Moderate Hyperglycemia Research Articles

Study of Na+/K+-ATPase and Components of the Ca2+-transporting System in Myocardium under Experimental Prediabetes and Type 1 Diabetes in Rats

One of the complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM), the molecular mechanisms of pathogenesis of which have not been fully studied. Previously, the involvement of Na+/K+-ATPase and components of the Ca2+ transport system in cardiomyocytes in the development of DCM was shown. The aim of the work was to study the expression and activity of Na+/K+-ATPase and Ca2+-ATPase (SERCA2) in the myocardium of male Wistar rats in a model of streptozotocin (STZ)-induced prediabetes and overt type 1 diabetes (T1DM). STZ was administered at once i. p. in dose of 30–35 mg/kg. Rats with glucose levels above 11 mM were considered diabetic (STZ-D1 group), and those with moderate hyperglycemia were considered prediabetic (STZ-preD1 group). The activity of Na+/K+-ATPase and Ca2+-ATPase was determined (by the rate of release of inorganic phosphate, Pi), and the expression of the genes α1- and α2-isoforms of Na+/K+-ATPase, SERCA2 and Kir6.1, Kv7.1 and Kv2.1 potassium channels. In the control (C) group, the activity of Mg2+-dependent ATPase (α1- and α2-isoforms of Na+/K+-ATPase), sensitive to 1 mM ouabain, was 6.03±0.6 mmol Pi/g/h. In the STZ-D1 and STZ-preD1 groups, Na+/K+-ATPase activity did not differ from group C. The level of gene expression of α1- and α2- subunits of Na+/K+-ATPase in the STZ-D1 group decreased by more than 45%, then both in the STZ-preD1 group increased by 64 and 81%, which may indicate a high sensitivity of expression to insulinopenia. The activity of Ca2+-ATPase and the expression of the SERCA2 gene did not differ between the groups – probably, the 4-week period after STZ administration is not sufficient for the development of Ca2+-ATPase deficiency in the rat heart. The level of expression of the genes of the potassium channel subtypes Kv2.1, Kir6.1 and Kv7.1 increased in the STZ-preD1 group, which may indicate a certain contribution of the studied potassium channel subtypes to the adaptation mechanism to moderate hyperglycemia.

Impact and outcomes of hyperglycemia among post-operative children who underwent repair of congenital cardiac defects in a tertiary care setup of Pakistan

Objective: To determine frequency of postoperative hyperglycemia in children who underwent repair of Congenital Cardiac Defects (CCDs) in a tertiary care hospital of Pakistan. The other objective was to compare outcomes in children with versus without postoperative hyperglycemia who underwent repair of CCDs in a tertiary care hospital of Pakistan. Methods: A descriptive study was conducted at the Cardiac Intensive Care Unit (CICU), Aga Khan University Hospital (AKUH), Karachi, Pakistan from October 3, 2020, to April 2, 2021. A total of 185 patients aged one month-18 years admitted to CICU underwent elective surgical repair of CCDs meeting the eligibility criteria were included. Glucose monitoring was collected at immediate, 4th and 8th postoperative hours on the first day and once daily on postoperative days Two and Three to assess hyperglycemia. Data including age, weight, gender, pre-operative diagnosis, type of surgery and variables such as CICU stay, duration of hospital stay and duration of mechanical ventilation were recorded. Results: The mean age of the patients was 40.40±48.63 months. Out of 185 patients, 115 (62.2%) were male while 70 (37.8%) were female. Hyperglycemia was found to be in 182 (98.4%) patients. Out of 182 hyperglycemic patients, 53 (28.6%) had moderate hyperglycemia while 129 (69.7%) had severe hyperglycemia. Mean duration of hospital stays was 9.24±7.45, mean duration of pediatric CICU stays was 141.61±169.02 hours and mean duration of mechanical ventilation was 80.59±98.54 hours. Conclusion: Hyperglycemia is a frequent finding in children who underwent repair of CCDs, and it is not significantly associated with duration of mechanical ventilation, length of hospital and CICU stay. doi: https://doi.org/10.12669/pjms.40.10.8763 How to cite this: Aslam Y, Ayaz Ur Rehman, Zehra T, Noor Ul Ain. Impact and outcomes of hyperglycemia among post-operative children who underwent repair of congenital cardiac defects in a tertiary care setup of Pakistan. Pak J Med Sci. 2024;40(10):2277-2280. doi: https://doi.org/10.12669/pjms.40.10.8763 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Diabetes mellitus and female sexual response: what do animal models tell us?

One of the less explored effects of diabetes mellitus (DM) is female sexual dysfunction. Females of different species have been used as models. To analyze the information of animal models of DM and female sexual response (FSR). The literature of FSR in models of DM was reviewed. Paradigm- and diabetes-dependent changes have been found in various aspects of the FSR. Females in a type 1 DM (DM1) model show a decrease in the number of proestrus events, and ovariectomized females treated with sex hormones have been used. In these females, a reduction in lordosis has been reported; in proceptivity, the data are contradictory. These females present a decrease in sexual motivation that was restored after exogenous insulin. In the type 2 DM (DM2) model, females show regular estrous cycles, normal levels of lordosis behavior, and, depending on the paradigm, decreased proceptivity. These females display normal preference for sexually active males or their olfactory cues when having free physical contact; they lose this preference when tested in paradigms where physical interaction is precluded. Preclinical data showing the high deleterious effects of a DM1 model and the less drastic effects under a DM2 model are in accordance with clinical data revealing a much higher prevalence of sexual dysfunction in women with DM1 than DM2. The main strength is the analysis of the changes in various components of FSR in 2 models of DM. The main limitation is the difficulty in extrapolating the data on FSR from rats to women and that most studies focus on evaluating the impact of severe or chronic-moderate hyperglycemia/hyperinsulinemia on the sexual response, without considering other pathophysiologic alterations generated by DM. Females with severe hyperglycemia have a decrease in FSR, while those with moderate hyperglycemia show much less drastic effects.

β-cell function and long-term glycemic control in patients newly diagnosed with type 2 diabetes with moderate hyperglycemia after a 6-month course of basal insulin therapy

AimsTo evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia. MethodsPatients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the β-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months. ResultsWe randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was − 2.06 ± 1.37 %, −0.43 ± 0.32 %, and − 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy. ConclusionA 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Empagliflozin (EMPA) showed antiapoptotic, oxidative and anti-inflammatory potential effect. EMPA attenuates the inflammation and oxidative stress biomarkers in patients with heart failure while significantly decreases the malondialdehyde (a lipid peroxidation marker) levels in the plasma of diabetic patients. The present study examined the effects of moderate hyperglycemia on reproductive function. Sixty male Wister rats ‎ were divided and randomly allocated into four groups of 15 animals each‎‎. Diabetes was induced by a single intraperitoneal injection of a prepared solution containing STZ diluted in 0.1 M sodium citrate buffer (pH 4.5) at a dosage of 40 mg/kg body weight in selected in groups II and III for seven days before starting the treatment with EMPA. The current study revealed that EMPA for eight weeks prevented testicular high glucose-induced oxidative stress markers such as penile nitric oxide (NO), glutathione peroxidase (GPX) and total anti-oxidant capacity (TAC) in STZ-induced hyperglycemia in a rat model. In addition, EMPA ameliorated the high levels of endogenous Interleukin-6 (IL-6) present in gonads in response to an acute inflammatory found in the hyperglycemic STZ-induced rats. The present study further suggested the protective effects of EMPA and how it has a beneficial role and can effectively attenuate hyperglycemia-induced testicular oxidative damage and inflammatory markers as well as androgen dependent testicular enzymes activity as a protective role against the consequences of hyperglycemia and male sub-infertility.

Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.

Mutations in the GCK gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a GCK mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses. Modulating maternal glycemia can thus be viewed as a form of personalized prenatal therapy, highly beneficial but not justifying the risk of invasive testing. We therefore developed a monogenic non-invasive prenatal diagnostic (NIPD-M) test to reliably detect the transmission of a known maternal GCK mutation to the fetus. A small amount of fetal circulating cell-free DNA is present in maternal plasma but cannot be distinguished from maternal cell-free DNA. Determining transmission of a maternal mutation to the fetus thus implies sequencing adjacent polymorphisms to determine the balance of maternal haplotypes, the transmitted haplotype being over-represented in maternal plasma. Here we present a series of such tests in which fetal genotype was successfully determined and show that it can be used to guide therapeutic decisions during pregnancy and improve the outcome for the offspring. We discuss several potential hurdles inherent to the technique, and strategies to overcome these. Our NIPD-M test allows reliable determination of the presence of a maternal GCK mutation in the fetus, thereby allowing personalized in utero therapy by modulating maternal glycemia, without incurring the risk of miscarriage inherent to invasive testing.

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.

Non-Insulin Antidiabetic Agents in the Management of Hyperglycaemia of Non-Critical Hospitalized Patients

Hyperglycaemia affects more than 30% of adults hospitalized for non-critical illness and is associated with an increased risk of adverse clinical outcomes. Insulin therapy is widely used for its safety and efficacy. However, given the growing availability of new drugs and new classes of antidiabetic agents with benefits beyond glycaemic control, challenges arise regarding their use in the hospital setting. This article aims to review and summarize the most recently available evidence and recommendations on the role of non-insulin antidiabetic agents in the management of hyperglycaemia in hospitalized patients. Insulin therapy remains the method of choice. Dipeptidyl peptidase 4 inhibitors can be considered in mild to moderate hyperglycaemia. Glucagon-like peptide 1 receptor agonists have recently shown promising results, with high efficacy in glycaemic control and low risk of hypoglycaemia. There are concerns regarding the increased risk of acidosis with metformin use, especially in cases of acute illness, although there is no evidence to support its suspension in selected patients with relative clinical stability. Sodium-glucose cotransporter-2 inhibitors should be discontinued in clinical situations that may predispose to ketoacidosis, including episodes of acute illness. The hospital use of sulfonylureas and thiazolidinediones is not advised.

Development of a requirement for exogenous insulin treatment in dogs with hyperglycemia.

It has been suggested that overt diabetes mellitus in dogs be defined based on a persistent fasting blood glucose concentration (BGC) >144 mg/dL. Determine the number of dogs with randomly identified hyperglycemia without insulin-treated diabetes mellitus (ITDM) that later develop a need for exogenous insulin treatment. A total of 1318 dogs examined at a university teaching hospital without ITDM and with randomly identified hyperglycemia. Retrospective longitudinal study. Hyperglycemia was defined as randomly identified BGC above >112 mg/dL, moderate hyperglycemia as BGC >144 mg/dL but <200 mg/dL and pronounced hyperglycemia as BGC ≥200 mg/dL. Dogs were defined as having ITDM if they were treated with insulin. Follow-up was attempted 7 to 12 years after hyperglycemia was documented to determine if over time dogs developed a need for exogenous insulin treatment. Twenty-nine of 824 dogs (3.5%) with hyperglycemia and follow-up information developed ITDM, including 3/824 dogs (0.4%) with moderate hyperglycemia, and 2/824 dogs (0.2%) with pronounced hyperglycemia. Most dogs with hyperglycemia that developed ITDM (24/29, 83%) had BGC ≤144 mg/dL. Among dogs that eventually developed a need for exogenous insulin treatment, no association was found between the degree of hyperglycemia and the time interval between documentation of hyperglycemia and diagnosis of ITDM. Logistic regression determined that BGC is not significantly associated with ITDM. Most dogs with randomly identified hyperglycemia did not develop a need for exogenous insulin treatment. Other criteria could be required to augment the definition of overt DM in non-insulin treated dogs.

Chemical analysis of freeze-dried seeds of Stenocereus stellatus (white tunillo) components and evaluation of their effect on prediabetes reversion in an experimental model in female Wistar rats.

Prediabetes is defined as a state of moderate hyperglycemia. Here, we used freeze-dried seeds of Stenocereus stellatus (white tunillo) as a possible therapeutic strategy for the treatment of prediabetes. In the aqueous extract of freeze-dried seeds of white tunillo, polyphenols were identified using the Folin-Ciocalteu technique, separated by UPLC and analyzed by infrared spectrophotometry. Five well-defined peaks with good resolution were observed in the chromatogram of the aqueous extract obtained by UPLC. Two of these peaks corresponded to polyphenols with similarity to quercetin and rutin. The subchronic oral administration of freeze-dried seeds of white tunillo for 14 days in a prediabetes model in female Wistar rats reversed hyperglycemia and glucose intolerance. Treatment with the freeze-dried seeds reversed the decrease in the hepatic expression of Akt, eNOS, and p-eNOSSer1177 but did not reverse the decrease in MnSOD, catalase, and GPx1. No changes in the expression of GPx4 and p-AktSer473 were observed in the pathological state or with the treatment but there was an increase in the expression and activity of eNOS. The bioactive compounds present in the freeze-dried seeds of Stenocereus stellatus could provide guidelines for studying the mechanisms of action through which they reverse signs of prediabetes.

DEPISTAGE DU DIABETE ET DES AUTRES FACTEURS DE RISQUE CARDIOVASCULAIRE DANS LA VILLE DE OUAHIGOUYA AU BURKINA FASO

introduction: Early detection of diabetes is essential to avoid complications and late treatment. In Burkina Faso, the northern region was the most affected by diabetes according to previous national surveys. Hence our initiative to do this work in order to determine the current prevalence of diabetes and to identify other cardiovascular risk factors in the city of Ouahigouya, capital of the Northern region. materials and methods: this was a cross-sectional study including volunteers aged 18 and over, received during a campaign to screen for diabetes and other cardiovascular risk factors in the town of Ouahigouya on the 24th and 25th. March 2022. results: A total of 630 participants were screened. The average age was 47.16 ± 14.36 years with a sex ratio of 0.81. Family history of diabetes and high blood pressure were found in 12.06% and 34.76% of cases respectively. The cardiovascular risk factors were smoking in 95 participants (15.08%), sedentary lifestyle in 59.52%, high blood pressure (31.11%), obesity (14.60%). We diagnosed diabetes mellitus in 48 participants (7.62%) and 2.70% cases of moderate fasting hyperglycemia. The average age of the diabetic subjects was 47.24 ± 12.2 years. Among diabetic subjects, 68.75% were sedentary and 58.33% hypertensive. Abdominal obesity, physical inactivity and high blood pressure were more common in diabetics with a significant difference for hypertension (p = 0.002). Conclusion: The prevalence of diabetes and other cardiovascular risk factors was high in our population. Raising awareness for early diagnosis and rapid treatment will reduce the risk of the occurrence of the dreaded complications.

Comprehensive Evaluation of the Clinical Efficacy of an Anti-Diabetic Polyherbal Formulation

Background: There are several clinical studies examining the health advantages of several single medicinal herbs utilized in traditional blood glucose-lowering treatments. But very few or no studies on herbal formulations were made as Polyherbal for the same goal. As a result, it is now necessary to confirm that patients with hyperglycemia can benefit from such Polyherbal medicines as Dolabi. Methods: This prospective open-label, herbal coded test drug-controlled, randomized trial was conducted at the Munshiganj and Dhaka area in Bangladesh. We enrolled 108 male and 104 female patients of 30-70 years with primary and moderate hyperglycemia. They were recruited from the OPD of an Unani &amp; Ayurvedic hospital in Munshiganj and different Unani clinics in Dhaka, Bangladesh after fulfilling the inclusion criteria. Patients were randomly assigned to receive metformin hydrochloride 500 mg two times daily and 2 tablets of Dolabi two times daily by using a random numbers table with the help of an assistant. Blood samples, height, weight, blood pressure, and personal data were recorded—laboratory results were obtained at the study baseline, after 1.5 months and after 3 months of intervention. Results: In the case of the test drug, results showed a significant decrease in blood glucose level between the baseline and after 3 months, in males, it was from 9.83±1.17 to 7.72±1.06 mg/dL for fasting glucose, from 16.60±2.35 to 8.23±1.17 mg/dL for 2 hours PP glucose, from 9.33±1.17 to 7.45±2.03 percent for HbA1c and for Insulin it reduces from 183.10±27.59 to 168.10±29.59 pmol/ L. The control drug metformin hydrochloride also showed a significant decrease in blood glucose level between baseline and after 3 months, in the case of males it was from 9.99±2.52 to 6.97±1.76 mg/dL for fasting glucose, from 17.43±5.05 to 7.89±2.42 mg/dL for 2 hours PP glucose, from 10.43±2.36 to 6.87±1.18 percent for HbA1c and for Insulin it reduces from 198.75±30.61 to 183.75±30.61p mol/L. In the case of females the test drug showed a significant reduction in fasting glucose, 2 hours PP glucose, HbA1c and Insulin between the baseline and after 3 months, it was from 10.02±1.11 to 7.78±0.93 mg/dL, from 16.88±2.21 to 8.16±1.11 mg/dL, from 9.84±1.04 to 7.45±1.03 percent and from 199.47±30.90 to 173.47±30.90 mg/dL respectively. In the case of females, the control drug showed a significant reduction in fasting glucose, 2 hours PP glucose, HbA1c and Insulin between baseline and after 3 months, it was from 10.18±1.92 to 6.71±1.59 mg/dL, from 18.70±3.88 to 7.60±3.74 mg/dL, from 10.58±1.08 to 6.98±1.08 percent and from 200.00±31.83 to 188.00±31.83 mg/dL respectively. Conclusions: We can infer the following from the present study’s findings: The polyherbal formulation Dolabi is able to reduce the blood glucose level. It can be an effective drug for primary hyperglycemic patients.

Diabetes Mellitus after COVID-19 Vaccination in a Patient with Impaired Glucose Metabolism: Case Report

SCIENTIFIC RELEVANCE. The clinical features of COVID-19 in patients with comorbidities, including diabetes mellitus (DM), have already been discussed in the medical literature. However, the available data on blood glucose levels in patients with DM during SARS-CoV-2 infection and after COVID-19 vaccination are clearly insufficient to estimate the importance of the changes taking place.AIM. The study aimed to show that patients with DM or impaired glucose metabolism need glycaemic monitoring during COVID-19 disease and after COVID-19 vaccination, drawing on the example of a clinical case.MATERIALS AND METHODS. The study analysed the medical records of a 58-year-old male patient newly diagnosed with DM. He received inpatient and outpatient treatment after COVID-19 vaccination and SARS-CoV-2 infection in February–November 2021. In 2014, the patient was diagnosed with impaired glucose metabolism, including fasting hyperglycaemia (≤ 9 mmol/L), which was corrected by diet.RESULTS. After vaccination with Gam-COVID-Vac component 1 in February 2021, the patient developed polydipsia, polyuria, and arterial hypertension. His laboratory findings were as follows: blood glucose, 25 mmol/L; glycated haemoglobin, 10.7%; fasting insulin, 28.4 μIU/mL; calcium, 2.45 mmol/L; and 25-hydroxyvitamin D, 21 ng/mL. The patient was diagnosed with new-onset type 2 DM, admitted to the endocrinology department of a multidisciplinary hospital, and discharged when his condition stabilised after 14 days of treatment. After vaccination with Gam-COVID-Vac component 2, the patient’s glucose levels did not change. In November 2021, the patient was diagnosed with SARS-CoV-2 infection. Even though all symptoms had resolved within 3 days, the virus persisted in the blood for 12 days without clinical manifestations of the disease. This was confirmed by repeated polymerase chain reaction testing. The patient had moderate hyperglycaemia despite antidiabetic treatment; his glucose levels were restored to normal without hospitalisation.CONCLUSIONS. Timely vaccination against COVID-19 in patients with DM, hypertension, and obesity contributes to a mild course of COVID-19 and helps avoid complications in the lungs and other organs. For patients with DM or glucose metabolism disorders, blood glucose monitoring is advisable for detecting and correcting possible hyperglycaemia after vaccination and/or recovery from COVID-19.

Biochemical Profile of People with Down syndrome: About 25 Cases

Down syndrome or trisomy 21 is a genetic disease resulting from an additional gain of chromosome 21. It predisposes to multiple pathologies including obesity, infections, diabetes, or hypothyroidism, responsible for various biological abnormalities. This work aimed to determine biochemical profile of congolese persons with Down syndrome, living in Brazzaville (Congo). The study was carried out on 25 persons with Down syndrome. They are cared for in four specialized centers for disabled children. The methodology was based on the determination of glycaemia, proteins and lipids by spectrophotometric and electrophoretic methods. Globally, normal values of total cholesterol, triglycerides, and glucose (except for one person who had moderate hyperglycaemia), were observed. We noted an hyperlipidemia associated with low levels of HDL, LDL, albumin, and alpha 1 globulin. In Conclusion: there is a disturbance in biochemical profile in subjects with Down syndrome, which predispose to diabetes, cardiovascular diseases and opportunistic infections.

Thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus patients in Ghana: A comparative cross-sectional study.

Thyroid disorders and diabetes mellitus coexist and are prevalent endocrinopathies among adult population. Thyroid dysfunction contributes to metabolic imbalances, increase beta-cell apoptosis and glucose intolerance. There is paucity of data and contradicting findings on how thyroid dysfunction influence glycaemic control. Therefore, we evaluated thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus (T2DM) patients in Ghana. A comparative cross-sectional study was conducted among 192 T2DM patients from Effia Nkwanta Regional Hospital. Three consecutive monthly fasting plasma glucose (FBG) and glycated haemoglobin (HbA1c) were analysed and the results were classified as, moderate hyperglycaemia (MH) (FBG = 6.1-12.0 mmol/L, HbA1c < 7%), severe hyperglycaemia (SH) (FBG ≥ 12.1 mmol/L, HbA1c > 7%) and good glycaemic controls (GC) (FBG = 4.1-6.0 mmol/L, HbA1c < 7%). Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), body mass index (BMI) and other clinical parameters were measured. Data analysis was done using R language version 4.0.2 and p < .05 was considered statistically significant. There were no significant differences in age (years) between patients in the various glycaemic groups (p = .9053). The overall prevalence of thyroid disorders was 7.8% among T2DM patients. The prevalence of thyroid disorders was higher in patients with SH (11.7%) followed by those with MH (7.5%) and then those with GC (5.4%). Serum levels of TSH and FT3/FT4 ratio were significantly lower in T2DM patients with SH compared to those with MH and the GC (p < .0001). However, FT4 was significantly higher in SH patients compared to the good glycaemic controls (p < .01). The first tertiles of TSH [aOR = 10.51, 95% CI (4.04-17.36), p < .0001] and FT3 [aOR = 2.77, 95% CI (1.11-6.92), p = .0290] were significantly and independently associated with increased odds of hyperglycaemia. The prevalence of thyroid dysfunction is high in T2DM and increases with hyperglycaemia. Reduced TSH and T3 may worsen glycaemic control. Periodic monitoring of thyroid function should be incorporated into management guidelines among T2DM patients in Ghana.

Adverse events associated with Pegaspargase biosimilar in pediatric patients with acute lymphoblastic leukemia: A prospective single-center study.

While Pegaspargase is an essential component of the treatment of acute lymphoid leukemia (ALL) in children, it causes adverse events (AEs) that sometimes make full use impossible. The objective was to investigate the safety of Pegaspargase biosimilar in pediatric ALL patients undergoing treatment according to ICiCLe ALL-14 protocol. A prospective study was carried out in a university teaching hospital located in the state of Maharashtra, India. Data on clinical factors and adverse reaction characteristics were gathered from hospital medical records. Suspected AEs were classified according to causality and severity. During the study period, 72 children had 52 suspicions of AEs during treatment with biosimilar Pegaspargase. The odds ratio of 1.11 (95%CI, 0.41-2.98) suggested that males and females were both equally likely to experience adverse drug events, despite the fact that the frequency of suspected AEs was higher in boys (66%) than in girls (33%). None of the patients experienced allergic reactions. The high-risk category had the highest number of suspected AEs (56%), followed by intermediate risk (20%) and standard risk (20%). These patients showed a high frequency of suspected AEs during the induction phase (43%) followed by the consolidation phase (26%). Sixty percent of the reactions were classified as grade 1 or 2. ALL cell type (p = 0.02), risk category (p = 0.04) and length of hospitalization (p = 0.003) were significantly correlated with suspected AEs. Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe.

Effect of Fenugreek Seeds and Its Bioactive Compounds on High Fructose High Fat Diet Induced Abnormalities in Sprague Dawley Rats

Fenugreek seeds are rich in various essential compounds and these components play a significant role in healing and treating diseases by regulating several biological activities. The purpose of this study was to evaluate the metabolic effects of fenugreek seed (FS) and its bioactive compounds such as Fenu pulse (FP), Fenu fiber (FF), Diosgenin (Dsg) in High Fructose High Fat (HFHF) induced diabetic rats.After hyperglycemia was confirmed in HFHF rats compared with controls, further HFHF groups were supplemented with FS, FP, FF, Dsg, and combinations of these compounds. The HFHF diet was given for 4 months which increased the body weight, body fat percentage, and decreased lean body mass (LBM) and fat-free mass (FFM) percentage compared with controls rats. The diet combination was continued for another four months and it did not show any further effect on their body composition. There was a significant but marginal effect on fasting glucose and insulin, so the animals did not have overt hyperglycemia, let alone be diabetic. The FS or its components individually or in combination within a diet-induced rat model of diabetes showed no significant antidiabetic effect (glucose tolerance/metabolic parameters), both in the fasting and fed states wherein it elevated the levels of total and HDL cholesterol but not triglycerides (TG) upon continuous feeding for four months. The reduced effect of FS and its components appears due to moderate hyperglycemia in the HFHF rats.

574-P: A Ketogenic Diet Improves Aerobic Capacity in Hyperglycemic Mice by Sex-Dependent Mechanisms

Hyperglycemia is associated with lower aerobic exercise capacity (VO2peak) in humans and rodent models. We tested whether reducing blood glucose levels with a dietary intervention can restore VO2peak in hyperglycemic mice. Male and female CD-1 mice were injected with low dose streptozotocin (STZ) to induce moderate hyperglycemia (&amp;gt;200 mg/dL). Hyperglycemic mice were randomized to receive a standard diet (STZ-CHOW) or a ketogenic diet (STZ-KETO). KETO significantly reduced blood glucose in STZ-treated mice. Next, both groups underwent similar volumes of exercise training by voluntary wheel running, or remained sedentary for 8 wks. In males, VO2peak during maximal exercise testing was similar in sedentary mice, regardless of diet. However, with training, VO2peak was significantly improved in STZ-KETO, but not STZ-CHOW males (see Figure). In females, KETO significantly increased VO2peak in sedentary mice, with no additional increase in response to training. Improved VO2peak with KETO in females was associated with a 50% increase in skeletal muscle mitochondrial ATP synthase protein. In contrast, ATP synthase was not regulated by diet in males. Our data demonstrate that a ketogenic diet can improve VO2peak in mice with hyperglycemia. In males, improved VO2peak with KETO was exercise-dependent, while in females, the beneficial effects of KETO on VO2peak and mitochondrial content were exercise-independent. Disclosure P.Pattamaprapanont: None. M.Formato: None. R.Nogueira soares: None. S.J.Lessard: None.

Stress-Induced (Not Diabetic) Hyperglycemia Is Associated With Mortality in Geriatric Trauma Patients

IntroductionStress-induced hyperglycemia (SIH) is associated with worse outcomes among trauma patients. It is also known that injured geriatric patients have higher mortality when compared to younger patients. We sought to investigate the association of all levels of SIH with mortality among geriatric trauma patients at a level 1 academic trauma center. We hypothesized that SIH in the geriatric trauma population would be associated with increased mortality. MethodsA retrospective review of all geriatric patients admitted to our level 1 trauma center over a 3-year period (January 2018-December 2020) was performed using the institutional trauma database. Data collected included demographics, injury severity score (ISS), emergency department (ED) blood glucose level, ED systolic blood pressure (SBP), and mortality. Patients were divided into 4 groups based on emergency room blood glucose level, as follows: normoglycemic (<120 mg/dL), mild hyperglycemia (120-150 mg/dL), moderate hyperglycemia (151-199 mg/dL), and severe hyperglycemia (≥200 mg/dL). Multivariable logistic regression analysis was performed to evaluate the association of SIH and in-hospital mortality adjusting for ISS, age, comorbidities, and ED SBP. ResultsA total of 4432 geriatric trauma patients were admitted during the study period, of which 3358 patients (75.8%) were not diabetic. There were 2206 females (65.7%), 2993 were White (89.2%), with a mean age of 81.5 y. There were 114 deaths (3.4%). Univariate results showed that there was a statistically significant association between mortality and glucose groups (P < 0.01). The number of deaths in the four glucose groups were, as follows: 30 (2.0%), 32 (3.8%), 20 (6.2%), and 10 (12.2%), respectively. Multivariable logistic regression analysis results showed that compared to the normoglycemic group, the risk of death was higher in the mild, moderate, and severe glucose groups, as follows: mild group (OR 1.80, 95% confidence interval [CI] 1.04-3.13, P 0.04), moderate group (OR 2.53, 95% CI 1.34-4.80, P < 0.01), and severe group (OR 5.04, 95% CI 2.18-11.67, P < 0.01). ConclusionsMild, moderate, and severe SIH are statistically significant predictors of death among geriatric trauma patients independently of ISS, age, comorbidities, and SBP.

Hyperglycemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model.

Hyperglycemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycemia that negatively impacts short- and long-term health of mother and child. However, relationships between severity and timing of pregnancy hyperglycemia and postpartum outcomes have not been systemically investigated. We investigated the impact of hyperglycemia developing during pregnancy (gestational diabetes mellitus, GDM) or already present pre-mating (pre-gestational diabetes mellitus, PDM) on maternal health and pregnancy outcomes. GDM and PDM were induced in C57BL/6NTac mice by combined 60% high fat diet (HF) and low dose streptozotocin (STZ). Animals were screened for PDM prior to mating, all underwent an OGTT on gestational day (GD)15. Tissues were collected at GD18 or at postnatal day (PN)15. Among HFSTZ-treated dams, 34% developed PDM and 66% developed GDM, characterized by impaired glucose-induced insulin release and inadequate suppression of endogenous glucose production. No increased adiposity or overt insulin resistance was observed. Furthermore, markers of non-alcoholic fatty liver disease (NAFLD) were significantly increased in PDM at GD18 and were positively correlated with basal glucose levels at GD18 in GDM dams. By PN15, NAFLD markers were also increased in GDM dams. Only PDM affected pregnancy outcomes such as litter size. Our findings indicate that GDM and PDM, resulting in disturbances of maternal glucose homeostasis, increase the risk of postpartum NAFLD development, related to the onset and severity of pregnancy hyperglycemia. These findings signal a need for earlier monitoring of maternal glycemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans. KEY POINTS: We studied the impact of high-fat diet/streptozotocin induced hyperglycemia in pregnancy (HIP) in mice and found that this impaired glucose tolerance and insulin release. Litter size and embryo survival were compromised by pre-gestational, but not by gestational diabetes. Despite postpartum recovery from hyperglycemia in a majority of dams, liver disease markers were further elevated by PN15. Maternal liver disease markers were associated with the severity of hyperglycemia at GD18. The association between hyperglycemic exposure and NAFLD signal a need for more rigorous monitoring and follow-up of maternal glycemia and health in diabetic pregnancy in humans. Abstract figure legend Streptozotocin and high fat diet were used to induce GDM in female BL6/NTac mice. Pregnant dams underwent an OGTT at GD15 to confirm GDM diagnosis. By GD18, dams were hyperglycemic and showed a reduction in pancreatic beta cells. By PN15, dams additionally had developed an increase in NAFLD markers, despite the majority of the dams having recovered from hyperglycemia. This article is protected by copyright. All rights reserved.