C-peptide Area Under The Curve Research Articles

Acute Caffeine Ingestion and Glucose Tolerance in Women With or Without Gestational Diabetes Mellitus

ObjectiveRecent work showing that caffeine impairs glucose tolerance may be of particular concern in pregnancy because of a possible negative effect on fetal outcome. The current study sought to assess the effect of acute caffeine ingestion on glucose tolerance in women with or without gestational diabetes mellitus (GDM). MethodsNineteen women whose routine GDM test was negative (control) and eight women with an initial positive GDM screen completed two trials one week apart in a double-blind randomized crossover study. Following an overnight fast, subjects ingested caffeine (3 mg/kg pre-pregnancy body weight) or an identical-appearing placebo (gelatin) capsule and one hour later began a 75 g 2-hour oral glucose tolerance test. ResultsIn the control group, caffeine did not significantly affect blood glucose, insulin, or C-peptide. In the GDM group, glucose area under the curve (AUC) was greater (P < 0.01), C-peptide AUC was greater (P < 0.05), and insulin sensitivity index was lower (18%, P < 0.05) after caffeine than after placebo. ConclusionCaffeine impaired insulin sensitivity in women with GDM. Additional research regarding more specific dietary caffeine recommendations for women with GDM is warranted.

Entero-insular axis and postprandial insulin differences in African American and European American children

Background:African Americans have a greater insulin response after glucose challenge than do European Americans. Factors underlying this response are unknown. Objective:We determined the insulin, C-peptide, and incretin responses to a mixed macronutrient meal in African American and European American children. We hypothesized that 1) African Americans would have greater postprandial insulin and C-peptide responses, 2) African Americans would have higher incretin responses, and 3) the greater β cell response among African Americans would be explained by greater incretin responses. Design:Subjects were 34 African American and 18 European American children. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured after the subjects consumed a liquid mixed meal. Insulin, C-peptide, and incretin responses were derived from the area under the curve (AUC) for minutes 0–30 (early response) and minutes 30–180 (late response) after meal ingestion. Results:The early insulin response was higher in African American (14 565 ± 6840 pmol/L × 30 min) than in European American (7450 ± 4077 pmol/L × 30 min; P < 0.01) children. Early C-peptide AUC did not differ by ethnicity (African Americans: 34.8 ± 12.5; European Americans: 28.6 ± 12.5 nmol/L × 30 min; P = 0.10). Early and late GLP-1 responses were lower in African Americans than in European Americans: 108.1 ± 56.4 compared with 160.5 ± 90.8 pmol/L × 30 min and 509.4 ± 286.9 compared with 781.9 ± 483.4 pmol/L × 150 min, respectively (P < 0.05 for both). The GIP response did not differ between groups. Conclusions:The greater early insulin response in African Americans than in European Americans is not due to differences in circulating GLP-1 or GIP and may be due to lesser insulin clearance. Further research is needed to determine the physiologic implications of lower GLP-1 among African Americans.

Insulin resistance, secretion and breakdown are increased 9 months following severe burn injury

Insulin resistance in the acute burn period has been well described, however, it is unknown if alterations in glucose metabolism persist beyond discharge from the acute injury. To measure the duration of insulin resistance following recovery from the acute burn injury, we performed a prospective cross-sectional study with a standard 2-h oral glucose tolerance test in 46 severely burned children at 6, 9 or 12 months following initial injury. Glucose uptake and insulin secretion were assessed following the glucose load. Results were compared to those previously published in healthy children. At 6 months after burn, the 2-h glucose concentration was significantly ( P < 0.001) greater than controls, and the area under the curve (AUC) of glucose was significantly higher compared to 12 months and to healthy children ( P = 0.027 and P < 0.001, respectively). The 9-month AUC glucose was higher than controls ( P < 0.01). The 6-month 2-h insulin was significantly higher than controls, as was the AUC of insulin in all time points post-burn. The AUC of C-peptide was significantly greater at 6 months after injury compared to 9 and 12 months ( P < 0.01 for both). Increased 2 h and AUC glucose and insulin indicate that glucose metabolism is still affected at 6 and 9 months after injury, and coincides with previously documented defects in bone and muscle metabolism at these time points. Insulin breakdown is also still increased in this population. Further study of this population is warranted to determine if specific treatment is needed.

Improvement of insulin sensitivity and β‐cell function by nateglinide and repaglinide in type 2 diabetic patients – a randomized controlled double‐blind and double‐dummy multicentre clinical trial

To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and beta-Cell function in patients with type 2 diabetes. A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A(1c) (HbA(1c)) (p > 0.05). However, the effect on HbA(1c) in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function indexes measured by HOMA-beta, DeltaI(30)/DeltaG(30) and (DeltaI(30)/DeltaG(30))/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and beta-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA(1c) is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and beta-cell function.

Patterns of Metabolic Progression to Type 1 Diabetes in the Diabetes Prevention Trial–Type 1

There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis. Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points. Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up. These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.

Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity.

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.

Residual C-peptide secretion and endothelial function in patients with Type II diabetes

Recent studies have demonstrated that C-peptide exerts beneficial effects on endothelial function. To investigate the relationship between residual pancreatic C-peptide secretion and endothelial function in patients with well controlled or poorly controlled Type II diabetes, we studied 100 patients with Type II diabetes that were free from diabetic neuropathy. In all patients, insulin resistance, residual pancreatic C-peptide secretion, endothelial function and oxidative stress were investigated using the homoeostasis model assessment (HOMA) index, glucagon bolus test, brachial reactivity, Trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid-reacting substances (TBARS). The patients were categorized into quartiles on the basis of plasma HbA(1c) (glycated haemoglobin) concentration. Analysis of the data showed significant increases in plasma glucose concentration, HOMA index, microalbuminuria and TBARS, and significant decreases in plasma C-peptide, AUC (area under the curve) plasma C-peptide and TEAC, through the different quartiles (from the lowest to the highest HbA(1c) concentration). With regard to parameters of endothelial function, changes in diameter showed a significant declining trend through the different quartiles. Endothelial-dependent changes in diameter were independently and significantly associated with AUC C-peptide levels, TEAC and TBARS. In conclusion, our study demonstrated that patients with Type II diabetes with good residual C-peptide secretion are better protected from endothelial dysfunction that those with poor C-peptide secretion.

Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism

This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 μg ethinyl estradiol (EE) and 75 μg gestodene (GSD) or 20 μg ethinyl estradiol and 150 μg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-μg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.

A double-blind comparative study of the effects of a 23-day oral contraceptive regimen with 20 μg ethinyl estradiol and 75 μg gestodene and a 21-day regimen with 30 μg ethinyl estradiol and 75 μg gestodene on hemostatic variables, lipids, and carbohydrate metabolism

In this double-blind study we compared the influence of two oral contraceptives, a 23-day regimen with 20 μg ethinyl estradiol and 75 μg gestodene (23-day 20/75) and a 21-day regimen with 30 μg ethinyl estradiol and 75 μg gestodene (21-day 30/75), on hemostatic variables, lipids, and carbohydrate metabolism. The volunteers received the preparations daily for six 28-day cycles. Hemostatic variables and lipids were measured at baseline and after six treatment cycles. Carbohydrate metabolism was assessed by determination of the area under the curve (AUC) of carbohydrate parameters after oral glucose tolerance tests performed at baseline and after three treatment cycles. Data from 33 volunteers in each group were obtained. No significant differences between the effects of both treatments on the hemostatic system were detected. Neither the overall change of all hemostatic variables from baseline to treatment Cycle 6 [defined as primary target variable in the study] nor the change of any of the individual hemostatic parameters differed significantly between the treatment groups. Likewise, no significant nor clinically relevant differences in the effects of both treatments on the volunteers’ lipid profiles were detected. The data on carbohydrate variables suggested a slightly more favorable influence of the 23-day 20/75 regimen. The increase of the glucose AUCs after three cycles tended to be stronger with the 21-day 30/75 regimen than with the 23-day 20/75 regimen. In addition, the AUCs for insulin and C-peptide were slightly reduced after three cycles with the 23-day 20/75 regimen but slightly increased with the 21-day 30/75 regimen. Both study treatments were safe and well tolerated by the volunteers as shown by the nature and frequency of adverse events, the routine laboratory examinations, and the physical and gynecological examinations. Both preparations provided adequate contraceptive reliability. The only pregnancy during treatment was attributable to intake errors. In conclusion, the prolongation of the treatment phase of an oral contraceptives with 20 μg ethinyl estradiol does not evoke more pronounced metabolic effects than a conventional 21-day regimen with 30 μg ethinyl estradiol.

Relationships of plasma C-peptide and gender to the urinary excretion of inositols in older people.

The urinary excretions of myo-inositol and D-chiro-inositol are elevated in diabetes, and have been suggested as possible markers or effectors of insulin action. The aim of the present study was to measure the urinary excretion of these compounds, and to assess possible relationships with the metabolic control of glucose, in older, non-diabetic men and women. 32 older (age range 54-71 yrs), moderately overweight (body mass index 29.1 +/- 0.4 kg/m2, mean +/- SEM), non-diabetic men (n = 17) and women (n = 15). 75 g oral glucose tolerance testing was done the day after all subjects had consumed nutrient-defined menus for five days. Plasma samples were analyzed for the concentrations of glucose, insulin, and C-peptide, and the 180-minute area under the curve (AUC) for each of these compounds was calculated. Samples from 24-hour urine collections were analyzed for the concentrations of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. The fasting glucose, insulin, and C-peptide, and the AUC for glucose and insulin, were not different between men and women. C-peptide AUC was greater in the men versus the women (p < 0.001). The median urinary excretions (micromol/g creatinine) of myo-inositol (p < 0.001), D-chiro-inositol (p < 0.001), L-chiro-inositol (p < 0.05), and pinitol (p < 0.001) were higher, and the myo-inositol:D-chiro-inositol ratio was lower (p < 0.001), in the men versus women. For all subjects combined, C-peptide AUC was positively correlated with the urinary excretion of each of the measured inositols, as well as the myo-inositol:D-chiro-inositol ratio. The correlations between C-peptide AUC and these inositols were strongly influenced by the co-linear relationship between C-peptide AUC and gender. Collectively, these data show that older, moderately overweight, non-diabetic men and women with gender-related differences in glucose-stimulated C-peptide AUC, an indirect indicator of insulin secretion, also display differences in the urinary excretion of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. The gender-related difference in the myo-inositol:D-chiro-inositol ratio suggests that, while the urinary excretion of all of the inositols measured were higher in the men than the women, the difference was more pronounced for D-chiro-inositol.

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.

To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

AGE-RELATED DIFFERENCES IN THE PANCREATIC ??-CELL RESPONSE TO HYPERGLYCEMIA FOLLOWING ECCENTRIC EXERCISE

136 Eccentric exercise results in delayed muscle soreness, muscle damage, insulin resistance, and increased insulin secretion in young individuals. The purpose of this investigation was to determine if older subjects differ from young subjects, in the pancreatic β-cell response to glucose following eccentric exercise. Hyperglycemic clamps (180 min, 10.0 mM) were performed on 8 young (age, 22 ± 1 yrs; body mass index, BMI, 23.4 ± 1.9 kg·m-2.; waist-to-hip ratio, WHR, 0.83 ± 0.02) and 8 older (age, 66 ± 2; BMI, 25.5 ± 1.2; WHR, 0.91 ± 0.01) sedentary healthy men with normal glucose tolerance, without exercise (CON) and 48 h after a single bout of eccentric exercise (ECC; leg extension and chest press, 10 sets X 10 reps, 100% 3-RM). ECC resulted in a 3-to-7-fold increase in muscle soreness ratings at 36 h in all subjects, and elevated (P< 0.02) plasma creatine kinase (CK) concentrations 48 h after ECC in young(1179 ± 480 vs. 58 ± 17 IU·I-1.; ECC vs. CON) and older subjects (629 ± 418 vs. 49 ± 15). Pancreatic β-cell secretion was similar in all subjects during CON clamps. When ECC was compared to CON, the first phase (0-10 min) C-peptide area under the curve (AUC) increased (P < 0.05) in young (4.2 ± 0.4 vs. 3.7 ± 0.6 nmol·I-1·min), but not among older subjects (3.2 ± 0.7 vs. 3.5 ± 0.7). The first phase C-peptide AUC response to ECC was significantly different (P < 0.02) between young and older subjects. Individual peak C-peptide concentrations were lower (P < 0.05) after ECC in older subjects (0.93 ± 0.16 vs. 1.12 ± 0.11 nmol·I-1), suggesting reduced first phase pancreatic β-cell secretion. In addition, first phase insulin-to-C-peptide molar ratios suggest opposite trends (P = 0.05) in insulin and/or C-peptide clearance for young and older subjects. Furthermore, the C-peptide AUC response to ECC was inversely related to WHR (r = -0.62, P < 0.02 and r = -0.66, P < 0.0006; first and second (10-180 min) phase, respectively). In conclusion, although all subjects experienced muscle soreness and apparent muscle damage after eccentric exercise, older subjects did not exhibit the increase in pancreaticβ-cell response to hyperglycemia that was observed among young subjects. Furthermore, abdominal adiposity may account for some of the age-related differences in pancreatic β-cell secretion following eccentric exercise.

Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent diabetes mellitus and renal failure

To test the hypothesis that renal failure has no effect on the pharmacokinetics of glyburide, five subjects with non-insulin-dependent diabetes mellitus (NIDDM) and end-stage renal disease requiring hemodialysis, and four NIDDM subjects with normal renal function were studied. On days 0, 1, and 15, subjects consumed 33 carbohydrate grams, and glucose, insulin, and C-peptide were measured for 4 hours. On day 1, subjects received 3 mg glyburide and measured plasma concentrations for 48 hours. On day 3, multiple dosing on 3 mg glyburide daily began. On day 15, plasma concentrations were measured for 48 hours. The pharmacokinetics and pharmacodynamics of glyburide, glucose, insulin, and C-peptide were determined as well as daily fasting blood glucose. Glucose area under the curve (AUC) and daily fasting glucose levels did not change in either controls or hemodialysis subjects. The mean serum glyburide blood levels and pharmacokinetics did not differ after initial or chronic glyburide administration in NIDDM subjects with end-stage renal disease treated with hemodialysis compared with controls. Glyburide half-life averaged 3.3 hours in control subjects and 5.0 hours in hemodialysis subjects. Hemodialysis subjects had increased C-peptide and insulin AUC with chronic dosing. Renal failure does not affect the pharmacokinetics of 3.0 mg oral glyburide.

Oral sensory stimulation improves glucose tolerance in humans: effects on insulin, C-peptide, and glucagon.

In animals, bypassing the oropharyngeal receptors by intragastric administration of glucose results in glucose intolerance. To determine whether the absence of oral sensory stimulation alters glucose tolerance in humans, we monitored plasma levels of glucose and hormones after intragastric administration of glucose, with and without subjects tasting food. Plasma glucose area under the curve (AUC) was significantly lower after oral sensory stimulation (3,433 +/- 783 vs. 5,643 +/- 1,397 mg.dl-1. 195 min-1; P < 0.03; n = 8). Insulin and C-peptide AUCs were higher during the first one-half of the sampling period (insulin, 5,771 +/- 910 vs. 4,295 +/- 712 microU. ml-1.75 min-1; P < 0.05; C-peptide, 86 +/- 10 vs. 66 +/- 9 ng.ml-1. 75 min-1; P < 0.03) and lower during the second one-half of the sampling period compared with the control condition (1,010 +/- 233 vs. 2,106 microU.ml-1. 120 min-1; P < 0.025; 31 +/- 8 vs. 56 +/- 18 ng.ml-1. 120 min-1; P < 0.05; insulin and C-peptide, respectively). Oral sensory stimulation markedly increased plasma glucagon compared with the control condition (1,258 +/- 621 vs. -2,181 +/- 522 pg.ml-1. 195 min-1; P < 0.002). These data provide evidence in humans that oral sensory stimulation influences glucose metabolism and suggest that the mechanisms elicited by this cephalic stimulation are necessary for normal glucose homeostasis.

Tolbutamide causes a modest increase in insulin secretion in cystic fibrosis patients with impaired glucose tolerance

We examined the effect of intravenous (IV) tolbutamide administration on glucose and hormone levels in cystic fibrosis (CF) patients with impaired first-phase insulin secretion and oral glucose tolerance (oral glucose tolerance test [OGTT]) and compared them with CF patients with only an impaired first-phase insulin secretion and healthy control subjects. Five CF patients with an impaired OGTT, ie, a serum glucose value of 7.8 mmol/L or greater 120 minutes after an oral glucose load (group I), five CF patients with a normal OGTT, ie, a serum glucose not exceeding 7.8 mmol/L 120 minutes after oral glucose (group II), and five healthy control (CON) subjects underwent IV glucose tolerance tests with glucose alone (IVGTT) and glucose administered in conjunction with tolbutamide ([IVTTT] 25 mg/kg; maximum dose, 1 g). Serum glucose levels were measured using the glucose oxidase method; insulin, C-peptide, and glucagon levels were measured by the double-antibody radioimmunoassay (RIA) technique. Serum immunoreactive trypsin (IRT) and hemoglobin A 1 (HbA 1) levels and height and weight were measured for each subject, and in addition, pulmonary function was assessed in those with CF. There were no significant differences in the area under the curve (AUC) for glucose or glucagon levels or the serum glucose disappearance rate ( k value) between group I, group II, or CON subjects during the IVGTT. First-phase insulin and C-peptide secretion was abnormal during IVGTT and IVTTT in the CF groups: in group I it was severely impaired, whereas in group II it was between group I and CON values. During the IVTTT serum glucose levels and glucose k values were not significantly altered in any of the three groups as compared with the IVGTT. Tolbutamide administration significantly increased the AUC for serum insulin in group II and CON subjects as compared with IVGTT values (67% and 135%, respectively, P < .05), with a modest ( P > .05) increase in group I levels (28%). Likewise, there were significant increases in the AUC for C-peptide with IVTTT in group II (49%, P < .05) and CON subjects (58%, P < .01), with a lesser increase in group I (21%). The glucagon AUC was not significantly altered in IVTTT as compared with IVGTT in any group. These observations suggest that endocrine function in CF subjects is a continuous spectrum from those with diabetes mellitus to normals. Only long-term studies will determine if the residual secretion of insulin in response to oral sulfonylurea is of clinical importance.

Increased insulin secretion in patients with multifollicular and polycystic ovaries and its impact on ovulation induction

To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs). Prospective study. Reproductive Endocrinology Center, University of Bologna, Bologna, Italy. Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs). A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression. Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH. Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO. [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.