Improved practicality of insulin measurements by using urine as a source: relationship between serum and urine measurements as a function of dietary intake (Preprint)

2019 ◽  
Author(s):  
Shilpa Tejpal ◽  
Narinder Sanghera ◽  
Vijayalaxmi Manoharan ◽  
Thomas M Barber ◽  
Louise Halder ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Food Intake ◽  
Dietary Intake ◽  
Mobile Health ◽  
Urine Samples ◽  
Metabolic Effects ◽  
Blood Insulin ◽  
Laboratory Conditions ◽  
Low Carbohydrate

BACKGROUND Obesity, insulin resistance and diabetes are taking epidemic proportions and novel approaches to addressing this world-wide public health challenge are required. The only molecular parameter that is currently routinely measured in this domain is blood glucose in patients with diabetes. However, measuring insulin concentrations would be more informative of the metabolic state of any person and applicable to people with obesity at varying levels of insulin resistance, including those with normal blood glucose levels. We recently demonstrated with 52 participants dieting the utility of determining insulin concentrations in urine as a molecular feedback mechanism. OBJECTIVE Our ultimate goal is to replace invasive blood insulin measurements with a more non-invasive approach. Towards this goal, we here demonstrate the use of a mobile health application to record diet and anthropometric data together with the measurement of insulin in urine and in blood, in controlled laboratory conditions and in the field. METHODS Five females aged 40-50 years were recruited and studied under laboratory conditions. Two of these were also studied in their work/home environment. The participants recorded events such as food intake, urine volume and exercise to the mobile health platform available as webinterface personalhealth.warwick.ac.uk and as mobile applications through the apple and google play stores. Urine samples were collected while varying dietary intake (low-carbohydrate, normal and ketogenic diets) and timing of food intake. Urine insulin values were measured by a highly sensitive immunosandwich electrochemiluminescence assay, which features 5 orders of magnitude in dynamic range and a fM detection limit. RESULTS We show that blood insulin and urine insulin values are linearly dependent, with urine concentrations being 3 times lower than the corresponding concentrations in serum. Characteristic urine insulin profiles were obtained by varying diet and participant and were found to be highly reproducible for the same diet/participant combination. As expected, concentrations of insulin were overall higher under normal diet conditions as compared to low-carbohydrate or ketogenic diet conditions. CONCLUSIONS This research demonstrates a practical and accurate approach to measure insulin in urine without the need for pre-processing of urine samples. The approach is applicable to a broad range of insulin concentrations as found under a variety of dieting conditions and inter-personal differences. Potential applications are improved diabetes care, and diet adherence monitoring, useful not only for clinicians but also for individuals who can thus obtain personalized metabolic feedback to food intake choices. This may empower individuals to visualize the metabolic effects of nutritional interventions with the quantitative biomarker insulin. CLINICALTRIAL NA

scholarly journals Leptin and hyperleptinemia - from friend to foe for cardiovascular function

2004 ◽  
Vol 181 (1) ◽  
pp. 1-10 ◽  
Author(s):  
J Ren
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
Cardiovascular Function ◽  
Metabolic Effects ◽  
Leptin Resistance ◽  
Elevated Plasma ◽  
The Metabolic Syndrome ◽  
Bodily Function ◽  
Plasma Leptin ◽  
Dependent Mechanism

The obese gene product, leptin, plays a central role in food intake and energy metabolism. The physiological roles of leptin in human bodily function have been broadened over the past decade since leptin was first discovered in 1994. Evidence has suggested that leptin plays a specific role in the intricate cascade of cardiovascular events, in addition to its well-established metabolic effects. Leptin, a hormone linking adiposity and central nervous circuits to reduce appetite and enhance energy expenditure, has been shown to increase overall sympathetic nerve activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin is capable of regulating cardiac and vascular contractility through a local nitric oxide-dependent mechanism. However, elevated plasma leptin levels or hyperleptinemia, have been demonstrated to correlate with hyperphagia, insulin resistance and other markers of the metabolic syndrome including obesity, hyperlipidemia and hypertension, independent of total adiposity. Elevated plasma leptin levels may be an independent risk factor for the development of cardiovascular disease. Although mechanisms leading to hyperleptinemia have not been well described, factors such as increased food intake and insulin resistance have been shown to rapidly enhance plasma leptin levels and subsequently tissue leptin resistance. These findings have prompted the speculation that leptin in the physiological range may serve as a physiological regulator of cardiovascular function whereas elevated plasma leptin levels may act as a pathophysiological trigger and/or marker for cardiovascular diseases due to tissue leptin resistance.

scholarly journals Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo

2018 ◽  
Vol 32 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Jacob S Ballon ◽  
Utpal B Pajvani ◽  
Laurel ES Mayer ◽  
Zachary Freyberg ◽  
Robin Freyberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
Healthy Volunteers ◽  
Second Generation ◽  
Metabolic Effects ◽  
Insulin Metabolism

Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.

scholarly journals Effect of High Versus Low Carbohydrate Intake in the Morning on Glycemic Variability and Glycemic Control Measured by Continuous Blood Glucose Monitoring in Women with Gestational Diabetes Mellitus—A Randomized Crossover Study

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 475 ◽  
Author(s):  
Louise Rasmussen ◽  
Maria Lund Christensen ◽  
Charlotte Wolff Poulsen ◽  
Charlotte Rud ◽  
Alexander Sidelmann Christensen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Crossover Study ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Low Carbohydrate ◽  
Randomized Crossover Study

Carbohydrate is the macronutrient that has the greatest impact on blood glucose response. Limited data are available on how carbohydrate distribution throughout the day affects blood glucose in women with gestational diabetes mellitus (GDM). We aimed to assess how a high-carbohydrate morning-intake (HCM) versus a low-carbohydrate-morning-intake (LCM), affect glycemic variability and glucose control. In this randomized crossover study continuous glucose monitoring (CGM) was performed in 12 women with diet treated GDM (75 g, 2-h OGTT ≥ 8.5 mmol/L), who went through 2 × 3 days of HCM and LCM. A within-subject-analysis showed a significantly higher mean amplitude of glucose excursions (MAGE) (0.7 mmol/L, p = 0.004) and coefficient of variation (CV) (5.1%, p = 0.01) when comparing HCM with LCM, whereas a significantly lower mean glucose (MG) (−0.3 mmol/L, p = 0.002) and fasting blood glucose (FBG) were found (−0.4 mmol/L, p = 0.01) on the HCM diet compared to the LCM diet. In addition, insulin resistance, expressed as Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), decreased significantly during HCM. Results indicate that a carbohydrate distribution of 50% in the morning favors lower blood glucose and improvement in insulin sensitivity in women with GDM, but in contrary gives a higher glycemic variability.

scholarly journals Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat

2015 ◽  
Vol 23 (4) ◽  
pp. 192-6
Author(s):  
Trinovita Andraini ◽  
Sophie Yolanda
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Resistance Index ◽  
Insulin Level ◽  
Hibiscus Sabdariffa ◽  
Blood Insulin ◽  
High Fructose Diet ◽  
Insulin Resistance Index ◽  
High Fructose

Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were administered with a high-fructose diet (10% ad libitum) and Hibiscus sabdariffa Linn. extract at a dose of 100, 200, and 400 mg/kgBW/d simultaneously for 5 weeks. At the end of study, fasting blood glucose level, fasting blood insulin level and insulin resistance index (HOMA-IR) were measured.Results: Fasting blood glucose, blood insulin, and HOMA-IR level of rats given high-fructose diet with Hibiscus sabdariffa Linn. at dose 100 mg/kgBW/d were not significantly different than the group of rats given only high-fructose fed. While at the dose of 400 mg/kgBW/d, they were significantly lower than the group given only high-fructose fed (4.84 mmol/L vs 6.11 mmol/L, 0.07 µU/L vs 0.3 µU/L, and 0.02 vs 0.08 respectively).Conclusion: Oral administration of Hibiscus sabdariffa Linn. could prevent the development of insulin resistance induced by high-fructose diet in the rat.

scholarly journals Antidiabetic and Antiobesity Effects of Artemether in db/db Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Guo ◽  
Wei Fu ◽  
Yakai Xin ◽  
Jinlei Bai ◽  
Huifang Peng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Food Intake ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Tunel Staining ◽  
Intragastric Administration

This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P<0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P<0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P<0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

scholarly journals Effect of Chia (Salvia hispanica L.) Flour on Glycemic Response and Energy Intake in Healthy Adults (P06-099-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Olivia Coelho ◽  
Daniela Rocha ◽  
Barbara Pereira da Silva ◽  
Alessandra Silva ◽  
Ana Paula Caldas ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Dietary Intake ◽  
Energy Intake ◽  
Repeated Measures ◽  
Normal Weight ◽  
Healthy Adults ◽  
Glycemic Response ◽  
Repeated Measures Anova ◽  
Anova Test

Abstract Objectives Postprandial glycemic control is essential in both healthy and diabetic people, as hyperglycemia predisposes to complications associated with diabetes. The consumption of fiber-rich meals help to prevent and control undesirable glycemic changes. This study aimed to evaluate the effect of one-day consumption of chia on glycemic response and energy intake in healthy adults. Methods Single-blind, randomized, crossover design study involving healthy adults, normal weight (BMI 18.5–24.9 kg/m2), euglycemic (100 mg/dL), with no diabetes family history. They attended to the laboratory after 10–12 h fasting and received either 350 ml of a shake containing 10 g of chia flour (4.44 g of fiber) or 350 ml of a control shake (1.1 g of fiber)- similar in calories and macronutrients, containing 51 g of available carbohydrate - on two non-consecutive days (washout period). At each testing day, 60 minutes after shake intake a glucose solution (25 g) was provided. Capillary blood glucose was measured in fasting state (−60 min), immediately before (0 min), and 15, 30, 45, 60, 90, 120 minutes after glucose load. In addition, food intake was assessed 24-hour dietary recall was performed after each testing day. Habitual dietary intake was estimated using the semi-quantitative QFCA. The study was approved by the Local Ethics Committee. Repeated-measures ANOVA test was used to compare habitual dietary intake and consumption after shake. Two-way repeated measures ANOVA test followed by Bonferroni's post-hoc was used to assess the differences in postprandial blood glucose. Incremental area under the curve (AUC) of postprandial glycemia was calculated using the trapezoidal rule and paired sample t-test was used to compare them. All analyses were conducted using SPSS software. Statistical significance was set as p < 0.05. Results Fifteen subjects completed the study (14 female and 1 male). Consumption of chia (10 g of chia flour) did not change the blood glucose (p > 0.05) nor food intake (p > 0.05) among adults (25 ± 1 years), euglycemic (87.88 ± 1.21 mg/dL), normal weight (21.06 ± 0.28 kg/m2 and 23.23 ± 1.19% body fat percentual). Conclusions The one-day consumption of chia flour did not affect the glycemic response and did not interfere in energy intake in healthy individuals. The long-term effect of chia should be assessed. Funding Sources CNPq, CAPES, FAPEMIG, FUNARBE, DNS-UFV. Supporting Tables, Images and/or Graphs

scholarly journals Dietary Intakes of Folic Acid During Pregnancy Determines Maternal Re-Set of Metabolism Post-Birth in Wistar Rat Dams (FS08-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Emanuela Pannia ◽  
Neil Yang ◽  
Mandy Ho ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Metabolic Pathways ◽  
Wistar Rat ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Carbon Pathways

Abstract Objectives Nutrition during pregnancy alters the “re-set” of maternal metabolism and in turn the mother's metabolic phenotype later in life. Folic acid (FA, synthetic folate) consumed at intakes above requirements during pregnancy by rats leads to increased weight gain and altered DNA methylation in central and peripheral pathways regulating food intake. The objectives of this study were to examine the effects of intakes below and above FA dietary requirements on the re-set of energy metabolic pathways in Wistar rat mothers early post-birth. Methods Pregnant Wistar rats (n = 12/group) were fed an AIN93G diet with 5 levels of FA: 0X, 1X (control, 2 mg FA/kg), 2.5X, 5X or 10X. Dams were fed 1X-FA during lactation up to 1-week post-weaning (PW) when maternal metabolism is thought to re-set to homeostasis and then terminated. Weekly body weight, food intake, expression of hypothalamic food-intake neurons, mRNA and protein expression of folate-related and energy metabolic genes, and glucoregulatory hormones were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was used as a surrogate index of insulin resistance. Results Below (0X) and above (5X and 10X) FA requirements during pregnancy suppressed expression of hepatic folate metabolism (methyltetrahydrofolate (MTHF) reductase, and methionine synthase; P < 0.05) genes and led to higher 5-MTHF (P < 0.005) in blood compared to control suggesting dysregulation of 1-carbon pathways. Dams fed 0X- and 5X-FA also had higher plasma insulin and HOMA-IR than controls and changes in glucose and lipid metabolism-regulating genes in muscle (Glucose transporter-4, and Peroxisome-proliferator activated receptors; P < 0.05) but not liver or adipose at 1-week PW. The diets did not affect expression of hypothalamic food intake neurons nor body weight or food intake of the dams from birth to 1-week PW. Conclusions FA below (0X) or above (5X, 10X) requirements during pregnancy induce dysregulation of 1-carbon pathways and delay re-set of energy metabolic pathways in Wistar rat dams by 4-weeks after birth, potentially programming long-term negative metabolic effects. Funding Sources This research was supported by: Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR-INMD); EP supported by NSERC Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program (CGS D).

THE INFLUENCE OF CORTISOL ON FOOD INTAKE AND GLUCOSE METABOLISM IN SHEEP

1963 ◽  
Vol 26 (4) ◽  
pp. 539-553 ◽  
Author(s):  
J. M. BASSETT
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Glucose Utilization ◽  
Nitrogen Excretion ◽  
Metabolic Effects ◽  
Urinary Nitrogen Excretion ◽  
Voluntary Food Intake ◽  
Urinary Nitrogen

SUMMARY Some metabolic effects of cortisol were investigated in non-pregnant ewes fed either ad lib. or on a restricted ration. Cortisol (25 mg./day) administered for a period of 21 days stimulated the voluntary food intake of fat ewes offered food ad lib. Higher levels of cortisol (50 and 75 mg./day) administered for similar periods subsequently had little additional effect on voluntary food intake, but an even greater cortisol dose (150 mg./day) resulted in a marked decline in voluntary food intake. Ewes fed a constant restricted ration did not refuse food at any time during cortisol administration. Urinary nitrogen excretion was increased during cortisol administration but sequential increases in the cortisol dose failed to increase urinary nitrogen excretion proportionately above the level attained during administration of 25 mg. cortisol/day. The blood glucose level was elevated progressively as the level of cortisol administered was increased. Similarly, tolerance for a glucose load was impaired progressively. Only very small changes in blood ketones and plasma free fatty acid levels were observed during cortisol administration. The changes in blood glucose during cortisol administration cannot be accounted for by changes in gluconeogenesis, and it is suggested that they reflect a progressive impairment of glucose utilization relative to the blood glucose level, though not a reduction in total glucose utilization.

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