Insulin Sensitivity In Healthy Subjects Research Articles

Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial

Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n=33/group). The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of -17.7% (-29.3% to -1.0%) in comparison to -2.8% (-30.7% to 40.6%) in the control group (P=0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350-1040 mU · L-1· min) to 671 mU · L-1· min (376-1010 mU · L-1· min) (P=0.04) was observed in the sucralose group for participants with adequate adherence. Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial.

ObjectiveThe aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes.MethodsEighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double‐blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic‐euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention.ResultsBody weight in both groups decreased significantly (−7.5% in the vitamin D group and −10% in the placebo group; P < 0.05 for both), with no between‐group differences. Serum 25‐hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg−1·min−1; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg−1·min−1; P = 0.84).ConclusionsCholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin‐resistant subjects with obesity.

Insulin sensitivity index (ISI 0-120) from oral glucose tolerance test in healthy young adults

Background: Insulin sensitivity (IS) is the body’s systemic responsiveness to glucose and it is the measure of the ability of endogenous insulin to reduce the glucose in extracellular fluids by inhibition of gluconeogenesis and increase peripheral glucose uptake. IS reflects on the efficiency of insulin in response to glucose intake in the body. In diabetics, IS subjects are interpreted to require smaller amounts of insulin to lower blood glucose levels than someone who has low sensitivity. There is a need to detect insulin resistance (IR) in the pre-disease state, i.e., before the onset of impaired glucose tolerance (IGT). Early detection of IR or decreased IS in healthy subjects before the onset of IGT is of importance as it facilitates implementation of preventive measures in subject with such high risk. Aims and Objectives: The objective of the study is detect early occurrence of low Insulin Sensitivity in healthy young adults, using Insulin Sensitivity Index derived from OGTT. Materials and Methods: A total of 80 healthy volunteers in the age group of 18-25 years were recruited for the study, 40 subjects were siblings of diabetics and 40 subjects were siblings of non-diabetics (SND) a standard (75 g) OGTT was performed for the study. Blood samples for determination of plasma glucose and insulin levels drawn at 0 (fasting), 30, 120 min after glucose solution ingestion. Assays of fasting (basal), 30, 120 min venous plasma glucose during OGTT was performed with glucose oxidase method on site using glucose auto analyzer. The serum plasma was stored at −20°C until assayed. Corresponding specific insulin concentration was determined using radioimmunoassay (RIA) with human specific antibody RIA kit IS was calculated using physiological OGTT based mathematical models. QUICKI was derived for fasting insulin and fasting glucose values. ISI 0-120: Uses OGTT values, using only 0 and 120 min post-glucose challenge insulin and glucose concentrations. The reference values for various IR and IS indexes for our urban population with normal OGTT (n = 79) are QUICKI = 0.31 (0.20-0.52) sibling of diabetics (SD) - 0.07, ISI 0-120 = 63.62 (27.37-134.79) SD - 22.71. We observed that SD had significantly lower IS indices ISI 0-120 (56.27, P < 0.002) and a trend toward significance for QUICKI (0.29578, P < 0.056). Results: We observed that the mathematical models ISI 0-120 to be a fairly reliable tool for assessment of IS in normoglycemic young adults, compared to QUICKI. ISI 0-120 take into consideration the all the parameters of the 2 h OGTT glucose and also includes insulin into consideration for evaluation. Simple OGTT based mathematical models can be used as a reasonable alternative to measure IS or IR instead of the cumbersome glucose clamp or other expensive techniques in epidemiological or general clinical settings. Conclusion: Detection of IR in pre-disease condition in healthy individuals, allows the physician to initiate preventive measures, such as lifestyle modification, diet and exercise, thereby preventing the high-risk subjects from progressing to disease state.

Acute caffeine ingestion reduces insulin sensitivity in healthy subjects: a systematic review and meta-analysis.

BackgroundAccording to previous meta-analyses, coffee consumption reduces the risk of type 2 diabetes mellitus. However, the underlying mechanism remains unknown. Whether caffeine, the key ingredient in coffee, has a beneficial effect on the glycemic homeostasis and the anti-diabetic effect is particularly controversial. The aim of this study was to summarize the effect of acute caffeine ingestion on insulin sensitivity in healthy men.MethodsA comprehensive literature search for papers published before April 2016 was conducted in EMBASE, PubMed, and Cochrane Library databases. Randomized controlled trials (RCTs) that investigated the effect of caffeine on insulin sensitivity in healthy humans without diabetes were included. A random effects meta-analysis was conducted using Review Manager 5.3.ResultsThe search yielded 7 RCTs in which caffeine intake was the single variant. Compared with placebo, caffeine intake significantly decreased the insulin sensitivity index, with a standardized mean difference of −2.06 (95% confidence interval −2.67 to −1.44, I2 = 49%, P for heterogeneity = 0.06).ConclusionAcute caffeine ingestion reduces insulin sensitivity in healthy subjects. Thus, in the short term, caffeine might shift glycemic homeostasis toward hyperglycemia. Long-term trials investigating the role of caffeine in the anti-diabetic effect of coffee are needed.

Impact of Endurance Exercise Training in the Fasted State on Muscle Biochemistry and Metabolism in Healthy Subjects: Can These Effects be of Particular Clinical Benefit to Type2 Diabetes Mellitus and Insulin-Resistant Patients?

Exercise trainingintervention is a cornerstone in the care of type2 diabetes mellitus (T2DM) and insulin resistance (IR), and it is pursued in order to optimize exercise interventions for these patients. In this regard, the nutritional state of patients during exercise (being in the fed or fasted state) can be of particular interest. The aim of the present review is to describe the impact of endurance exercise (training) in the fasted versus fed state on parameters of muscle biochemistry and metabolism linked to glycemic control or insulin sensitivity in healthy subjects. From these data it can then be deduced whether exercise training in the fasted state may be relevant to patients with T2DM or IR. In healthy subjects, acute endurance exercise in the fasted state is accompanied by lower blood insulin and elevated blood free fatty acid concentrations, stable blood glucose concentrations (in the first 60-90min), superior intramyocellular triacylglycerol oxidation and whole-body lipolysis, and muscle glycogen preservation. Long-term exercise training in the fasted state in healthy subjects is associated with greater improvements in insulin sensitivity, basal muscle fat uptake capacity, and oxidation. Therefore, promising results of exercise (training) in the fasted state have been found in healthy subjects on parameters of muscle biochemistry and metabolism linked to insulin sensitivity and glycemic control. Whether exercise training intervention in which exercise sessions are organized in the fasted state may be more effective in improving insulin sensitivity or glycemic control in T2DM patients and insulin-resistant individuals warrants investigation.

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

This review addresses the effects of growth hormone on diurnal insulin sensitivity in normal, patients with type 2 diabetes mellitus (T2DM) and animal models described in our previous studies. Results confirmed the presence of diurnal insulin sensitivity, or greater insulin sensitivity in the morning, in normal subjects. The exact cause of this circadian rhythm in plasma glucose levels in healthy subjects has not been established, and nocturnal surges in growth hormone secretion remain a possible explanation. Results showed that growth hormone is an important factor controlling the diurnal variation of glucose tolerance and insulin sensitivity in rats. Data from our previous study provided direct evidence that the role of growth hormone in regulating insulin sensitivity in healthy subjects may be related to changes in the metabolic clearance rate of insulin and the metabolism of non-esterified fatty acids. A different circadian rhythm for plasma glucose appears to be present in patients with T2DM with nadirs in the early evening and peaks in the early morning, indicating greater insulin sensitivity in the evening. As in normal subjects, the exact cause of these circadian rhythms in the plasma glucose levels of patients with T2DM provided direct evidence that the reduction in insulin sensitivity may be due to the nocturnal surge of growth hormone in the early morning hours.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial

Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23g of inositols in 250ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24h after consumption of the IEB. Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Adipose tissue μ-crystallin is a thyroid hormone-binding protein associated with systemic insulin sensitivity.

Circulating thyroid hormones have been described to be intrinsically associated with insulin sensitivity in healthy subjects. μ-Crystallin is a nicotinamide adenine dinucleotide phosphate-dependent thyroid hormone-binding protein that has been shown to bind T3 in the cytoplasm. We aimed to study μ-Crystallin expression in adipose tissue and in muscle in association with insulin action and thyroid function. μ-Crystallin gene expression was studied in 81 visceral and 75 sc adipose tissue samples and in 26 muscle samples from a cohort of subjects with a wide spectrum of adiposity (cohort 1). μ-Crystallin was also evaluated in 30 morbidly obese subjects in whom insulin action was evaluated using euglycemic clamp (cohort 2) and in 22 sc adipose tissue samples obtained before and after bariatric surgery-induced weight loss (cohort 3). μ-Crystallin was also evaluated during differentiation of human adipocytes. μ-Crystallin was overexpressed in human sc adipocytes using lentiviruses. μ-Crystallin gene expression was 2.6- to 3-fold higher in sc vs visceral adipose tissue in direct association with the expression of thyroid hormone receptor α 1 in cohort 1 and cohort 2. Visceral, but not sc, adipose tissue μ-Crystallin was positively associated with the serum T3/T4 ratio in cohort 1 and with insulin sensitivity in cohort 2. In fact, μ-Crystallin gene expression was significantly decreased in visceral adipose tissue (-43%) and in muscle (-26%) in subjects with impaired fasting glucose and type 2 diabetes. Weight loss did not result in significant sc adipose tissue μ-Crystallin changes. μ-Crystallin overexpression led to increased insulin-induced (Ser473)Akt phosphorylation in sc adipocytes. During differentiation of adipocytes, μ-Crystallin gene expression decreased in both visceral (P = .006) and sc (P = .003) adipocytes from obese subjects. Visceral, but not sc, adipose tissue μ-Crystallin is an adipose tissue factor linked to parameters of thyroid hormone action (T3/T4 ratio) and might mediate the interaction of thyroid function and insulin sensitivity.

Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans

The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m(2)). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC(0-120)Glucose) and insulin sensitivity index were calculated. A subgroup (n = 494) underwent hyperinsulinaemic-euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (p = 0.001, adjusted for gender, age, and BMI). Age strongly interacted (p < 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC(0-120)Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity.

A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects

A limited amount of research suggests that oral ingestion of pinitol (3-O-methyl-d-chiro-inositol) positively influences glucose tolerance in humans. This study assessed the effects of different doses of pinitol supplementation on glucose tolerance, insulin sensitivity and plasma pinitol concentrations. Thirty healthy subjects underwent two one-day trials in which they consumed a nutritive beverage (Fruit Up®) containing 2.5, 4.0 or 6.0g of pinitol and a corresponding placebo equivalent in both energy and carbohydrates. Blood samples were collected frequently over the 240-min test period. The pinitol-enriched beverage reduced serum glucose and insulin at 45 and 60min, but only at a dose of 6.0g. Plasma pinitol concentrations, maximum concentration and AUC increased according to the dose administered. The results show that a single dose of pinitol from a naturally-occurring food ingredient at the highest dose administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects.

Insulin Resistance Induced by Maximal Exercise Correlates With a Post-Exercise Increase in Uridine Concentration in the Blood of Healthy Young Men

Uridine is postulated to participate in the development of insulin resistance. Since exercise is an effective tool in the treatment of insulin resistance it appeared justified to assess the impact of maximal exercise on plasma uridine and insulin sensitivity indices (e.g. insulin and HOMA-IR) in healthy subjects. The study included forty-four healthy males (18.5+/-2.92 years, VO₂max 50.2+/-6.26 ml kg⁻¹ min⁻¹). Subjects performed a single maximal exercise on a bicycle ergometer. Blood samples were taken three times: immediately before exercise, immediately after exercise and at the 30(th) min of rest. Uridine concentrations were determined in the whole blood using high-performance liquid chromatography. Serum insulin levels were measured by a specific ELISA method. Insulin sensitivity was assessed by homeostasis model assessment method (HOMA-IR). A maximal exercise-induced increase in the concentration of uridine correlated with post-exercise increases in insulin levels and HOMA-IR. Our results indicate a relationship between the concentration of uridine in the blood and indicators of insulin sensitivity in healthy subjects. We are the first to demonstrate that a maximal exercise-induced increase in the concentration of uridine is correlated with post-exercise increases in insulin levels and HOMA-IR in healthy subjects. It appears that uridine may be an indicator of insulin resistance.

Frontiers in fiber nutrition: research and applications.

Frontiers in fiber nutrition: research and applications.

Aldosterone Production and Insulin Resistance in Healthy Adults

Aldosterone production is associated with insulin resistance in obese and hypertensive subjects. However, its effect on insulin sensitivity in healthy subjects is not clear. The objective of this study was to test the hypothesis that increased aldosterone production is associated with lower insulin sensitivity in healthy subjects. This is an analysis of data previously collected during studies conducted as part of the International Hypertensive Pathotype Consortium. Eighty-four subjects free of any medical or psychiatric illness were included in this study. They were studied after 7 d of a standardized high-sodium diet confirmed by 24-h urine sodium above 200 mEq. Insulin sensitivity index (ISI) was calculated after a 75-g oral glucose load with glucose and insulin measurements at 0, 30, 60, and 120 min. Serum aldosterone levels were measured after 45 min of angiotensin II (3 ng/kg/min) infusion. There were significant negative correlations between ISI and age, body mass index (BMI), diastolic blood pressure, and angiotensin II-stimulated aldosterone level (P < 0.01). On multivariate regression analysis, stimulated aldosterone level was an independent predictor of ISI after adjusting for age, BMI, and diastolic blood pressure. Stimulated aldosterone level predicted 8% of the variance in ISI (P = 0.003) with age, BMI, and diastolic blood pressure together predicting 23% of the variance in ISI. Thus, the final regression model predicted 31% of the variance in ISI (P < 0.0001). Aldosterone production is associated with insulin resistance in normotensive healthy subjects independent of traditional risk factors.

Colonic fermentation of indigestible carbohydrates of a previous evening meal increases tissue glucose uptake

Evening meals rich in indigestible carbohydrates have been shown to lower postprandial glucose concentrations after ingestion of a high glycemic index breakfast. This phenomenon is linked to colonic fermentation of indigestible carbohydrates but the underlying mechanism is not fully elucidated. We examined in which way glucose kinetics after the breakfast are changed due to colonic fermentation. In a cross‐over manner 10 healthy male subjects (21 ± 2 years, BMI: 21,4 ± 1 kg/m2) ingested as an evening meal either white wheat bread or cooked barley kernels, rich in indigestible carbohydrates. In the morning the dual isotope technique was applied to determine glucose kinetics after intake of 50 g 13C‐enriched glucose. Plasma insulin and non‐esterified fatty acid concentrations were measured as well as hydrogen excretion in breath. Postprandial glucose response was 29 % lower after the barley evening meal, whereas the concentrations of insulin and non‐esterified fatty acids were the same. Exogenous glucose appearance in the systemic circulation and endogenous glucose production did not differ, but tissue glucose uptake was increased after the barley evening meal. Hydrogen excretion was higher after the barley meal indicating increased colonic fermentation. Factors related to colonic fermentation of indigestible carbohydrate seem to have the ability to increase tissue insulin sensitivity in healthy subjects.

Effects of trans MUFA from dairy and industrial sources on muscle mitochondrial function and insulin sensitivity

Epidemiological studies suggest that chronic consumption of trans MUFA may alter muscle insulin sensitivity. The major sources of dietary trans MUFA (dairy fat vs. industrially hydrogenated oils) have different isomeric profiles and thus probably different metabolic consequences. These effects may involve alterations in muscle mitochondrial oxidative capacity, which may in turn promote insulin resistance if fatty acid oxidation is reduced. We report that in Wistar rats, an 8 week diet enriched (4% of energy intake) in either dairy, industrial, or control MUFA did not alter insulin and glucose responses to an intraperitoneal glucose tolerance test (1g/kg). In C2C12 myotubes, vaccenic and elaidic acids did not modify insulin sensitivity compared with oleic acid. Furthermore, the ex vivo total, mitochondrial and peroxisomal oxidation rates of [1-(14)C]oleic, vaccenic, and elaidic acids were similar in soleus and tibialis anterior rat muscle. Finally, an 8 week diet enriched in either dairy or industrial trans MUFA did not alter mitochondrial oxidative capacity in these two muscles compared with control MUFA but did induce a specific reduction in soleus mitochondrial ATP and superoxide anion production (P<0.01 vs. control). In conclusion, dietary trans MUFA of dairy or industrial origin have similar effects and do not impair muscle mitochondrial capacity and insulin sensitivity.

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

Insulin Secretion and Insulin Sensitivity in Relation to Fasting Glucose in Healthy Subjects

This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose. A total of 148 healthy women (aged 53-70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and >28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR1, AIR2, and AIR3) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range <4.32; 4.33-4.84; 4.85-5.22; and 5.23-6.1 mmol/l, respectively). The results show that 1) AIR1 was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR3 was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR2 did not show a similar trend to be increased at higher fasting glucose. It is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.

Growth hormone and IGFBP-3 but not IGF-1 are independent predictors of insulin sensitivity in healthy subjects: on the role of hGH in the metabolic syndrome

Growth hormone and IGFBP-3 but not IGF-1 are independent predictors of insulin sensitivity in healthy subjects: on the role of hGH in the metabolic syndrome

Glucagon secretion in relation to insulin sensitivity in healthy subjects

The study evaluated whether glucagon secretion is regulated by changes in insulin sensitivity under normal conditions. A total of 155 healthy women with NGT (aged 53-70 years) underwent a glucose-dependent arginine-stimulation test for evaluation of glucagon secretion. Arginine (5 g) was injected i.v. under fasting conditions (plasma glucose 4.8+/-0.1 mmol/l) and after raising blood glucose concentrations to 14.8+/-0.1 and 29.8+/-0.2 mmol/l. The acute glucagon response (AGR) to arginine during the three glucose levels (AGR(1), AGR(2), AGR(3)) was estimated, as was the suppression of baseline glucagon by the increased glucose. All women also underwent a 2-h euglycaemic-hyperinsulinaemic clamp study for estimation of insulin sensitivity. Insulin sensitivity was normally distributed, with a mean of 73.2+/-29.3 (SD) nmol glucose kg(-1) min(-1)/pmol insulin l(-1). When relating the variables obtained from the arginine test to insulin sensitivity, insulin resistance was associated with increased AGR and with increased suppression of glucagon levels by glucose. For example, the regression between insulin sensitivity and AGR(2) was r=-0.38 (p<0.001) and between insulin sensitivity and suppression of glucagon levels by 14.8 mmol/l glucose r=0.36 (p<0.001). Insulin sensitivity also correlated negatively with insulin secretion; multivariate analysis revealed that changes in insulin sensitivity and insulin secretion were independently related to changes in glucagon secretion. The body adapts to insulin resistance by increasing the glucagon response to arginine and by increasing the suppression of glucagon levels by glucose. Hence, not only the islet beta cells but also the alpha cells seem to undergo compensatory changes during the development of insulin resistance.

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects

To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased.