Beta-adrenoceptors desensitization may modulate catecholamine induced insulin resistance in human pheochromocytoma

Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of glibenclamide treatment on the insulin and glucagon responses to oral glucose and galactose in maturity onset diabetics.

Glibenclamide has been shown to stimulate an insulin releasing factor in the duodenum. The possibility that this effect is of importance in its hypoglycaemic action was investigated by studying the effect of galactose on insulin release before and after treatment with glibenclamide; galactose stimulates insulin release when given orally but has no effect when given parenterally; thus its ability to release insulin appears to reside in an action on a gut factor. Measurements of plasma glucose, insulin and glucagon were made on twelve maturity onset diabetic patients following an oral glucose tolerance test and an oral galactose tolerance test before and after one week of treatment with glibenclamide. Glibenclamide significantly reduced the blood glucose levels. Both basal insulin and basal glucagon levels were unchanged. The insulin response to oral glucose was enhanced. Glucagon levels before treatment did not suppression of glucagon levels. Galactose stimulated insulin release but insulin levels before and after treatment were identical. An effect of glibenclamide on gut insulin releasing activity was not demonstrated but the galactose tolerance test provides a useful technique by which to examine the enteroinsular axis.     

Metabolic follow-up after long-term pancreas graft survival

DESIGN: Successful pancreas transplantation results in insulin independence and normoglycemia. This prospective study was performed to investigate long-term metabolic changes after pancreas transplantation. METHODS: Thirty-eight type 1 diabetic patients after simultaneous pancreas/kidney transplantation (SPK) with a pancreas graft survival for at least 10 years were studied in a prospective manner. HbA(1c) and glucose levels before and during an oral glucose tolerance test (OGTT) were analyzed from 3 months to 10 years after SPK. In addition, insulin secretion and glucagon response were measured. RESULTS: Fasting glucose increased slightly and continuously from 3 months to 10 years (from 78 +/- 3 to 91 +/- 2 mg/dl). Even HbA(1c) levels showed a mild but significant increase from 3 months to 10 years after SPK. Glucose tolerance deteriorated markedly 10 years after SPK. Insulin secretion during OGTT remained stable for 10 years. Parameters of insulin resistance and sensitivity did not change significantly but glucagon secretion increased significantly during the course after SPK. Late after SPK, glucagon levels were higher in patients with an impaired or diabetic glucose tolerance. CONCLUSIONS: Pancreas transplantation is able to restore endogenous insulin secretion for 10 years or more. Especially, late after SPK, a deterioration of glycemic control was detected, even if glucose values were within the normal range. During prospective long-term follow-up, an increase of glucagon secretion but no decrease of insulin secretion was detected.     

Comparative insulinogenic effects of glucose,arginine and glucagon in patients with diabetes mellitus,endocrine disorders and liver disease

Summary In order to compare the insulinogenic effects of glucose, arginine and glucagon, plasma immunoreactive insulin levels following oral glucose loading (50 g), intravenous arginine infusion (30 g for 45 min) and intravenous glucagon injection (1 mg) were determined in patients with diabetes mellitus, various endocrine diseases and chronic hepatitis. In patients with Cushing’s syndrome, plasma insulin responses to all three stimuli were exaggerated, whereas they were low in patients with pheochromocytoma. In other diseases, certain disparities were observed in plasma insulin responses. In patients with mild diabetes mellitus, insulin secretion elicited by glucose seems to be selectively impaired, because arginine and glucagon caused a rise in plasma insulin not significantly different from that in normal subjects. In patients with hyperthyroidism, plasma insulin responses to arginine and glucagon were either absent or limited, although rather a exaggerated response was noted following oral glucose loading. On the contrary, exaggerated responses to arginine and glucagon, and limited response to glucose were observed in hypothyroidism. In patients with chronic hepatitis, the responses of plasma insulin to glucose and arginine were both exaggerated, whereas the response to glucagon was comparable to that in normal subjects. These disparate responses suggest that glucose, arginine and glucagon act on the B-cell via different mechanisms.     

Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults

In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.     

Insulin, glucagon and growth hormone responses during glucose, arginine and insulin tolerance tests in children with hyperthyroidism

There are many reports of glucose intolerance in adult patients with hyperthyroidism but few reports of glucose intolerance in hyperthyroid children. In this study, we measured plasma levels of glucose, insulin, glucagon and growth hormone in hyperthyroid children and control subjects by the use of three kinds of tolerance tests: an oral glucose tolerance test, an arginine tolerance test and an insulin tolerance test. In the oral glucose tolerance test, mean fasting glucose levels (79.6 +/- 1.4 mg/dl) rose to maximum levels (157.3 +/- 4.3 mg/dl) at 30 min in hyperthyroid children which were significantly higher than the levels in control subjects (p less than 0.01). The maximum levels of glucose fell slowly and returned to fasting levels at 180 min. In this test, plasma insulin levels increased from basal levels (12.7 +/- 1.9 microU/ml) to maximum levels (120.8 +/- 22.1 microU/ml) at 30 min in the prepubertal age group of hyperthyroidism. On the other hand, in the pubertal age group of hyperthyroidism, maximum levels of insulin were observed at 60 min, but not at 30 min. These maximum levels of insulin of both hyperthyroid age groups were significantly higher than those in the control subjects (p less than 0.05, p less than 0.01 respectively). There was no difference in insulin-glucose ratio at 30 min (delta IRI/delta BG) and insulinogenic index (I.I.) at 0 to 60 min between these two groups of hyperthyroid children and control subjects. However, I.I. at 0 to 120 min and 0 to 180 min decreased significantly in the pubertal age group of hyperthyroidism as compared with those in the control group (p less than 0.05, p less than 0.02 respectively). In the oral glucose tolerance test, plasma glucagon levels decreased from basal levels (74.1 +/- 4.3 pg/ml) to minimum levels (36.4 +/- 4.7 pg/ml) at 90 min in hyperthyroidism, which were significantly lower than those in the controls (p less than 0.05). However, there was no difference in -epsilon delta IRG/epsilon delta BG (cumulative glucagon response/cumulative glucose response) between the subjects with hyperthyroidism and the controls. On the other hand, lower responses of blood glucose, insulin, glucagon and growth hormone to arginine were observed in subjects with hyperthyroidism than in the controls. Moreover in the insulin tolerance test, there was no difference in glucagon and growth hormone response between the subjects with hyperthyroidism and the controls. Thus our conclusions are as follows: A marked increase in blood glucose after oral glucose load was observed in spite of normal insulin-glucose ratio in hyperthyroid children, suggesting the existence of peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)     

Minor physiological relevance of oral glucose tolerance test

The physiological relevance of the oral glucose tolerance test was evaluated in ten healthy nonobese subjects and nine subjects with slightly impaired glucose tolerance. In random order, all subjects received a 50 g oral glucose tolerance test or a standardized breakfast meal of equivalent carbohydrate content. Changes in plasma glucose, insulin, and pancreatic glucagon concentrations were measured. In both groups, plasma glucose increased significantly during the oral glucose tolerance test and the meal test but the incremental glucose area (0-60 min) of the oral glucose tolerance test was about 350% and 120% greater than that of the mean test (p less than 0.001) in the normals and the patients with impaired glucose tolerance, respectively. In both groups, insulin responded almost similarly to the oral glucose tolerance test and the meal test whereas plasma glucagon declined significantly during the oral glucose tolerance test only (p less than 0.001). Glucagon remained unchanged during the meal test in the normals and increased slightly (p less than 0.05) in the group with impaired glucose tolerance. These data show that the response of glucose, insulin and glucagon to an oral glucose tolerance test in various respects is different to that obtained by the more physiological stimulation with a breakfast meal.     

ABNORMALITIES OF GLUCAGON METABOLISM IN DIABETES MELLITUS

Fasting plasma glucagon has been measured by a specific radioimmunoassay in twenty-three untreated maturity onset diabetic patients and twenty-three matched normal controls. Significant fasting hyperglucagonaemia was demonstrated in the diabetic subjects in spite of their raised blood glucose and insulin concentrations. Oral glucose tolerance tests were performed on ten diabetic subjects and ten normal controls and variations in blood glucose, insulin and glucagon concentration studied. Glucagon concentration was shown to increase significantly after oral glucose in the diabetic subjects and to fall in the normal controls. The differences between the changes in glucagon concentration in the two groups could not be related to the differences in insulin response. It is proposed that these findings provide evidence of derangement of metabolism within the alpha cell in maturity onset diabetes.     

Glucose intolerance in liver cirrhosis

Glucose intolerance and hyperinsulinemia frequently occur in patients with chronic liver failure. To investigate the importance of glucose counterregulating factors, an oral glucose tolerance test was performed on 18 patients with compensated liver cirrhosis, matched for liver function tests and degree of portal hypertension, and 10 healthy controls. Blood glucose, immunoreactive insulin, C-peptide, immunoreactive glucagon, glucagon like immunoreactivity, growth hormone, cortisol and free fatty acids were determined in both groups at 30 min intervals for 240 min. Despite the similarity in the severity of liver damage five cirrhotic patients showed normal glucose tolerance, eight impaired glucose tolerance and five overt diabetes. Immunoreactive insulin was significantly higher in cirrhotic patients than in controls both before and during the oral glucose tolerance test. As basal C-peptide values were significantly higher and C-peptide/immunoreactive insulin ratio was significantly lower in cirrhotic patients than in the control subjects, both hyperproduction and hypodegradation seem to be responsible for the high insulin levels. Immunoreactive glucagon and cortisol showed no statistical differences between cirrhotic patients and control subjects whereas high basal growth hormone and free fatty acids values were observed in the cirrhotic group. Basal values and maximum increase or decrease of all the factors examined were tested by a correlation analysis with the blood glucose at 120 min and evaluated by a stepwise linear regression analysis. Only basal blood glucose, basal free fatty acids and immunoreactive insulin increment correlated significantly with blood glucose at 120 min. By the stepwise procedure these factors were found to account for 86% of the variance of the glucose level at 120 min. In chronic liver disease we failed to establish a pathogenetic role of hormones involved in the glucose counterregulating system. Free fatty acids may play an important role in glucose intolerance in chronic liver failure.     

The mechanism of glucose intolerance in patients with Graves' disease]

To investigate the mechanism of glucose intolerance in patients with Graves' disease, a 2-hour oral glucose tolerance test and euglycemic glucose clamp study using Biostator were performed in patients with Graves' disease and control subjects. 80 per cent of the patients showed impaired glucose tolerance. Insulinogenic index in the patients with borderline or diabetic glucose response was lower than that in subjects with normal glucose response. Insulinogenic index was inversely correlated with sigma PG during the test. Despite normal basal plasma glucose concentrations, basal plasma insulin levels in the patients with Graves' disease were higher than in the controls. Using the euglycemic glucose clamp technique, the glucose utilization rate (M value), the metabolic clearance rate of glucose (MCRG) and the insulin sensitivity index (M/I x 100) in the patients with Graves' disease were lower than in the controls. After treatment with antithyroid drug in 3 patients, glucose tolerance completely normalized, and there was a significant increase in the M value and the MCRG and a significant decrease in the metabolic clearance rate of insulin (MCRI) compared to the values before treatment. In the patients with Graves' disease, basal serum glucagon levels were higher than in the controls, and glucagon suppression during insulin infusion was found to be decreased. From these data, it is concluded that the decrease in glucose tolerance in patients with Graves' disease can be explained by 1) the impairment of early insulin release response to rapid intestinal glucose absorption, 2) increased insulin metabolic clearance and 3) hyperglucagonemia.     

The effect of hGH deficiency on the insulin response to glucagon after oral glucose loading

Summary Six children and adolescents (aged from 2 6/12 to 16 years) with isolated hGH deficiency were subjected to a standard oral glucose tolerance test (OGTT) followed by the administration of IV glucagon at 180 mins. Three of them underwent a second test after several months of hGH therapy. Nine patients underwent a separate IV glucagon test and two of these patients had both tests. As controls served 14 endocrinologically normal children and adolescents, who underwent both tests. It was found that the patients with isolated hGH deficiency had lower basal plasma insulin and blood glucose levels and that their insulin response to IV glucagon even after oral glucose preloading was significantly lower than in the control group. This response was partially restored by several months of hGH treatment in the three patients tested. These findings are interpreted as further evidence for an insulinotrophic effect of hGH.Established Investigator of the Chief Scientist's Bureau, Ministry of Health     

Glucose intolerance in thyrotoxicosis roles of insulin, glucagon and somatostatin

The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P less than 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P less than 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P less than 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P less than 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P less than 0.02). Our findings suggest that decreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness.     

Glucose tolerance in early pregnancy

The effect of pregnancy on oral glucose tolerance (50 g of glucose) and plasma insulin and glucagon responses to oral glucose was studied in weeks 10 and 32 of pregnancy and again 1 year post partum in 12 normal women. Already in week 10, fasting plasma glucose was decreased and the glucose-induced insulin secretion increased as compared with post partum. However, glucose tolerance was not affected at this time. In week 32, glucose tolerance had deteriorated, although the levels of both fasting and glucose-induced insulin were higher than those found in early pregnancy and post partum. At all investigations fasting plasma glucagon and the suppression of plasma glucagon after oral glucose were similar, indicating that glucagon is not implicated in the changes in glucose homeostasis seen in pregnancy. It is concluded that glucose tolerance is unaltered by pregnancy in week 10. Pregnancy has, however, at this very early stage already affected glucose homeostasis as seen by the decrease in fasting plasma glucose and the increase in the insulin response to glucose.     

Clinical benefits and mechanisms of a sustained response to intermittent insulin therapy in type 2 diabetic patients with secondary drug failure

To test the hypothesis that short-term insulin therapy may induce long-lasting metabolic improvements in patients with type 2 diabetes resistant to oral therapy, 19 patients were studied before and four weeks after insulin therapy, and again four weeks after resumption of oral medication. The mechanisms associated with changes of glycemic control after discontinuation of insulin therapy were also evaluated. During insulin therapy, blood glucose levels (228 +/- 13 versus 123 +/- 18 mg/dl, p less than 0.001) and the basal glucose production rate (p less than 0.001) decreased, and the insulin secretory response to glucagon at a standardized glucose level, insulin action in vivo, and insulin binding and action in vitro in fat cells improved significantly. During the post-insulin oral therapy, blood glucose levels increased (194 +/- 11 mg/dl, p less than 0.001) but remained below pre-insulin treatment values (p less than 0.01). The mean daily glucose concentration after post-insulin oral therapy correlated with the initial pre-insulin therapy glucose concentration (r = 0.83, p less than 0.001). The improved rate of in vivo glucose disposal and the enhanced insulin secretory response persisted during oral therapy whereas the basal glucose production rate returned to its pre-insulin therapy value. It is concluded that patients with type 2 diabetes in whom oral therapy fails show favorable responses to insulin therapy. After discontinuation of insulin therapy, blood glucose concentrations tend to return to their individual initial values. Therefore, most of these patients require long-term insulin therapy. The mechanism behind the change of glycemic control after cessation of insulin therapy seems to be an increase in the basal glucose production rate rather than deterioration of extrahepatic insulin action or the insulin secretory response.     

Preoperative insulin secretion ability and pancreatic parenchymal thickness as useful parameters for predicting postoperative insulin secretion in patients undergoing pancreaticoduodenectomy

Periampullary malignant neoplasms have been increasing in Japan, mainly in response to an increase in the incidences of pancreatic cancer, and glucose intolerance due to deterioration of insulin secretion is an important problem. We investigated preoperative parameters to predict postoperative insulin secretion and the need for insulin therapy in patients undergoing pancreaticoduodenectomy (PD). Thirty-six patients with malignant neoplasms of periampullary lesions were enrolled. Preoperative pancreatic parenchymal thickness was evaluated by computed tomography. Insulin secretion and glucose tolerance were evaluated by a 75-g oral glucose tolerance test and an intravenous glucagon loading test. The relationships between postoperative insulin secretion and preoperative parameters and the cut-off values for predicting the need for postoperative insulin therapy for glycemic control were investigated. Pancreatic parenchymal thickness and other preoperative parameters, including the increment of serum C-peptide (Δ C-peptide), fasting plasma C-peptide (F-CPR), insulinogenic index (I.I.) and fasting plasma glucose (FPG), were significantly associated with postoperative insulin secretion. Multiple regression analyses revealed that preoperative Δ C-peptide or F-CPR was the most significant determinant of postoperative insulin secretion, followed by pancreatic parenchymal thickness. In the receiver operating characteristic curve, the best preoperative cut-off values for predicting the need for postoperative insulin therapy were a Δ C-peptide of 0.65 ng/mL, a F-CPR of 0.85 ng/mL and a pancreatic parenchymal thickness of 6.0 mm. Both preoperative insulin secretion and pancreatic parenchymal thickness effectively predict postoperative insulin secretion and identify subjects who need postoperative insulin therapy for glycemic control.     

Amino acid modulation of glucose-induced insulin and glucagon release in diabetic patients

In order to determine whether amino acids have a beneficial effect on glucose tolerance in diabetes, the effect of intravenous infusion of mixed amino acids on plasma insulin, glucagon, and blood glucose responses to oral glucose loading was studied in patients with mild to moderate diabetes. Intravenous infusion of mixed amino acids over a period of 30 min which was started 30 min or immediately before oral glucose loading significantly augmented the insulin response but did not improve the blood glucose curve, probably due to excessive glucagon response. However, amino acid infusion over a period of 60 min started immediately before oral glucose loading evoked a sustained rise of plasma insulin associated with a lesser degree of glucagon secretion, thus causing significant improvement of the blood glucose curve.     

Possible glucagon-mediated hypocholesterolemic activity of a nicotinic acid derivative (sorbinicate)

The antilipolytic activity of nicotinic acid was investigated in 7 patients with type II b hyperlipoproteinemia and in 7 with type IV hyperlipoproteinemia treated for two months with a nicotinic acid derivative, sorbinicate (1600 mg daily, ie 1454 mg NA). Before and after treatment the blood levels of total cholesterol and triglycerides were determined and three dynamic tests -- oral glucose tolerance test, insulin test and tolbutamide test -- were done to check in each test the variations in blood glucose, NEFA, insulin (excluding obviously the insulin test), glucagon and growth hormone levels. At the end of the treatment, there was a significant reduction of cholesterol (type IIb and type IV) and of triglycerides (type IV), a marked reduction of the glucagon response, a slight increase in the insulin response and in the basal secretion of the growth hormone. It is suggested that the antilipolytic activity of nicotinic acid (and hence of sorbinicate) is at least partly mediated by an inhibition of glucagon secretion (and/or synthesis).     

Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics

A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus.     

Endocrine pancreatic secretion in patients after acute pancreatitis

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.     

Carbohydrate metabolism and insulin resistance in myotonia dystrophica.

Carbohydrate metabolism was studied in fourteen patients with myotonia dystrophica (MD) using oral glucose, fructose and galactose tolerance tests. Insulin responses to tolbutamide, glucagon, arginine and leucine were determined and insulin resistance was measured with exogenous iv insulin. Glucose tolerance was impaired in twelve of the four teen subjects while hyperinsulinism was found in all patients studied. Insulin response to the various substances was excessive. The insulin tolerance test revealed insulin resistance in all patients and this generally correlated well with the degree of hyperinsulinism to provocative tests. Serum galactose levels after an oral load were much lower in MD compared to normal subjects and were associated with a correspondingly greater rise in glucose, indicating an increased conversion of galactose to glucose. A similar response to oral galactose was found in diabetics. The hyperinsulinism seen with the fructose and galactose tests corresponded well to the rise in glucose during the test. Urinary sorbitol excretion was normal. It is concluded that the impaired carbohydrate metabolism seen in MD is due to peripheral insulin resistance affecting various organs including the liver and it is suggested that the excessive beta-cell response is secondayr to the peripheral resistance.