Glycemic effects of spaghetti and potato consumed as part of mixed meal on IDDM patients.

Recently, we demonstrated that spaghetti caused a significantly lower glycemic response in isoinsulinemic insulin-dependent diabetic (IDDM) subjects than an exchangeable amount of potato. The question is, however, whether the difference of the glucose response in IDDM patients is preserved if these carbohydrate-rich foods are taken as part of a mixed meal. To answer this question, we evaluated blood glucose, free-insulin, and glucagon responses to exchangeable amounts of spaghetti and potato when ingested together with bolognese sauce in seven IDDM patients who had attained euglycemia with the artificial pancreas before meal intake. The potato (200 g raw wt) with bolognese sauce (167 g) and spaghetti (50 g raw wt) with bolognese sauce (167 g) had approximately identical caloric content (435 and 447 kcal, respectively), fat (18 g each), protein (23 and 26 g, respectively), and carbohydrate (47 and 48 g, respectively). Blood glucose increment after white spaghetti and bolognese sauce was only approximately 50% of that seen in response to potato and bolognese sauce. Similar constant insulin levels and increments in glucagon were seen. A major determinant of the postmeal glucose rise in IDDM patients seems to be dependent on the kind of carbohydrate in the meal. The approach by which the insulinemia was kept constant by the artificial pancreas seems to be a valuable tool for studying glycemic responses to different meals in IDDM patients who otherwise show great variations in circulating insulin and glucose levels when treated by subcutaneously administered insulin.

Insulin action in insulin-dependent diabetics after short-term thiazide therapy.

The influence of short-term thiazide treatment on peripheral tissue and liver sensitivity to insulin in insulin-dependent diabetes mellitus was determined by the euglycemic insulin clamp technique. A sequential three-step hyperinsulinemic clamp was performed in six insulin-dependent diabetics before and after 2 wk of hydroflumethiazide (HFT) administration in a daily dose of 75 mg. Insulin was infused at rates of 0.5, 2.0, and 4.0 mU X kg-1 X min-1, and each dose was given for at least 120 min. Glucose uptake during the last 30 min of each step was almost identical in the two situations (2.7 +/- 0.6 vs. 2.4 +/- 0.5 mg X kg-1 X min-1, 9.6 +/- 0.9 vs. 9.7 +/- 1.2 mg X kg-1 X min-1, and 12.0 +/- 1.3 vs. 12.6 +/- 1.5 mg X kg-1 X min-1). Serum insulin levels were also similar, and blood glucose was kept at 100 +/- 3, 99 +/- 4, and 97 +/- 3 mg/dl before thiazides and at 93 +/- 6, 93 +/- 6, and 94 +/- 6 mg/dl after thiazides. Another five insulin-dependent diabetics were infused with tritiated glucose followed by insulin infusion at two rates: 0.45 and 1.0 mU X kg-1 X min-1. Basal glucose output was comparable before and after thiazides (3.63 +/- 0.24 vs. 2.97 +/- 0.26 mg X kg-1 X min-1), as was the liver response to increasing insulin concentrations. The metabolic state as assessed by HbA1c and fasting blood glucose did not differ in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo insulin action in type 1 (insulin-dependent) diabetic pregnant women as assessed by the insulin clamp technique.

To determine the influence of pregnancy on insulin sensitivity in patients with type 1 diabetes mellitus in more detail, a hyperinsulinemic euglycemic clamp study was performed in six pregnant type 1 diabetic women and eight nonpregnant women with type 1 diabetes mellitus. All of the pregnant women were studied three times: in early pregnancy (mean, week 13), late pregnancy (mean, week 34), and within a week after delivery. Insulin was infused in a constant rate of 1.0 mU/kg X min, which resulted in steady state serum free insulin levels (I) of 44 +/- 3 (+/- SEM), 56.6 +/- 6, and 55 +/- 8 microU/ml in the pregnant diabetic women and 52 +/- 4 microU/ml in the nonpregnant women. Mean glucose disposal (M) was 5.6 +/- 0.3 mg/kg X min early in pregnancy and 3.4 +/- 0.5 mg/kg X min late in pregnancy (P less than 0.02). However, in the early postpartum period, M was again higher (7.2 +/- 0.7 mg/kg X min; P less than 0.02) and similar to values in early pregnancy and nonpregnant diabetic women (7.2 +/- 0.6 mg/kg X min). When tissue sensitivity to insulin was expressed as the M to I ratio, similar results were obtained (nonpregnant women, early stage of gestation, and postpartum vs. late stage of gestation: 0.13 +/- 0.01, 0.13 +/- 0.01, and 0.15 +/- 0.03 mg/kg X min per microU/ml vs. 0.06 +/- 0.1 mg/kg X min per microU/ml; P less than 0.03 in all). There tended to be an inverse relationship between serum levels of human placental lactogen and the M to I ratio during pregnancy (r = -0.74; P = 0.09). However, we found no association between changes in the impairment of insulin action and serum estradiol, progesterone, or cortisol levels. In conclusion, pregnant type 1 diabetic women have insulin resistance in peripheral tissues in the late stage of gestation. Insulin sensitivity returns to values found in nonpregnant diabetic women within the first week after delivery.

Influence of growth hormone on glucose-induced glucose uptake in normal men as assessed by the hyperglycemic clamp technique.

To determine whether physiological increments in circulating GH concentrations influence glucose-induced glucose uptake (GIGU), two-step sequential hyperglycemic clamp (plasma glucose, 6 and 14 mmol/L) studies were performed in six normal subjects with and without GH infusion (40 ng/kg.min). The latter resulted in serum GH levels of 15 +/- 1 (+/- SE) microgram/L. Infusion of somatostatin (250 micrograms/h during step 1 and 750 micrograms/h during step 2) together with a replacement dose of insulin (1.1 pmol/kg.min) resulted in serum insulin levels comparable to basal levels in both studies. The GIGU ([3-3H]glucose), assessed as the difference between steps 2 and 1 glucose utilization during the final 60 min of each step (150 min) was markedly impaired during GH infusion (with GH, 1.1 +/- 0.2 mg/kg.min; without GH, 3.1 +/- 0.3 mg/kg.min; P less than 0.001). Moreover, the percent increase in glucose uptake was considerably reduced during hypersomatotropinemia (with GH, 44 +/- 9%; without GH, 97 +/- 11%; P less than 0.01). In the GH infusion as well as control studies, endogenous glucose production (EGP) was similar at the two levels of glycemia, whereas GH infusion approximately doubled EGP [2.3 +/- 0.2 vs. 1.1 +/- 0.3 mg/kg.min and 2.0 +/- 0.4 vs. 1.1 +/- 0.4 mg/kg.min (step 1 and 2, respectively)]. We conclude that moderate hypersomatotropinemia for several hours is characterized by impaired GIGU as well as augmented EGP.

Comparison of blood glucose and insulin responses in non-insulin dependent diabetic patients. Studies with spaghetti and potato taken alone and as part of a mixed meal.

Recently, we demonstrated that spaghetti caused significantly lower glycaemic response than rice and potato in insulin-dependent diabetic (IDDM) subjects and that this difference was also present when spaghetti and potato were taken as part of a mixed meal. We have now compared the blood glucose and insulin responses to 50 g of carbohydrate in the form of white bread, potato and white spaghetti in 6 non-insulin-dependent diabetic (NIDDM) patients. The blood glucose response after white spaghetti observed over a 3-h period was only 60 +/- 10 per cent (P less than 0.02) of that seen in response to potato (395 +/- 116 mmol/l x 180 min vs 641 +/- 108 mmol/l x 180 min) and 47 +/- 9 per cent (P less than 0.01) of that seen in response to white bread (395 +/- 116 mmol/l x 180 min vs 805 +/- 93 mmol/l x 180 min). Insulin responses showed an identical pattern reflecting the glycaemic responses. To see if the difference in the glucose responses in NIDDM patients is preserved if these carbohydrate-rich foods are taken as part of a mixed meal we looked at the blood glucose and insulin responses to 50 g of carbohydrate in the form of potato and white spaghetti when ingested together with bolognese sauce (167 g) in 7 NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of hyperglycemia on glucose uptake and hepatic glucose production in non-dialyzed uremic patients.

To determine whether the deranged glucose metabolism in uremia, in addition to insulin resistance can be attributed also to reduced glucose-induced glucose uptake, a two-step sequential hyperglycemic clamp (plasma glucose: 120 and 300 mg/dl) was performed in 6 non-dialyzed uremic and 8 healthy subjects. A constant infusion of somatostatin (300 micrograms/h) and soluble insulin (0.2 mU/kg/min) resulted in peripheral serum insulin slightly higher than basal in both uremics (16 +/- 3 and 22 +/- 3 microU/ml; step 1 and 2, respectively) and controls (20 +/- 2 and 22 +/- 1 microU/ml). The glucose-induced glucose uptake (3-3H-glucose) assessed as the difference between step 2 and 1 glucose disposal at the final 30 min of each step was markedly reduced in uremics (3.2 +/- 0.5 mg/kg/min) compared to healthy subjects (5.7 +/- 0.8 mg/kg/min; p less than 0.03). However, the percentage increment in glucose uptake from step 1 to step 2 hyperglycemia was comparable in the two groups (134 +/- 27 and 148 +/- 17%). Modest hyperglycemia (120 mg/dl) and slightly raised insulinemia resulted in comparable suppression of the endogenous (hepatic) glucose production (EGP) in healthy (1.6 +/- 0.2 mg/kg/min) and uremic subjects (1.5 +/- 0.3 mg/kg/min). In controls, pronounced hyperglycemia (300 mg/dl) further reduced EGP (0.6 +/- 0.3 mg/kg/min; p less than 0.01) while EGP in uremics on the contrary tended to rise (2.0 +/- 0.4 mg/kg/min; p = 0.09), thus indicating an abnormal reaction of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of furosemide and indapamide upon pancreatic insulin and somatostatin secretion in vitro.

Antihypertensive treatment with furosemide and indapamide may eventually cause impairment of glucose metabolism. To study if this was due to a direct effect on the endocrine pancreas, we examined the effects of furosemide and indapamide on the release of insulin and somatostatin from the isolated perfused pancreas of normal dogs. Furosemide at concentrations ranging between 1-30 micrograms/ml inhibited insulin in a dose-dependent manner (2p less than 0.01) whereas the somatostatin secretion was left unchanged. Also the infusion of indapamide at doses ranging between 0.05-1 micrograms/ml subdued B-cell secretion at the two highest concentrations of 0.5 (by 15 +/- 2%, p less than 0.01) and 1 microgram/ml (by 22 +/- 5%, p less than 0.02) while pancreatic D-cell secretion did not alter. The results suggest, that furosemide and indapamide possess the ability to directly inhibit insulin secretion. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during therapy remains, however, uncertain.

Differential glycaemic effects of potato, rice and spaghetti in type 1 (insulin-dependent) diabetic patients at constant insulinaemia.

The blood glucose responses to cooked potato, rice and spaghetti were studied in six Type 1 (insulin-dependent) diabetic patients who had attained euglycaemia by the artificial pancreas prior to the meal intake. The amount of potato (raw weight 200 g), parboiled rice (raw weight 50 g), and spaghetti (raw weight 50 g) had approximately identical caloric content (range 203-225 kcal) and amount of available carbohydrate (range 39.4-43.4 g). The postprandial blood glucose response areas after cooked potato and cooked parboiled rice were similar (180 min values: cooked potato: 1190 +/- 110 mmol/l X min, cooked rice: 1160 +/- 140 mmol/l X min and 240 min values: cooked potato: 1690 +/- 140 mmol/l X min, cooked rice: 1740 +/- 210 mmol/l X min). In contrast, the response after cooked spaghetti was slower and less pronounced (180 min value: 830 +/- 80 mmol/l X min and 240 min value: 1320 +/- 120 mmol/l X min), and was significantly smaller than those of cooked potato (180 min: 2p less than 0.01 and 240 min: 2p less than 0.01) as well as cooked rice (180 min: 2p less than 0.01 and 240 min: 2p less than 0.02). Our study emphasizes the importance of determining the glycaemic response of foodstuffs under conditions of isoinsulinaemia.

Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism.

UNLABELLED: Insulin action on glucose utilization was characterized in adipocytes from 10 thyrotoxic patients, 6 hypothyroid patients and 10 age- and sex-matched control subjects. In thyrotoxic patients insulin binding at low insulin concentrations was reduced (P less than 0.05) and accompanied by impaired insulin sensitivity of glucose transport (P less than 0.02), glucose oxidation (P less than 0.05) and lipogenesis (P less than 0.05). Glucose transport and glucose oxidation rates also exhibited depressed maximal insulin responsiveness (P less than 0.05). In hypothyroid patients insulin binding was reduced, too, (P less than 0.05) and associated with impaired sensitivity to insulin of glucose transport (P less than 0.05). Both glucose transport and lipogenesis rates showed decreased maximal insulin responsiveness (P less than 0.05). IN CONCLUSION: In man, both hyper- and hypothyroidism are characterized by insulin resistance of adipocyte glucose utilization localized to insulin binding as well as to insulin-stimulated glucose transport and metabolism.

A prospective study on infection with cytomegalovirus in renal allograft recipients immunosuppressed with cyclosporine A and low dose prednisone.

To investigate the course of infection with cytomegalovirus (CMV) in renal allograft recipients treated with cyclosporine A, 10 patients were followed for 1 year after transplantation. Virus cultures from blood, urine and throat washings were performed employing a quantitative technique. Complement-fixing and IgM antibodies to CMV were measured at scheduled intervals. The incidence 90% and course of CMV infections were found not to differ from those reported in patients receiving conventional immunosuppressive therapy. The quantitative virus cultures showed a consistent pattern with viremia most prominent at the beginning of an infection, and the highest concentration found in the one patient who developed symptoms of viral disease. It is suggested that information about the concentration of virus in a specimen will improve the diagnostic value of virus cultures in this group of patients.

Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects.

To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45 mU/kg X min or in identical amounts in pulses of 1 1/2 to 2 1/4 min followed by intervals of 10 1/2 to 9 3/4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 microU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7 +/- 0.7 vs 6.8 +/- 0.9 ml/kg X min, P less than 0.01, and 330-354 min: 8.9 +/- 0.5 vs 7.4 +/- 0.9 ml/kg X min, P less than 0.05). The superior efficacy of pulsatile insulin delivery on glucose uptake was not consistently found until after 210 min of insulin administration. In both infusion protocols, endogenous glucose production as estimated by the [3-3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion.

Marked impairment of the effect of hyperglycaemia on glucose uptake and glucose production in insulin-dependent diabetes.

The effect of hyperglycaemia per se on glucose utilization and glucose production was evaluated in 12 patients with insulin-dependent diabetes and in 9 non-diabetic control subjects. In diabetic patients normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin infusion. During the study endogenous insulin secretion was suppressed by somatostatin (300 micrograms h-1) and replaced by infusion of insulin (0.2 mU kg-1 min-1). Glucose utilization and hepatic glucose production rates were quantified at two plasma glucose concentrations (6.7 and 16.7 mmol l-1) using the two-step sequential hyperglycaemic clamp technique in combination with 3-3H-glucose tracer infusion. Duration of each step was 120 min. In diabetic patients glucose utilization, at a glucose concentration of 6.7 mmol l-1, was not different from normal (mean +/- SE: 2.9 +/- 0.2 vs 3.6 +/- 0.3 mg kg-1 min-1, 0.05 less than p less than 0.10), but the response to marked hyperglycaemia was significantly reduced (5.4 +/- 0.5 vs 9.4 +/- 1.0 mg kg-1 min-1, p less than 0.01). Hepatic glucose production was also normal at 6.7 mmol l-1 (1.4 +/- 0.1 vs 1.4 +/- 0.1 mg kg-1 min-1, NS), but whereas in control subjects glucose production was suppressed during hyperglycaemia of 16.7 mmol l-1 (0.3 +/- 0.4 mg kg-1 min-1, p less than 0.01), a slight increase was observed in diabetic patients (2.0 +/- 0.2 mg kg-1 min-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)