Mean Plasma Glucose Levels Research Articles

Pancreatic Polypeptide Administration Reduces Insulin Requirements of Artificial Pancreas in Pancreatectomized Dogs

An artificial endocrine pancreas is a mechanical device that frequently measures blood glucose and adjusts the rate of insulin infusion to maintain normoglycemia. In this study, we evaluated the effect of pancreatic polypeptide (PP) on insulin requirements after total pancreatectomy. However, other endocrine hormones are needed not only to facilitate the effect of insulin, but also to regulate insulin functions in vivo. In this study, the effect of PP infusion on insulin requirements after total pancreatectomy in dogs is examined. After total pancreatectomy, five dogs were supported by artificial endocrine pancreas model STG-22 for 72 h. In a second group of five dogs, both insulin and PP were infused. Mean blood glucose levels and insulin requirements were compared between the two groups. There was no difference in mean plasma glucose levels between the two groups. In all 10 dogs, the mean blood glucose level for 72 h was 110 +/- 4 mg/dL and was tightly controlled between 65 and 190 mg/dL. However, the insulin requirement for the first and second postoperative days in the group treated with PP was significantly less than that of the control group (90.0 +/- 20.8 mU/kg vs. 445.0 +/- 151.9 mU/kg; P < 0.05, and 562.7 +/- 126.5 mU/kg vs. 1007.7 +/- 144.9 mU/kg; P < 0.05, respectively). We conclude that infusion of PP reduces the insulin requirement for the initial 48 h in pancreatectomized dogs treated with an artificial endocrine pancreas.

Diabcare Asia 2001 - Korea : Country Report on Outcome Data and Analysis

BackgroundThe Diabcare-Asia study was designed for the purpose of describing diabetes control and management, and late complication status in the diabetic population.MethodsFrom the 1st of July 2001 to the 1st of September 2001, data from 1170 diabetic patients were collected in 21 centers (one university hospital and 20 clinics located in Seoul and in Gyeonggi, Korea), and blood samples were collected for centralized HbA1c measurements.ResultsOnly 16.8% of patients at the clinics reported self-monitoring their blood glucose. The mean HbA1c was 7.3±1.4% at the hospital and 7.5±1.5% at the clinics, and the mean fasting plasma glucose (FPG) levels were 7.0±3.3 mmol/L at the hospital and 7.9±2.5 mmol/L at the clinics. About 40% of patients had a HbA1c and FPG above the normal upper limits. Screening for microalbuminuria was rarely performed. The available data represents only about 0.9% of the patients at the hospital and 12.3% of the patients at the clinics. Nephropathy (serum creatinine >2 mg/dL) was found in 0.8% of the patients at the hospital and in 3.4% of the patients at the clinics. Retinopathy and neuropathy were commonly reported diabetic complications. The prevalence of other severe late complications was relatively low.ConclusionThe data revealed suboptimal glycemic control in about 40% of patients.

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The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats.

It is well known that the multiple direct and indirect consequences of hyperglycemia in diabetic individuals have been linked to a number of abnormal host effector mechanisms that could lead to an increased risk of developing periodontal disease. The aim of this study was to investigate the effect of short-term experimental diabetes and insulin therapy on the severity of alveolar bone loss in rats, and the effect of experimental periodontitis on glycemic control. Seventy-two male Wistar rats were divided into four groups: group I animals were submitted to dental ligature around lower right first molars (ligated); group II consisted of streptozotocin (STZ)-diabetic, ligated rats; group III represented STZ-diabetic, unligated rats; and group IV consisted of insulin-treated (6 U/day), STZ-diabetic, ligated rats. Blood glucose of all diabetic rats was monitored at regular intervals. Standardized digital radiographs were taken after killing at 7, 15 and 30 days to measure the amount of bone loss about the mesial root surface of the first molar tooth in each rat. No significant (p < 0.05) changes in plasma glucose levels of insulin-treated diabetic rats were found among the different examinations after the beginning of insulin therapy. Rats from group II showed significantly greater increases in mean plasma glucose levels at 15 and 30 days after ligature placement compared with rats from group III (p < 0.05). Furthermore, in spite of the significant alveolar bone loss progression that was observed in groups I, II and IV (p < 0.00001; two-way anova), no significant differences among these groups regarding the severity of bone loss (p = 0.77) and no significant interaction between treatment group and time (p = 0.81) were found. Within the limits of this study, it can be suggested that the severity of periodontal disease was not affected by short-term diabetes, and that experimental periodontitis increased blood glucose levels in uncontrolled diabetic rats.

Acute hyperglycaemia following thermal injury: friend or foe?

Hyperglycaemia and insulin resistance are common in severely burned patients, even if they have not previously had diabetes. Conventionally, hyperglycaemia is considered a part of the hypermetabolic stress response and blood glucose levels up to 215 mg/dl are tolerated before insulin therapy is initiated. Recent studies suggest that hyperglycaemia and insulin resistance are harmful and that correcting blood glucose to normal levels with insulin might improve the prognosis significantly. The purpose of this clinical study was to evaluate blood glucose levels in severely burned patients with conventional management and to analyse the association between early hyperglycaemia and clinical outcome. Clinical, prospective, descriptive study. Thirty seven severely burned adults (>25% total body surface area). Hyperglycaemia was treated according to conventional clinical practice. This included the infusion of insulin based on a blood glucose level >215 mg/dl and the maintenance of the glucose level between 180 and 200 mg/dl. Measurements of whole-blood glucose were performed at 8, 16, 24, 36 and 48 h after the thermal injury. Additional measurements were performed if indicated. A total of 185 measurements were obtained and significant elevations of blood glucose levels (>140 mg/dl) were found in 108 (64%) of the measurements. Peak blood glucose values exceeded 140 mg/dl in all but three of the patients; however, only 17 patients received insulin treatment during the shock period. The inadequacy of the insulin treatment is shown by the mean glucose values, which exceeded 200 mg/dl in 27% of the patients. Despite a non-significant difference in the extent of burn (P=0.055), patients who died showed significantly higher maximum glucose values than patients who survived the thermal injury (P<0.05). Even though not statistically significant, blood glucose control was poorer in patients who later developed sepsis or acute renal failure (P>0.05). No correlation was found between burned surface area (TBSA) and mean plasma glucose levels during the first 48 h of resuscitation (r=0.12). Hyperglycaemia is very frequent during the resuscitation period of thermal injury and current guidelines for insulin therapy are inadequate to correct plasma glucose to normal levels. As an association between early hyperglycaemia and subsequent mortality seems to exist, more aggressive manoeuvres to reduce blood glucose may be warranted in this group of patients.

Acute hyperglycaemia following thermal injury: friend or foe?

<h2>Abstract</h2> <i>Introduction:</i> Hyperglycaemia and insulin resistance are common in severely burned patients, even if they have not previously had diabetes. Conventionally, hyperglycaemia is considered a part of the hypermetabolic stress response and blood glucose levels up to 215 mg/dl are tolerated before insulin therapy is initiated. Recent studies suggest that hyperglycaemia and insulin resistance are harmful and that correcting blood glucose to normal levels with insulin might improve the prognosis significantly. <i>Study objective:</i> The purpose of this clinical study was to evaluate blood glucose levels in severely burned patients with conventional management and to analyse the association between early hyperglycaemia and clinical outcome. <i>Design:</i> Clinical, prospective, descriptive study. <i>Patients:</i> Thirty seven severely burned adults (>25% total body surface area). <i>Interventions:</i> Hyperglycaemia was treated according to conventional clinical practice. This included the infusion of insulin based on a blood glucose level >215 mg/dl and the maintenance of the glucose level between 180 and 200 mg/dl. <i>Measurements and results:</i> Measurements of whole-blood glucose were performed at 8, 16, 24, 36 and 48 h after the thermal injury. Additional measurements were performed if indicated. A total of 185 measurements were obtained and significant elevations of blood glucose levels (>140 mg/dl) were found in 108 (64%) of the measurements. Peak blood glucose values exceeded 140 mg/dl in all but three of the patients; however, only 17 patients received insulin treatment during the shock period. The inadequacy of the insulin treatment is shown by the mean glucose values, which exceeded 200 mg/dl in 27% of the patients. Despite a non-significant difference in the extent of burn (<i>P</i>=0.055), patients who died showed significantly higher maximum glucose values than patients who survived the thermal injury (<i>P</i><0.05). Even though not statistically significant, blood glucose control was poorer in patients who later developed sepsis or acute renal failure (<i>P</i>>0.05). No correlation was found between burned surface area (TBSA) and mean plasma glucose levels during the first 48 h of resuscitation (<i>r</i>=0.12). <i>Conclusion:</i> Hyperglycaemia is very frequent during the resuscitation period of thermal injury and current guidelines for insulin therapy are inadequate to correct plasma glucose to normal levels. As an association between early hyperglycaemia and subsequent mortality seems to exist, more aggressive manoeuvres to reduce blood glucose may be warranted in this group of patients.

Pramlintide for the treatment of diabetes mellitus.

To provide an overview of the role of amylin, as well as that of pramlintide, a synthetic analog of amylin, in maintaining glucose homeostasis; and discuss the pharmacology, pharmacokinetics, efficacy, adverse effects, and role of pramlintide in the control of postprandial hyperglycemia. The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. MEDLINE searches (1986-March 2003) using the search terms pramlintide and amylin were conducted to identify clinical trials and review articles. Additionally, the bibliographies of the identified articles were reviewed. Clinical trials have demonstrated that amylin in combination with insulin controls postprandial glucose levels by decreasing food intake, slowing gastric emptying, and suppressing glucagon secretion. Clinical trials also showed significant decreases in mean plasma glucose levels and glycosylated hemoglobin, as well as the added benefits of weight loss and reduction in insulin doses. The most commonly reported adverse effects associated with pramlintide in clinical trials were gastrointestinal complaints and hypoglycemia, which occurred most frequently during initiation of therapy. The administration of insulin alone often does not result in optimal metabolic control. The treatment of amylin deficiency, in addition to insulin deficiency, may be warranted in order to obtain glucose homeostasis. The role of pramlintide, an amylin analog, will become clearer as more clinical data become available.

The pharmacokinetics of s.c. Semitard MC, human NPH ge, Rapitard MC and human NPH 30:70 ge insulin in healthy, non-diabetic subjects

Background: Plasma glucose and insulin responses to Semitard MC versus human NPH ge and Rapitard MC versus human NPH 30:70 ge were examined in fasted healthy, non-diabetic subjects. Methods: Twelve male subjects with a mean (±S.D.) age of 33.9±11.1 years and a BMI of 24.9±2.9 kg/m 2 were each involved on four separate study days 1 week apart. After fasting samples were taken, 0.2 U/kg of the allocated insulin preparation was injected subcutaneously (s.c.) as a bolus into the anterior abdominal wall. Blood samples were taken over the next 24 h. Results: Subcutaneous injection of Semitard MC caused a greater fall in plasma glucose concentration and lower mean plasma glucose levels throughout the study compared to NPH, reflecting the higher insulin concentrations observed during the 24-h study period. Following s.c. Rapitard MC the plasma glucose levels were consistently higher than those achieved with human NPH 30:70 ge as a result of the lower concentrations of insulin with Rapitard MC insulin. Conclusions: To obtain the same level of glycaemic control, transferring patients from Semitard MC to human NPH may require a dose increase of 30% in the first instance to be adjusted upwards as deemed necessary. Transferring patients from Rapitard MC to human NPH 30:70 ge, a dose reduction of 25% may be required. Frequent home blood glucose monitoring should be carried out.

Cut-Off Fasting Plasma Glucose Level To Determine Impaired Glucose Metabolism In Obesity

Objective: Our aim was to find out which fasting glucose level should be the cut-off point for impaired glucose metabolism in obese patients. Subjects: 257 patients (195 females, 62 males) whose body mass indexes (BMI) were above 30kg/m² participated in this study. After all cases had underwent a 75gr oral glucose tolerance test (OGTT) the patients were divided into four groups according to their fasting plasma glucose values ( group 1:80-89mg/dl (4.4-4.9mmol/l), group 2:90-99mg/dl (5.0-5.5mmol/l), group 3:100-109mg/dl (5.6-6.0mmol/l), group 4 :110-125mg/dl (6.1-6.9mmol/l) ). According to OGTT results we defined patients as cases who were normal, who had impaired fasting glucose, and who had impaired glucose metabolism (diabetes mellitus and impaired glucose tolerance). Results: No difference was found between age, gender, BMI, systolic and diastolic blood pressure, and lipid profiles of the groups. The number of patients who were diagnosed as impaired glucose metabolism increased apparently in the third group (%50.7) (p<0.05). Mean fasting plasma glucose level of the third group was 104,16±2,73mg/dl (5.78±0,15mmol/l). Although there was no statistically difference between the groups, mean homeostasis model assessment (HOMA) values were above 4 in the third and fourth groups, in the patients who had impaired fasting glucose and impaired glucose metabolism. Conclusion: We think that it is necessary to apply a OGTT to obese patients whose fasting plasma glucose levels are above 104 mg/dl in order to reduce the mortality and morbidity of the cardiovascular diseases.

Random Capillary Blood Sugar and Coronary Risk Factors in a South Kerala Population

High prevalence of type 2 diabetes in one subdivision of a district in south India prompted us to look at the prevalence of other major coronary risk factors, and relate these to random blood sugar values.Cross-sectional survey of all adult residents of four wards (clusters of households) of a subdivision. Detailed investigation for diabetes and blood lipids in a selected subsample with random blood sugar (RBS) >109 mg/dl by glucometer.From the selected wards, we conducted a standard oral glucose tolerance test and serum lipids in all those who had RBS above 109 mg/dl by glucometer. Risk factors such as smoking, obesity (body mass index > 29.9), high blood pressure (systolic pressure > 139; diastolic pressure > 89 mmHg) and sedentary habits were assessed in all irrespective of RBS.Prevalence of all risk factors increases with age. Mean RBS ranges from 92.9 +/- 15.7 to 108.8 +/- 35.7 mg/dl in males and 88.6 +/- 16.0 to 117.3 +/- 61.6 mg/dl in females, between the age groups 20-29 to > 69. Risk factor prevalence varied with area of residence, with urban population reporting highest prevalence for type 2 diabetes and obesity, and coastal population for hypertension. For increasing levels of fasting plasma glucose (FPG < 100, 100-124 and > 125 mg/dl), serum total cholesterol values were 5.21 +/- 1.08 mM/l, 5.38 +/- 0.86 mM/l and 5.63 +/- 1.37 mM/l for males. For females, corresponding values were 5.23 +/- 1.11 mM/l, 5.54 +/- 1.15 mM/l, and 5.49 +/- 1.10 mM/l respectively.Risk factor prevalence varies with area of residence within the study population. Mean plasma lipid levels are high among both sexes, tending to rise with increasing mean fasting plasma glucose levels.

Random capillary blood sugar and coronary risk factors in a south Kerala population.

High prevalence of type 2 diabetes in one subdivision of a district in south India prompted us to look at the prevalence of other major coronary risk factors, and relate these to random blood sugar values. Cross-sectional survey of all adult residents of four wards (clusters of households) of a subdivision. Detailed investigation for diabetes and blood lipids in a selected subsample with random blood sugar (RBS) >109 mg/dl by glucometer. From the selected wards, we conducted a standard oral glucose tolerance test and serum lipids in all those who had RBS above 109 mg/dl by glucometer. Risk factors such as smoking, obesity (body mass index > 29.9), high blood pressure (systolic pressure > 139; diastolic pressure > 89 mmHg) and sedentary habits were assessed in all irrespective of RBS. Prevalence of all risk factors increases with age. Mean RBS ranges from 92.9 +/- 15.7 to 108.8 +/- 35.7 mg/dl in males and 88.6 +/- 16.0 to 117.3 +/- 61.6 mg/dl in females, between the age groups 20-29 to > 69. Risk factor prevalence varied with area of residence, with urban population reporting highest prevalence for type 2 diabetes and obesity, and coastal population for hypertension. For increasing levels of fasting plasma glucose (FPG < 100, 100-124 and > 125 mg/dl), serum total cholesterol values were 5.21 +/- 1.08 mM/l, 5.38 +/- 0.86 mM/l and 5.63 +/- 1.37 mM/l for males. For females, corresponding values were 5.23 +/- 1.11 mM/l, 5.54 +/- 1.15 mM/l, and 5.49 +/- 1.10 mM/l respectively. Risk factor prevalence varies with area of residence within the study population. Mean plasma lipid levels are high among both sexes, tending to rise with increasing mean fasting plasma glucose levels.

Reduction of hepatic glycogen synthesis and breakdown in patients with agenesis of the dorsal pancreas.

In a family with agenesis of the dorsal pancreas only the mother presents with insulin-dependent diabetes mellitus, whereas her sons are glucose tolerant. We examined whether metabolic defects can be detected early in this disease. Plasma glucose profiles were obtained from patients with dorsal pancreas agenesis and from matched healthy subjects. Hepatic glycogen synthesis and breakdown were determined from the time course of glycogen concentrations using noninvasive (13)C nuclear magnetic resonance spectroscopy. Gluconeogenesis was calculated from the difference between glucose production (measured with D-[6,6-(2)H(2)]glucose) and glycogen breakdown. Frequently sampled iv glucose tolerance tests were performed to assess insulin secretion and sensitivity. The mean plasma glucose level was higher (12.9 +/- 0.4 vs. 5.9 +/- 0.1 mmol/liter), whereas the peak plasma insulin level was lower (236 vs. 397 +/- 23 pmol/liter) in the diabetic mother than in her nondiabetic sons and healthy subjects. In all patients, however, glycogen synthesis and breakdown were reduced by approximately 55% (P < 0.05) and 40% (P < 0.02), respectively. Gluconeogenesis (6.8 +/- 0.8 vs. 4.2 +/- 0.3 micro mol/kg.min; P < 0.05) and hepatic insulin clearance (6.8 +/- 1.3 vs. 2.8 +/- 1.0 ml/kg.min) were increased in all patients. In conclusion, patients with complete agenesis of the dorsal pancreas exhibit marked defects in hepatic glycogen metabolism, which are present even in the nondiabetic offspring.

Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia.

Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Glucoregulatory abnormalities have also been associated with the use of antipsychotic medications themselves. While antipsychotics may increase adiposity, which can decrease insulin sensitivity, disease- and medication-related differences in glucose regulation might also occur independent of differences in adiposity. Modified oral glucose tolerance tests were performed in schizophrenic patients (n = 48) receiving clozapine, olanzapine, risperidone, or typical antipsychotics, and untreated healthy control subjects (n = 31), excluding subjects with diabetes and matching groups for adiposity and age. Plasma was sampled at 0 (fasting), 15, 45, and 75 minutes after glucose load. Significant time x treatment group interactions were detected for plasma glucose (F(12,222) = 4.89, P<.001) and insulin (F(12,171) = 2.10, P =.02) levels, with significant effects of treatment group on plasma glucose level at all time points. Olanzapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at all time points, in comparison with patients receiving typical antipsychotics as well as untreated healthy control subjects. Clozapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at fasting and 75 minutes after load, again in comparison with patients receiving typical antipsychotics and untreated control subjects. Risperidone-treated patients had elevations in fasting and postload glucose levels, but only in comparison with untreated healthy control subjects. No differences in mean plasma glucose level were detected when comparing risperidone-treated vs typical antipsychotic-treated patients and when comparing typical antipsychotic-treated patients vs untreated control subjects. Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.

Insulin resistance and hypertension in postmenopausal women.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

Gliclazide modified release.

Gliclazide modified release (MR) is a new formulation of the drug gliclazide and is given once daily. The hydrophilic matrix of hypromellose-based polymer in the new formulation effects a progressive release of the drug which parallels the 24-hour glycaemic profile in untreated patients with type 2 diabetes mellitus. The formulation shows high bioavailability and its absorption profile is unaffected by coadministration with food. Mean plasma glucose levels are significantly reduced over a 24-hour period in patients with type 2 diabetes mellitus treated with gliclazide MR once daily, in both fasting and postprandial states. No cardiovascular ATP-sensitive potassium channel interaction has been observed at therapeutic concentrations of gliclazide MR. Gliclazide MR has also demonstrated antioxidant properties that are independent of glycaemic control. In a randomised, double-blind, multicentre study, gliclazide MR 30 to 120 mg once daily showed similar efficacy to gliclazide immediate release (IR) 80 to 320 mg/day (in divided doses for doses >80 mg) in patients with type 2 diabetes mellitus over a 10-month period, reducing glycosylated haemoglobin (HbA(1c)) and fasting plasma glucose (FPG) to a similar extent. The drug appeared most efficacious in patients who had previously been treated by diet alone, where significant reductions in HbA(1c) from baseline of 0.9% and 0.95% were seen at 10 and 24 months. Similarly, a sustained effect of gliclazide MR was observed in a subgroup of elderly patients defined a priori; HbA(1c) was decreased to a similar degree to that observed in the general study population. Gliclazide MR showed similar tolerability to gliclazide IR after 10 months' treatment in the randomised trial. The most commonly observed adverse events were arthralgia, arthritis, back pain and bronchitis (each <5%). Bodyweight remained stable. In this study no episodes of nocturnal hypoglycaemia or hypoglycaemia requiring third party assistance were observed during treatment with gliclazide MR. Episodes of symptomatic hypoglycaemia were infrequent, occurring in approximately 5% of patients.

Relationship between the Effects of Cisapride on Gastric Emptying and Plasma Glucose Concentrations in Diabetic Gastroparesis

Background/Aims: The effect of erythromycin on gastric emptying is attenuated during hyperglycaemia. The aim of this study was to determine in patients with diabetic gastroparesis whether the effect of cisapride on gastric emptying of solids and liquids is influenced by the plasma glucose concentration. Methods: Nineteen patients with type 1 diabetes mellitus, who had delayed gastric emptying of solids and/or liquids, were studied. On 2 separate days, each patient received cisapride (20 mg) or placebo orally 60 min before scintigraphic measurement of gastric emptying of a mixed solid (ground beef) and liquid (dextrose) meal. The plasma glucose concentrations were measured at –5, 30, 60, 90, and 120 min during each gastric emptying measurement. Results: Cisapride accelerated both solid (retention at 100 min 43 ± 4 vs. 69 ± 4%, p < 0.001) and liquid (T₅₀ 27 ± 2 vs. 39 ± 2 min, p < 0.001) gastric emptying. The mean plasma glucose level was not significantly different after placebo when compared with cisapride (19.5 ± 1.1 vs. 18.2 ± 1.0 mmol/l). The change in the 50% emptying time (T₅₀) for liquid, but not solid, emptying was related (r = 0.55, p = 0.01) to the change in the plasma glucose AUC from 0 to 30 min between the placebo and cisapride tests, i.e., the acceleration was greater if the plasma glucose concentration was relatively less during the gastric emptying test performed on cisapride. Conclusion: The effect of cisapride on gastric emptying, at least that of liquids, in patients with diabetic gastroparesis appears to be dependent on the plasma glucose concentration.

Changes in diet and physical activity prevented type 2 diabetes mellitus in people with impaired glucose tolerance

(2001) N Engl J Med 344, 1343. Tuomilehto J, Lindström J, Eriksson JG, et al, . for the Finnish Diabetes Prevention Study Group. . Prevention of type 2 diabetes mellitus...

Effects of short-term improvement of insulin treatment and glycemia on hepatic glycogen metabolism in type 1 diabetes.

Insufficiently treated type 1 diabetic patients exhibit inappropriate postprandial hyperglycemia and reduction in liver glycogen stores. To examine the effect of acute improvement of metabolic control on hepatic glycogen metabolism, lean young type 1 diabetic (HbA1c 8.8 +/- 0.3%) and matched nondiabetic subjects (HbA1c 5.4 +/- 0.1%) were studied during the course of a day with three isocaloric mixed meals. Hepatic glycogen concentrations were determined noninvasively using in vivo 13C nuclear magnetic resonance spectroscopy. Rates of net glycogen synthesis and breakdown were calculated from linear regression of the glycogen concentration time curves from 7:30-10:30 P.M. and from 10:30 P.M. to 8:00 A.M., respectively. The mean plasma glucose concentration was approximately 2.4-fold higher in diabetic than in nondiabetic subjects (13.6 +/- 0.4 vs. 5.8 +/- 0.1 mmol/l, P < 0.001). Rates of net glycogen synthesis and net glycogen breakdown were reduced by approximately 74% (0.11 +/- 0.02 vs. 0.43 +/- 0.04 mmol/l liver/min, P < 0.001) and by approximately 47% (0.10 +/- 0.01 vs. 0.19 +/- 0.01 mmol/l liver/min, P < 0.001) in diabetic patients, respectively. During short-term (24-h) intensified insulin treatment, the mean plasma glucose level was not different between diabetic and nondiabetic subjects (6.4 +/- 0.1 mmol/l). Net glycogen synthesis and breakdown increased by approximately 92% (0.23 +/- 0.04 mmol/l liver/min, P = 0.017) and by approximately 40% (0.14 approximately 0.01 mmol/l liver/min, P = 0.011), respectively. In conclusion, poorly controlled type 1 diabetic patients present with marked reduction in both hepatic glycogen synthesis and breakdown. Both defects in glycogen metabolism are improved but not normalized by short-term restoration of insulinemia and glycemia.

Voglibose administration before the evening meal improves nocturnal hypoglycemia in insulin-dependent diabetic patients with intensive insulin therapy

Nocturnal hypoglycemia is one of the serious complications of intensive insulin therapy in patients with insulin-dependent diabetes mellitus (IDDM; type 1 DM). We assessed the effect of voglibose (alpha-glucosidase inhibitor) administration before the evening meal on nocturnal hypoglycemia in IDDM patients with intensive insulin therapy. Ten IDDM patients received 0.3 mg voglibose just before the evening meal for 5 days. The diet and insulin regimen were not changed throughout the study. Nocturnal plasma glucose levels (10 PM, 3 AM, and 7 AM) were studied in these patients before and during voglibose administration. Blood glucose levels were measured at 3 AM before and during voglibose treatment. The mean plasma glucose level at 3 AM was 3.4+/-0.4 mmol/L before voglibose treatment and 7.3+/-1.0 mmol/L during treatment. Plasma glucose at 3 AM was elevated in 9 of 10 patients with voglibose. The decrease in plasma glucose from 10 PM to 3 AM was 6.5+/-0.8 mmol/L before voglibose administration but 3.2+/-0.9 mmol/L during treatment (P < .01). The hypoglycemia rate was 52% (17 of 33 nights) before voglibose administration but only 9.1% (3 of 33 nights) during treatment. We conclude that voglibose administration before the evening meal improves nocturnal hypoglycemia in IDDM patients with intensive insulin therapy.

PIG-TO-PRIMATE ISLET XENOGRAFTS REVERSE DIABETES BEFORE UNDERGOING ACUTE CELLULAR REJECTION

31 The functional response and immunobiology of primarily non-vascularized islet cell xenografts remain poorly defined in relevant pre-clinical models. This project was therefore aimed to delineate the initial functional response and basic mechanisms operative in the rejection process of adult porcine islets transplanted to a clinically applicable site in non-immunosuppressed non-human primates. Six streptozotocin-diabetic and two non-diabetic female Rhesus monkeys were used as recipients and adult pigs served as donors. After pretreatment in culture for two days, 20,000 islet equivalents/kg body weight were transplanted into the portal vein of heparinized, non-immunosuppressed recipient animals. Plasma glucose, fasting serum porcine C-peptide, complement activation products (C3a, sC5b-9), xenoreactive natural antibodies (XNAb), and serum nitrite were measured pre-transplant and at intervals post-transplant. Two monkeys each were sacrificed at 12, 24, 48, and 72 hrs after transplantation. Livers bearing islet xenografts were examined by routine histology and immunohistochemistry. Mean fasting plasma glucose levels in diabetic recipients were 75, 42, 85, and 157 mg/dl at 12, 24, 48 hrs, and 72 hrs posttransplant. Porcine C-peptide, negative in all animals pretransplant, was present in 8/8, 5/6, 4/4, and 1/2 recipients at 12, 24, 48, and 72 hrs posttransplant, respectively. Levels of C3a and sC5b-9 showed no evidence of complement activation. Pretransplant IgM XNAb serum levels varied between animals. On day 1, 2, and 3 after xenograft, IgM XNAb levels remained unchanged compared to pretransplant levels in the same primates. Nitrite levels increased significantly (38 mM) in 2 primates on day 2. Histopathological findings varied considerably between recipient animals. Embolized islets were discernable at each time point. Insulin-positivity was however significantly reduced at 48 and 72 hrs. At 12 and 24 hrs, islets were found associated with thrombi. Strong immunostaining for IgG, IgM, C3, C5, and C9 was seen at 12 and 24 hrs, and minimal at 72 hrs. Neutrophils and few T cells were adherent to the islets as early as 12 hrs. At 48 hrs, neutrophils had disappeared, and macrophages became increasingly discernable. However, T cells were the predominant cells from 24 to 72 hrs posttransplant. Only few B cells were noted, whereas NK cells remained absent in the developing granulomatous lesions. Pig-to-Rhesus monkey intraportal islet xenografts normalized blood glucose for 48 hrs. Antibody and complement deposition may not be solely due to the intravascular location of the graft. Islet xenografts succumbed to acute cellular rejection, initially dominated by T cells followed by granulomatous lesions.