Reproducibility of glucose and insulin responses to mixed meal in type II diabetic patients.

OBJECTIVE: The reproducibility of glucose and insulin responses to a mixed meal were studied in 24 consecutive non-insulin-dependent (type II) diabetic patients, the diet of which matched the tested diet. Patients received their usual treatment throughout the study. RESEARCH DESIGN AND METHODS: A standardized diet was followed for 3 days, and responses were measured on the 2nd and 3rd days. Glucose and insulin responses were studied after lunches with the 180-min positive area under the curve, and were analyzed with paired t test and Pearson's linear regression. RESULTS: Glucose responses did not vary (217 +/- 50 vs. 217 +/- 38 min x mM, NS) and were significantly correlated (r = 0.64, P less than 0.01). Insulin responses did not vary (35,224 +/- 5768 vs. 35,305 +/- 7779 min x pM, NS) and were strongly correlated (r = 0.83, P less than 0.001). CONCLUSIONS: These results suggest that glucose and insulin responses to a test meal are reproducible in type II diabetic patients.

Biological effects and irradiation dose induced in human lymphocytes in vitro by an intracellular radionuclide:99mTc.

Since lymphocyte radiolabeling is widely used for in vitro and in vivo studies and may interfere with the properties of the cells, the purpose of this work was to investigate the effects of 99mTc labeling on lymphocyte morphology and functions. Two ranges of 99mTc activity were used, 37 and 370 MBq, and their effects were compared to those produced by a graduated external irradiation. Electron microscopy was performed and T cells were studied using biological markers (E-Rosette formation, cell proliferation under lectin reactivity, and specific cell-mediated cytolysis). After 370-MBq labeling, an intense cytotoxic effect was observed on cell morphology, drastically impeding T-lymphocyte functions. Thirty-seven-megabecquerel labeling and sham procedure did not significantly affect cell functions. The external irradiation dose-response curve indicated a clear radiation-induced inhibitory effect, especially over 10 Gy. This effect was less intense than that obtained with 370-MBq 99mTc labeling. The labeling cytotoxic effect can then be attributed to a radiolesion due to a radiation dose which is probably higher than 10 Gy. In fact, the dose received by lymphocytes during the 370-MBq labeling procedure was estimated as 70 Gy by calculations, taking into account all emissions of 99mTc.

Postprandial amplification of lipoprotein abnormalities in controlled type II diabetic subjects: relationship to postprandial lipemia and C-peptide/glucagon levels.

Lipoprotein abnormalities, mainly high very-low-density lipoprotein (VLDL) and low high-density lipoprotein (HDL) levels, increase the risk of coronary heart disease (CHD) in type II diabetic patients. To investigate the relationship between these lipoprotein abnormalities and the postprandial (PP) lipid-clearing capacity, triglyceride (TG) and hormonal levels were determined hourly up to the 4th hour after a mixed meal containing 32.5 g lipids/m2 body surface in 14 treated non-obese type II diabetic patients with adequate nutritional and glycemic control (hemoglobin A1C [HbA1C] < 7%) and in 12 healthy subjects matched for age, sex, and body mass index (BMI). Mean cholesterol levels did not differ between patients and controls, with fasting TG moderately increased in diabetics (140 +/- 70 v 66 +/- 34 mg/dL, P < .01). Whereas fasting TG levels in patients showed a continuous distribution from 55 to 250 mg/dL, postprandial TG clearly identified two different subgroups. A "high-responder" or hypertriglyceridemic subgroup (HTG) showed PP TG levels significantly higher than control levels (290 +/- 62 v 106 +/- 41 mg/dL, P < .001), with higher fasting TG as well (181 +/- 52, P < .01), whereas both fasting and PP TG levels were not different from control levels in the normotriglyceridemic (NTG) diabetic subgroup. The magnitude of the PP triglyceridemic area showed a negative correlation with HDL2 cholesterol (r = .66, P < .001) and a positive correlation with PP HDL2 TG enrichment (r = .80, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

The thermogenic and metabolic effects of food in liver cirrhosis: consequences on the storage of nutrients and the hormonal counterregulatory response.

The thermogenic effect of food and the rates of oxidation and storage of nutrients were evaluated by indirect calorimetry in 10 cirrhotic patients and seven normal controls for a 6-hour period, after they had consumed a standard meal supplying 15 kcal/kg body weight with 15%, 30%, and 55% protein, fat, and carbohydrate calories, respectively. Although the thermogenic response to food was not significantly lower in patients than in controls (51.6 +/- 13.5 v 72.2 +/- 8.8 kcal/6 h), patients exhibited a delayed and blunted increment of energy expenditure after the meal intake (P less than .025). The greater part of the glucose load was oxidized in patients (70.2 +/- 3.9% v 50.4 +/- 3.9% in controls; P less than .01), suggesting a defective glucose storage as glycogen. This result could be related to insulin resistance, which was evidenced by a large increase in glucose and insulin levels after the meal intake in patients (P +/- .001). Conversely, lipid oxidation was sharply reduced and de novo lipogenesis occurred in patients, so that the rate of lipid storage was increased. The profiles of circulating levels of catecholamines, thyroid hormones (free thyroxine [FT4] and triiodothyronine [T3]), and glucagon were assayed during the test. Norepinephrine and glucagon levels remained higher in patients throughout the test (P less than .001), whereas thyroid hormones stayed in the same range in the two groups. After an initial increase, glucose levels decreased sharply, inducing an activation of counterregulatory hormones, glucagon, and notably, epinephrine, for which the increment was correlated with the decrease of glucose (r = -.917; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and metabolic changes during exercise in cirrhotic patients.

The metabolic response to exercise was compared in 10 cirrhotic patients (P) in a stable clinical condition and in 6 sedentary, age-matched, normal subjects (C) performing 32 minutes of treadmill exercise with the same constant workload corresponding to three to four times their resting oxygen uptake. Taking indirect calorimetry as reference, respiratory exchanges indicated that cirrhotic patients consumed carbohydrates almost exclusively, unlike the normal controls, who consumed lipids and glucids in about the same proportions (RQ: 0.98 +/- 0.04 v 0.87 +/- 0.04, P less than .0001). In the patients, this carbohydrate path of exercise metabolism lowered glycemia from the resting value of 5.23 +/- 0.16 mmol/L to 4.03 +/- 0.37 mmol/L (P less than .0001) and raised the plasma lactate concentration from 2.08 +/- 0.24 mmol/L at rest to 3.48 +/- 0.32 mmol/L at the eighth minute of exercise (P less than .001), thus suggesting defective liver glyconeogenesis. Fatty free acids and glycerol remained almost constant during exercise, whereas catecholamines increased. Insulin levels were high in patients at rest (67.1 +/- 14.5 U/mL v 15.1 +/- 3.5 U/mL); they declined sharply at the onset of exercise but nevertheless remained high compared to those observed in the controls (P less than .0001). Glucagon increased in exercising patients from 88.3 +/- 21.3 pg/mL to 127.4 +/- 30.6 pg/mL (NS). Esterified plasma carnitine declined in the patients from 13.0 +/- 2.2 mumol/L to 8.6 +/- 1.5 mumol/L (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional and metabolic consequences of basal hyperinsulinemia in alcoholic liver cirrhosis: relationship with postprandial changes in erythrocyte insulin-receptor affinity.

The nutritional and metabolic consequences of basal hyperinsulinemia were investigated in a group of 13 alcoholic cirrhotic patients; 7 healthy subjects were studied as a control group. Two groups of patients were defined on the basis of fasting insulin level: group 1 (n = 7) displayed acute hyperinsulinemia (> mean of control group + 2SD), and group 2 (n = 6) had lower insulin levels. Nutrition status was assessed by means of anthropometric parameters; the rates of nutrient oxidation were measured after an overnight fast and 2 h after a standard meal intake. Group 1 had better nutrition status in terms of fat mass than group 2 (p < 0.05). Although the basal rates of nutrient oxidation were in the same range in the three groups, postprandially, the rate of lipid oxidation was significantly different (p < 0.01). Moreover, group 1 showed greater inhibition of postprandial lipid oxidation than the control group (p < 0.05), whereas there was no difference between group 2 and the control group. In the postprandial phase, erythrocyte insulin-receptor binding and affinity increased paradoxically in group 1, whereas they decreased in group 2 and healthy subjects (changes in binding, p < 0.025; changes in affinity, p < 0.01). In conclusion, basal hyperinsulinemia in alcoholic liver cirrhosis is related to more marked inhibition of postprandial lipid oxidation and better-preserved nutrition status and may lead to a paradoxical postprandial increase in insulin-receptor affinity.

[Energy expenditure and the use of nutriments in cirrhotic patients fasting and at rest. Influence of alcoholic hepatitis and the severity score of the disease]. / Dépenses énergétique et utilisation des nutriments chez le cirrhotique à jeun et au repos. Influence de l'hépatite alcoolique et du score de gravité de la maladie.

Resting energy expenditure and nature of fuels consumed after an overnight fast have been evaluated in 30 cirrhotic patients and 10 normal subjects by indirect calorimetry. Basal metabolic requirements in patients were slightly increased although most of them had as poor nutritional condition assessed by a decreased muscular mass (17.3 +/- 0.8 vs 22.5 +/- 1.2 kg, p less than 0.001). Resting energy expenditure was significantly elevated in 16.7 p. 100 of patients. This hypermetabolic state was related to alcoholic hepatitis. Surface area and the Harris-Benedict equation did not accurately predict the resting energy expenditure. Compared to normal subjects, all patients had higher levels of free fatty acids (0.408 +/- 0.05 vs 0.182 +/- 0.03 mmol/l, p less than 0.001), glycerol (0.109 +/- 0.009 vs 0.035 +/- 0.003 mmol/l, p less than 10(-9)) and ketone bodies (0.137 +/- 0.012 vs 0.099 +/- 0.012 mmol/l, p less than 0.03). The respiratory quotient was lower in cirrhotic patients (0.740 +/- 0.01 vs 0.832 +/- 0.02, p less than 10(-5)). These results show increased lipolysis and a preferential use of fat as fuel substrates in cirrhotic patients: 70 p. 100 of the total calorie expenditure was derived from fat. Fat mobilization was influenced by nutritional status: a positive correlation has been found between fat mass and free fatty acids (p less than 0.02) and between fat mass and glycerol (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Thermic and metabolic effects of meals in liver cirrhosis assessment of oxidation and storage rates of nutrients]. / Effets thermogénique et métabolique du repas chez le cirrhotique: étude des capacités d'oxydation et de stockage des nutriments.

The thermic effect of food was evaluated in 10 cirrhotic patients and 7 normal controls by indirect calorimetry during 6 hours following intake of a mixed meal supplying 15 kcal/kg of body weight and containing 30, 15 and 55 percent as lipid, protein and carbohydrate calories respectively. The rates of storage and oxidation of nutriments, as well as variations of blood glucose, insulin, plasma lactates, free fatty acids, glycerol, and ketonic corps were also evaluated. The thermogenic response to food was lower (p less than 0.025) and delayed in cirrhotic patients. In cirrhotic patients the rate of glucose oxidation was significantly increased (70.2 +/- 3.9 vs 50.4 +/- 3.9 percent of the glucose load; p less than 0.01) suggesting a defect in glycogen storage. These results can be related to insulin resistance as attested by a larger increase of glucose and insulin levels in cirrhotics than in controls (p less than 0.001 and p less than 0.001, respectively). Compared with controls, lipolysis in cirrhotic patients was more suppressed as shown by a sharper decrease of free fatty acids and glycerol levels (p less than 0.001 and p less than 0.02, respectively). Furthermore, the rate of lipid oxidation decreased more in cirrhotic as compared with controls (p less than 0.001) before becoming completely suppressed. De novo lipogenesis appeared between the 2nd and 4th hours. Consequently, the rate of lipid oxidation was significantly reduced in cirrhotic vs controls (14.3 +/- 5.0 vs 30.5 +/- 3.7 percent of the lipid load; p less than 0.02) showing an increased rate of lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Microautoradiography of gamma-emitters: interest of latensification process.

Two techniques of microautoradiography were compared in order to assess their respective values to detect gamma-emitters usually used in nuclear medicine. Grain density microautoradiography (GD MARG) and track microautoradiography (T MARG) were performed on lymphocytes labeled with 99mTc, whose conversion electrons are able to provide a signal in nuclear emulsion. Microautoradiographs are presented, that clearly demonstrate the higher sensitivity, specificity and resolution obtained by T MARG. This technique seems particularly adapted to assess the distribution of gamma-emitters in cells and tissues.

Influence of non-carbohydrate foods on glucose and insulin responses to carbohydrates of different glycaemic index in type 2 diabetic patients.

In order to study the influence of non-carbohydrate foods on responses to carbohydrates during mixed meals, 30 Type 2 (non-insulin-dependent) diabetic patients followed a standardized diet for 5 consecutive days. On days 2, 3, 4, and 5, four different lunches were eaten in a randomized order. Lunches consisted of rice or glucose (50 g carbohydrate) eaten either alone, or as part of a mixed meal (32 g protein, 20 g fat). Glucose and insulin levels prior to the lunches did not differ significantly. Glucose and insulin responses differed (p less than 0.001), responses to rice being lower than responses to glucose, and responses to the meal plus rice lower than responses to the meal plus glucose. The ratios of glucose responses to rice and glucose (glycaemic index) were similar (alone, 47 +/- 4%; meal, 47 +/- 4%; NS). The ratios of the insulin responses did not differ (78 +/- 8 vs 96 +/- 7%; NS). The blood glucose responses to mixed meals were lower than responses to the carbohydrates eaten alone, the ratios being similar (rice, 52 +/- 3%; glucose, 58 +/- 5%; NS). Serum insulin responses were however higher, and the ratios differed (172 +/- 13 vs 138 +/- 14%; p = 0.05). These results suggest that the glycaemic index of isolated carbohydrate foods can predict the relative response to mixed meals in the same individuals with Type 2 diabetes. They also support the insulin secretagogue effect of non-carbohydrate foods, which may vary according to the source of carbohydrate in the meal.

Imaging and assessment of regional clearances of indium-111 labelled circulating immune complexes in humans.

The in vivo function of the reticulo-endothelial system in humans is currently studied by the blood clearance of 51Cr labeled RBC sensitized with IgG anti-Rh. By replacing 51Cr by 111In we developed a method which allows imaging and assessment of clearances of circulating immune complexes (CIC) by individual organs. Nine normal subjects were studied successively with 51Cr labelled CIC and 111In-labelled CIC by blood sampling and sequential imaging. Time activity curves were obtained over spleen, liver, heart lungs and kidneys. The blood clearance values were similar with 111In (T1/2 +/- SD = 23.4 min +/- 6.4 min) and 51 Cr (T1/2 = 22.9 min +/- 5.8 min). The blood clearance derived from the time activity curve obtained over the cardiac area (T1/2 = 26.6 min +/- 8.4 min) was not significantly different from that obtained by blood sampling. Most of the CIC were taken up by the spleen with a T1/2 of 20.3 min +/- 4.1 min. Although hepatic uptake was observed in all subjects, it was lower than that of the spleen and CIC were subsequently released from the liver in five of the nine patients. The spleen/liver ratio increased with time, reaching a plateau averaging 24.0 +/- 5.8 within 80 min in all subjects. CIC imaging allows, by a non-invasive procedure, the computation of CIC blood clearance and the estimation of the respective role of spleen and liver in phagocytic function.

Reduction of postprandial lipemia after acute exposure to high altitude hypoxia.

The effects of acute exposure to high altitude hypoxia upon plasma levels of lipids and lipoproteins were studied in 6 healthy subjects observed under strict dietary control. Fasting and postprandial values, first measured at low altitude (< 300 m), were compared to values measured 7 days after transfer by helicopter to the Observatoire Vallot (4350 m) near Mont-Blanc. Plasma levels of catecholamines and thyroid hormones were measured in parallel. Under normoxic conditions, a rise in plasma levels of cholesterol, triglycerides and phospholipids was found 4 hr after the test-meal, whereas circulating norepinephrine fell. Under hypoxic conditions, postprandial effects on lipid parameters disappeared, lipemic responses to the test-meal were dramatically reduced and plasma levels of norepinephrine increased. These effects were accompanied by a fall in triglyceride-rich lipoproteins, generally associated with a slight elevation of HDL-cholesterol, especially the less dense HDL2 fraction. When all results obtained in normoxic and hypoxic conditions were analyzed together, a series of highly significant correlations were found between the magnitude of postprandial lipidemia and various lipid parameters, in particular HDL2-cholesterol which was negatively correlated. These observations strongly suggest that high altitude hypoxia, independent of interfering variables such as exercise training or cold exposure, induced a net stimulation of the lipolysis of plasma triglycerides.