Discordance Between Glucose Levels Measured in Interstitial Fluid vs in Venous Plasma After Oral Glucose Administration: A Post-Hoc Analysis From the Randomised Controlled PRE-D Trial

AimsThe oral glucose tolerance test (OGTT) is together with haemoglobin A1c (HbA1c) gold standard for diagnosing prediabetes and diabetes. The objective of this study was to assess the concordance between glucose values obtained from venous plasma versus interstitial fluid after oral glucose administration in 120 individuals with prediabetes and overweight/obesity.Methods120 adults with prediabetes defined by HbA1c 39-47 mmol/mol and overweight or obesity who participated in the randomised controlled PRE-D trial were included in the study. Venous plasma glucose concentrations were measured at 0, 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT) performed on three different occasions within a 26 weeks period. During the OGTT, the participants wore a CGM device (IPro2, Medtronic), which assessed glucose concentrations every five minutes.ResultsA total of 306 OGTTs with simultaneous CGM measurements were obtained. Except in fasting, the CGM glucose values were below the OGTT values throughout the OGTT period with mean (SD) differences of 0.2 (0.7) mmol/L at time 0 min, -1.1 (1.3) at 30 min, -1.4 (1.8) at 60 min, and -0.5 (1.1) at 120 min). For measurements at 0 and 120 min, there was a proportional bias with an increasing mean difference between CGM and OGTT values with increasing mean of the two measurements.ConclusionsDue to poor agreement between the OGTT and CGM with wide 95% limits of agreement and proportional bias at 0 and 120 min, the potential for assessing glucose tolerance in prediabetes using CGM is questionable.

Acute Hepatitis due to Hepatic Glycogenosis after Insulin Overdose and Oral Glucose Administration in an Adolescent

Background Hepatic glycogenosis (HG) has been reported after intravenous (IV) dextrose administration to treat insulin overdose. We describe a case of HG in a patient with T1DM due to insulin overdose treated with oral glucose administration. Clinical course An adolescent boy with T1DM on a basal bolus insulin regimen presented with abdominal discomfort, nausea, vomiting and hypoglycemia of few hours. His glucose was 71 mg/dl, AST 119 U/L and ALT 65 U/L. Hypoglycemia was treated with juice, and 12 hours later AST and ALT were 979 U/L and 700 U/L respectively. Work up for infectious, autoimmune, metabolic, and toxic causes of hepatitis was negative. The transaminases improved by the next day and normalized within 3 weeks. Two weeks after discharge the patient returned with hypoglycemia, nausea, and right sided abdominal pain of 13 hours. Hypoglycemia persisted despite multiple courses of glucose tablets and juice. Laboratory studies showed glucose 58 mg/dl, AST 776 U/L, ALT 496 U/L, negative toxicology studies, and normal abdominal ultrasound. His serum insulin level was 249.7 mU/L and, c-peptide was <0.1 ng/ml consistent with insulin overdose. He received IV fluids with dextrose, and insulin was held. Transaminases improved by the following day. Repeat serum insulin while on home regimen was normal. Conclusions Along with other diagnoses, HG should be considered in patients treated with insulin who present with hypoglycemia and acute hepatitis. HG can occur in cases of insulin overdose treated with repeated oral glucose administration.

High Carbohydrate Diet Increased Glucose Transporter Protein Levels in Jejunum but Did Not Lead to Enhanced Post-Exercise Skeletal Muscle Glycogen Recovery

We examined the effect of dietary carbohydrate intake on post-exercise glycogen recovery. Male Institute of Cancer Research (ICR) mice were fed moderate-carbohydrate chow (MCHO, 50%cal from carbohydrate) or high-carbohydrate chow (HCHO, 70%cal from carbohydrate) for 10 days. They then ran on a treadmill at 25 m/min for 60 min and administered an oral glucose solution (1.5 mg/g body weight). Compared to the MCHO group, the HCHO group showed significantly higher sodium-D-glucose co-transporter 1 protein levels in the brush border membrane fraction (p = 0.003) and the glucose transporter 2 level in the mucosa of jejunum (p = 0.004). At 30 min after the post-exercise glucose administration, the skeletal muscle and liver glycogen levels were not significantly different between the two diet groups. The blood glucose concentration from the portal vein (which is the entry site of nutrients from the gastrointestinal tract) was not significantly different between the groups at 15 min after the post-exercise glucose administration. There was no difference in the total or phosphorylated states of proteins related to glucose uptake and glycogen synthesis in skeletal muscle. Although the high-carbohydrate diet significantly increased glucose transporters in the jejunum, this adaptation stimulated neither glycogen recovery nor glucose absorption after the ingestion of post-exercise glucose.

Effect of Glucose Administration on Biomass, ?-Carotene and Protein Content of Dunaliella sp. under Mixotrophic Cultivation

Dunaliella sp. is a prospective green microalga that can utilize both organic and inorganic carbon simultaneously. This study was aimed to determine the influence of various glucose concentrations on biomass concentration, β-carotene, and protein content of Dunaliella sp. under mixotrophic cultivation. Different glucose supplementation of 0.05 g/L, 0.10 g/L, 0.15 g/L, and 0.20 g/L were applied mixotrophically. The culture condition of Dunaliella sp. was also performed under photoautotrophic cultivation. The results exhibited that glucose administration significantly influenced the growth, biomass concentration, β-carotene, and protein production of Dunaliella sp. (P < 0.05). Supplementation of glucose in the mixotrophic culture remarkably improved cell growth, biomass production, β-carotene, and protein content of Dunaliella sp. compared to photoautotrophic culture. Increasing glucose concentration from 0.05 to 0.15 g/L increased biomass yield, β-carotene, and protein content of Dunaliella sp. The maximum specific growth rate and biomass concentration were produced at the glucose administration of 0.15 g/L with a value of 1.058 per day and 0.896 g/L, respectively. Moreover, supplementation of 0.15 g/L glucose resulted in the highest β-carotene and protein content. The results also noted that nitrate and phosphate consumption was highly related to biomass, β-carotene, and protein content of Dunaliella sp. In conclusion, the supplementation of glucose under mixotrophic conditions could improve the biomass, β-carotene, and protein content of Dunaliella sp. and could be practically used in mass-scale production. © 2021 Friends Science Publishers

Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity

Impaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in healthy and obese states, we constructed and analyzed transomics glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multiomics time course data from wild-type and leptin-deficient obese (ob/ob) mice after orally administered glucose. In wild-type mice, metabolic reactions were rapidly regulated within 10 min of oral glucose administration by glucose-responsive metabolites, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-induced changes in the expression of glucose-responsive genes encoding metabolic enzymes. In ob/ob mice, the majority of rapid regulation by glucose-responsive metabolites was absent. Instead, glucose administration produced slow changes in the expression of carbohydrate, lipid, and amino acid metabolic enzyme–encoding genes to alter metabolic reactions on a time scale of hours. Few regulatory events occurred in both healthy and obese mice. Thus, our transomics network analysis revealed that regulation of glucose-responsive liver metabolism is mediated through different mechanisms in healthy and obese states. Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, whereas slow changes in gene expression dominate the obese state.