Glucose Tolerance In Type Research Articles

A Randomized Controlled Trial of Prenatal Physical Activity to Prevent Gestational Diabetes: Design and Methods

Women diagnosed with gestational diabetes mellitus (GDM) are at substantially increased risk of developing type 2 diabetes and obesity, currently at epidemic rates in the United States. GDM, therefore, identifies a population of women at high risk of developing type 2 diabetes and provides an opportunity to intervene before the development of this disorder. It is well recognized that acute as well as chronic physical activity improves glucose tolerance in type 2 diabetes. To date, however, primary prevention trials have not been conducted to test whether an increase in physical activity reduces risk of developing GDM among women at high risk of this disorder. The aims of this study are to investigate the effects of a motivationally targeted, individually tailored 12-week physical activity intervention on (1) development of GDM, (2) serum biomarkers associated with insulin resistance, and (3) the adoption and maintenance of exercise during pregnancy. Women at high risk of GDM are recruited in early pregnancy and randomized to either an individually tailored exercise intervention or a comparison health and wellness intervention. The overall goal of the exercise intervention is to encourage pregnant women to achieve the American College of Obstetricians and Gynecologists guidelines for physical activity during pregnancy through increasing walking and developing a more active lifestyle. The intervention takes into account the specific social, cultural, economic, and physical environmental challenges faced by pregnant women of diverse socioeconomic and ethnic backgrounds.

Effects of cevoglitazar, a dual PPARα/γ agonist, on ectopic fat deposition in fatty Zucker rats

By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors alpha/gamma (PPARalpha/gamma) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPARalpha/gamma, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPARalpha agonist, and pioglitazone, a PPARgamma agonist. Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat-exposure alone followed by a 4-week dosing period. Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPARalpha- and PPARgamma-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPARalpha agonism resulting in increased beta-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot.

Effect of the organophosphorus pesticide diazinon on glucose tolerance in type 2 diabetic rats

We have reported that the toxicity of the organophosphorus pesticide diazinon (DZN) and its metabolites is increased in streptozotocin-induced diabetic rats (type 1 diabetic rats). In the present study, we have investigated the effect of DZN on glucose tolerance in genetic type 2 diabetic rats, Goto-Kakizaki (GK) rats. Oral glucose tolerance test (OGTT) (2 g/(5 ml kg)) was assessed before, and 1 and 2 weeks after intraperitoneal injection of DZN (6.5 mg/kg) in Wistar and GK rats. DZN significantly increased the levels of glucose in plasma at designated blood sampling points in GK rats. The activity of hepatic drug-metabolizing enzymes and expression of hepatic cytochrome P450 (CYP) 1A2, CYP3A2 and CYP2D1, which oxidize DZN to DZN-oxon, a potent ChE inhibitor, were measured before DZN injection. There were no significant differences in the activity and expression of CYPs between both rat groups, indicating that the ability of metabolic activation might be almost the same in Wistar and GK rats. DZN dramatically decreased the activity of cholinesterase (ChE) in plasma by approximately 40% in both Wistar and GK rats. However, no significant differences in the activity of ChE in plasma were observed between Wistar and GK rats for 5 days after DZN injection. No massive necrotic and apoptotic areas, leukocyte infiltration and immunoreactive insulin-positive cells (β-cells) were observed in pancreas 2 weeks after DZN injection. Moreover, DZN might not affect plasma insulin levels in Wistar and GK rats. These results suggest that DZN deteriorates the glucose tolerance in GK rats. It is unlikely that this phenomenon is due to differences in ChE activity and/or DZN-oxon production levels between Wistar and GK rats.

Increased glucose tolerance in Type II Diabetics treated with a citrus extract: A pilot study

Increased glucose tolerance in Type II Diabetics treated with a citrus extract: A pilot study

Improvement of Glucose Tolerance in Type 2 Diabetic Patients: Traditional vs. Modern Insulin Regimens (Results from the Austrian Biaspart Study)

Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

(394) Antimutagenicity, Antioxidant Activity, and Polyphenolic Contents of Bitter Melon Varieties (Momordica charantia L.)

Bitter melon (Momordica charantia L.), an annual vegetable of Cucurbitaceae family, is a vegetable with important nutritional and medicinal qualities. Four adaptable lines/varieties were tested in replicated field trials for productivity, and biochemical and medicinal characteristics at the University of Arkansas at Pine Bluff. The total phenolic contents of the oven-dried and freeze-dried tissues, and seeds, ranged from 5.39–7.75, 6.72–8.02, 6.40–8.90, and 4.67–6.69 mg·g-1 on a dry weight basis, respectively. The total phenolic content of bitter melon from India green (IG), India white (IW), China green (CG) and China white (CW) varieties were 4.67–6.72, 6.03–8.02, 5.39–7.81, and 6.69–8.90 mg·g-1 dry material, respectively. The main phenolic acids in bitter melon flesh were gallic acid, gentisic acid, catechin, chlorogenic acid, and epicatechin. Bitter melon seeds had the phenolic acids, gallic acid, catechin, and epicatechin. The antioxidant activities of methanolic extracts from the bitter melons varieties IG, IW, CG, and CW ranged from 79% to 85%, 79% to 83, 80% to 85, and 79% to 86% inhibition, respectively. The antioxidant activities of the seed ranged from 79% to 84% inhibition. Methanolic extracts of freeze-dried flesh and seed from var. IW and CG showed very high antimutagenic effects against benzo(a)pyrene with Salmonella TA98 (92% to 100% inhibition) TA100 (79% to 86% inhibition), but lower antimutagenicity activities against sodium azide that ranged from 46% to 54% and 17% to 32% inhibition, respectively. The popular belief that bitter melon improves glucose tolerance in Type II diabetes and lowers blood cholesterol is being investigated. It has not been determined which alkaloids, polypeptides, or combination of chemicals found in bitter melon are responsible for the beneficial medicinal effect.

New Insights into the Regulation of Glucagon Secretion by Glucagon-like Peptide-1

Glucagon-like peptide-1 (GLP-1) is a potent incretin hormone currently under investigation for use as a novel therapeutic agent in the treatment of type 2 diabetes. One of several therapeutically important biological actions of GLP-1 in type 2 diabetic subjects is ability to induce strong suppression of glucagon secretion. The glucagonostatic action of GLP-1 results from its interaction with a specific G-protein coupled receptor resulting in the activation of adenylate cyclase and an increase in cAMP generation. In the pancreatic alpha-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion-channel activity and exocytosis of the glucagon-containing granules. In this short review, we will focus on recent advances in our understanding on the cellular mechanisms proposed to underlie the glucagonotropic action of GLP-1 and attempt to incorporate this knowledge into a working model for the control of glucagon secretion. Studies on the effects of GLP-1 on glucagon secretion are relevant to the pathogenesis of type 2 diabetes due to the likely contribution of hyperglucagonemia to impaired glucose tolerance in type 2 diabetes.

Bitter Melon (Momordica charantia L.) a Potential Vegetable for Special Nutritional and Medicinal Values in America

Foods from plants can provide enough energy and essential nutrients for maintaining human health as well as for prevention of many serious diseases. Many exotic vegetables are known for their special nutritional and medicinal properties. Bitter Melon (Momordica charantia L.), an annual vegetable of Cucurbitaceae family, is found to be one of the important vegetables of special nutritional and medicinal qualities. Germplasm lines and land races of Bitter Melon were evaluated in 2000 and 2001 for their adaptability in Southeast Arkansas. Seven adaptable lines/varieties were tested in replicated field trials for productivity at the Univ. of Arkansas at Pine Bluff Agricultural Research Center in 2002 and 2003. Melons were harvested at their marketable stages beginning in June and ending in September for yield estimation. Nutritional qualities of Bitter Melons were examined by chemical analyses conducted at the Univ. of Arkansas, Fayetteville (UAF) Food Science Laboratory. Analyses for antioxidants and other compounds as well as cooking qualities are currently underway. Several recipes have been tasted for consumer acceptance. The popular belief of bitter melon to improve glucose tolerance in Type II diabetes and lower blood cholesterol are being investigated. It is still to be determined if the chemical constituents such as certain alkaloids and polypeptides found in bitter melons are effective individually or in combination.

Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes

Aims: Glycation of insulin has been demonstrated within pancreatic β-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. Methods: Ten patients (5 M/5 F, age 57.8±1.9 years, HbA 1c 7.6±0.5%, fasting plasma glucose 9.4±1.2 mmol/l, creatinine 81.6±4.5 μmol/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. Results: Plasma glucose and glycated insulin responses were reduced by 9% ( P=0.005) and 38% ( P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% ( P=0.005) and 25% ( P=0.007) by nateglinide. Conclusions: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide.

Does dietary modification and/or physical activity reduce the progression from impaired glucose tolerance to type 2 diabetes?

Does dietary modification and/or physical activity reduce the progression from impaired glucose tolerance to type 2 diabetes?

Endothelin A-receptor blockade in experimental diabetes improves glucose balance and gastrointestinal function.

Secondary complications of diabetes mellitus often involve gastrointestinal dysfunction. In the experimental Goto Kakizaki rat, a model of Type II diabetes, hyperglycaemia and reduced glucose clearance is associated with elevated plasma endothelin (ET)-1 levels and selective decreases in nitric oxide synthase in circular muscle, longitudinal muscle and neuronal elements of the gastrointestinal tract. Functionally, this is accompanied by decreased nitrergic relaxatory responses of jejunal longitudinal muscle to tetrodotoxin-sensitive electrical field stimulation. Long-term treatment with a selective ET A-type receptor antagonist, markedly reduced hyperglycaemia and restored plasma glucose clearance rates towards normal. This was associated with a restoration of N(G)-nitro-L-arginine methyl ester-sensitive relaxatory responses of jejunal longitudinal muscle to electrical field stimulation. The results indicate that beneficial effects of ETA receptor blockade on gastrointestinal function may result from an improvement in insulin sensitivity with concomitant reduction of the severity of hyperglycaemia. ETA receptor blockade may represent a new therapeutic principle for improving glucose tolerance in Type II diabetes and could be beneficial in alleviating or preventing hyperglycaemia-related secondary complications in this condition.

Suppression of nocturnal fatty acid concentrations by bedtime carbohydrate supplement in type 2 diabetes: effects on insulin sensitivity, lipids, and glycemic control

Bedtime ingestion of slow-release carbohydrates leads to sustained nocturnal fatty acid suppression and improved glucose tolerance in type 2 diabetic patients. This study assessed the effects of 2 different doses of bedtime carbohydrate supplement (BCS) on morning glycemic control and glycated hemoglobin (Hb A(1c)) in type 2 diabetic patients. In addition, the effects of the high-dose BCS on insulin sensitivity and postprandial glucose and triacylglycerol concentrations were assessed. Two BCS doses were studied separately in 7-wk randomized, placebo-controlled, double-blind studies with either a parallel (low-dose BCS; n = 24 patients) or crossover (high-dose BCS; n = 14 patients) design. The effects of the low and high doses (0.30 and 0.55 g uncooked cornstarch/kg body wt, respectively) were compared with those of a starch-free placebo. Compared with the starch-free placebo, the high-dose BCS ( approximately 45 g) produced enhanced nocturnal glucose (P < 0.01) and insulin (P < 0.01) concentrations as well as a 32% suppression of fatty acid concentrations (P < 0.01). Moreover, glucose tolerance (P < 0.05) and C-peptide response (P < 0.05) improved after breakfast the next morning. The low-dose BCS ( approximately 25 g) improved fasting blood glucose concentrations (P < 0.05). However, there were no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or Hb A(1c) after 7 wk. Nocturnal fatty acid suppression by BCS improved fasting and postprandial blood glucose concentrations in type 2 diabetic patients the next morning. In contrast, no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or long-term glycemic control assessed by Hb A(1c) were seen after BCS supplementation.

Classification Of Type 2 Diabetes By Clinical Response To Metformin-Troglitazone Combination And C-Peptide Criteria

ObjectiveTo assess the ability of basal and stimulated C-peptide levels and stimulated glucose values after oral administration of glucose to predict a successful response to metformin and troglitazone combination therapy after discontinuation of insulin therapy. MethodsAt the onset of the study, plasma glucose and C-peptide levels were measured in a group of 64 obese patients with insulin-treated type 2 diabetes while they were fasting and 2 hours after a challenge of 100 g of glucose administered orally. Then combination metformin-troglitazone treatment was initiated while insulin therapy was gradually tapered over 8 to 12 weeks. Subjects who successfully tolerated insulin withdrawal after the metformin-troglitazone combination were categorized as non-insulin-requiring responders, whereas those who needed insulin to obtain glycemic control were categorized as insulin-requiring nonresponders. Basal and glucose-stimulated C-peptide levels as well as stimulated glucose values were contrasted in the responder versus nonresponder groups. In a second protocol, eight obese patients with insulin-treated type 2 diabetes who successfully stopped insulin therapy were reassessed for C-pep-tide and glucose variables during the 2-hour oral glucose tolerance test. This reassessment followed a 12-week period of therapy to determine whether treatment of insulin resistance with the combination of metformin and troglitazone could normalize the impaired glucose tolerance in type 2 diabetes. ResultsAfter metformin-troglitazone therapy, 48 study subjects (75%) could later be managed without insulin, whereas 16 (25%) needed insulin to achieve acceptable glycemic control. In a comparison of the noninsulin-requiring responder and insulin-requiring nonresponder groups, the responder group had significantly higher glucose-stimulated C-peptide levels and much lower stimulated glucose levels. The mean basal plasma C-peptide level was higher in the responder than in the nonresponder group, but a small degree of overlap was found between the two groups. Combination treatment with metformin and troglitazone for 12 weeks resulted in a significant reduction in the C-peptide response and glucose variables after the glucose load. ConclusionThe results of this study indicate that stimulated C-peptide and glucose levels may be useful criteria to identify whether combination metformin-troglitazone treatment can successfully replace insulin therapy in the management of obese patients with type 2 diabetes. Inability to normalize glucose intolerance after restoring insulin resistance with insulin sensitizers is supportive of the presence of both disturbed beta-cell function and insulin resistance in patients with type 2 diabetes. (Endocr Pract. 1999;5:305-313)

Homologous physiological effects of phenformin and chromium picolinate

The insulin-sensitizing drug phenformin, in addition to its clinical utility in type II diabetes, has been reported to lower blood lipids, reduce body fat, enhance cellular immunity, and—in rodents—to increase mean lifespan and retard the development of growth of cancer. Initial studies with the insulin-sensitizing nutrient chromium picolinate indicate that it aids glucose tolerance in type II diabetes, lowers elevated LDL cholesterol, reduces body fat while increasing lean mass, and—in rats—increases median lifespan. These effects are thus analogous to those reported for phenformin; chromium picolinate should be tested to determine whether it likewise has a favorable impact on cellular immunity and cancer risk. The ability of both phenformin and chromium picolinate to increase lifespan suggests that age-related insulin resistance may play a profound role in the aging process. It may not be coincidental that caloric restriction—the best documented technique for increasing lifespan—markedly increases insulin sensitivity. Safe, appropriate measures for promoting lifelong insulin sensitivity include a low-fat diet, exercise training, and supplemental chromium picolinate.

The acute effect of preprandial exogenous and endogenous sulphonylurea-stimulated insulin secretion on postprandial glucose excursions in patients with type 2 diabetes.

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin response to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p < 0.01), whereas total insulin release was equally improved (78% and 54% vs control; p < 0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol x min l-1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p < 0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol x min l-1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol x min l-1; p < 0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral premeal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.

Lack of β2-adrenoceptor induced long-acting effect on glucose tolerance in type 2 diabetic patients

The long-acting effect of a 10-min pulse infusion of the β 2-adrenergic agonist fenoterol on oral glucose tolerance tests in controls and in normotensive patients with type 2 diabetes mellitus on diet was compared. During an oral glucose load starting 2 h after fenoterol control persons showed hyperglycemia (area: 25950 ± 467 vs. 22650 ± 410, P < 0.01), hyperinsulinemia (area: 13 980 ± 1050 vs. 8160 ± 405, P < 0.02) and a pronounced fall of serum potassium (area: 775 ± 26 vs. 748 ± 25, P < 0.02). The patient group showed no late response to fenoterol: plasma glucose (area: 51000 ± 382 vs. 51300 ± 413, n.s.), serum insulin (area: 7215 ± 233 vs. 8280 ± 410, n.s.), serum potassium (area: 748 ± 26 vs. 750 ± 24, n.s.). The data show that there is a defect of the β 2-adrenergic long-acting effect on glucose metabolism and on insulin release in type 2 diabetes mellitus.

Secretion of islet amyloid polypeptide in response to glucose

The content of isolet amyloid polypeptide (IAPP) in isolated rat pancreatic islets was determined by a radioimmunoassay. Reverse-phase high-performance liquid chromatography analysis revealed that a main peak of IAPP immunoreactivity in the extracts from the islets corresponded to a synthetic rat IAPP. Secretion of IAPP from the cells is regulated by the extracellular glucose concentration. Thus, IAPP may be a novel regulator for glucose homeostasis and changes in the secretion perhaps relate to insular amyloid deposits and impaired glucose tolerance in type 2 diabetes mellitus.

Pulsatile insulin infusion and glucose-homeostasis in well-controlled type 1 (insulin-dependent) diabetic patients.

Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U kg-1 idealised body weight were given, each of 20 s duration, with intervals of 6 min, three times per day covered with adequate administration of glucose) on 2 successive days on glucose-tolerance in nine well-controlled Type 1 diabetic patients on continuous subcutaneous insulin infusion therapy (age 26 (7) years, mean (SD); duration of diabetes 10 (7) years; body mass index 23.4 (2.3) kg m-2; HbA1c 6.0 (0.6)%). On the days before and after the insulin pulsing, the patients were subjected to metabolic assessments by an oral glucose tolerance test (1 g glucose kg-1 body weight) 30 min after the subcutaneous injection of 0.15 U kg-1 body weight regular human insulin and a subsequent bicycle-ergometer test. During these metabolic assessments, plasma free insulin concentrations, plasma glucagon and the non-protein respiratory quotient remained unaffected by the insulin pulsing. However, glucose tolerance deteriorated significantly (maximal glucose concentration 120 min after glucose load was 10.0 mmol l-1 before and 13.9 mmol l-1 after insulin pulsing, P less than 0.01). In conclusion, the pattern of insulin pulsing used in this study did not ameliorate oral glucose homeostasis in well-controlled Type 1 (insulin dependent) diabetic patients.

A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the β cell response or glucose tolerance in type 2 diabetes mellitus

Newly diagnosed, previously untreated patients with type 2 diabetes mellitus ( n = 6) were studied on two separate days after overnight fasts. On each day they were given a 500-kcal mixed meal plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (GIP) (0.75 pmol/kg/min) or control solution (CS) from 0 to 30 min in random order. Frequent measurements of plasma glucose, C-peptide, insulin and GIP concentrations were made. Fasting GIP levels were similar on both days. During the meal plus GIP infusion plasma GIP levels increased from a basal value of 7.6 ± 1.5 pmol/l to a peak of 88.6 ± 5.4 pmol/l at 30 min. Following the meal and infusion of CS GIP increased from a fasting level of 10.3 ± 1.2 pmol/l to a significantly lower peak of 58.0 ± 8.3 pmol/l at 60 min. During the meal plus GIP infusion GIP levels were higher at 10–45 min and at 90 min ( P < 0.05−0.001). Fasting and postprandial glucose, C-peptide and insulin levels were, however, similar on both study days. A supplementary infusion of porcine GIP with a mixed meal did not significantly alter the β cell response or glucose tolerance in this group of patients with type 2 diabetes mellitus.

Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal profiles in insulin-treated type II diabetic patients.

Five type II diabetic patients were studied after secondary failure of oral agents, with and without the addition of the new long-acting somatostatin analogue SMS 201-995 to an intermediate-acting insulin regimen. SMS 201-995 was administered twice daily, before breakfast and dinner, as 100 micrograms sc injections, and resulted in a lowering of plasma glucose, as well as of plasma glucagon and serum C-peptide levels. SMS 201-995 abolished postprandial glycemic and xylosemic peaks related to meals and to oral d-xylose when they were taken shortly after the administration of the analogue, while it had no effect on glycemic and xylosemic increments that followed the midday meal. The new somatostatin analogue improves glucose tolerance in type II diabetic patients, both by inhibiting counterregulatory hormones and by delaying and reducing intestinal absorption of nutrients. Its administration could lead to a reduction of daily insulin requirements. Our findings indicate that SMS 201-995 may have a role as an adjunct to insulin in the management of type II diabetic patients after secondary failure of oral agents.