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CPT: Pharmacometrics & Systems... Oct 2023The TIGG model is the first model to integrate glucose and insulin regulation, incretin effect, and triglyceride (TG) response in the lipoprotein subclasses of...
The TIGG model is the first model to integrate glucose and insulin regulation, incretin effect, and triglyceride (TG) response in the lipoprotein subclasses of chylomicrons and VLDL-V6. This model described the response following a high-fat meal in individuals who are lean, obese, and very obese and provided insights into the possible regulation of glucose homeostasis in the extended period following a meal. Often, total TGs are analyzed within clinical studies, instead of lipoprotein subclasses. We extended the existing TIGG model to capture the observed total TGs and determined if this model could be used to predict the postprandial TG response of chylomicron and VLDL-V6 when only total TGs are available. To assess if the lipoprotein distinction was important for the model, a second model (tTIGG) was developed using only the postprandial response in total TGs, instead of postprandial TG response in chylomicrons and VLDL-V6. The two models were compared on their predictability to characterize the postprandial response of glucose, insulin, and active GLP-1. Both models were able to characterize the postprandial TG response in individuals who are lean, obese, or very obese following a high-fat meal. The extended TIGG model resulted in a better model fit of the glucose data compared to the tTIGG model, indicating that chylomicron and VLDL-V6 provided additional information compared to total TGs. Furthermore, the expanded TIGG model was able to predict the postprandial TG response of chylomicrons and VLDL-V6 using the total TGs and could therefore be used in studies where only total TGs were collected.
Topics: Humans; Triglycerides; Insulin; Glucose; Glucagon-Like Peptide 1; Lipoproteins; Chylomicrons; Obesity; Blood Glucose; Postprandial Period
PubMed: 37667531
DOI: 10.1002/psp4.13030 -
Frontiers in Endocrinology 2024Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically...
Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.
INTRODUCTION
Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT).
PATIENTS AND METHODS
In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed.
RESULTS
Serum FGF21 significantly increased in the fasting state ( < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD ( < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC ( < 0.05) and was an independent factor for MAFLD ( < 0.05, OR=1.403).
CONCLUSION
Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.
Topics: Humans; Fibroblast Growth Factors; Male; Female; Postprandial Period; Middle Aged; Adult; Inflammation; Lipids; Non-alcoholic Fatty Liver Disease; Triglycerides; Dietary Fats; Biomarkers; Fatty Acids, Nonesterified
PubMed: 38828414
DOI: 10.3389/fendo.2024.1343853 -
MedRxiv : the Preprint Server For... Dec 2023Continuous glucose monitors (CGMs) are being used to characterize postprandial glycemic responses and thereby provide personalized dietary advice to minimize glycemic...
Imprecision nutrition? Duplicate meals result in unreliable individual glycemic responses measured by continuous glucose monitors across four dietary patterns in adults without diabetes.
BACKGROUND
Continuous glucose monitors (CGMs) are being used to characterize postprandial glycemic responses and thereby provide personalized dietary advice to minimize glycemic excursions. However, the efficacy of such advice depends on reliable CGM responses.
OBJECTIVE
To explore within-subject variability of CGM responses to duplicate meals in an inpatient setting.
METHODS
CGM data were collected in two controlled feeding studies (NCT03407053 and NCT03878108) in 30 participants without diabetes capturing 1056 meal responses in duplicate ~1 week apart from four dietary patterns. One study used two different CGMs (Abbott Freestyle Libre Pro and Dexcom G4 Platinum) whereas the other study used only Dexcom. We calculated the incremental area under the curve (iAUC) for each 2-h post-meal period and compared within-subject iAUCs using the same CGM for the duplicate meals using linear correlations, intra-class correlation coefficients (ICC), Bland-Altman analyses, and compared individual variability of glycemic responses to duplicate meals versus different meals using standard deviations (SDs).
RESULTS
There were weak to moderate positive linear correlations between within- subject iAUCs for duplicate meals (Abbott r=0.47, p<0.0001, Dexcom r=0.43, p<0.0001), with low within-participant reliability indicated by ICC (Abbott 0.31, Dexcom 0.14). Bland-Altman analyses indicated wide limits of agreement (Abbott -31.3 to 31.5 mg/dL, Dexcom -30.8 to 30.4 mg/dL) but no significant bias of mean iAUCs for duplicate meals (Abbott 0.1 mg/dL, Dexcom -0.2 mg/dL). Individual variability of glycemic responses to duplicate meals was similar to that of different meals evaluated each diet week for both Abbott (SD = 10.7 mg/dL , SD =12.4 mg/dL, SD =11.6 mg/dL, =0.38) and Dexcom (SD = 11.1 mg/dL, SD = 11.5 mg/dL, SD =11.9 mg/dL, =0.60).
CONCLUSIONS
Individual postprandial CGM responses to duplicate meals were unreliable in adults without diabetes. Personalized diet advice based on CGM measurements in adults without diabetes requires more reliable methods involving aggregated repeated measurements.
PubMed: 37503002
DOI: 10.1101/2023.06.14.23291406 -
The Journal of Nutrition Feb 2024Protein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Protein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability.
OBJECTIVE
Our objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients.
METHODS
Sixteen patients who were mechanically ventilated in intensive care unit (ICU) at risk of malabsorption received a primed continuous infusion of L-[ring-H]-phenylalanine and L-[ring-3,5-H]-tyrosine after an overnight fast. Patients were randomly allocated to receive 20 g intrinsically L-[1-C]-phenylalanine-labeled milk protein or an equivalent amount of amino acids labeled with free L-[1-C]-phenylalanine via a nasogastric tube over a 2-h period. Protein digestion and amino acid absorption kinetics and whole-body protein net balance were assessed throughout a 6-h period.
RESULTS
After enteral nutrient infusion, both plasma phenylalanine and leucine concentrations increased (P-time < 0.001), with a more rapid and greater rise after free amino acid compared with intact protein administration (P-time × treatment = 0.003). Diet-derived phenylalanine released into the circulation was 25% greater after free amino acids compared with intact protein administration [68.7% (confidence interval {CI}: 62.3, 75.1%) compared with 43.8% (CI: 32.4, 55.2%), respectively; P < 0.001]. Whole-body protein net balance became positive after nutrient administration (P-time < 0.001) and tended to be more positive after free amino acid in provision (P-time × treatment = 0.07).
CONCLUSIONS
The administration of free amino acids as opposed to intact protein further increases postprandial plasma amino acid availability in critically ill patients, allowing more diet-derived phenylalanine to become available to peripheral tissues. This trial was registered at clinicaltrials.gov as NCT04791774.
Topics: Humans; Amino Acids; Critical Illness; Dietary Proteins; Muscle Proteins; Phenylalanine; Postprandial Period
PubMed: 38103646
DOI: 10.1016/j.tjnut.2023.12.015 -
Food Research International (Ottawa,... Jun 2024Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet,...
Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adult; Permeability; Obesity; Fasting; Male; Glucagon-Like Peptide 2; Intestinal Mucosa; Gastrointestinal Microbiome; Nutrients; Young Adult; Haptoglobins; Endotoxemia; Lipopolysaccharide Receptors; Acute-Phase Proteins; Biomarkers; Membrane Glycoproteins; Dietary Fats; Glucose; Intestinal Barrier Function; Carrier Proteins; Protein Precursors
PubMed: 38729719
DOI: 10.1016/j.foodres.2024.114338 -
BMJ Open Feb 2024The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth,...
INTRODUCTION
The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown.
METHODS AND ANALYSIS
The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis.
ETHICS AND DISSEMINATION
The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings.
TRIAL REGISTRATION NUMBER
NCT05124808.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Diabetes, Gestational; Fetal Macrosomia; Hypoglycemia; Multicenter Studies as Topic; Obesity; Overweight; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 38423770
DOI: 10.1136/bmjopen-2023-082126 -
Nutrition (Burbank, Los Angeles County,... Jun 2024Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain...
BACKGROUND
Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain and increased insulin resistance, but detailed knowledge on how chemotherapy impact metabolic and endocrine mechanisms remain unknown.
OBJECTIVES
We performed a thorough, preliminary study to elucidate the differing mechanisms of postprandial absorption and metabolism in postmenopausal early breast cancer (EBC) patients treated with adjuvant chemotherapy compared to healthy controls. We hypothesize that chemotherapy has a negative impact on metabolism in EBC patients.
METHODS
We examined four postmenopausal women shortly after treatment with chemotherapy for EBC and four age-matched healthy women who served as controls using isotopic tracers during a mixed meal-test. Blood was sampled during the 240 min meal-test to examine postprandial absorption and endogenous synthesis of lipid and carbohydrate metabolites.
RESULTS
We found that insulin concentrations were numerically higher before the meal-test in the EBC patients compared to controls (76.3 pmol/L vs 37.0 pmol/L; P = 0.06). Glucose kinetics was increased postprandial (most pronounced at 30 min, 9.46 mmol/L vs 7.33 mmol/L; P = 0.51), with no difference between the groups regarding liver glucose output. Fatty acid kinetics showed a numeric increase in oleic acid rate of appearance in BC patients, but only during the first hour after the mixed meal. There was no significant difference in VLDL-TAG synthesis between the two groups.
CONCLUSIONS
This preliminary study is unique in using advanced tracer methods to investigate in vivo metabolism of EBC patients after chemotherapy although no statistical differences in glucose and fatty acid kinetics was seen compared to controls. However, during the first two postprandial hours, oral glucose and oleic acid appearance in the systematic circulation was elevated in the EBC patients. This could be due to changes in gastrointestinal uptake and further studies with altered set-up could provide valuable insights.
Topics: Humans; Female; Glucose; Breast Neoplasms; Oleic Acid; Postmenopause; Preliminary Data; Blood Glucose; Insulin; Fatty Acids; Postprandial Period; Triglycerides
PubMed: 38458062
DOI: 10.1016/j.nut.2024.112394 -
Therapeutic Advances in Endocrinology... 2023Handling of the dawn phenomenon (DP) with multiple daily insulin injection (MDII) regimen is a real challenge.
BACKGROUND
Handling of the dawn phenomenon (DP) with multiple daily insulin injection (MDII) regimen is a real challenge.
OBJECTIVE
We aimed to demonstrate the effectiveness of a dual-basal-insulin (a long-acting glargine and an intermediate-acting neutral protamine Hagedorn (NPH)) regimen for the management of DP in children with type 1 diabetes mellitus (T1DM). The primary efficacy outcome was to overcome morning hyperglycemia without causing hypoglycemia during the non-DP period of the night.
DESIGN
Retrospective cohort study.
METHOD
Charts of 28 children with T1DM (12 female; 42.8%, mean age 13.7 ± 2.1 years) treated with MDII were retrospectively reviewed. The median duration of diabetes was 4.5 years (range 2-13.5 years). DP was diagnosed using a threshold difference of 20 mg/dL (0.1 mmol/L) between fasting capillary blood glucose at 3 a.m. and prebreakfast. NPH was administered at midnight in addition to daily bedtime (08.00-09.00 p.m.) glargine (dual-basal-insulin regimen). Midnight, 03:00 a.m., prebreakfast and postprandial capillary blood glucose readings, insulin-carbohydrate ratios, and basal-bolus insulin doses were recorded the day before the dual-basal-insulin regimen was started and the day after the titration of the insulin doses was complete. Body mass index standard deviation scores (BMI SDS) at the onset-3rd-12th month of treatment were noted.
RESULTS
Before using dual basal insulin, prebreakfast capillary blood glucose levels were greater than those at midnight and at 03:00 a.m. ( = 64.985, < 0.01). After titration of the dual-basal-insulin doses, there were significant improvements such that there were no statistically significant differences in the capillary blood glucose measurements at the three crucial time points (midnight, 03.00 a.m., and prebreakfast; = 1.827, = 0.172). No instances of hypoglycemia were reported, and the total daily insulin per kilogram of body weight did not change. The BMI SDS remained steady over the course of the 1-year follow-up.
CONCLUSION
In this retrospective cohort study, the dual-basal-insulin regimen, using a long-acting glargine and an intermediate-acting NPH, was effective in overcoming early morning hyperglycemia due to insulin resistance in the DP. However, the effectiveness of the dual-basal-insulin regimen needs to be verified by prospective controlled studies using continuous glucose monitoring metrics or frequent blood glucose monitoring.
PubMed: 38152658
DOI: 10.1177/20420188231220130 -
International Journal of Surgery Case... Nov 2023Polycystic liver disease (PCLD) is a genetic disorder characterized by the growth of >10 cysts in the liver. PCLD is associated with polycystic kidney disease (PKD) in...
INTRODUCTION
Polycystic liver disease (PCLD) is a genetic disorder characterized by the growth of >10 cysts in the liver. PCLD is associated with polycystic kidney disease (PKD) in 80-90%of cases (Kothadia et al., 2023 [1]). PCLD can occur in isolation though rarely in children. We present a case report of a child with symptomatic isolated PCLD.
CASE PRESENTATION
A 23-month old female child presented with a 17-month history of gradual increase in abdominal mass. She had acute onset of postprandial vomiting and shortness of breath while lying flat. On examination, she was irritable with massive abdominal distension. Liver function test done showed markedly elevated liver enzymes with preservation of liver synthesis function. Computed tomography (CT) scan showed a large intra-abdominal cyst and normal kidneys bilaterally. During laparotomy, we found multiple exophytic cysts arising from segment IVa of the liver. Hepatic resection was done successfully and patient recovered uneventfully. Histology showed Von Meyenburg complexes characteristic of PCLD.
CLINICAL DISCUSSION
The goal of management should be to counter symptomatology by intervening on developed cysts. The therapeutic options are individualized to address the symptoms and improve the patients' quality of life. Follow up of the patients is based on the presentation and intervention performed, during which period recurrence of cysts is assessed. Complete resection of the liver cysts is recommended to avoid the risk of cholangiocarcinoma.
CONCLUSION
Close follow up by physical examination, laboratory tests and imaging modalities is necessary to detect any recurring masses and malignancy transformation of the cysts to enable timely intervention.
PubMed: 37837666
DOI: 10.1016/j.ijscr.2023.108950 -
Food Research International (Ottawa,... Jul 2024Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of chickpea hummus on postprandial blood glucose, insulin and gut hormones in healthy humans combined with mechanistic studies of food structure, rheology and digestion kinetics.
Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is increasing evidence that food structure plays a crucial role in influencing the bioaccessibility and digestion kinetics of macronutrients. The aims of this study were to compare the effects of two hummus meals, with different degrees of cell wall integrity, on postprandial metabolic responses in relation to the microstructural and rheological characteristics of the meals. A randomised crossover trial in 15 healthy participants was designed to compare the acute effect of 27 g of starch, provided as hummus made from either intact chickpea cells (ICC) or ruptured chickpea cells (RCC), on postprandial metabolic responses. In vitro starch digestibility, microstructural and rheological experiments were also conducted to evaluate differences between the two chickpea hummus meals. Blood insulin and GIP concentrations were significantly lower (P < 0.02, P < 0.03) after the consumption of the ICC meal than the meal containing RCC. In vitro starch digestion for 90 min was slower in ICC than in RCC. Microscopic examination of hummus samples digested in vitro for 90 min revealed more intact chickpea cells in ICC compared to the RCC sample. Rheological experiments showed that fracture for ICC hummus samples occurred at smaller strains compared to RCC samples. However, the storage modulus for ICC was higher than RCC, which may be explained by the presence of intact cells in ICC. Food structure can affect the rate and extent of starch bioaccessibility and digestion and may explain the difference in the time course of metabolic responses between meals. The rheological properties were measured on the two types of meals before ingestion, showing significant differences that may point to different breakdown mechanisms during subsequent digestion. This trial was registered at clinicaltrial.gov as NCT03424187.
Topics: Humans; Cicer; Postprandial Period; Insulin; Blood Glucose; Digestion; Cross-Over Studies; Rheology; Adult; Male; Female; Young Adult; Starch; Gastric Inhibitory Polypeptide; Healthy Volunteers; Kinetics
PubMed: 38823849
DOI: 10.1016/j.foodres.2024.114517