Plasma Glucose Concentrations Research Articles

The evolution and future of diagnostic criteria for diabetes mellitus

Background: The diagnostic criteria for diabetes mellitus have evolved over time, taking into account new evidence. Here, the author would like to review the evolution of diagnostic criteria for diabetes mellitus, the current diagnostic criteria, and future perspectives.Current Concepts: For the first time, in 1965, the World Health Organization (WHO) recommended that a 2-hour plasma glucose concentration of 130 mg/dL or more after taking a 50-g or 100-g oral glucose bolus may be used to make the diagnosis in people younger than 45 years and that other clinical data might be used to make the diagnosis in people older than 45 years. The 2003 American Diabetes Association Diagnostic Criteria set the threshold for normal fasting glucose at 100 mg/dL. The International Expert Committee (IEC) in 2009, the American Diabetes Association in 2010, and the WHO in 2011 proposed new diagnostic criteria for diabetes: glycated hemoglobin (HbA1c) of 6.5% or higher. More recently, diabetes has been diagnosed via a fasting blood glucose of 126 mg/dL or higher after fasting for at least 8 hours, a 2-hour postprandial blood glucose of 200 mg/dL or higher, glycated hemoglobin of 6.5% or higher, or a random blood glucose of 200 mg/dL or higher with symptoms of hyperglycemia.Discussion and Conclusion: Further research is needed on the accuracy of other markers, such as HbA1c, fructosamine, and 1,5-anhydroglusitol, in the diagnosis of diabetes, and sufficient evidence is required to determine whether it is appropriate to use the same diagnostic criteria for diabetes in aged people and different ethnic groups.

Characteristics of glucose and lipid metabolism and the interaction between gut microbiota and colonic mucosal immunity in pigs during cold exposure

BackgroundCold regions have long autumn and winter seasons and low ambient temperatures. When pigs are unable to adjust to the cold, oxidative damage and inflammation may develop. However, the differences between cold and non-cold adaptation regarding glucose and lipid metabolism, gut microbiota and colonic mucosal immunological features in pigs are unknown. This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation. Moreover, the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.ResultsCold and non-cold-adapted models were established by Min and Yorkshire pigs. Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models (Yorkshire pigs), decreasing plasma glucose concentrations. In this case, cold exposure enhanced the ATGL and CPT-1α expression to promote liver lipolysis and fatty acid oxidation. Meanwhile, the two probiotics (Collinsella and Bifidobacterium) depletion and the enrichment of two pathogens (Sutterella and Escherichia-Shigella) in colonic microbiota are not conducive to colonic mucosal immunity. However, glucagon-mediated hepatic glycogenolysis in cold-adapted pig models (Min pigs) maintained the stability of glucose homeostasis during cold exposure. It contributed to the gut microbiota (including the enrichment of the Rikenellaceae RC9 gut group, [Eubacterium] coprostanoligenes group and WCHB1-41) that favored cold-adapted metabolism.ConclusionsThe results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa. During non-cold adaptation, cold-induced glucose overconsumption promotes thermogenesis through lipolysis, but interferes with the gut microbiome and colonic mucosal immunity. Furthermore, glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Cardiac growth and metabolism of the fetal sheep are not vulnerable to a 10 day increase in fetal glucose and insulin concentrations during late gestation

AimsTo evaluate the effects of fetal glucose infusion in late gestation on the mRNA expression and protein abundance of molecules involved in the regulation of cardiac growth and metabolism. Main methodsEither saline or glucose was infused into fetal sheep from 130 to 140 days (d) gestation (term, 150 d). At 140 d gestation, left ventricle tissue samples were collected. Quantitative real-time RT-PCR and Western blot were used to determine the mRNA expression and protein abundance of key signalling molecules within the left ventricle of the fetal heart. Key findingsAlthough intra-fetal glucose infusion increased fetal plasma glucose and insulin concentrations, there was no change in the expression of molecules within the signalling pathways that regulate proliferation, hypertrophy, apoptosis or fibrosis in the fetal heart. Cardiac Solute carrier family 2 member 1 (SLC2A1) mRNA expression was decreased by glucose infusion. Glucose infusion increased cardiac mRNA expression of both Peroxisome proliferator activated receptor alpha (PPARA) and peroxisome proliferator activated receptor gamma (PPARG). However, there was no change in the mRNA expression of PPAR cofactors or molecules with PPAR response elements. Furthermore, glucose infusion did not impact the protein abundance of the 5 oxidative phosphorylation complexes of the electron transport chain. SignificanceDespite a 10-day doubling of fetal plasma glucose and insulin concentrations, the present study suggests that within the fetal left ventricle, the mRNA and protein expression of the signalling molecules involved in cardiac growth, development and metabolism are relatively unaffected.

Effects of faba bean, blue lupin and rapeseed meal supplementation on amino acid metabolism of dairy cows fed grass silage-based diets.

Information about the amino acid (AA) supply of locally produced protein supplements to dairy cow metabolism is needed to design sustainable diets for milk production. In this dairy cow experiment, grass silage and cereal-based diets supplemented with isonitrogenous amounts of rapeseed meal (RSM), faba beans (FB) and blue lupin seeds (BL) were compared with a control diet (CON) without protein supplementation. The diets were arranged as a 4×4 Latin Square using periods of 21days, and four rumen-cannulated Nordic Red dairy cows were used in the experiment. The intake of all AAs increased in response to protein supplementation and was for many individual AAs higher when RSM rather than the grain legumes FB and BL were fed. The total AA flow at the omasal canal was 3026, 3371, 3373 and 3045g/day for cows fed CON, RSM, FB and BL, respectively, but only RSM resulted in higher milk protein output. This may be explained by the higher provision of essential AA for milk protein synthesis when RSM was fed. The cows fed FB showed some positive features such as a tendency for greater omasal flow of branched-chain AA compared with BL. Overall, low plasma methionine and/or glucose concentrations in all treatments suggest that their supply was possibly limiting further production responses under the dietary conditions of the current study. It seems that the benefits of grain legume supplementation are limited when high-quality grass silage and cereal-based diets are used as the basal diet, but higher responses in amino acid supply and subsequent production responses can be expected when RSM is used.

Use of Saliva to Assess the Adherence to Treatment with Oral Hypoglycemic Agents in Patients with Type 2 Diabetes.

The diagnosis of Type 2 Diabetes Mellitus (T2DM) is made by demonstrating the hypoglycemic condition, which involves the determination of plasma glucose, and the follow-up of hypoglycemic treatment is performed by assessing the glycated hemoglobin (HbA1c) concentration. The aim of this study was to evaluate the saliva as an alternative sample in assessing the adherence to treatment with oral hypoglycemic agents in patients with Type 2 Diabetes. We selected 68 patients with T2DM, who were subjected to venous blood and saliva collection, in addition to answering a standardized questionnaire on adherence to hypoglycemic treatment. Laboratory tests performed on saliva, whole blood, serum or plasma included assessment of glycemia, urea, creatinine, uric acid, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and glycated hemoglobin. It was concluded that 82% of the patients adhered to hypoglycemic treatment based on glycated hemoglobin concentration (cut-off value of 7.0%). Comparing the groups that adhered to hypoglycemic treatment and those that did not adhere, statistical differences (P<0.05) were observed in the glucose, HDL-cholesterol, triglycerides, and insulin use (insulin therapy) parameters. Plasma glucose and urea serum concentration showed positive correlations when compared to saliva samples. Regarding the questionnaire, it was found that 35% of the patients presented positive screening for belief barriers and 83% positive score for recall barriers, and the positive screening correlated with glycated hemoglobin. Data have shown that it is possible to use saliva as an alternative sample to the laboratory assessment of hypoglycemic treatment adherence in T2DM patients.

Hypoglycemia awareness and its associated risk factors, in non-insulin-dependent diabetes in Hail region, Saudi Arabia.

Hypoglycemia is one of the avoidable complications of diabetes mellitus type 1 or 2, which occurs in between 24% to 60% of diabetic patients. It is a state of low plasma glucose concentration, either with or without symptoms, that can expose the patient to risks. Hypoglycemia is associated with impaired brain function, cardiovascular and visual effects, and increased mortality. This study was conducted to assess the knowledge of hypoglycemia as a complication of diabetes mellitus type 2 and the awareness of risk factors among the Hail City population, Kingdom of Saudi Arabia. We conducted a cross-sectional study targeting diabetic patients with type 2 in Hail province from April to August 2022. We used an online questionnaire distributed through popular social media, which included questions on age group, gender, BMI, social status, occupation, education, and income. Approximately 48.2% of patients had episodes of hypoglycemia in the previous three months, while 43% did not have hypoglycemic episodes. Among patients, 424 (73.7%) had less than three hypoglycemic episodes during the previous three months, and 121 (21%) had 3-6 episodes. Hypoglycemic episodes among diabetic patients have critical effects on the patient and may lead them to avoid diabetic drugs, causing hyperglycemia.

Association between Arterial Hypertension and Laboratory Markers, Body Composition, Obstructive Sleep Apnea and Autonomic Parameters in Obese Patients.

Systemic arterial hypertension (SAH) is a multifactorial disease, highly prevalent and associated with health risks. The purpose of this study was to investigate the association between SAH and laboratory, anthropometric, heart rate variability (HRV), and obstructive sleep apnea markers and, secondarily, to analyze the sensitivity and specificity of the variables that are independent factors in the association. Cross-sectional study with 95 obese patients treated at an obesity referral clinic in Salvador, BA, Brazil. SAH data were obtained from electronic medical records. The sample was stratified in the Normotensive Group (NG) and the Hypertensive Group (HG), and laboratory markers, body composition, polysomnography, and HRV were measured to evaluate the association of SAH with the predictor variables. For the analysis, p<0.05 was adopted. The average age of the NG was 36.3 ± 10.1 and HG 40.4 ± 10.6 years; 73.7% were women in the NG and 57.9% in HG; 82.4% in HG had insulin resistance. In the multivarious logistics regression model with adjustments in age, sex, height, and oxyhemoglobin saturation, SAH was inversely associated with fasting plasma glucose mg/dL (odds ratio [OR] = 0.96; 95% confidence interval [CI] = 0.92-0.99) and visceral fat area (VFA) cm2(OR = 0.98; 95% CI = 0.97-0.99). The area under the VFA curve was 0.728; CI 95% (0.620-0.836); fasting plasma glucose 0.693;CI 95% (0.582-0.804). Lower VFA and fasting plasma glucose concentrations were inversely associated with SAH. In addition, fasting plasma glucose and VFA showed a high sensitivity for SAH screening.

Osmotic and metabolic responses to cold acclimation and acute cold challenge in a freeze avoidant lizard, Podarcis siculus

Ectotherms survive exposure to subzero temperatures through freeze tolerance or freeze avoidance. Among vertebrate ectotherms, glucose is commonly used as a cryoprotectant in freeze tolerant strategies and as an osmolyte in freeze avoidant strategies, while also functioning as a metabolic substrate. Whereas some lizard species are capable of both freeze tolerance and freeze avoidance, Podarcis siculus is limited to freeze avoidance through supercooling. We hypothesized that, even in a freeze-avoidant species such as P. siculus, plasma glucose would accumulate with cold acclimation and would increase in response to acute exposure to subzero temperatures. To investigate this, we tested whether plasma glucose concentration and osmolality would increase in response to a subzero cold challenge before and after cold acclimation. In addition, we examined the relationship between metabolic rate, cold acclimation, and glucose by measuring metabolic rate during the cold challenge trials. We found that plasma glucose increased during the cold challenge trials, and that the increase was more pronounced after cold acclimation. However, baseline plasma glucose decreased throughout cold acclimation. Interestingly, total plasma osmolality did not change, and the increase in glucose only slightly altered freezing point depression. Metabolic rate during the cold challenge decreased after cold acclimation, and changes in respiratory exchange ratio suggest an increased relative use of carbohydrates. Overall, our findings demonstrate an important role for glucose in the response of P. siculus to an acute cold challenge, thus adding evidence for glucose as an important molecule for overwintering ectotherms that use freeze avoidant strategies.

A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND). We studied 18 obese ND and 16 T2D undergoing three meal tolerance tests (MTT) on three occasions (breakfast, lunch, and dinner). We used plasma glucose, insulin, and FFA concentrations collected at breakfast to test a battery of models and selected the best one based on physiological plausibility, ability to fit the data, precision of parameter estimates, and the Akaike parsimony criterion. The best model assumes that the postprandial suppression of FFA lipolysis is proportional to the above basal insulin, while FFA disposal is proportional to FFA concentration. It was used to compare FFA kinetics in ND and T2D along the day. The maximum lipolysis suppression occurred significantly earlier in ND than T2D (39 ± 6 min vs. 102 ± 13 min, 36 ± 4 min vs. 78 ± 11 min, and 38 ± 6 min vs. 84 ± 13 min, P < 0.01, at breakfast, lunch, and dinner, respectively), making lipolysis significantly lower in ND than T2D. This is mainly attributable to the lower insulin concentration in the second group. This novel FFA model allows to assess lipolysis and insulin antilipolytic effect in postprandial conditions.NEW & NOTEWORTHY In this study, we propose a new mathematical model able to quantify postprandial FFA kinetics and adipose tissue insulin sensitivity in both subjects with obesity without type 2 diabetes (ND) and subjects with type 2 diabetes (T2D). Results show that the slower postprandial suppression of lipolysis in T2D contributes to the higher free fatty acid (FFA) concentration that, in turn, may contribute to hyperglycemia.

Effects of dietary starch and ruminally undegraded protein on glucogenic precursors in lactating dairy cows

Gluconeogenesis is a large contributor to the blood supply of glucose carbons. The impact of varying dietary starch and ruminally degraded protein (RDP) on glucose entry, and the contributions of propionate and lactate to total plasma glucose entry were evaluated. Six cannulated, lactating, Holstein cows were fed one of four treatment diets arranged as a 2 × 2 factorial within a 4 × 4 partially replicated Latin Square design: (1) 8% RDP (LRDP) and 16% starch (LSt), (2) LRDP and 30% starch (HSt), (3) 11% RDP (HRDP) and LSt, or (4) HRDP and HSt. On d 12 of each period, 2-[13C]-sodium propionate (0.15 g/h) was ruminally infused for 4 h; on d 13, 1,2-[13C2]-glucose (0.2 g/h) was infused into the jugular vein for 1 h followed by 1-[13C]-lactate (0.1 g/h) for 1 h. Blood samples were serially collected starting prior to the infusions, and analyzed for plasma glucose, propionate, and lactate isotopic ratios. A one-compartment, glucose carbon model with inputs from lactate, propionate, and other glucogenic precursors (Oth, primarily absorbed glucose plus amino acids) was fitted to the isotope ratio data to derive glucose entry rates and conversion of the precursors to glucose. Milk protein production additively increased when HSt and HRDP were fed (P = 0.05 and P = 0.02, respectively). Plasma glucose and propionate concentrations increased with HSt (P = 0.04 and P = 0.01, respectively) and LRDP (P = 0.02 and P < 0.01, respectively). Total glucose and Oth entry increased (P = 0.03 and P = 0.03, respectively) with HSt, indicating greater glucose absorption from the small intestine or conversion of amino acids to glucose in the liver. However, neither entry rate was affected by RDP. The lack of an RDP effect suggests the increase in microbial outflow in response to RDP did not significantly alter glucose precursor supplies. Entry rates of propionate and lactate carbon to glucose carbon were not affected by treatment suggesting that neither starch nor RDP significantly affected fermentation or lactate production. Derivation of absolute entry rates and contributions to glucose using isotopic tracers is complicated by single carbon removals in the pentose phosphate (PPP), tri-carboxylic acid (TCA), and gluconeogenic pathways, and label randomization with the PPP and TCA pathways. Multiple tracers must be used to avoid assumptions regarding the proportional entries. These results provide insights on glucose supply and contributors, and draw attention to significant label cycling when utilizing isotope techniques.

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjectsreceived 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p<0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p<0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.

Rational Design and Efficacy of Glucose-Responsive Insulin Therapeutics and Insulin Delivery Systems by Computation Using Connected Human and Rodent Models.

Glucose-responsive insulins (GRIs) use plasma glucose levels in a diabetic patient to activate a specifically designed insulin analogue to a more potent state in real time. Alternatively, some GRI concepts use glucose-mediated release or injection of insulin into the bloodstream. GRIs hold promise to exhibit much improved pharmacological control of the plasma glucose concentration, particularly for the problem of therapeutically induced hypoglycemia. Several innovative GRI schemes are introduced into the literature, but there remains a dearth of quantitative analysis to aid the development and optimization of these constructs into effective therapeutics. This work evaluates several classes of GRIs that are proposed using a pharmacokinetic model as previously described, PAMERAH, simulating the glucoregulatory system of humans and rodents. GRI concepts are grouped into three mechanistic classes: 1) intrinsic GRIs, 2) glucose-responsive particles, and 3) glucose-responsive devices. Each class is analyzed for optimal designs that maintain glucose levels within the euglycemic range. These derived GRI parameter spaces are then compared between rodents and humans, providing the differences in clinical translation success for each candidate. This work demonstrates a computational framework to evaluate the potential clinical translatability of existing glucose-responsive systems, providing a useful approach for future GRI development.

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses

Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover study. Serum insulin concentrations during the OGT revealed that six horses were hyperinsulinemic (HI) while six were not (NON-HI). To describe the glucose response to IV injected PZI, the decline of plasma glucose concentration within the first 30 min was analyzed. Glucose reduction was similar in horses with and without HI during the 2-step IRT over time. Additionally, none of the horses reached a glucose reduction of ≥ 50% at 30 min. The results of the present study indicated that a comparable insulin mediated glucose uptake may be observed in horses with and without HI during a modified 2-step IRT. While six out of twelve horses were identified as HI by the OGT, all twelve horses were identified as IR by the modified 2-step IRT performed with PZI underlining the importance, but difficulty in choosing the right diagnostic tool in clinical settings to assess ID.

1586-P: Post-OGTT Low Blood Glucose in Individuals with Metabolic Syndrome, Metabolic Phenotypes, and Metabolic-Associated Fatty Liver Disease

Introduction: Post-prandial low blood glucose (LBG) is usually associated with late postprandial hyperinsulinemia in metabolic syndrome (MetS), but have not been well studied. Objectives: We aimed to 1) characterize insulin/glucose metabolism associated with LBG post 75g OGTT in a sample of individuals with MetS; and 2) assess the association between MAFLD (≥ 5% liver fat at MRI) and LBG. Methods: Plasma glucose, insulin and c-peptide concentrations were measured on OGTT over 180 mins. Insulin sensitivity and secretion were assessed with the Oral Minimal Model. During OGTT, we defined glucose ≤ 50 mg/dl as LBG, glucose &amp;gt; 70 mg/dl as no LBG and glucose 51-70 mg/dl as undefined status and were excluded from this analysis. Results: Of 82 participants, 50 were included and 15 (18 %) experienced LBG. Of the 33 participants who underwent MRI, 48% had MAFLD. Median age and BMI were 59 [IQR: 49-74] years and 28 [IQR: 26-31] kg/m2 respectively. Women represented 70% (n=35) of participants and experienced less LBG (p=0.0002) than men. Individuals experiencing LBG had higher insulin sensitivity (p=0.02), higher ß cell function (p=0.03), earlier glucose peaks (p&amp;lt;0.0001) and lower c-peptide peaks (p=0.007) than those without LBG. MAFLD was not associated with more LBG (p=0.7), but was associated with a different insulin curve. LBG+MAFLD status was associated with higher and later c-peptide and insulin levels compared to LBG without MAFLD status. Conclusion: In contrary to our hypothesis, individuals with MetS without MAFLD experiencing glucose ≤ 50 mg/dl during OGTT displayed a healthier metabolic profile. However, individuals with MAFLD experiencing a LBG during OGTT had a glucose phenotype similar to the late post-prandial hyperinsulinemic hypoglycemia often found in prediabetes state and associated with worst metabolic parameters. This suggests that MAFLD may be an important feature of MetS associated with a different post-OGTT glucose metabolism. Disclosure T.Gignac: None. A.Morissette: None. A.Agrinier: None. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. M.Vohl: None. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. A.Carreau: Advisory Panel; Novartis, Consultant; Valbiotis, Speaker's Bureau; Novo Nordisk Canada Inc.

882-P: Effects of YG1699 and Sotagliflozin on Intestinal Glucose Absorption and GLP-1 in Mice

Background and Aims: YG1699, a dual inhibitor of SGLT1 and SGLT2, recently showed greater glucose reduction than dapagliflozin in patients with type 1 diabetes. This study examined whether YG1699 provides gastrointestinal SGLT1 inhibition. Materials and Methods: Male BALB/c mice (n=105) were randomly divided into five groups: vehicle, YG1699 at low (1mg/kg), medium (3mg/kg), and high doses (10mg/kg), and LX4211 (sotagliflozin) 10mg/kg by oral gavage. Animals received a 5g/kg glucose challenge 15 minutes after study drug. Animals were euthanized at various times to examine intestinal plasma GLP-1 and glucose content in small intestine, cecum, and colon. Differences between groups were evaluated by ANOVA. Results (See Table 1): Small intestinal glucose content 1 hour after glucose challenge increased in a dose-related fashion with YG1699 compared to vehicle (p&amp;lt;0.001 for each YG1699 group vs. vehicle). Similar results were found in cecum (p&amp;lt;0.05 for each YG1699 group vs. vehicle). Plasma GLP-1 and PYY concentrations at 1 hour were higher on YG1699 vs. vehicle. Intestinal glucose content in the sotagliflozin group was similar to vehicle and the plasma GLP-1 were only numerically increased in this group. Conclusion: YG1699 delays intestinal glucose absorption and induces an incretin response in BALB/c mice, indicating significant gastrointestinal SGLT1 inhibition. Disclosure J.Li: None. R.W.Xu: Consultant; Youngene Therapeutics. J.He: None. P.Lapuerta: Board Member; 4M Therapeutics, Consultant; Youngene Therapeutics, ViaCyte, Inc., Encuragen, Capsida, Provention Bio, Inc., Decibel Therapeutics, Crinetics, Next Phase Therapeutics.

285-LB: LEAP2 Reduces Preprandial and Postprandial Glucose Levels and Ad Libitum Food Intake in Obese Men

The naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP2) has gained interest as a ghrelin receptor antagonist. Recently, we reported food intake and plasma glucose-lowering effects of exogenous LEAP2 in lean healthy males. Here, we investigated the effects of LEAP2 infusion on ad libitum food intake and postprandial glucose tolerance in obese men. Twenty obese men (mean (SEM) age 44.2 (2.2) years; BMI 36.3 (0.8) kg/m2; body fat percentage 37.4 (0.9)%) were enrolled in this randomized, double-blind, placebo-controlled, crossover study comprising two experimental days. Experimental days involved a ~5-hour intravenous (iv) infusion of LEAP2 or placebo during which a liquid mixed meal test (MMT) and a subsequent ad libitum meal test were performed. Plasma glucose measures included fasted (preprandial), Cmax and Tmax values as well as area under the curve (AUC) during MMT. Ad libitum food intake was measured in kilojoule (kJ) and kJ/kg body weight. Compared to placebo, LEAP2 infusion lowered preprandial plasma glucose (mean (SEM): 5.03 (0.08) vs. 5.19 (0.06) mmol/L, P=0.0095) as well as Cmax (6.58 (0.18) vs. 6.98 mmol/L (0.18), P=0.0001) and AUC for plasma glucose during MMT (1,506 (33.4) vs. 1564 (30.4) min×mmol/L, P=0.0005), but not Tmax. Ad libitum food intake was reduced by ~13% during LEAP2 infusion compared to placebo (2,939 (266) vs. 3,378 (258) kJ, P=0.0118; 25.0 (2.4) vs. 28.4 (2.0) kJ/kg body weight, P=0.0140). We conclude that a continuous iv LEAP2 infusion reduces pre- and postprandial plasma glucose concentrations as well as ad libitum food intake in obese men. Disclosure A. Englund: None. C. A. Hagemann: Employee; Gubra ApS. L. S. Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. F. K. Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.

222-OR: Metformin Reduces Fasting Glycemia in Well-Controlled Type 2 Diabetes by Promoting Aerobic Glycolysis Independent of Decreasing Endogenous Glucose Production

It is well established that metformin improves glycemic control in individuals with poorly-controlled type 2 diabetes (T2D) by reducing rates of endogenous glucose production (EGP) mediated by inhibition of hepatic gluconeogenesis. However, the mechanism by which metformin reduces blood glucose levels in well-controlled individuals with T2D is still unknown. To address this question, we examined rates of EGP, lactate turnover and hepatic triglyceride (TAG), ATP and glycogen content in near-normoglycemic individuals with T2D (n=10, HbA1c 7±1%) with (M+; 1000 mg bid x 2 wks) and without (M-; 2 wks) metformin treatment using the PINTA method with [2H7]glucose and [3-13C]lactate tracer infusions in combination with 1H- /31P- /13C- magnetic resonance spectroscopy. Metformin treatment did not affect rates of EGP, but reduced fasting plasma glucose concentrations by 30% (p&amp;lt;0.01 vs. M-), which could be attributed to increased rates of glucose clearance (+18%, p&amp;lt;0.005 vs. M-) resulting in increased lactate production (+14%, p&amp;lt;0.01 vs. M-). These changes were associated with decreased hepatic ATP content (-20%, p&amp;lt;0.05 vs. M-), increased hepatic glycogen content (+40%, p&amp;lt;0.05 vs. M-) and no changes in hepatic TAG content. Conclusion: In contrast to the glucose-lowering effect of metformin in poorly-controlled T2D, which is due to reductions in gluconeogenesis, this study demonstrates that in well-controlled T2D metformin reduces fasting glycemia - independent of reductions in EGP - primarily by increasing rates of aerobic glycolysis as reflected by increased peripheral glucose clearance and lactate production as well as reduced hepatic ATP content, which is consistent with metformin-induced inhibition of mitochondrial electron transport chain activity. Disclosure T.Sarabhai: None. T.E.Lamoia: None. S.Friesl: None. M.Jonuscheit: None. K.Petersen: Advisory Panel; Novo Nordisk, Research Support; Merck Sharp &amp; Dohme Corp., Gilead Sciences, Inc. G.I.Shulman: Consultant; Novo Nordisk, DiCerna Pharmaceuticals, Inc., Bayer Consumer Care AG, Kriya Therapeutics, Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Other Relationship; AstraZeneca, Merck &amp; Co., Inc., Janssen Research &amp; Development, LLC, iMetabolic Biopharma Corporation, Maze Therapeutics, 89bio, Inc., Equator Therapeutics, Inc., Generian Pharmaceuticals, Fortress Biotech, Inc., OrsoBio, Aro Biotherapeutics Company, Stock/Shareholder; Levels Health, Inc. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi.

1293-P: Diagnosing GDM in the Indian Population with Country-Specific Glucose Cut-Off Values

Introduction: In India, about 5 million pregnancies are affected with gestational diabetes mellitus (GDM), which triggers unfavourable pregnancy outcomes. Infants that experience intrauterine hyperglycemia are more likely to develop obesity and diabetes. Insulin resistance is associated with the Indian phenotype's propensity to accumulate excessive central fat. This study aimed to ascertain how different plasma glucose concentrations affected the ability of participants in an Indian birth cohort to predict unfavourable outcomes for both mothers and babies. Methods: We looked at a prospective cohort of pregnant women in public hospitals in Bihar, India. Pregnant women between 24 and 36 weeks underwent a 2-hour 75g oral glucose tolerance test. Following delivery, we measured the skinfold thickness of infants at the biceps, triceps, and subscapular regions of the body. For predicting the risk of SSFT new-borns and caesarean deliveries with the FBS and PPBS, 240 reliable Poisson models were built. FBS≥87 up to 92 mg/dL and PPBS≥134 up to 153 mg/dL with a one-unit increase were tested with sum of skinfold thickness (SSST) and C section delivery. Results: We discovered that 46.91% of the mothers underwent caesarean sections, and 10.65% of the new-borns had SSFT. Results show that after correcting for age, parity, socioeconomic status, height, and maternal obesity, FBS87 mg/dL and PPBS of 134 mg/dl were linked with risk of higher SSST in new-borns and caesarean delivery. Conclusion: In India, pregnant women are more likely to experience negative birth outcomes due to lower glucose cut-off readings than in other international classification systems. These results provide information for revising the cutoff points in light of the contextual conditions in LMIC nations. Disclosure S.C.Jha: None. N.Kumar: None.

针对建立高糖钳夹试验中的护理研究

Objective: Explore the establishment of high sugar clamp test and nursing research and problem improvement. Method: Nineteen healthy adult males residing in the Beijing area were selected to undergo two high-glucose clamp tests each to test their insulin secretion ability under high glucose conditions. Nursing issues and corresponding problem-solving strategies that occurred during the operation of the high-glucose clamp test were analyzed. Result: All 19 subjects successfully conducted a total of 38 high glucose clamp tests. The plasma glucose concentration can reach the desired ideal platform within the specified time in the experiment. The insulin and C-peptide levels of the subjects were detected and showed biphasic secretion. Due to the cumbersome and lengthy operation of this experiment, some problems were encountered during the experiment. With the cooperation of the operators, they were successfully resolved, resulting in the successful establishment of 38 high sugar clamp experiments. Conclusion: Adequate preparation should be made before conducting the high sugar clamp test, and necessary psychological care should be provided to the subjects. This is a necessary condition for the success of the experiment. Nursing staff should be proficient in the experimental steps throughout the entire process, maintain blood vessel patency, observe the local skin condition at the blood collection site, and ultimately ensure the smooth completion of the clamp test.