Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca²⁺]_i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca²⁺-signals were completely inhibited by removal of extracellular Ca²⁺, confirming their dependence on influx of extracellular Ca²⁺. The 4-αPDD Ca²⁺-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca²⁺-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca²⁺-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months’ streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy.     

Effects of Hyperglycemia and Protein Kinase C on Connexin43 Expression in Cultured Rat Retinal Pigment Epithelial Cells

Previous results demonstrated that the intercellular communication mediated by gap junctions in retinal pigment epithelial (RPE) cells from the healthy Long Evans (LE) rat strain is higher than that from the dystrophic Royal College of Surgeons (RCS) rat strain. We examined connexin (Cx) expression in both cell types. At the mRNA level, a qualitatively similar expression pattern was found whereby Cx26, Cx32, Cx36, Cx43, Cx45 and Cx46 were all expressed. At the protein level, only Cx43 and Cx46 were detected. Expression of both isoforms was higher in LE-RPE as compared to RCS-RPE by a factor of 1.25 and 2 respectively. Phosphorylation of Cx43 was increased upon activation of protein kinase C (PKC) by 1 μM phorbol 12-myristate 13-acetate (PMA). The phosphorylation status was not changed in hyperglycemic conditions, but this treatment strongly decreased total Cx43 levels to about 75 and 40% (in LE-RPE and RCS-RPE cells respectively) of the control level in LE-RPE cells. This decrease could be overcome by PKC downregulation. These results demonstrate that PKC activation and hyperglycemic conditions have different effects on Cx43 and that PKC is involved in the metabolic pathway induced by hyperglycemic conditions. Received: 21 July 2000/Revised: 19 January 2001     

Effect of Diabetes on Glycogen Metabolism in Rat Retina

Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.     

Effect of Experimental Diabetes on the Catecholamine Metabolism in Rat Brain

The levels of epinephrine, norepinephrine, and dopamine and the activities of tyrosine hydroxylase and monoamine oxidase were estimated in four regions of rat brain during alloxan-induced hyperglycemia and insulin-induced hypoglycemia. Catecholamine levels were estimated by HPLC, and the insulin levels were quantified by radioimmunoassay. The results demonstrated significant increases in the activities of the metabolizing enzymes and levels of catecholamines during experimental conditions. The levels of catecholamines were highest in the cerebral hemispheres, the region associated with high activities of the metabolizing enzymes. Insulin-induced hypoglycemia caused a decrease in the activities of the metabolizing enzymes followed by their recovery within 2 h.     

Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes

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The Association of Diabetes and Hyperglycemia on Inpatient Readmissions

ObjectiveTo evaluate the association between inpatient glycemic control and readmission in individuals with diabetes and hyperglycemia (DM/HG).MethodsTwo data sets were analyzed from fiscal years 2011 to 2013: hospital data using the International Classification of Diseases, Ninth Revision (ICD-9) codes for DM/HG and point of care (POC) glucose monitoring. The variables analyzed included gender, age, mean, minimum and maximum glucose, along with 4 measures of glycemic variability (GV), standard deviation, coefficient of variation, mean amplitude of glucose excursions, and average daily risk range.ResultsOf 66 518 discharges in FY 2011-2013, 28.4% had DM/HG based on ICD-9 codes and 53% received POC monitoring. The overall readmission rate was 13.9%, although the rates for individuals with DM/HG were higher at 18.9% and 20.6% using ICD-9 codes and POC data, respectively. The readmitted group had higher mean glucose (169 ± 47 mg/dL vs 158 ± 46 mg/dL, P < .001). Individuals with severe hypoglycemia and hyperglycemia had the highest readmission rates. All 4 GV measures were consistent and higher in the readmitted group.ConclusionIndividuals with DM/HG have higher 30-day readmission rates than those without. Those readmitted had higher mean glucose, more extreme glucose values, and higher GV. To our knowledge, this is the first report of multiple metrics of inpatient glycemic control, including GV, and their associations with readmission.     

诱导回输胰岛素分泌细胞对大鼠糖尿病的疗效

目的:研究胰岛素分泌细胞的体外诱导方法及其对大鼠糖尿病的疗效.方法:分离培养大鼠骨髓干细胞,用尼克酰胺及肠促胰岛素类似物诱导其分化为胰岛素分泌细胞.将24只Wistar大鼠随机分为对照组、糖尿病组和诱导组.后两组建立糖尿病模型,将该胰岛素分泌细胞回输至诱导组体内,监测大鼠体重、血糖(空腹及OGTT 120分血糖)及空腹...     

Alterations in the Retinal Dopaminergic Neuronal System in Rats with Streptozotocin-Induced Diabetes

Neurochemical alterations, which may be associated with the development of diabetic retinal dysfunction, were investigated using streptozotocin (STZ)-induced hyperglycemia in rats. Young male Wistar rats, weighing 100-150 g, were made diabetic with daily intraperitoneal injections of STZ (30 mg/kg) for 5 days. This treatment caused a continuous hyperglycemia (400-600 mg/dl) and suppressed gain in body weight. Nine weeks after the STZ treatment, a significant increment in retinal valine and a decline in phenylalanine were noted, while the concentrations of other neuroactive amino acids, such as gamma-aminobutyric acid and aspartic acid, in the retina remained unchanged. On the other hand, the concentration of retinal dopamine (DA) was found to decrease significantly from the third week of hyperglycemia, when [3H]spiperone binding showed a tendency to increase in the retinal particulate fraction. However, the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase (AADC) and the uptake of [3H]tyrosine showed no alteration in the retina of diabetic rats. The accumulation rate of 3,4-dihydroxyphenylalanine (DOPA) in vivo in the retina of diabetic rats, measured following the administration of the AADC inhibitor m-hydroxybenzyl-hydrazine (100 mg/kg i.p.), was also unchanged. Although [3H]DA uptake by retinal tissue was similar in control and diabetic animals, the spontaneous efflux of [3H]DA from the retina was found to be significantly accelerated in STZ-treated animals. In addition, the release of preloaded [3H]DA, elicited by repeated photic stimulation, was significantly attenuated in retina from diabetic rats. These results suggest that an accelerated efflux of DA, possibly leading to the depletion of DA from the retinal DA system, may account for early retinal dysfunctions known to occur in diabetic subjects.     

Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina

Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-d-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p–c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.     

Effect of Long-Lasting Diabetes Mellitus on Rat and Human Brain Monoamines

Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.     

In the Early Stages of Diabetes,Rat Retinal Mitochondria Undergo Mild Uncoupling due to UCP2 Activity

In order to maintain high transmembrane ionic gradients, retinal tissues require a large amount of energy probably provided by a high rate of both, glycolysis and oxidative phosphorylation. However, little information exists on retinal mitochondrial efficiency. We analyzed the retinal mitochondrial activity in ex vivo retinas and in isolated mitochondria from normal rat retina and from short-term streptozotocin-diabetic rats. In normal ex vivo retinas, increasing glucose concentrations from 5.6mM to 30mM caused a four-fold increase in glucose accumulation and CO₂ production. Retina from diabetic rats accumulated similar amounts of glucose. However, CO₂ production was not as high. Isolated mitochondria from normal rat retina exhibited a resting rate of oxygen consumption of 14.6 ± 1.1 natgO (min.mg prot)^-1 and a respiratory control of 4.0. Mitochondria from 7, 20 and 45 days diabetic rats increased the resting rate of oxygen consumption and the activity of the electron transport complexes; under these conditions the mitochondrial transmembrane potential decreased. In spite of this, the ATP synthesis was not modified. GDP, an UCP2 inhibitor, increased mitochondrial membrane potential and superoxide production in controls and at 45 days of diabetes. The role of UCP2 is discussed. The results suggest that at the early stage of diabetes we studied, retinal mitochondria undergo adaptations leading to maintain energetic requirements and prevent oxidative stress.     

新生血管特异性结合肽GX1二聚体抑制大鼠视网膜微血管内皮细胞血管生成的实验研究

目的:探讨新生血管特异性结合肽GX1二聚体对视网膜新生血管生成的影响。方法:化学合成GX1二聚体、GX1单体、对照肽二聚体,通过CCK-8实验、管状结构形成实验、迁移实验研究GX1二聚体对大鼠视网膜内皮细胞(RMEC)增殖、微管形成、迁移能力的影响,流式细胞学技术分析其对细胞周期分布和凋亡的影响。结果:CCK-8结果显示,与对照肽二聚体及阴性对照组相比,100-200μM GX1二聚体及单体均可抑制RMEC增殖(P<0.05),且随着GX1二聚体及单体浓度升高,抑制作用逐渐增强,呈剂量依赖性;各浓度GX1二聚体均较单体抑制作用增强,并有统计学差异(P<0.05)。管状结构形成实验、细胞损伤迁移实验结果显示与对照肽二聚体及PBS组相比,GX1二聚体及GX1单体均可明显抑制视网膜内皮细胞管状结构的形成及迁移,且二聚体抑制作用强于单体;对照肽二聚体仅有轻微的抑制视网膜内皮细胞管状结构形成的作用,对细胞迁移无明显抑制作用。流式细胞术分析显示与对照肽及阴性对照组相比,GX1二聚体及GX1单体均可诱导细胞凋亡(P<0.05),且GX1二聚体的诱导作用强于GX1单体(P<0.05),而对细胞周期分布则无明显影响。结论:GX1二聚体和GX1单体均可抑制视网膜新生血管内皮细胞增殖、微管形成、迁移能力及诱导凋亡,且GX1二聚体较GX1单体作用增强。GX1二聚体有望代替单体成为糖尿病视网膜病变新生血管靶向治疗小肽类药物。     

Prophylactic Effects of the Glucagon-Like Peptide-1 Analog Liraglutide on Hyperglycemia in a Rat Model of Type 2 Diabetes Mellitus Associated with Chronic Pancreatitis and Obesity

The objective of this study was to investigate the effects of liraglutide, an analog of human glucagon-like peptide 1 (GLP1), on WBN/Kob-Lepr^fa (fa/fa) rats, which spontaneously develop type 2 diabetes mellitus with pancreatic disorder and obesity. Male fa/fa rats (age, 7 wk) were allocated into 4 groups and received liraglutide (37.5, 75, 150 μg/kg SC) or saline (control group) once daily for 4 wk. All rats in the control group became overweight and developed hyperglycemia as they aged. Although the rats given liraglutide showed a dose-dependent reduction in food intake, no significant effects on body weight or fat content occurred. In the liraglutide groups, the development of hyperglycemia was suppressed, even as plasma insulin concentrations increased in a dose-dependent manner. Intravenous glucose tolerance testing of the liraglutide-treated rats confirmed improvement of glucose tolerance and enhanced insulin secretion. Histologic examination revealed increased numbers of pancreatic β-cell type islet cells and increased proliferation of epithelial cells of the small ducts in the liraglutide-treated groups. Although our study did not reveal a significant decrease in obesity after liraglutide administration, the results suggest a marked antidiabetic effect characterized by increased insulin secretion in fa/fa rats with pancreatic disorders.Abbreviations: GLP1, glucagon-like peptide-1; IVGTT, intravenous glucose tolerance testing; T2DM, type 2 diabetes mellitusThe number of patients diagnosed with diabetes has more than doubled over the last 30 y, and diabetes has become an important public health concern worldwide.⁶ Approximately 90% of patients with diabetes are diagnosed with type 2 diabetes mellitus (T2DM).³¹ The onset of T2DM is determined by multiple factors that lead to reduced insulin secretion or insulin resistance, including genetic predisposition and lifestyle-associated habits such as lack of exercise, overeating, and obesity. Many drugs are already used clinically to treat T2DM;^9,11 nevertheless, the search and development of more efficient and safe drugs is currently underway. In this regard, incretin has recently gained attention as a member of a class of drugs used to treat T2DM.^9,11Enteroendocrine cells secret incretin hormones, which augment glucose-induced insulin secretion in response to food ingestion, in a glucose-dependent manner. Currently, the 2 confirmed incretins are glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP1). Research has shown that GLP1 derivatives have functions in addition to the promotion of insulin secretion, including facilitation of β-cell proliferation,²⁸ suppression of β-cell apoptosis,¹² and promotion of β-cell differentiation or de novo formation of β cells.^29,30 GLP1 derivatives have been reported to have multiple nonpancreatic functions, including suppression of appetite and body weight,^7,13 suppression of gastric secretions,¹⁹ reduction of lipid accumulation in the liver,¹⁷ and promotion of sensitivity to insulin in adipose cells and skeletal muscle.^8,22WBN/Kob-type male rats are a relevant animal model for diabetes without obesity. These rats typically show disease conditions including chronic pancreatitis and pancreatic endocrine disorders.^18,26 A new model rat for diabetes was established recently by crossing rats carrying the Lepr^fa obesity gene with wild-type WBN/Kob rats, yielding a fa/fa congenic strain.¹ The obesity gene (Lepr^fa) is a spontaneous mutation derived from Zucker-fatty rats that leads to dysfunction of the leptin receptor. Rats homozygous for this gene are obese, resistant to insulin, and hyperinsulinemic.^4,16,32 Male WBN/Kob-Lepr^fa rats (hereafter referred to as fa/fa rats) represent a new animal model in which the animals spontaneously develop diabetes in addition to endogenous insulin resistance. Compared with the parental strains, fa/fa rats are characterized by an earlier onset of diabetes and more severe pancreatic complications.^1,2 Our previous investigations have revealed that fa/fa rats present with hyperinsulinemia at a prediabetic stage as a compensatory response to insulin resistance, but these rats show high blood glucose levels because of a difficulty in maintaining blood insulin concentrations as a consequence of declining pancreatic β-cell function associated with advancing age.¹⁴In the current study, to further validate fa/fa rats as a T2DM model, we investigated the effects of a GLP1 analog in fa/fa rats with hyperglycemia (age, 7 to 11 wk). We used liraglutide, a human GLP1 analog, which has been shown to be clinically effective in T2DM patients.^9,11     

SD大鼠视网膜小胶质细胞原代培养方法的改良

目的对经典的原代视网膜小胶质细胞体外纯化培养方法进行简单的改良以提高细胞产量。方法在视网膜小胶质细胞原代培养过程中以McCarthy等的经典方法为基础,寻找适当的初始种植密度,并在初次振荡分离后继续培养以获得多次产出,使用免疫细胞化学染色方法进行小胶质细胞纯度鉴定。结果视网膜小胶质细胞原代培养最宜初始种植密度为1×106/mL,多次分离纯化获得的视网膜小胶质细胞均达到97%以上的纯度。结论视网膜小胶质细胞原代培养过程中,以适当的初始种植密度和多次振荡分离方法可在保证有效纯度的基础上提高细胞产量。     

Effect of Cocaine on the Histaminergic Neuron System in the Rat Brain

Abstract: To examine the effect of cocaine on the brain histamine neuron system, histamine levels and histamine N -methyl-transferase activity in the rat brain were measured after the administration of cocaine. Moreover, we examined the effect of l -histidine on cocaine-induced wheel-running behavior. The administration of cocaine (20 mg/kg) increased histamine levels and histamine N -methyltransferase activity in the striatum, nucleus accumbens, and amygdala 1 h later. The pretreatment with l -histidine (350 and 700 mg/kg) inhibited the cocaine (20 mg/kg)-induced increase of wheel-running activity in a dose-dependent manner. These findings suggest that cocaine activates the brain histamine neuron system, which may play the role of inhibiting the cocaine-induced wheel-running behavior.     

Proactive Protocol-Based Management of Hyperglycemia and Diabetes in Colorectal Surgery Patients

Objective: The management of diabetic patients undergoing elective abdominal surgery continues to be unsystematic, despite evidence that standardized perioperative glycemic control is associated with fewer postoperative surgical complications. We examined the efficacy of a pre-operative diabetes optimization protocol implemented at a single institution in improving perioperative glycemic control with a target blood glucose of 80 to 180 mg/dL.Methods: Patients with established and newly diagnosed diabetes who underwent elective colorectal surgery were included. The control group comprised 103 patients from January 1, 2011, through December 31, 2013, before protocol implementation. The glycemic-optimized group included 96 patients following protocol implementation from January 1, 2014, through July 31, 2016. Data included demographic information, blood glucose levels, insulin doses, hypoglycemic events, and clinical outcomes (length of stay, re-admissions, complications, and mortality).Results: Patients enrolled in the glycemic optimization protocol had significantly lower glucose levels intra-operatively (145.0 mg/dL vs. 158.1 mg/dL; P = .03) and postoperatively (135.6 mg/dL vs. 145.2 mg/dL; P = .005). A higher proportion of patients enrolled in the protocol received insulin than patients in the control group (0.63 vs. 0.48; P = .01), but the insulin was administered less frequently (median [interquartile range] number of times, 6.0 [2.0 to 11.0] vs. 7.0 [5.0 to 11.0]; P = .04). Two episodes of symptomatic hypoglycemia occurred in the control group. There was no difference in clinical outcomes.Conclusion: Improved peri-operative glycemic control was observed following implementation of a standardized institutional protocol for managing diabetic patients undergoing elective colorectal surgery.Abbreviations: HbA1c = glycated hemoglobin A1c; IQR = interquartile range     

Effect of Hyperglycemia and Its Prevention by Insulin Treatment on the Incorporation of 32P into Polyphosphoinositides and Other Phospholipids in Peripheral Nerve of the Streptozotocin Diabetic Rat

The influence of varying doses of streptozotocin and preventive insulin treatment on phospholipid metabolism in sciatic nerve in vitro from diabetic rats was studied. Animals were given 30, 45, and 60 mg/kg injections of streptozotocin and 10 weeks later nerves were removed and incubated in the presence of [32P]-orthophosphate. The quantity of isotope incorporated into phosphatidylinositol-4,5-bisphosphate (PIP2) was progressively greater with increasing drug dosage, whereas uptake of label into other phospholipids was unchanged. Rats were made diabetic and within 72 h were implanted with long-acting, insulin-containing osmotic minipumps and the incorporation of [32P]orthophosphate into phospholipids of intact and epineurium-free nerves was examined 8 weeks later. For whole nerve, increased labeling in nerves from diabetic animals occurred only in PIP2 and phosphatidylinositol-4-phosphate (PIP) and was completely prevented by insulin treatment. Isotope incorporation into polyphosphoinositides was also markedly elevated (greater than or equal to 100%) in desheathed diabetic nerves, but not in nerves from insulin-treated animals. Other phospholipids in epineurium-free nerves displayed some rise in isotope uptake, but the increases were not prevented by insulin treatment and appeared unrelated to hyperglycemia. Morphological examination of nerves extended previous findings that prolonged insulin treatment produces axonal degeneration. These observations indicate that abnormal nerve polyphosphoinositide metabolism is at least in part a consequence of hyperglycemia. The metabolic alterations may be intimately involved in reduced nerve conduction velocity, which is characteristic of diabetic neuropathy.     

Using a Diabetes Risk Score to Identify Patients Without Diabetes at Risk for New Hyperglycemia in the Hospital

ObjectiveTo assess the value of a validated diabetes risk test, the Cambridge Risk Score (CRS), to identify patients admitted to hospital without diabetes at risk for new hyperglycemia (NH).MethodsThis retrospective cross-sectional study included adults admitted to a hospital over a 4-year period. Patients with no diabetes diagnosis and not on antidiabetics were included. The CRS was calculated for each patient, and those with available glycated hemoglobin (HbA1C) results were investigated in a second analysis. Multivariate regression analyses were performed to assess the association among CRS, HbA1C, and the risk for NH.ResultsA total of 19,830 subjects comprised the sample, of which 38% were found to have developed NH, defined as a blood glucose level ≥140 mg/dL. After accounting for covariates, the CRS was significantly associated with NH (odds ratio [OR], 1.19 [1.16, 1.22]; P < .001). Only 17% of patients had their HbA1C values checked within 6 months of admission. Compared with patients without diabetes, patients with prediabetes based on their HbA1C level (OR, 1.59 [1.37, 1.86]; P < .001) and patients with undiagnosed diabetes (OR, 5.95 [3.50, 10.65]; P < .001) were also significantly more likely to have NH.ConclusionResults of this study show that the CRS and HbA1C levels were significantly associated with the risk of developing NH in inpatient adults without diabetes. Given that an HbA1C level was missing in most medical records of hospitalized patients without diabetes, the CRS could be a useful tool for early identification and management of NH, possibly leading to better outcomes.