Immunoreactive Insulin Response Research Articles

A Trial of Analysis Method for Insulin Secretion Response to Carbohydrate Loading

Authors et al. have continued diabetic practice and research for long, and started Low Carbohydrate Diet (LCD) first in Japan. We developed social LCD movement by Japanese LCD Promotion Association (JLCDPA), and proposed petite-, standard-, super LCDs with carbohydrate 40%, 26%, 12%, respectively. Methods included 9 healthy medical staffs and two exams of 75g Oral Glucose Tolerance Test (OGTT) and Meal Tolerance Test (MTT). MTT means super-LCD breakfast with carbohydrate 6g. Results showed that blood glucose / immunoreactive insulin (IRI) at 0-30 min on average changed 88.0-130.6 mg/dL/5.1-46.5 μU/mL for GTT, and 90.1-86.3 mg/dL/4.8-12.5 μU/mL for MTT. IRI responses in GTT and MTT were calculated by 3 methods, which are i) increment (delta), ii) Area Under the Curves (AUC), iii) Multiple (times) of basal value. Both data from GTT and MTT showed significant correlation in i) and ii) (p<0.05), but not significant in iii) (p=0.07, n=9). These results suggested that insulin secretion in MTT would be enough and relatively excessive for 6g of carbohydrate, leading to relatively decreased glucose at 30 min. Current analyses methods will become some reference for future development of diabetic research.

The relationship of plasma glucagon to the hyperglycaemia and hyperinsulinaemia of surgical operation

In a controlled metabolic study of 42 patients undergoing abdominal surgery a significant increase in basal values of immunoreactive glucagon (IRG) was found 24 hours postoperatively. No correlation between the onset and duration of hyperglycaemia and the increase of IRG was observed. No increase in immunoreactive insulin (IRI) was seen during operation, but there was a rise 24 hours postoperatively. The infusion of arginine was accompanied by a rise in IRG both pre-and postoperatively, but despite the high values obtained there was no accompanying further increase in basal plasma glucose in the postoperative situation. The pre- and postoperative IRI responses were similar. Our evidence suggests that glucagon is not a primary mediator of the stress response, or of the hyperglycaemia of surgical operation in these patients.

Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians and their USA counterparts

Conventional risk factors for coronary heart disease (CHD) do not completely account for the observed increase in premature CHD in people from the Indian subcontinent or for Asian Indians who have immigrated to the USA. The objective of this study was to determine the effect of immigration to the USA on plasma levels of lipoprotein [a] (Lp[a]) and other independent risk factors for CHD in Asian Indians. Three subject groups were studied: group 1, 57 subjects living in India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians living in the USA. Fasting blood samples were drawn to determine plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein [LDL cholesterol (LDL-Chol)], high density lipoprotein [HDL cholesterol (HDL-Chol)], apolipoprotein B-100 (apoB-100), and Lp[a]. Apolipoprotein [a] (apo[a]) size polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lp[a] concentrations were higher in CHD patients than in control and USA groups. CHD patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB-100 and lower HDL-Chol than control subjects. Plasma Lp[a] levels were inversely correlated with the relative molecular weight of the more abundant of each subject's two apo[a] isoforms (MAI), and CHD patients showed higher frequencies of lower relative molecular weights among MAI. Our observed changes in lipid profiles suggest that immigrating to the USA may place Asian Indians at increased risk for CHD. This study suggests that elevated plasma Lp[a] confers genetic predisposition to CHD in Asian Indians, and nutritional and environmental factors further increase the risk of CHD. This is the first report implicating MAI size as a predictor for development of premature CHD in Asian Indians. Including plasma Lp[a] concentration and apo[a] phenotype in screening procedures may permit early detection and preventive treatment of CHD in this population.

Elevated plasma levels of glucagon-like peptide-1 after oral glucose ingestion in patients with pancreatic diabetes.

The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes. An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis. The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups. The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.

Elevated plasma levels of glucagon-like peptide-1 after oral glucose ingestion in patients with pancreatic diabetes

OBJECTIVE: The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes. METHODS: An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis. RESULTS: The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups. CONCLUSIONS: The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.

Brain insulin response to feeding in the rat is both macronutrient and area specific

GEROZISSIS, K., C. ROUCH, S. NICOLAÏDIS AND M. OROSCO. Brain insulin response to feeding in the rat is both macronutrient and area specific. PHYSIOL BEHAV 65(2) 271–275, 1998.—Using microdialysis, we showed recently that hypothalamic immunoreactive insulin (IRI) levels increased after a meal of chow and decreased in response to a fat meal. In the present study, we have compared extracellular hypothalamic and extrahypothalamic basal IRI levels and investigated the effect of meals composed exclusively of either carbohydrates (85% starch, 15% sucrose) or casein on both plasma and medial hypothalamic (PVN-VMH) insulin. The response of IRI to a carbohydrate meal was also investigated in the cerebellum. Basal hypothalamic IRI was twofold higher in the hypothalamus as compared to the cerebellum (33 ± 4 and 15 ± 2 pg/mL, respectively). Hypothalamic IRI increased twofold in response to the carbohydrate meal (72 ± 15 pg/mL) but remained unchanged during the casein meal. No IRI change was found in the cerebellum after a meal of carbohydrates (16 ± 2 pg/mL). Insulinemia was increased by both the carbohydrate and the casein meal. However, the protein-induced increase was less pronounced (maximum + 359% compared to 1650% for carbohydrates). The present data show a dual specificity of brain insulin response to feeding; in addition to the macronutrient specific variations, a regional specificity was also observed. Taken together with previous observations, the present data are in favor of an involvement of PVN-VMH insulin in the control of feeding and macronutrient-specific appetites.

Glucoregulatory disorders in school refusal students

Our previous studies demonstrated autonomic nervous system disorders and cerebral blood hypoperfusion in school refusal students with underlying emotional distress due to fear or anxiety associated with school attendance. Because severe stress is known to affect glucoregulatory metabolism, this study used the oral glucose tolerance test (OGTT) to measure glucose metabolism in school refusal students. A three-hour OGTT was performed. In preparation for the test, students fasted overnight. After a fasting blood sample was drawn, students were given solutions containing a predetermined amount of glucose based on their body weight (1.75 g/kg to a maximum 75 g). After glucose ingestion, blood samples were drawn at 30, 60, 90, 120, 150, and 180 mm to measure blood glucose (BG), immunoreactive insulin (IRI), pancreatic glucagon (IRG) and growth hormone (GH) levels. BG levels, IRI response, cumulative BG (sigma BG), cumulative IRI (sigma IRI), insulin/glucose ratio (delta IRI/delta BG), and insulinogenic index (sigma IRI/sigma BG) were then compared to previously reported normal control data. As an index of emotional difficulties, the self-rating depressive scale (SDS) was carried out. Eighty-one school refusal students (40 males and 41 females), 11-19 years of age (14.8 +/- 2.1), were studied. Their school refusal periods ranged from one month to eight years. All students were within -15 to +20% (-0.04 +/- 8.6) of ideal body weight. BG levels were determined using a glucose oxidase reaction method. Serum hormones were measured by radioimmunoassay. BG levels at all OGTT time intervals and sigma BG were significantly higher in school refusal students than the normal control data (sigma BG: 39.5 +/- 4.4 vs 33.3 +/- 3.4 mmol/l P < 0.001). Although the insulin response was abnormally low relative to the prevailing hyperglycaemia (sigma IRI/ sigma BG: subjects vs control = 232 +/- 129 vs 375 +/- 271, P < 0.01), normal beta cell secretory ability was speculated (sigma IRI: subjects vs controls = 2805 +/- 1274 vs 2523 +/- 1219 pmol/l). This suggests a relative suppression of insulin secretion. A paradoxical increase of GH was observed in 19 students after glucose ingestion. Glucoregulatory disorders observed in school refusal students may be caused by emotional distress. Multiple factors including autonomic nervous system disorders, derangement of neuropeptides in the hypothalamus, and hormonal imbalances may also affect glucoregulatory metabolism, predisposing these students to hyperglycaemia. We speculate that the glucoregulatory system compensates for decreased blood flow to the brain by increasing blood glucose concentrations, thereby providing sufficient glucose as the primary energy source used during normal brain metabolism.

Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly diagnosed adult-onset diabetes mellitus

This study aimed to determine the prevalence of antibodies against glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to β-cell function in adults newly-diagnosed with diabetes mellitus. β-cell function was assessed in adults aged 25–70 years newly-diagnosed with diabetes mellitus ( n = 84) and control subjects ( n = 34) using a 1.6 MJ mixed meal test procedure. β-cell function was evaluated by the true insulin (defined as immunoreactive insulin minus proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true insulin curve (normal 16 830–107 700 pmol min/l) and the sum of the 30 and 60 min incremental response (normal 285–3295 pmol/l). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were insulin deficient showing little or no true insulin release. Of the insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without insulin deficiency ( P < 0.001). Seven (58%) insulin deficient subjects were ICA positive, whereas only two (3%) non-insulin deficient subjects were ICA positive ( P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not insulin deficient ( P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both antibodies for detecting insulin deficiency was 50%. The specificity for detecting insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus as a new diagnosis are insulin deficient using our criteria. Loss of β-cell function in two thirds of individuals who are insulin deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of β-cell damage creates the potential for immune modulation to limit such damage.

Changes in immunoreactive insulin, C-peptide immunoreactivity, and immunoreactive glucagon in acute viral hepatitis

Insulin and glucagon are thought to play important roles as hepatotrophic factors in acute viral hepatitis (AVH); however, few reports have investigated the responses and relationships of each of these hormones to liver damage in detail. We studied insulin and glucagon responses during the acute and recovery phases of AVH. We performed a glucose tolerance test (GTT) and an insulin sensitivity test (IST) in each phase in 11 patients with AVH. In 8 additional patients in the acute phase (total n = 19), were compared immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) levels with transaminase levels. In the acute phase, IRI concentrations were normal from fasting to 60 min, despite an increased CPR level. In the recovery phase, IRI and CPR levels increased significantly. Immunoreactive glucagon levels in both phases did not differ significantly from those in controls. During the IST, the insulin sensitivity index in both phases was significantly lower than that in the controls. Fasting IRI and sigma IRI showed significant negative correlations with transaminase levels. We found enhanced insulin secretion and a decrease in plasma insulin in the acute phase of AVH. The discrepancy between IRI and CPR responses in the acute phase suggests an increase in the degradation or consumption of insulin in the liver.

Effects of obesity and inheritance on the development of non-insulin-dependent diabetes mellitus in Otsuka-Long-Evans-Tokushima Fatty rats

We studied whether obesity or inheritance was the more important factor in the development of non-insulin-dependent diabetes mellitus (NIDDM) using female Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) possessing one of the diabetic genes, ODB-1, and male Long-Evans-Tokushima-Otsuka rats (LETO) possessing no ODB-1, neither of which were diabetic when bred normally. Diabetes-resistant male LETO rats and female OLETF rats (4 weeks old) were assigned to three groups of 6 rats each, respectively; two groups in which obesity was induced by high calorie ‘cafeteria’ diet (D), or ventromedial hypothalamus lesions (V) with normal chow diet and a control group fed on normal chow (C). Six male OLETF rats were used as NIDDM positive controls. The mean daily energy intakes of obese male LETO and female OLETF rats were higher than those of the respective C groups. At 27 weeks of age, the average body weights of the obese LETO and female OLETF rats were significantly higher than those of the respective C groups and similar to that of the male OLETF group. Abdominal fat deposits of the obese groups were significantly higher than those of the respective C groups. At 28 weeks of age, the cumulative incidence of diabetes mellitus in obese LETO rats was 0% in group D and 17% in group V, while that of obese female OLETF rats in groups D and V were 100%. At 29 weeks of age, the plasma immunoreactive insulin (IRI) responses to glucose in obese female OLETF rats, groups D and V, were higher than that in group C. In obese LETO rats, insulin-stimulated glucose disposal in vivo was similar to that in group C, but in obese female OLETF rats, it was reduced to 41% in group D and 37% in group V of that in group C. Sections of islets of the pancreas of obese LETO rats appeared histologically normal, whereas those of obese female OLETF rats showed enlarged multilobulated fibrotic islets. These results demonstrate that obesity is necessary, but not sufficient alone for the development of NIDDM in these rat models.

Analysis of carbohydrate-intolerant profiles of mothers with normal glucose tolerance tests and their large for gestational age neonates

To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates. We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them. Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates. All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

A glimpse of the ‘natural history’ of established Type 2 (non-insulin dependent) diabetes mellitus from the spectrum of metabolic and hormonal responses to a mixed meal at the time of diagnosis

The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose in subjects with Type 2 diabetes have not always been consistent. This may have resulted from variations in the method of glucose administration, the ethnic backgrounds of subjects, the diagnostic criteria applied, the duration of the disease or IRI assay methods. The use of a mixed meal rather than glucose has been shown to provide a more physiological stimulus to the pancreatic β-cell due to both glucose and non-glucose secretagogues. We have analysed the metabolic and hormonal responses of 188 newly diagnosed Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500 kcal mixed meal. The diabetic subjects were stratified according to fasting plasma glucose (FPG) (<9, 9–12, 12–15 and ≧ 15 mmol/l) and body mass index (BMI) (<26.5, 26.5–30 and ≧ 30 kg/m 2). Increasing FPG was associated with higher peak glucose concentrations and increasing failure to achieve basal glucose levels by 4 h. Median fasting IRI concentrations were similar to those of normal subjects, but all diabetic subjects had reduced early-phase insulin secretion. Diabetic subjects with FPG < 9 mmol/l showed augmented IRI area under the curve (AUC) at 2 and 4 h, whereas those with FPG > 9 mmol/l had progressive falls in IRI AUC to below that of the normal subjects ( P < 0.0001 for the trend). Peak IRI concentrations declined progressively with increasing FPG. Despite equivalent glucose exposure simple trends of increasing AUC, IRI with increasing BMI were statistically significant ( P < 0.001, P < 0.02, P < 0.001 and P < 0.01, respectively for each FPG group). Both fasting and AUC non-esterified fatty acid concentrations increased significantly with FPG regardless of BMI ( P < 0.001 for the trends). These results using a more physiological mixed meal challenge in a large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked and increasing loss of β-cell secretory function with increasing fasting hyperglycaemia aggravated by insulin resistance with increasing obesity.

Differences in Plasma Insulin Responses in Urban and Rural Indians: A Study in Southern‐Indians

Fasting and 2 h post glucose plasma immunoreactive insulin (fasting IRI and 2 h IRI) responses were measured in urban (n = 149) and rural (n = 40) individuals with normal glucose tolerance during an epidemiological survey. In this survey, 900 urban and 1038 rural subjects were screened for glucose intolerance by capillary blood sampling. The respective response rates were 91% and 88%. We had planned to collect venous blood for IRI estimation, i.e. from 180 urban and 200 rural subjects. The compliance for the same was poor from the rural subjects and therefore the number available for IRI estimation was small. The mean +/- SD ages of the urban and rural groups were similar (35.3 +/- 9.9 and 38.6 +/- 13.1 years, respectively). The rural population had lower body mass index (BMI) and subscapular:triceps ratio compared to the urban group (p < 0.001). The total calorie consumption was lower and physical activity was higher in rural population. Fasting and 2 h insulin values in urban population were 16.6 +/- 9.4 mU l-1 and 60.6 +/- 42.5 mU l-1 and in rural 6.7 +/- 5.1 mU l-1 and 32.4 +/- 27.8 mU l-1, respectively; the values being significantly lower in the rural population (p < 0.001). Multiple regression analysis showed that in urban population the fasting insulin was correlated to the BMI and the 2h IRI to 2 h glucose, BMI and the subscapular:triceps ratio. In the rural population, similar results were obtained, except in that the 2 h IRI was influenced by the gender also.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin, C-peptide, androgens, and beta-endorphin response to oral glucose in patients with polycystic ovary syndrome.

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.

Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy

There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% ± 1.8% (mean ± SEM) of ideal body weight (IBW), and following partial restoration were 84.3% ± 1.4%. Body weights in normal controls were 96.3% ± 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls ( P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls. Blood glucose levels following the oral glucose load were essentially the same as those observed in the controls; however, changes in levels of IRI following the glucose load in AN patients before and after treatment were significantly less than those in the controls. These data indicate that basal CCK levels are abnormally elevated in AN patients, and that diminished responses to an oral glucose load are essentially normalized after therapy and partial restoration of body weight. The significance of the elevated basal CCK levels in AN remains to be elucidated.

Blood sugar, serum insulin and serum non-esterified fatty acid levels during thiopentone anaesthesia in dogs

The purpose of this study was to determine the effect of thiopentone anaesthesia on glucose metabolism. Blood sugar (BS), serum immunoreactive insulin (IRI) and serum non-esterified fatty acid (NEFA) concentrations were measured during the course of (1) an intravenous glucose tolerance test (IVGTT), and (2) an intravenous insulin test (ITT), in conscious and anaesthetized fasted dogs. The IVGTTs were repeated in dogs under alpha- or beta-adrenergic blockade, induced by phentolamine or propranolol. During the IVGTT, the anaesthetized dogs showed glucose intolerance (blood sugar levels were higher than in the control group) and little serum IRI response to hyperglycaemia was detected. An attenuated initial decrease and a slower rebound of NEFA concentration was observed in anaesthetized animals than in controls. Phentolamine administration (5 mg.kg-1 iv) partly restored the IRI response without affecting the BS levels; propanolol (1 mg.kg-1 iv) had no effect. Anaesthetized dogs showed a moderate resistance to insulin induced hypoglycaemic action and a lack of serum NEFA response during counter-regulation of hypoglycaemia, while in conscious controls an intense rebound was observed. Hyperinsulinaemia after iv insulin administration was longer in anaesthetized dogs than in controls. The insulin distribution space was 78% of body weight and insulin t1/2 in blood group compared with 54% and 16 min, in controls. We conclude that thiopentone provokes disturbances in glucose and serum NEFA metabolisms and abolishes the serum IRI response to hyperglycaemia. These effects are influenced by extrapancreatic factors regulating serum IRI levels and by an alpha-adrenergic mechanism, via the inhibition of insulin secretion.

Clinical and biochemical studies in the prediabetic phase of tropical calcific pancreatitis.

The frequency of diabetes is much higher in tropical calcific pancreatitis (TCP) as compared with alcoholic chronic pancreatitis. We report 97 patients with tropical calcific pancreatitis and compare the profile of 21 patients without diabetes (called TCP for the purpose of this report) with that of 76 patients with diabetes, called fibrocalculous pancreatic diabetes (FCPD) according to the World Health Organization (WHO) study group classification of diabetes. TCP patients were a decade younger and had marginally higher body mass indices (BMIs) as compared with the FCPD group. Of the TCP patients, 13 had abnormal glucose tolerance tests (GTT) and the others had normal GTT. Immunoreactive insulin (IRI) responses to glucose load in the TCP group did not differ significantly from that of the control group. This study shows the existence of early stages of glucose intolerance in TCP.

Effect of insulin resistance and hyperglycemia on proinsulin release in a primate model of diabetes mellitus.

An elevated plasma proinsulin (PI) to immunoreactive insulin (IRI) ratio occurs in relatives of patients with insulin-dependent diabetes mellitus and in subjects with non-insulin-dependent diabetes mellitus. To determine whether this alteration is the result of B-cell dysfunction and/or insulin resistance, we infused nicotinic acid for 3 weeks to produce insulin resistance in five adolescent male baboons before and after the administration of streptozocin (200 mg/kg). We measured basal PI and IRI levels and the acute incremental PI (APIR) and IRI (AIRIR) responses to iv arginine. The quantity of IRI comprised of PI was calculated in the basal state (PI/IRI) and following arginine injection (APIR/AIRIR). Streptozocin administration did not change the fasting plasma glucose (FPG) compared to that in the normal animals (4.7 +/- 0.3 vs. 4.3 +/- 0.2 mM) but raised the PI/IRI (16.4 +/- 3.4 vs. 5.9 +/- 1.7%) and APIR/AIRIR (7.1 +/- 1.0 vs. 2.8 +/- 1.0%) due to a concurrent reduction in IRI and increase in PI concentrations. The induction of experimental insulin resistance with nicotinic acid in the normal animals had no effect on the FPG (4.4 +/- 0.2 mM) but in the streptozocin treated animals, fasting hyperglycemia (8.3 +/- 1.7 mM) developed. Neither the basal PI/IRI (10.2 +/- 2.2%) or the APIR/AIRIR (2.3 +/- 0.6%) increased in the insulin-resistant streptozocin animals thus being no different to that of normal control animals before or during experimental insulin resistance. We conclude that disproportionate proinsulinemia is a manifestation of B-cell damage from streptozocin which is not exacerbated by insulin resistance or hyperglycemia.

Comparison of Diagnostic Criteria of IGT, Borderline, and GDM: Blood Glucose Curve and IRI Response

A 75-g oral glucose tolerance test (OGTT) was performed in 615 nonobese pregnant women (mean +/- SD age 29.7 +/- 4.3 yr) who were referred to the Division of Internal Medicine at our diabetes center because of glycosuria. Seventy-seven cases were found to have urinary glucose at the first trimester, 185 at the second trimester, and 353 at the third trimester. With their 75-g OGTT results, the diagnostic criteria of borderline (formulated by the Japan Diabetes Society), impaired glucose tolerance (IGT; defined by the World Health Organization [WHO]), and gestational diabetes mellitus (GDM; determined by the Japan Society of Obstetrics & Gynecology standards) were compared through blood glucose (BG) curves and immunoreactive insulin (IRI) responses. Borderline (fasting BG greater than or equal to 6.1 and less than 7.8 mM and 2-h BG greater than or equal to 6.7 and less than 11.1 mM) is neither diabetes nor normal. IGT is as referred to by the WHO. GDM exceeds two points of fasting BG greater than or equal to 5.6 mM, 1-h BG greater than or equal to 10.0 mM, or 2-h BG greater than or equal to 8.3 mM. Diabetes mellitus (DM) is as referred to by the Japan Diabetes Society (same as the WHO). The prevalence of abnormal glucose tolerance among all 615 pregnant women was 54.6% in borderline, 24.5% in IGT, 7.3% in GDM, and 3.4% in DM. The 2-h BG levels in IGT during the first trimester were higher than in borderline (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine-Metabolic Function in Remission-Phase IDDM During Administration of Cyclosporine

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)