion: Integrating Madhumeha ghana vati, ayurveda diet, and yoga with standard treatment yielded positive subjective and objective outcomes for Prameha, without significant adverse events. This suggests the potential benefits of combining Ayurvedic approaches with conventional care in managing prameha.

Avian Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with Ara as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16). Diagnosis of DM was based on the presence of clinical signs and persistent hyperglycemia 100% (16/16), often with glucosuria 93% (13/14), response to insulin therapy 80% (8/10), and pancreatic pathology 90% (9/10). Specific treatment for DM was initiated in 14 patients, but blood glucose regulation for 6 months or longer was only achieved in 6 birds. Five of the regulated birds were managed with injectable long-acting insulin and 1 with oral glipizide combined with dietary modifications. However, glipizide yielded poor results in other cases, likely attributable to a lack of functional beta cells. Three diabetic birds progressed to remission. Treatment proved unsuccessful for 7 patients with a mean survival time of 36 days from diagnosis. One patient was lost to follow-up, and 2 were euthanized immediately following diagnosis. Histological examination of the pancreas frequently (90%, 9/10) revealed abnormalities including atrophy, fibrosis, and vacuolization of the endocrine islets with or without lymphoplasmacytic pancreatitis. Comorbidities, including hemosiderosis and infection, were common. This review suggests that birds diagnosed with DM are primarily affected by a type I diabetes as observed in dogs and humans. In contrast to mammalian species, avian DM is often associated with underlying disease and a complete clinical workup is essential to diagnose and address secondary disease conditions prior to initiating long-term insulin therapy.

Uncommon dermatologic manifestation (paronychia) in a cat with diabetes mellitus

A 3.5-year-old male intact domestic short hair cat presented for a chronic wound and crusts over the claw and claw folds over several months. The cat was diagnosed with diabetes mellitus based on the presence of persistent hyperglycemia, glucosuria, and compatible clinical signs which consist of polyuria, polydipsia, polyphagia, and weight loss. Glipizide (Glucotrol XL, Pfizer, Indonesia) 2.5 mg orally twice daily was prescribed. By the seventeenth day, the patient's claws and skin around the paw had normalized and the abnormal claw sloughed off, revealing a normal claw underneath. Blood glucose, urinalysis and serum fructosamine were also normalized by the thirtieth day. The patient underwent diabetic remission, and the skin and claw lesions have remained in remission and not recurred since the treatment of the diabetes mellitus. This is the first report of a diabetic cat with dermatologic changes to the skin and claw regions. As the diabetes mellitus went into clinical remission, so too did the dermatologic manifestations, even without any specific dermatologic treatment.

Relationship between the Duration of Suffering from Diabetes and HbA1c Levels with the Degree of Liver Stiffness in Type 2 Diabetes Mellitus Patients

BACKGROUND : Type 2 diabetes mellitus (DM) is one of the major problems faced by the health system. Diabetes is a multifactorial, chronic and progressive metabolic disorder characterized by chronic hyperglycemia. Persistent hyperglycemia is associated with long-term damage to the liver. Ultrasound elastography is one of imaging modality that can assess liver stiffness, thus can assist clinicians in determining therapy, evaluating, and predicting disease progression. AIMS : Aim of this study was to determine the relationship between liver stiffness degree by using ultrasound elastography with the duration of T2DM and HbA1c levels. METHOD : This study was an observational analytic research with a cross-sectional approach which carried out from May to September 2022 at the radiology department of Dr. Kariadi Hospital Semarang. Fifty subjects were included in this study and Rank-Spearman correlation test was used to analyze the relationship between liver stiffness degree with T2DM duration and HbA1c levels. RESULT : Using ultrasonography elastography, the liver stiffness average was 7.92 + 6.72 kPa. The average of HbA1c levels was 8.55 + 2.63%. T2DM duration average was 9.10 + 6.50 years. The rank-spearman test showed a significant correlation between HbA1c levels and the degree of liver stiffness (p = 0.000) with a correlation coefficient (r) of 0.68. There was no significant correlation between the T2DM duration and the degree of liver stiffness (p = 0.052). CONCLUSION : There was a significant correlation between liver stiffness and HbA1c levels, but there is no correlation between liver stiffness and T2DM duration

Unveiling Anti-Diabetic Potential of Baicalin and Baicalein from Baikal Skullcap: LC-MS, In Silico, and In Vitro Studies.

Type 2 diabetes mellitus (T2DM) is marked by persistent hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction, imposing substantial health burdens and elevating the risk of systemic complications and cardiovascular diseases. While the pathogenesis of diabetes remains elusive, a cyclical relationship between insulin resistance and inflammation is acknowledged, wherein inflammation exacerbates insulin resistance, perpetuating a deleterious cycle. Consequently, anti-inflammatory interventions offer a therapeutic avenue for T2DM management. In this study, a herb called Baikal skullcap, renowned for its repertoire of bioactive compounds with anti-inflammatory potential, is posited as a promising source for novel T2DM therapeutic strategies. Our study probed the anti-diabetic properties of compounds from Baikal skullcap via network pharmacology, molecular docking, and cellular assays, concentrating on their dual modulatory effects on diabetes through Protein Tyrosine Phosphatase 1B (PTP1B) enzyme inhibition and anti-inflammatory actions. We identified the major compounds in Baikal skullcap using liquid chromatography-mass spectrometry (LC-MS), highlighting six flavonoids, including the well-studied baicalein, as potent inhibitors of PTP1B. Furthermore, cellular experiments revealed that baicalin and baicalein exhibited enhanced anti-inflammatory responses compared to the active constituents of licorice, a known anti-inflammatory agent in TCM. Our findings confirmed that baicalin and baicalein mitigate diabetes via two distinct pathways: PTP1B inhibition and anti-inflammatory effects. Additionally, we have identified six flavonoid molecules with substantial potential for drug development, thereby augmenting the T2DM pharmacotherapeutic arsenal and promoting the integration of herb-derived treatments into modern pharmacology.

Effects of Ethanolic Extract of Cyperus esculentus (Tiger Nut) Tubers on Blood Glucose Level and Lipid Profile in Alloxan-Induced Diabetes Mellitus in Male Wistar Rats

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. The prevalence of Diabetes mellitus is expected to increase to 5.3% by 2030. This study aimed to determine the effects of ethanolic extract of Cyperus esculentus tubers on alloxan-induced diabetes mellitus and lipid profile in male Wistar rats. A total of 25 Wistar rats were used for the study. Diabetes was induced by injection of alloxan 100 mg/kg and rats with blood glucose levels 200 mg/kg and above were considered diabetic. The rats were randomly divided into five groups (n = 5), group 1, normal control, group II, negative (diabetic) control, and Group III and Group IV were diabetic rats treated with 400mg/Kg and 800mg/Kg body weight of the ethanolic extract of Cyperus esculentus tubers and group V were diabetic rats treated with 10mg/Kg body weight Metformin. All treatments lasted for 28 days and Blood glucose levels were checked at weeks 0, 1, 2, 3, and 4 respectively. At the end of the treatment period, the rats were sacrificed and the blood samples collected were used to determine serum insulin level and lipid profile. The result obtained revealed a statistically significant (P&lt;0.05) decrease in blood glucose levels in groups III, IV, IV, and V as compared to the diabetic untreated group. The results of serum total cholesterol revealed a significant decrease in group I and group IV. However, high-density lipoprotein shows a significant decrease in group V as compared to the diabetic untreated group. There was also a statistically significant decrease (P&lt;0.05) in low-density lipoprotein (LDL) levels in groups I, III, and IV when compared with the diabetic untreated group. There was also a statistically significant (p &lt; 0.05) increase in serum insulin level in the normal control group and the group treated with 800mg/kg of extract. This study revealed the potential benefits of the ethanolic extract of Cyperus esculentus tubers in reducing blood glucose levels and its effects in reversing hyperlipidemia associated with diabetes mellitus.

Global and regional estimates of tuberculosis burden attributed to high fasting plasma glucose from 1990 to 2019: emphasis on earlier glycemic control

BackgroundPrevious studies have shown subjects suffering from diabetes or persistent hyperglycemia were more likely to develop tuberculosis (TB). However, the global burden of TB attributed to high fasting plasma glucose (HFPG) remains unclear. This study aimed to characterize the global, regional, and national TB burden attributed to HFPG from 1990 to 2019.MethodsWith Global Burden of Disease study 2019, the numbers and age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALY) rates (ASDR) of TB attributed to HFPG at global, regional, and national levels from 1990 to 2019 were extracted. The locally weighted regression model was applied to estimate the TB burden for different socio-demographic index (SDI) regions.ResultsGlobally, the ASMR and ASDR attributed to HFPG were 2.70 (95% UI, 1.64–3.94) and 79.70 (95% UI, 50.26–112.51) per 100,000 population in 1990, respectively. These rates decreased to 1.46 (95% UI, 0.91–2.08) and 45.53 (95% UI, 29.06–62.29) in 2019. The TB burden attributed to HFPG remained high in low SDI and Central Sub-Saharan Africa regions, while it declined with most significantly in high SDI and East Asia regions. Additionally, the ASMR and ASDR of TB attributed to HFPG were significantly higher in the male and the elderly population.ConclusionsThe global TB burden attributable to HFPG decreased from 1990 to 2019, but remained high in low SDI regions among high-risk populations. Thus, urgent efforts are required to enhance the awareness of early glycemic control and TB treatment to alleviate the severe situation.

Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway.

Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.

Postoperative Outcomes After Emergency Surgery in COVID-19 Patients: An Ambispective Matched Cohort Study.

Purpose There is limited data from the Indian subcontinent regarding the surgical outcomes of coronavirus disease (COVID-19) patients. In this observational study, we aimed to evaluate the postoperative outcomesafter emergency surgery in COVID-19 patients compared to concurrent age and gender-matched controls. We also sought to analyze the possible predictors of postoperative mortality in COVID-19 patients. Methods This matched cohort study was conductedin a tertiary care teaching hospital in central India, between 1st July 2021 and 30th June 2022. COVID-19-positive patients undergoing emergency surgery under anesthesia were recruited as cases. Age and gender-matched COVID-19-negative patients undergoing a similar nature of surgery in the same period served as concurrent controls. The cases and controls were compared for the 30-day mortality and perioperative complications. Results The COVID-19-positive surgical cohort had a 12.3 times greater 30-day postoperative overall mortality risk as compared to a matched cohort of patients with a negative COVID-19 test. A positive COVID-19 status was associated with more postoperative complications of acute respiratory distress syndrome (ARDS), sepsis, shock, and persistent hyperglycemia. On analysis of predictors of mortality, the presence of preoperative dyspnea, ARDS, American Society of Anesthesiologists Physical Status (ASA-PS) Class IIIE/IVE, increase in sequential organ failure assessment (SOFA) score, Quick SOFA>1, higher creatinine, bilirubin, and lower albumin were observed to be associated with increased mortality. Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients undergoing emergency surgery is significantly associated with higher postoperative complications and increased 30-day postoperative mortality.

Time-frequency analysis reveals an association between the specific nuclear magnetic resonance (NMR) signal properties of serum samples and arteriosclerotic lesion progression in a diabetes mouse model.

Diabetes causes arteriosclerosis, primarily due to persistent hyperglycemia, subsequently leading to various cardiovascular events. No method has been established for directly detecting and evaluating arteriosclerotic lesions from blood samples of diabetic patients, as the mechanism of arteriosclerotic lesion formation, which involves complex molecular biological processes, has not been elucidated. "NMR modal analysis" is a technology that enables visualization of specific nuclear magnetic resonance (NMR) signal properties of blood samples. We hypothesized that this technique could be used to identify changes in blood status associated with the progression of arteriosclerotic lesions in the context of diabetes. The study aimed to assess the possibility of early detection and evaluation of arteriosclerotic lesions by NMR modal analysis of serum samples from diabetes model mice. Diabetes model mice (BKS.Cg db/db) were bred in a clean room and fed a normal diet. Blood samples were collected and centrifuged. Carotid arteries were collected for histological examination by hematoxylin and eosin staining on weeks 10, 14, 18, 22, and 26. The serum was separated and subjected to NMR modal analysis and biochemical examination. Mice typically show hyperglycemia at an early stage (8 weeks old), and pathological findings of a previous study showed that more than half of mice had atheromatous plaques at 18 weeks old, and severe arteriosclerotic lesions were observed in almost all mice after 22 weeks. Partial least squares regression analysis was performed, which showed that the mice were clearly classified into two groups with positive and negative score values within 18 weeks of age. The findings of this study revealed that NMR modal properties of serum are associated with arteriosclerotic lesions. Thus, it may be worth exploring the possibility that the risk of cardiovascular events in diabetic patients could be assessed using serum samples.

Long-Term Persistence of COVID-Induced Hyperglycemia: A Cohort Study.

Although the short-term mortality of patients with COVID-19 infection and hyperglycemia has been well documented, there is little available data regarding longer-term prognosis. The presence of diabetes has not only influenced disease severity but has also impacted its transmission dynamics. In this study, we followed a historical cohort of patients without previous history of diabetes who presented with moderate to severe COVID-19 and were found to have hyperglycemia (random blood glucose >140 mg/dL) at the time of admission. We evaluated the need for antidiabetic therapy in these patients at the end of 6 months and the risk factors associated with persistent hyperglycemia determined by monthly values of self-monitored blood glucose. Of the seventy participants who were followed telephonically, 54 (77%) continued to receive antidiabetic therapy or have persistent hyperglycemia (>140 mg/dL) at the end of 6 months. Persistent hyperglycemia at the end of follow-up, was found to be associated with a higher blood glucose at presentation.

Effects of Diabetes and Hyperlipidemia in Physiological Conditions - A Review.

Diabetes mellitus (DM) is an autoimmune manifestation defined by persistent hyperglycemia and alterations in protein, fatty substances, and carbohydrate metabolism as an effect of problems with the secretion of insulin action or both. Manifestations include thirst, blurred eyesight, weight loss, and ketoacidosis, which can majorly lead to coma. There are different types of diabetes according to class or by cellular level. They are interrelated with hyperlipidemia as they are involved in the metabolism and regulation of physiological factors. Most parameters are seen at cellular or humoral levels, yet the underlying concern remains the same. To create a systematic correlation between the disease and locate the exact mechanism and receptors responsible for it. So, this article covers a proper way to resolve the conditions and their manifestation through literacy and diagrammatic. Hence, this will be an insight for many scholars to understand the exact mechanism involved in the process.

Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.

Hyperglycemia is a risk factor for the development of insulin resistance, beta-cell glucotoxicity, and vascular complications of diabetes. We propose the hypothesis, hexokinase-linked glycolytic overload and unscheduled glycolysis, in explanation. Hexokinases (HKs) catalyze the first step of glucose metabolism. Increased flux of glucose metabolism through glycolysis gated by HKs, when occurring without concomitant increased activity of glycolytic enzymes-unscheduled glycolysis-produces increased levels of glycolytic intermediates with overspill into effector pathways of cell dysfunction and pathogenesis. HK1 is saturated with glucose in euglycemia and, where it is the major HK, provides for basal glycolytic flux without glycolytic overload. HK2 has similar saturation characteristics, except that, in persistent hyperglycemia, it is stabilized to proteolysis by high intracellular glucose concentration, increasing HK activity and initiating glycolytic overload and unscheduled glycolysis. This drives the development of vascular complications of diabetes. Similar HK2-linked unscheduled glycolysis in skeletal muscle and adipose tissue in impaired fasting glucose drives the development of peripheral insulin resistance. Glucokinase (GCK or HK4)-linked glycolytic overload and unscheduled glycolysis occurs in persistent hyperglycemia in hepatocytes and beta-cells, contributing to hepatic insulin resistance and beta-cell glucotoxicity, leading to the development of type 2 diabetes. Downstream effector pathways of HK-linked unscheduled glycolysis are mitochondrial dysfunction and increased reactive oxygen species (ROS) formation; activation of hexosamine, protein kinase c, and dicarbonyl stress pathways; and increased Mlx/Mondo A signaling. Mitochondrial dysfunction and increased ROS was proposed as the initiator of metabolic dysfunction in hyperglycemia, but it is rather one of the multiple downstream effector pathways. Correction of HK2 dysregulation is proposed as a novel therapeutic target. Pharmacotherapy addressing it corrected insulin resistance in overweight and obese subjects in clinical trial. Overall, the damaging effects of hyperglycemia are a consequence of HK-gated increased flux of glucose metabolism without increased glycolytic enzyme activities to accommodate it.

O-03 Adrenalectomy for Cushing's syndrome during pregnancy

Abstract Introduction Cushing's syndrome (CS) is rare in pregnancy because CS itself is a cause of anovulatory infertility due to excess cortisol secretion. Moreover it is also difficult to diagnose CS in pregnancy because placental production of corticotropin releasing and adrenocorticotropic hormone (ACTH), increased maternal production of estrogen induced corticosteroid binding globulin leads to physiological hypercortisolism during pregnancy. So physicians face a clinical overlap in many features of CS such as weight gain, fatigue, edema, hypertension, hyperglycemia, stretch marks, mood changes that can also be attributed to pregnancy. Thus their coexistence represents a diagnostic challenge. Herein we report a case of CS that was diagnosed and successfully treated during pregnancy. Clinical Case A 43-year-old gravida 3 female was consulted at the 21st week of gestation with persistent high blood pressure and hyperglycemia for a month. She had an obstetric history of 2 spontaneous first term abortion, 2 healthy labor 18 years ago and she was healthy after. She was in such a depressive mood that she was consulted with psychiatry many times. On physical examination edema, proximal weakness of lower extremities and hirsutism (modified Ferriman–Gallwey score of 9) was detected. Initial laboratory tests were all within normal range except potassium level (2.7 mmol/L), the results were not consistent with preeclampsia and there was a suspicious adrenal mass detected on ultrasound. She was currently receiving high dose antihypertensive treatment with methyldopa, calcium channel blockers, rapid acting and detemir insulin for diabetes and i.v. potassium replacement. We ruled out conns syndrome with normal plasma aldosterone renin ratio and found catecholamine levels normal. Hormonal analyses revealed with high plasma cortisol levels, increased nocturnal cortisolemia, a suppressed plasma ACTH and dehydroepiandrosterone sulfate level and distinctly elevated 24-hour urinary cortisol greater than 3-fold the upper normal reference range. Non contrast magnetic resonance imaging demonstrated a 47×32 mm left adrenal mass. Laparoscopic adrenalectomy was performed in the 26th week of gestation and the following histopathology revealed an adrenocortical adenoma. Antihypertensive medication was progressively reduced, glycemic control and hypokalemia reversal were achieved. She was followed up with appropriate glucocorticoid replacement. At 34 weeks of gestation, after sudden labor pain and regular uterine contractions a 2586 g male infant with Apgar scores of 8 was born by cesarean section. They were discharged in good health. Conclusion CS should be kept in mind especially in the case of hypertension and diabetes that started before the 20th gestational age. Analysis of the urinary free cortisol level and circadian rhythm of cortisol is necessary to diagnose. Despite the diagnostic challenge we can achieve better maternal and fetal outcomes with proper management.Figure 1.Non-contrast magnetic resonance imaging of the patient Table 1.Patient's laboratuary test results Table 2.Patient's laboratory test results