Insulin Shock Research Articles

Lactate supplementation after hypoglycemia alleviates cognitive dysfunction induced by recurrent non-severe hypoglycemia in diabetic mice

Recurrent non-severe hypoglycemia (RH) in diabetes is an independent risk factor for cognitive dysfunction. However, the mechanisms and potential therapeutic strategies remain poorly understood. In this study, we aimed to elucidate the mechanisms underlying RH-induced diabetic cognitive impairment. We investigated the effects of RH on lactate metabolism and cognitive function in male C57BL/6 J diabetic mice. After RH, diabetic mice showed decreased brain lactate and adenosine triphosphate levels, decreased expression of lactate transporter proteins MCT1 and MCT4, increased neuroapoptosis, and decreased astrocyte glycolysis in vitro. This was accompanied by increased neuronal mitochondrial reactive oxygen species levels, decreased mitochondrial COX IV activity, impaired mitochondrial morphology and function, impaired synaptic morphology, and decreased expression of synaptic plasticity proteins. Intraperitoneal lactic acid injection improved lactate transport restored neuronal mitochondrial morphology and function, upregulated synaptic plasticity proteins brain-derived neurotrophic factor and early growth response 1, enhanced synaptic ultrastructure, and ultimately improved cognitive dysfunction following RH in diabetic mice. These findings provide insights into the prevention and treatment of cognitive dysfunction in patients with diabetes mellitus caused by RH.

Endocrinology: Updated ICD-10-CM Diabetes and Hypoglycemia Codes

This article reviews code changes that will be implemented for services on and after October 1, 2024. Topics addressed in this article include the following: Presymptomatic type 1 diabetes (T1D)Hypoglycemia levels

Hypoglycemia in a non - diabetic patient: a case report

Non diabetic hypoglycemia (or endogenous hypoglycemia) is an uncommon clinical problem, their study and treatment are a complex process. Under normal physiologic conditions, counterregulatory mechanisms prevent hypoglycemia. The use (involuntary or prescribed) of drugs associated with hypoglycemia (meglitinides, sulfonylureas and insulin) must always be ruled out. In healthy patients the main cause is an insulinoma (a type of neuroendocrine pancreatic tumor) and demands multidisciplinary management. The key for the diagnosis of insulinoma is the Whipple's triad described in 1930 by Allen Whipple (an American surgeon); symptoms occur during fasting or exercise, and are weird after eating. Surgical treatment is usually the only curative option. We aim to improve the diagnosis approach and our comprehension about these rare cases in clinical practice. Below we present a clinical case of a 51-year-old female patient with no history of diabetes admitted to our institution due to persistent hypoglycemia.

A potential role for GPR107 in the development of Hypoglycemia Unawareness

Diabetes remains one of the largest health burdens in modern society and while an estimated 37.3 million people suffer from either type 1 or type 2 diabetes worldwide, a further 96 million people are currently estimated to be prediabetic. So far, most efforts for diabetic therapies have been focused on insulin-replacement therapies and secretagogues; however, a common risk associated with these therapies is hypoglycemia. Hypoglycemia is defined as low plasma glucose levels (< 70 mg/dl) and can lead to loss of consciousness and death. Recently, it has been established that repeated exposure to bouts of hypoglycemia in diabetic individuals likely impairs sympathoadrenal counter regulation, and shifts the glycemic threshold for symptoms to lower plasma glucose concentrations, close to levels which result in cognitive failure. This pathology has been titled hypoglycemia unawareness (HU) and constitutes a major risk factor for developing severe hypoglycemia. The development of severe hypoglycemia in diabetics accounts for a six-fold increase in mortality, compared to diabetic individuals who do not experience severe hypoglycemia. Thus, it is important to understand how to prevent and reverse its development. We have developed a novel rat model of HU in which rats are exposed to insulin-induced recurrent hypoglycemia for five consecutive days. In this model of HU, we found that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Our group previously identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone, which can exert anorexigenic actions in the hypothalamus. Using a GPR107-flox rat model we are currently evaluating the effect of hypothalamic knock-down of GPR107 on the development of HU and basal feeding behavior. We anticipate that if knock-down of GPR107 reverses HU, the development of NST antagonists could potentially be useful therapeutically for diabetic patients who experience recurrent hypoglycemia. Our GPR107-flox rat model will enable us to identify upstream and downstream interacting partners of GPR107/NST. This could reveal hypothalamic pathways involved in the development of HU that also could serve as potential therapeutic targets for this devastation consequence of iatrogenic hypoglycemia. Internal Funds St. Louis University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization study

BackgroundThis study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot’s foot.MethodsGM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications.ResultsAfter multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors.ConclusionExtensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.

Forensic Hypoglycaemia & Neuroglycopenia — A Clinical Legal Social Endocrinology Challenge for 2024, Forensic Law in Hypoglycaemia 4

Forensic Hypoglycaemia & Neuroglycopenia — A Clinical Legal Social Endocrinology Challenge for 2024, Forensic Law in Hypoglycaemia 4

Expert consensus recommendations on the evaluation and management of hypoglycemia in diabetes: DGENius Group Diabetes India

Abstract Background and Aim: Hypoglycemia, marked by low blood glucose levels, presents significant challenges in diabetes care. This review outlines the evidence-based recommendations formulated by the DGENius Experts Consensus Group for managing hypoglycemia in people with diabetes. The goal was to furnish well-defined, evidence-based recommendations for addressing and comprehending hypoglycemia within diverse contexts, encompassing diabetes management, and various medical conditions. Materials and Methods: The consensus statement was crafted through an extensive literature review involving peer-reviewed articles, clinical guidelines, and relevant publications. A diverse panel of experts with broad knowledge and experience convened for structured deliberation, followed by multiple rounds of rigorous review and meetings to reach the final consensus statement. Results: The consensus introduces the importance of effective hypoglycemia in people with diabetes management, addressing both type 1 and type 2 diabetes mellitus separately, with tailored recommendations. It also covers impact of hypoglycemia on cardiovascular health and related recommendations. The document extends its scope to co-existing medical conditions, encompassing chronic renal dysfunction, hepatic and neoplastic disorders; hypoglycemia in specialized circumstances, such as during physical exertion, administration of oral antidiabetic agents, fasting periods, hospital-based care, reduced symptomatic awareness, nocturnal episodes, alcohol intake, pregnancy, and following metabolic surgical interventions; hypoglycemia in the context of nonantidiabetic medications; and hypoglycemia among the elderly. Quality of life and patient awareness are emphasized, and the statement concludes with prevention, treatment, and technology utilization recommendations. Conclusion: This comprehensive consensus statement is designed to guide healthcare professionals in managing hypoglycemia optimally. The goal is to heighten awareness of this critical condition, improve patient outcomes, and enhance their quality of life.

Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study

AimsGlomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-β-d-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status.MethodsThis cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated.ResultsThe results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7–7.1) and 2.2 (1.4–3.4) μg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5–10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8–6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4–11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971–0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957–0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr.ConclusionThe findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.

Genetic Insights into the causal relationship between cannabis use and diabetic phenotypes: A genetic correlation and Mendelian randomization study

BackgroundPrevious studies have highlighted the association between cannabis use and diabetes and its complications; however, the causality remains ambiguous. MethodsUnivariate Mendelian randomization (MR), multivariate MR, mediation MR, and linkage disequilibrium score (LDSC) analysis to assess the causal relationship between cannabis use and 12 diabetic phenotypes. Summary statistics for lifetime cannabis use (N = 184,765) and cannabis use disorder (CUD) (N = 374,287) from genome-wide association studies. The primary method used was inverse-variance-weighted (IVW). A range of sensitivity analyses ensured the robustness of the results. ResultsLDSC analysis revealed a significant genetic correlation between CUD and T2DM, as well as between lifetime cannabis use and four diabetic phenotypes (P < 0.05). After correction by false discovery rate (FDR), the primary IVW analysis indicates that the genetically predicted CUD is positively associated with the risk of diabetic hypoglycemia (OR = 1.11, 95% CI 1.04–1.20, P = 0.003, PFDR = 0.04) and proliferative diabetic retinopathy (PDR) (OR = 1.12, 95% CI 1.04–1.19, P = 4.89×10−4, PFDR =0.01). Additionally, suggestive evidence links CUD with increased risks of diabetic nephropathy, type 1 diabetes mellitus (T1DM), diabetic retinopathy, and T1DM associated with diabetic ketoacidosis (P < 0.05 &PFDR > 0.05). No causal relationship was detected between lifetime cannabis use and diabetic phenotypes (P > 0.05 &PFDR > 0.05). Multivariable and mediation MR analyses revealed that glycated hemoglobin A1c partially mediates the causal effect of CUD on PDR and diabetic hypoglycemia. ConclusionThis MR study suggests that CUD may have a causal role in several diabetic disease phenotypes.

Диабетическая гипогликемия и ее последствия в оценке качества ведения сахарного диабета

В статье дается обзор основных положений, касающихся диабетической гипогликемии. Рассматриваются клинические проявления и причины гипогликемии и гипогликемической комы при сахарном диабете (СД). Приводятся классификации гипогликемий, предложенные Американской диабетической ассоциацией (ADA) и российскими «Алгоритмами специализированной помощи больным сахарным диабетом». Показана распространенность гипогликемий у пациентов с СД1 и СД2 по данным крупных международных исследований. Рассматриваются основные механизмы развития бессимптомной гипогликемии. Особый акцент делается на описании последствий гипогликемических состояний в оценке качества ведения сахарного диабета. На основании собственного клинического опыта описываются ситуации, в которых наиболее часто наблюдается симптомная гипогликемия 2–3-го уровня. Выделяются приоритеты при управлении гипогликемией. The article presents literature review on the problem of diabetic hypoglycemia. The symptoms and causes of hypoglycemia and hypoglycemic coma in patients with diabetes mellitus are considered. The classifications of hypoglycemia proposed by the American Diabetes Association (ADA) and Russian Standards of specialized diabetes care are given. The frequency of hypoglycemia in patients with type 1 and type 2 diabetes is shown. The mechanisms involved in the development of asymptomatic hypoglycemia are described. Special attention is paid to consequences of hypoglycemic episodes in assessing the quality of management of diabetes mellitus. Risk factors for symptomatic level 2 and level 3 hypoglycemia are determined based on our own clinical experience. Priorities in the management of hypoglycemia are highlighted.

Disturbed hippocampal histidine metabolism contributes to cognitive impairment induced by recurrent nonsevere hypoglycemia in diabetes

Hypoglycemia is a common adverse reaction to glucose-lowering treatment. Diabetes mellitus (DM) combined with recurrent nonsevere hypoglycemia (RH) can accelerate cognitive decline. Currently, the metabolic pattern changes in cognition-related brain regions caused by this combined effect of DM and RH (DR) remain unclear. In this study, we first characterized the metabolic profiles of the hippocampus in mice exposed to DR using non-targeted metabolomic platforms. Our results showed that DR induced a unique metabolic pattern in the hippocampus, and several significant differences in metabolite levels belonging to the histidine metabolism pathway were discovered. Based on these findings, in the follow-up experiment, we found that histidine treatment could attenuate the cognitive impairment and rescue the neuronal and synaptic damage induced by DR in the hippocampus, which are closely related to ameliorated mitochondrial injury. These findings provide new insights into the metabolic mechanisms of the hippocampus in the progression of DR, and l-histidine supplementation may be a potential metabolic therapy in the future.

Practicality of non-invasive glucagon-loaded dissolving microneedle for life-saving treatment of severe hypoglycemia in a diabetic rat model

The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections, microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.

The use of assistance dogs in the detection of hypoglycemic episodes in type 1 diabetes: a descriptive and comprehensive review

Introduction: Type 1 diabetes mellitus (T1DM) is a disease of autoimmune and polygenic origin, characterized by the destruction of the beta cells of the pancreatic islets and, consequently, the absence of insulin production. The treatment aims at imitating the physiological secretion of insulin in individuals without comorbidity, using insulin therapy. Hypoglycemia is defined as any event of abnormally low blood glucose, putting the person at potential risk. Tachycardia, tremors, pallor, cold sweating, lingual paresthesia, and blurred vision, possibly leading to coma, are its main signs and symptoms. The recognition of serious clinical conditions transmitted by both visual and olfactory signals can be understood and elaborated by the dog's cognitive system, allowing the rapid detection of a hypoglycemic episode and, thus, allowing adequate conduct before a serious episode. Objective: To analyze the advances, both in studies and in professional practices, in the use of assistance dogs to identify hypoglycemia in diabetics 1, as well as to seek to understand the consequences of unidentified and untreated hypoglycemia. Methods: The most relevant studies searched using the keywords "hypoglycemia AND diabetes", in addition to "diabetes alert dogs" in Google Scholar, were analyzed, with 4 corresponding to the objectives of the current research. Finally, pathology books and official documents from the Ministry of Health and the Brazilian Society of Diabetes were used to build a theoretical explanation. Results and Discussion: Dogs are conditioned to respond with specific alert behaviors, such as barking or licking, when levels of their owner's blood sugar levels are below the ideal range, as identified by the amount of isoprene released in the individual's breath. This attitude causes the patient to measure his plasma glucose level, helping him to carry out the appropriate measures to keep the levels back to normal. The hesitation of the occurrence of hypoglycemia causes some type 1 diabetic to contain their lifestyle to try to reduce the probability of the occurrence of a hypoglycemic episode, negatively affecting their quality of life and psychological well-being. In addition, they can intentionally maintain hyperglycemia to avoid a sudden drop in glucose, however, this practice results in late problems such as nephropathy, neuropathy, and cardiopathy. Conclusions: Hypoglycemia is one of the main threats for people with diabetes, as it results in severe symptoms that can lead to coma if not treated quickly. Possibly, dogs perceive plasma glycemic variations using, in addition to the olfactory apparatus, perceptions captured through other senses, mainly vision, but the scarcity of studies carried out with dogs trained to support people with diabetes problems, mainly in Brazil, makes the efficiency of these animals to detect alterations of glucose in the blood remains debatable.

1-LB: Evaluating the Effectiveness of the Novel Somatostatin Receptor Antagonist (SSTR2a) ZT-01 for Hypoglycemia Prevention in a Rodent Model of Type 2 Diabetes

Background: Few pharmacological strategies exist to prevent hypoglycemia in diabetes, other than reducing the intensity of glucose-lowering therapy. SSTR2a treatment increases glucagon counterregulation and reduces the time spent in hypoglycemia in rodent models of type 1 diabetes (T1D), but the utility of this approach in type 2 diabetes (T2D) is unclear. The purpose of this study was to test the effect of acute SSTR2a treatment in a rodent model of hypoglycemia in T2D. Methods: High fat fed (HFF), low dose streptozotocin (35 mg/kg) T2D rats received SSTR2a treatment (subcutaneous ZT-01 3 mg/kg) or vehicle (N=9-11/group) 60 min before the induction of hypoglycemia using rapid-acting insulin (12 U/kg). Glycemia, glucagon and c-peptide levels were measured intermittently pre- and post-dosing. Results: T2D in the rats was characterized by significantly higher baseline glucose (21.8 ± 4.7 vs 6.5 ± 0.7 mmol/L, p&amp;lt;0.05) and HbA1c (8.6 ± 0.6% vs 5.5 ± 0.5%; p&amp;lt;0.0001) levels relative to HFF controls (n=3). T2D rats also displayed reduced c-peptide levels relative to controls (3.1 ± 1.3 vs 6.1 ± 1.2 ng/ml, p&amp;lt;0.05). During hypoglycemic challenge (T2D rats only), SSTR2a elevated glucagon levels relative to vehicle treatment (glucagon Cmax: 156 ± 50 vs 77 ± 46 pg/ml, p&amp;lt;0.01) and reduced the incidence of hypoglycemia by ~40% (5/8 SSTR2a treated vs 9/9 vehicle treated rats). In those that developed hypoglycemia, the average time to hypoglycemia onset was delayed (103.1± 24.6 vs 66.1 ± 23.6 min, p&amp;lt;0.05) with SSTR2a compared to vehicle. Conclusion: SSTR2a treatment increases glucagon levels in this rodent model of T2D, which appears to reduce the risk for hypoglycemia following bolus insulin dosing. Disclosure N. C. D'souza: None. M. Nejad-mansouri: None. R. Liggins: Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics. O. Chan: None. M. C. Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Indigo Diabetes, Consultant; Lilly Diabetes, Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi, Stock/Shareholder; Supersapiens, Zucara Therapeutics. P. Zaree bavani: None. J. Aiken: None. E. G. Hoffman: None. S. C. Atherley: None. S. Champsi: None. N. Aleali: None. D. Shakeri: None. M. El-zahed: None. N. Akbarian: None. Funding GlycoNet (CD-85)

392-P: Optimizing Duration and Threshold of Sensor Glucose for Identifying Symptomatic Hypoglycemia in Insulin-Treated Diabetes—Hypo-METRICS Study

Many episodes of hypoglycemia defined by the ATTD consensus are asymptomatic. We investigated if optimizing the glucose threshold and duration for sensor detected hypoglycemia (SDH) improves precision and sensitivity for identifying symptomatic hypoglycaemia from continuous glucose monitoring (CGM) data. We analysed 10 weeks of blinded CGM (Libre 2) and FitBit data from 435 participants [217 type 1, 218 type 2] with intact hypoglycemic awareness (Gold score &amp;lt;4). They self-reported symptomatic hypoglycemia on the Hypo-METRICS smartphone app. We used particle Markov chain Monte Carlo optimisation to generate the threshold and duration of SDH that maximizes detection of symptomatic hypoglycemia across our population and assessed impact of sleep status and diabetes type. The optimized threshold and duration were 70mg/dl for 27 min, with 2% gain of precision but 8% loss of sensitivity vs level 1 SDH (70mg/dl &amp;gt;15 min). Both level 1 SDH and our optimized definition had 3-fold increased sensitivity vs level 2 SDH (54mg/dl &amp;gt;15 min), with minimal loss of precision (Table). Our data validate ATTD level 1 hypoglycemia. Overall precision for detection of symptomatic hypoglycemia remains low despite optimization. Disclosure P.Divilly: None. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. Z.Mahmoudi: Employee; Novo Nordisk. G.Martine-edith: Other Relationship; Novo Nordisk A/S. D.Boiroux: Employee; Novo Nordisk A/S. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. M.Gomes: Employee; Novo Nordisk A/S. A.A.Vaag: None. B.E.De galan: Research Support; Novo Nordisk. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)

48-OR: Maternal Triglycerides in Diet-Controlled GDM Correlate with Newborn Triglycerides and Infant Fat Mass at Four Months of Life

The early hours of newborn (NB) life are critical for metabolic transition from the prenatal to postnatal period and possibly subsequent metabolic development. Although the relationship between maternal glucose and neonatal hypoglycemia in gestational diabetes (GDM) is strongly supported, little is known about the relationship between maternal and NB triglycerides (TG). We tested the hypothesis that maternal TG in GDM would correlate positively with NB pre-feed TG (NBpfTG) at 24hrs, and that NBpfTG would correlate with infant adiposity (Inf%fat). After GDM diagnosis (~28-30 wks), 16 diet-controlled GDM women (mean±SD; BMI 32±1) were randomized to eucaloric diets differing in carbohydrate and fat percentages (all food provided). Fasting (F) and 1-hr/2-hr postprandial (PP) glucose, insulin, and TG were measured during breakfast test meals at 31 and 36 wks. Newborn “fasting” blood (NBpfTG, NBpfGluc) was collected at 24 hrs. Inf%fat was measured at 24 hrs and 4 mos (PeaPod). All women met conventional glucose targets with diet alone; no neonates had hypoglycemia. At 31 but not 36 wks, maternal FTG and PPTG were correlated with NBpfTG (92±7mg/dL)(r=0.52-0.53, p=0.03 both) and NBpfTG correlated with 24 hr Inf%fat (r=0.50, p=0.06). Maternal fasting insulin, HOMA-IR, glucose and PP glucose at 31 and 36 wks correlated with Inf%fat at 24 hrs (r=0.47-0.68, p&amp;lt;0.05 all). Strikingly, NBpfTG were uniquely and highly correlated with Inf%fat at 4 mos (r=0.81, p&amp;lt;0.0001); NBpfGluc was not. Inf%fat was similar between maternal diet groups (p&amp;gt;0.05). These data show that maternal TG soon after GDM diagnosis correlated with NBpfTG, which in turn correlated with Inf%fat at 24 hrs, but had a sustained, stronger correlation with Inf%fat at 4 mos. This connection between 32 wk maternal TG and NBpfTG, and their association with Inf%fat from 24 hrs to 4 mos support future studies to address whether maternal TG might be therapeutically targeted to normalize fetal growth in well-controlled GDM. Disclosure P.J.Rozance: None. L.A.Barbour: None. E.Z.Dunn: None. S.S.Farabi: None. N.Hirsch: None. K.P.Rolloff: None. J.E.Friedman: None. T.L.Hernandez: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101659); Janssen Research and Development; National Center for Advancing Translational Sciences (UL1TR002535)

Hypoglycemia in Patients with Type-2 Diabetes Mellitus Nephropathy

Objective: To find out the frequency of hypoglycemia in Type-2 Diabetics having nephropathyMethodology: This cross-sectional observational study was carried out in Medical Teaching Institute Khyber Teaching Hospital. Department of Medicine, from August 21, 2020, to January 21, 2021. Two-hundred and eighty-one (281) patients with Type 2 diabetic nephropathy were observed in due course and were subjected to detailed history and examination. A sample of 5 ml venous blood was obtained from the patients to measure blood glucose levels to detect hypoglycemia. Experienced pathologists analyzed all investigations.Results: The mean ± Standard deviation (SD) of age in this study was 60± 10.26 years. Female patients outnumbered males in this study. Hypoglycemia was reported in 21% of patients while 79% did not have hypoglycemia.Conclusion: Type-2 diabetics having nephropathy are prone to hypoglycemia. These patients should be carefully observed for clinical and biochemical features of hypoglycemia .

Incidence and costs of hypoglycemia in insulin-treated diabetes in Switzerland: A health-economic analysis

AimsWe assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland. MethodsWe developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies. ResultsThe number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia. ConclusionsHypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden.

Forensic Law in Hypoglycaemia-1

Hypoglycaemia, low Blood Glucose BG when BG falls below 3.0mmol/l exhibits Physiological Symptoms of Tremor, Sweating and Hunger, requiring prompt glucose treatment input which if not corrected leads to Confusion, Sensory Disturbance and Behaviour Change at 2.0mmol/l described as Neuroglycopenia. If Blood Glucose BG falls to 1.0mmol/l or 18mg/dl Diabetic Coma is likely to occur leading to unconsciousness and without fast acting glucose severe risk of death. An estimated 600 million patients with Diabetes are thought to exist in the World in 2022 and an estimated 4.5 million in the UK. It is estimated 10% of Diabetes patients are T1D Type 1 Diabetes Insulin Dependent and 90% T2D Type 2 Diabetes Patients Non-Insulin Dependent. Many T2D Patients may require Insulin Treatment several years after diagnosis. Does society really understand the daily burden the diabetes patient faces and the need if things go wrong to provide emergency patient support or the need for A1 Red Alert Emergency support in a hospital, and Paramedic Ambulance support in the Community? This is identified in the UK alone as over 95,000 Emergency Diabetes Hypoglycaemia Calls every year, many of which are potentially avoidable with better understanding and education with family and/or friend witness support.

Promising influences of hesperidin and hesperetin against diabetes and its complications: a systematic review of molecular, cellular, and metabolic effects.

Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.