Plasma Glucose In Type Research Articles

The impact of prolonged walking on fasting plasma glucose in type 2 diabetes: A randomised controlled crossover study.

In many low-income countries, fasting glucose is the primary measure for monitoring glycaemic control. Many patients in these countries walk long distances to the clinic, but the impact of walking on fasting glucose in type 2 diabetes is unknown. We aimed to determine the impact of walking on fasting glucose in people with type 2 diabetes. In a randomised crossover trial, the change in glucose from baseline in the fasting state was compared between walking on a treadmill at a predetermined speed of 4.5 km/h for 1 h and not walking (resting) in people with type 2 diabetes. In all, 45 participants were enrolled and all completed both visits; 21/45 (46.7%) were women, and the median age was 51. Glucose during and after walking was similar to glucose while at rest; the glucose difference (walking minus rest) was -0.15 (95% CI: -0.55, 0.26) and -0.10 (95% CI: -0.50, 0.31) mmol/L at 1 and 2 h, respectively, p > 0.4 for both. Fasting plasma glucose is not meaningfully affected by prolonged walking in participants with type 2 diabetes; therefore, the reliability of fasting glucose for monitoring glycaemic burden is unlikely to be altered in patients who walk to the clinic.

Observer-based control for plasma glucose regulation in type 1 diabetes mellitus patients with unknown input delay.

This article introduces an observer-based control strategy tailored for regulating plasma glucose in type 1 diabetes mellitus patients, addressing challenges like unknown time-varying delays and meal disturbances. This control strategy is based on an extended Bergman minimal model, a nonlinear glucose-insulin model to encompass unknown inputs, such as unplanned meals, exercise disturbances, or delays. The primary contribution lies in the design of an observer-based state feedback control in the presence of unknown long delays, which seeks to support and enhance the performance of the traditional artificial pancreas by considering realistic scenarios. The observer and control gains for the observer-based control are computed through linear matrix inequalities formulated from Lyapunov conditions that guarantee closed-loop stability. This design deploys a soft and gentle dynamic response, similar to a natural pancreas, despite meal disturbances and input delays. Numerical tests demonstrate the scheme's effectiveness in glycemic level regulation and hypoglycemic episode avoidance.

Mesenchymal Stem Cell in Pancreatic Islet Transplantation.

Pancreatic islet transplantation is a therapeutic option for achieving physiologic regulation of plasma glucose in Type 1 diabetic patients. At the same time, mesenchymal stem cells (MSCs) have demonstrated their potential in controlling graft rejection, the most fearsome complication in organ/tissue transplantation. MSCs can interact with innate and adaptive immune system cells either through direct cell-cell contact or through their secretome including exosomes. In this review, we discuss current findings regarding the graft microenvironment of pancreatic islet recipient patients and the crucial role of MSCs operation as cell managers able to control the immune system to prevent rejection and promote endogenous repair. We also discuss how challenging stressors, such as oxidative stress and impaired vasculogenesis, may jeopardize graft outcomes. In order to face these adverse conditions, we consider either hypoxia-exposure preconditioning of MSCs or human stem cells with angiogenic potential in organoids to overcome islets' lack of vasculature. Along with the shepherding of carbon nanotubes-loaded MSCs to the transplantation site by a magnetic field, these studies look forward to exploiting MSCs stemness and their immunomodulatory properties in pancreatic islet transplantation.

Correlation of Glycated Hemoglobin with Plasma Glucose in Type 2 Diabetic Patients

Correlation of Glycated Hemoglobin with Plasma Glucose in Type 2 Diabetic Patients

Correlation of Glycated Hemoglobin with Plasma Glucose in Type 2 Diabetic Patients

Correlation of Glycated Hemoglobin with Plasma Glucose in Type 2 Diabetic Patients

Glucose measurement: Comparison of venous and capillary glucose measurements in type II diabetes mellitus.

Objective: To determine the comparison between the capillary glucose and venous plasma glucose in type II diabetic patients. Study Design: Cross Sectional Observational study. Setting: Al–Tibri Medical College and Hospital Karachi. Period: 1st January 2020 to 30th April 2020. Material & Methods: A total of 86 diabetic patients from the out-patient department with non-probability consecutive sampling were selected. Subjects were diagnosed cases of type II diabetes based on the screening recommendation by the American Diabetes Association between 35-75 years of age of either gender included in this study. Patients with type I diabetes, pregnant females and hematocrit of more than 55% or less than 35%, and patients taking medications like Acetaminophen, and Ascorbic acid were excluded from the study. Each participant was measured for the capillary blood glucose levels by using Accu Chek, Easy max and On-call EZII, using strips by Glucose Oxidase Method. A venous sample was collected within 5 minutes of finger-prick test in a sodium fluoride tube. A Statistical Package for Social Sciences version 22 was used for data analysis. Results: Out of 86 patients in the study, 48(55.8%) were females and 38((44.2%) were males with a mean age of 47.16±9.916. The mean blood sugars by venous plasma glucose were 249.58±110.75 mg/dl, by Accu Chek 250.47±117.071 mg/dl, by EasyMax 259.26±119.751 mg/dl, and by On-call EZII 249.33±124.380 mg/dl which shows statistically significant correlation with a p value of <0.001. The glucometers accuracy was determined by using Error grid analysis showed a strong positive correlation between the Accu Chek R2= 0.917, EasyMax R2= 0.917, and Oncall glucometers R2= 0.868 with venous plasma glucose with a statistically significant (p <0.001). Conclusion: This study shows a strong positive correlation between capillary and venous glucose measurements.

A Study of Relationship Between Serum Uric Acid, and Fasting Plasma Glucose in Type 2 Diabetes Mellitus Patients

The current study was conducted to observe the relationship between serum uric acid, lipid profile and fasting plasma glucose in type 2 DM patients. It was a cross-sectional study. A total of 618 participants were included in the study (203-healthy, 206-prediabetic and 209-T2DM). One way analysis of variance was used to compare the mean between these three groups. A linear regression model was used to find the relationship between SUA and FPG in T2DM. The mean values of serum uric acid in pre-diabetes and T2DM (4.929±1.33 and 4.69±1.41 mg/dl, respectively) were lower compared to healthy (5.40±1.08 mg/dl). SUA showed a significant positive correlation with serum triglycerides in T2DM (p<0.05). The linear regression model showed that SUA was inversely associated with FPG in T2DM after adjustment for age and gender. The biological interrelationship observed in the current study raises the possibility of potential pathogenic overlap between SUA and FPG. SUA might be involved in a metabolic imbalance which in turn leads to T2DM.

A Doubled-Blind, Crossover-RCT in T2DM for Evaluating Hypoglycemic Effect of <I>P. indicus</I>, <I>M. charantia</I>, <I>P. vulgaris</I> and <I>A. paniculata</I> in Central Java

This study investigated whether mixture extract of <em>Pterocarpus indicus, Momordica charantia, Phaseolus vulgaris</em> and <em>Andrographis paniculata</em> could lower plasma glucose in Type 2 Diabetes Mellitus (T2DM) patients. 43 T2DM patients, consist of 10 male and 33 female patients participated in this possitive-controlled, double-blind, and crossover clinical study with administration of either mixture extract (22 mg/kg BW) or glibenclamide 5 mg daily in breakfast time. Treatment of extract or glibenclamide was administered for a month, then medication was changed after a week of washout period and finally combination therapy was administered after wash out period as well. The efficacy of mixture extracts was measured by using Fasting Plasma Glucose (FPG) and two-hour Postprandial Plasma Glucose (PPG). Forty-one subjects completed the study. Data was analyzed using SPSS 19 with Student's t test, and p<0.05 was considered significant. FPG level significantly decreased 16.07 mg/dl after extract, 43.34 mg/dl after glibenclamide and 50.16 mg/dl after combination treatment. Two-hour PPG level decreased 25.88 mg/dl after extract, 66.61 after glibenclamide and 58.93 after combination treatment. We concluded that extract administration could lower FPG and PPG although not as good as glibenclamide treatment did and combination treatment was the best to lower FPG.

Sustaining Effect of Intensive Nutritional Intervention Combined with Health Education on Dietary Behavior and Plasma Glucose in Type 2 Diabetes Mellitus Patients.

Diabetes mellitus is very common in elderly Chinese individuals. Although nutritional intervention can provide a balanced diet, the sustaining effect on at-home dietary behavior and long-term plasma glucose control is not clear. Consequently, we conducted a long-term survey following one month of experiential nutritional intervention combined with health education. Based on the Dietary Guidelines for a Chinese Resident, we found that the food items met the recommended values, the percentages of energy provided from fat, protein, and carbohydrate were more reasonable after one year. The newly formed dietary patterns were “Healthy”, “Monotonous”, “Vegetarian”, “Japanese”, “Low energy”, and “Traditional” diets. The 2h-PG of female participants as well as those favoring the “Japanese diet” decreased above 12 mmol/L. Participants who selected “Japanese” and “Healthy” diets showed an obvious reduction in FPG while the FPG of participants from Group A declined slightly. “Japanese” and “Healthy” diets also obtained the highest DDP scores, and thus can be considered suitable for T2DM treatment in China. The results of the newly formed dietary patterns, “Japanese” and “Healthy” diets, confirmed the profound efficacy of nutritional intervention combined with health education for improving dietary behavior and glycemic control although health education played a more important role. The present study is encouraging with regard to further exploration of comprehensive diabetes care.

The effect of the glycaemic response of three commonly consumed meals on postprandial plasma glucose in type 2 diabetics at the University of Nigeria Teaching Hospital, Enugu

Objectives: This study evaluated the glycaemic response of three commonly consumed meals, and the resultant effect on postprandial plasma glucose response in type 2 diabetes mellitus patients at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State, Nigeria.Design: This was an experimental study on 100 consenting type 2 diabetes mellitus patients who were on medical nutrition therapy only, attending the University of Nigeria Teaching Hospital medical outpatient clinic between May 2012 and March 2013.Subjects and setting: One hundred non-diabetic healthy University of Nigeria Teaching Hospital workers served as the control. Participants consumed served portions of each meal containing 50 g of glycaemic carbohydrate. Only the control consumed 50 g glucose to establish glycaemic response. The three test meals comprised pap and bambara nut pudding; meat and okro soup with fermented cassava dough; and meat, beans and corn pottage with spinach.Outcome measures: Plasma glucose was measured quarter hourly, for two hours, from which glycaemic index (GI) and glycaemic load (GL) values were calculated per serving.Results: Two meals, namely meat, beans and corn pottage with spinach; and pap and bambara nut pudding; provided a lower glycaemic response and reduced postprandial plasma glucose peak compared to meat and okro soup with fermented cassava dough at 30, 45, 60, 90 and 120 minutes in non-diabetic and type 2 diabetes mellitus patients (p-value < 0.050). The lowest GI and GL values per serving were attributed to the meat, beans and corn pottage with spinach (33.00 ± 1.25 and 4.76 ± 0.67), while the highest respective values were found for the meat and okro soup with fermented cassava dough (74.50 ± 4.91 and 21.59 ± 1.06).Conclusion: Compared to the other two meals, the meal of meat, beans and corn pottage with spinach resulted in a lower glycaemic response, reduced postprandial plasma glucose in non-diabetic and type 2 diabetes mellitus patients, and constituted a healthy alternative to the other two.

Role of exercise intensity on GLUT4 content, aerobic fitness and fasting plasma glucose in type 2 diabetic mice.

Type 2 diabetes mellitus (T2D) results in several metabolic and cardiovascular dysfunctions, clinically characterized by hyperglycaemia due to lower glucose uptake and oxidation. Physical exercise is an effective intervention for glycaemic control. However, the effects of exercising at different intensities have not yet been addressed. The present study analysed the effects of 8 weeks of training performed at different exercise intensities on type 4 glucose transporters (GLUT4) content and glycaemic control of T2D (ob/ob) and non-diabetic mice (ob/OB). The animals were divided into six groups, with four groups being subjected either to low-intensity (ob/obL and ob/OBL: 3% body weight, three times/week/40 min) or high-intensity (ob/obH and ob/OBH: 6% body weight, three times per week per 20 min) swimming training. An incremental swimming test was performed to measure aerobic fitness. After the training intervention period, glycaemia and the content of GLUT4 were quantified. Although both training intensities were beneficial, the high-intensity regimen induced a more significant improvement in GLUT4 levels and glycaemic profile compared with sedentary controls (p < 0.05). Only animals in the high-intensity exercise group improved aerobic fitness. Thus, our study shows that high-intensity training was more effective for increasing GLUT4 content and glycaemia reduction in insulin-resistant mice, perhaps because of a higher metabolic demand imposed by this form of exercise.

Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated protein kinase

Apolipoprotein a1, which is a major lipoprotein component of high-density lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes. Although recent studies also have shown that apolipoprotein a1 is involved in triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1 increased mitochondrial DNA and mitochondria contents through sustained AMPK activation in myotubes. This resulted in enhanced fatty acid oxidation and attenuation of free fatty acid-induced insulin resistance features in skeletal muscle. The increment of mitochondria was mediated through induction of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear transcription factor 1 (NRF-1). The inhibition of AMPK by a pharmacological agent inhibited the induction of mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1 occurs through activation of upstream kinase LKB1. Finally, we confirmed that scavenger receptor Class B, type 1 (SR-B1) is an important receptor for apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our study suggests that apolipoprotein a1 can alleviate obesity related metabolic disease by inducing AMPK dependent mitochondrial biogenesis.

Relationship of Glycosylated Hemoglobin with Fasting Plasma Glucose and 2 Hours After Breakfast Plasma Glucose in Type 2 Diabetes

Background: Glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and 2 hours (2-hr) after breakfast (ABF) plasma glucose, are often used to monitor and manage glycemia in stable diabetic patients. Data regarding the relationship and relative contribution of FPG and 2-hr ABF plasma glucose to HbA1c level in Type 2 diabetes mellitus (T2DM) are insufficient. Objective: To examine the correlation of FPG, and 2-hr ABF with HbA1c in known patients having T2DM; and to find out which one of FPG and ABF is the dominant contributor to overall glycemia in monitoring diabetes. Study Design and Methods: The study was carried on 664 known T2DM patients under treatment and routine follow-up at a tertiary care hospital in Bangladesh. FPG & 2-hr ABF plasma glucose concentrations were measured by hexokinase method. HbA1c was measured by high performance liquid chromatography based hemoglobin assay system. The Pearson correlation coefficient was used to investigate the relationship of FPG and ABF with HbA1c and their significance. Results: Both FPG and ABF levels were correlated with HbA1c but higher correlation was seen between FPG and HbA1c. The correlation coefficients between FPG and HbA1c and between ABF and HbA1c were 0.722 and 0.664 respectively. Both the correlations were found statistically significant (p<0.001). Conclusion: In patients with T2DM, FPG and ABF both were significantly correlated with HbA1c; and in our study we found that overall correlation of HbA1c with FPG was higher than ABF plasma glucose level.

Serum glycated albumin as a new glycemic marker in pediatric diabetes.

PurposeSerum glycated albumin (GA) has been recently used as another glycemic marker that reflects shorter term glycemic control than glycated hemoglobin (HbA1c). Insulin secretory function and glycemic fluctuation might be correlated with the ratio of GA to HbA1c (GA/HbA1c) in diabetic adult patients. This study investigated the association of GA and GA/HbA1c ratio with the levels of fasting C-peptide, fasting plasma glucose in type 1 and type 2 pediatric diabetes.MethodsTotal 50 cases from 42 patients were included. The subjects were classified into type 1 diabetes mellitus (T1DM) (n=30) and type 2 diabetes mellitus (T2DM) (n=20) group. The associations among HbA1c, GA, and GA/HbA1c ratio were examined. The relationship between the three glycemic indices and fasting glucose, fasting C-peptide were analyzed.ResultsMean values of GA, the GA/HbA1c ratio were significantly higher in T1DM than T2DM. GA (r=0.532, P=0.001), HbA1c (r=0.519, P=0.002) and the GA/HbA1c ratio (r=0.409, P=0.016) were correlated with the fasting plasma glucose. Fasting C-peptide level arranged 4.22±3.22 ng/mL in T2DM, which was significantly above the values in T1DM (0.26±0.49 ng/mL). There were no significant correlation between HbA1c and fasting C-peptide level. However, GA and the GA/HbA1c ratio exhibited inverse correlations with fasting C-peptide level (r=-0.214, P=0.002; r=-0.516, P<0.001).ConclusionGA seems to more accurately reflects fasting plasma glucose level than HbA1c. GA, GA/HbA1c ratio appear to reflect insulin secretory function.

Abstract 9918: Novel and Profound Lipid Effects of GSK1292263, a Potent and Selective GPR119 Agonist, in Dyslipidemic Subjects

GSK1292263 (GSK263), a GPR119 agonist, improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. Unexpectedly, GSK263 lowered fasting LDLc and triglycerides (TG), while increasing HDLc in these diabetic subjects. The study aim was to determine whether GSK263 improves lipid profiles in dyslipidemic, non-diabetic subjects when dosed alone or with atorvastatin (NCT# 01218204). Eligible subjects on statin/Vytorin therapy were washed off these drugs for 4 weeks. After washout, they were randomized to receive (i) 100mg (n=11), 300mg (n=12) or 800mg (n=13) QD of GSK263 or placebo (n=11) for 2 weeks; or (ii) 10mg atorvastatin (A10) or 80mg atorvastatin (A80) for a 4-week Run-in period. After the atorvastatin Run-in, (i) A10 was co-dosed with: 100mg (n=11), 300mg (n=11), 800mg (n=11) QD GSK263, placebo (n=12) or 10mg ezetimibe (n=13), and (ii) A80 was co-dosed with: 800mg (n=12) QD GSK263 or placebo (n=13). Fasting plasma lipids and NMR lipoprotein particles (LipoProfile) were measured at baseline and after 2 weeks of dosing. By ANCOVA (change from baseline), 800mg GSK263 significantly increased fasting HDLc by 20.7% (95% CI 9.8 to 31.6%), reduced fasting LDLc by 21.8% (95% CI -32.1 to -11.2%), and reduced fasting TGs by 54.8% (95% CI -70.8 to -38.9%) when compared to placebo. TG AUCs (wm 0-24h) fell by 41.3% (95% CI -61.9 to -20.8%). Similar effects were seen when co-dosed with A10 and A80. The lipid effects were dose-dependent, with GSK263 100mg having minimal effect. GSK263 may reduce apoB100, apoE and CRP, but had no clear effect on apoA1. NMR analysis suggests that GSK263 (i) reduced VLDL and chylomicron particle number and VLDL particle size, (ii) reduced LDL and IDL particle number and increased LDL particle size, and (iii) increased HDL particle number and size, especially when co-administered with atorvastatin. GSK263 was generally well tolerated over the dose range of 100mg to 800mg QD administered for 14 days. The majority of AEs associated with GSK1292263 were mild in intensity. GSK263 has significant effects on plasma lipids and lipoprotein particles in dyslipidemic patients when dosed alone and with atorvastatin. Studies are on-going to investigate the novel mechanisms underlying these lipid effects.

Normal Postprandial Nonesterified Fatty Acid Uptake in Muscles Despite Increased Circulating Fatty Acids in Type 2 Diabetes

OBJECTIVEPostprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes.RESEARCH DESIGN AND METHODSThigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [11C]acetate and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups.RESULTSIn the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol ⋅ g−1 ⋅ min−1, P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol ⋅ g−1 ⋅ min−1, P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005).CONCLUSIONSPostprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon.

Expression and purification of exendin-4, a GLP-1 receptor agonist, in Escherichia coli

Exendin-4 is a 39 amino acid peptide isolated from salivary secretions of Gila monster ( Heloderma suspectum). It shows 53% sequence similarity to glucagon-like peptide-1 (GLP-1), which is evaluated for the regulation of plasma glucose in type 2 diabetes. Exendin-4 is a potent and long-acting agonist of GLP-1 receptor. In the present study, the exendin-4 gene obtained by PCR with an enterokinase site at N-terminus and a termination codon at C-terminus was expressed in Escherichia coli strain BL21 (DE3) harboring pET32a(+). The fusion protein was purified by chromatography on Ni–NTA–agarose column. Recombinant exendin-4 was obtained by enterokinase cleavage of the fusion protein and subsequent purification. The yield of recombinant exendin-4 was 3.15 mg/10 g bacteria. The obtained recombinant exendin-4 shows glucose-lowering action in vivo.

Comparison of lunch and bedtime NPH insulin plus mealtime insulin Lispro therapy with premeal regular insulin plus bedtime NPH insulin therapy in type 2 diabetes

Aim: Nonfasting plasma glucose is claimed to be a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. In this study we compared the efficacy and safety profile of two different intensive insulin treatment strategies in patients with uncontrolled type 2 diabetes despite using a twice-daily insulin regimen. Methods: We studied 60 insulin-treated patients who had uncontrolled type 2 diabetes. The study was a 6-month, open- label, randomised, parallel clinical trial conducted in two diabetes centres. The main end-points for analysis were weekly self-monitored blood glucose readings, HbA 1c levels, total daily insulin dose, weight gain and the number of hypoglycaemic episodes. Results: The breakfast 2-h, lunch 2-h and dinner 2-h postprandial glucose values and pre-dinner glucose values were significantly lower in the Lispro group than the regular insulin group. The HbA 1c value at the end of the study was significantly lower in the Lispro group (7.3±0.7%) compared with the regular insulin group (7.7±0.7%; P<0.05). Mean insulin doses were similar in the treatment groups initially and at the end. There was a statistically significant increase in insulin dose in both groups from baseline to the end of the study ( P<0.05). Overall hypoglycaemia rates were comparably low and similar in both groups during the study. Conclusions: We have shown that mealtime insulin Lispro plus additional lunch and bedtime NPH insulin is superior to premeal regular insulin plus bedtime NPH insulin for overall glyceamic regulation with similar weight gain and comparable rates of hypoglycaemia.

The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes.

Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol x kg(-1) x min(-1)) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects.

The Insulinotropic Effect of Acute Exendin-4 Administered to Humans: Comparison of Nondiabetic State to Type 2 Diabetes

Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol·kg−1·min−1) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects.