Pancreatic B-cell function in non-insulin-dependent diabetes mellitus during successive periods of sulfonylurea and insulin treatment: serum C-peptide response to glucagon and urine C-peptide excretion

Serum C-peptide responses to glucagon and daily urine C-peptide excretion in successive periods of different treatment in two groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) (mean interval between two tests less than 1 month) were compared. In group A patients (n = 8), the glycemic control was improved after transferring the treatment from sulfonylurea (SU) to insulin (fasting plasma glucose: SU: 192 +/- 47, insulin: 127 +/- 21 mg/dl, mean +/- S.D., p less than 0.01). Fasting serum C-peptide immunoreactivity (CPR) was significantly lower at the period of insulin treatment (SU: 1.93 +/- 1.01, insulin: 1.47 +/- 0.79 ng/ml, p less than 0.05), but there was no difference in the increase in serum CPR (maximal--fasting) (delta serum CPR) during glucagon stimulation in the two periods of treatment (SU: 1.70 +/- 0.72, insulin: 1.47 +/- 0.98 ng/ml). In group B patients (n = 7), there was no significant difference in glycemic control after transferring the treatment from insulin to SU (fasting plasma glucose: insulin: 127 +/- 24, SU: 103 +/- 13 mg/dl). Fasting serum CPR was significantly lower during the period of insulin treatment (insulin: 1.39 +/- 0.64, SU: 2.21 +/- 0.86 ng/ml, p less than 0.025), but delta serum CPR during glucagon stimulation still showed no significant difference between the two periods (insulin: 1.97 +/- 1.16, SU: 2.33 +/- 1.57 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Standard breakfast test: an alternative to glucagon testing for C-peptide reserve?

We measured C-peptide after glucagon and breakfast tests to compare the effectiveness of both tests in evaluating residual beta cell function in normal and diabetic subjects. A significantly higher C-peptide response was elicited after standard breakfast in patients with insulin-dependent diabetes mellitus of less than two years' evolution, ranging from 0.12 +/- 0.07 to 0.83 +/- 0.18 ng/ml (P less than 0.05). In nonobese noninsulin-dependent diabetes mellitus the response ranged from 0.86 +/- 0.02 to 1.89 +/- 0.48 ng/ml (P less than 0.0025); in obese NIDDM from 1.02 +/- 0.37 to 1.55 +/- 0.46 ng/ml (P less than 0.05), and in normal subjects from 0.77 +/- 0.23 to 2.11 +/- 1.22 ng/ml (P less than 0.0025). We conclude that the standard breakfast test is a useful and practical approach to the study of residual beta cell function.     

Metabolic factors affecting residual beta cell function assessed by C-peptide secretion in patients with newly diagnosed type 1 diabetes.

BACKGROUND: In recent onset of type 1 diabetes, the residual beta cell function, assessed by baseline and/or stimulated C-peptide secretion, can be a useful parameter to establish the extension of beta cell destruction. How metabolic parameters at diagnosis influence residual C-peptide secretion is not well established. PATIENTS AND METHODS: We analyzed 553 consecutive patients with recent onset (<4 weeks) of type 1 diabetes (250 females and 303 males, mean age 15+/-8 years). Baseline and stimulated C-peptide by i.v. glucagon were evaluated using a highly sensitive radio-immunoassay. Metabolic parameters including blood glucose, HbA1c, insulin dose, and BMI were also evaluated. RESULTS: Baseline and stimulated C-peptide were 0.26+/-0.22 and 0.47+/-0.38 nmol/l and correlated positively with age (p<0.001). There was no significant correlation between C-peptide and blood glucose at diagnosis. BMI was positively correlated with both baseline and stimulated C-peptide secretion (p<0.001). By contrast, HbA1c levels inversely correlated with both baseline and stimulated C-peptide secretion (p<0.001). CONCLUSION: In type 1 diabetes at diagnosis, baseline and stimulated C-peptide are higher in pubertal and young adult patients compared with pre-pubertal patients suggesting that such parameter can be used as an end point marker for studies aimed at protecting and/or restoring beta cells in patients with substantial beta cell function. High levels of HbA1c and lower BMI are dependent variables of C-peptide values.     

Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes.

The role of preserved beta-cell function in preventing ketoacidosis in type I insulin-dependent diabetes was assessed in eight patients with and seven patients without residual beta-cell function as determined from C-peptide concentrations. After 12 hours of insulin fatty-acid, and glycerol concentrations were all significantly higher in patients without beta-cell function than in those with residual secretion. Mean blood glucose concentrations reached 17.2 +/- SE of mean 1.3 mmol/l (310 +/- 23 mg/100 ml) in the first group compared with 8.8 +/- 1.4 mmol/l (159 +/- 25 mg/100 ml) in the second (P less than 0.01), while 3-hydroxybutyrate concentrations rose to 5.5 +/- mmol/l (57 +/- 5 mg/100 ml) and 1.4 +/- 0.3 mmol/l (15 +/- 3 mg/100 ml) in the two groups respectively (P less than 0.01). Individual mean C-peptide concentrations showed a significant inverse correlation with the final blood glucose values (r = -0.91; P less than 0.02). These findings strongly suggest that even minimal residual insulin secretion is important for metabolic wellbeing in diabetes and may prevent the development of severe ketoacidosis when insulin delivery is inadequate.     

Changes in insulin secretion after secretin administration and the implications in diabetes mellitus

Secrepan (Eisai Co. Tokyo, Japan) was administered to 9 healthy volunteers and 36 patients with non-insulin dependent diabetes mellitus (NIDDM) to clarify the effect of secretin on the pancreatic B-cell, by determining the changes in blood of insulin (IRI). Whereas IRI in healthy subjects showed a monophasic change, reaching a peak (delta IRI = 43 +/- 7.3 microunits/ml, M +/- SE) 5 min after secretin loading and returning to the basal level in 15 min, NIDDM patients on diet therapy (delta IRI = 40.2 +/- 7.6 microunits/ml) showed no significant difference from the control group, but NIDDM patients on sulfonylurea (SU) (15.5 +/- 2.4 microunits/ml) and those on insulin therapy (5.3 +/- 1.4 microunits/ml), both showed a significant depression in responsiveness. Further, the changes in insulin secretion after atropine administration in healthy subjects and the changes in IRI response to Secrepan in vagotomized patients were also determined. As a result, data which preclude the possibility of association of the vagus nerve and cholinergic nerve with the stimulation of insulin secretion by secretin were obtained, and a direct action of secretin on the cell of islets of Langerhans was suggested. The maximum IRI response after a secretin load had a significant positive correlation with the IRI response after a 75-gm GTT and the content of C-peptide immunoreactivity in 24-hour urine. Therefore, insulin response to a secretin load can be useful in assessing endogenous insulin secretion and provides a pertinent clinical guide for the selection of an appropriate therapy for diabetes mellitus.     

Insulin resistance in Fibrocalculous (tropical) pancreatic diabetes

Insulin resistance was assessed by Insulin Tolerance Test (ITT) in 12 patients with FCPD, 10 with NIDDM and 12 age and sex matched control subjects. The mean BMI of the FCPD was lower than the NIDDM and control groups (P less than 0.001). There was no significant difference between the mean fasting plasma glucose or HbA1 between the FCPD and NIDDM patients. The mean fasting C-peptide of the FCPD group was significantly lower than the NIDDM and control groups (P less than 0.001). The mean glucose disposal rate (KITT) was 5.57 +/- 2.28 in the control group, 2.15 +/- 2.00 in the FCPD and 1.77 +/- 0.91 in the NiDDM group (P less than 0.001, control vs FCPD and NIDDM). The difference in KITT between FCPD and NIDDM groups was not significant statistically. The data suggests that patients with FCPD have evidence of insulin resistance and this is similar to that seen in NIDDM patients.     

The release and metabolism of pancreatic hormones after major hepatectomy in the dog.

Major hepatectomy in the dog induced a 50% decrease in peripheral serum glucose, a 11-fold increase in portal plasma glucagon and a 36-fold increase in the portal glucagon/insulin ratio 3 hr after operation. Peripheral serum glucose levels were inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.50, p less than 0.01) and that of the portal glucagon/insulin ratio (r = -0.85, p less than 0.01) for 1-6 hr after operation. The ratio of peripheral to portal plasma glucagon was also inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.59, p less than 0.01). In case of glucose infusion, plasma glucagon levels were not elevated after major hepatectomy. The data suggest that glucose deficiency after major hepatectomy in the dog may cause hyperglucagonemia with an enhanced glucagon requirement.     

Beta cell function in long term NIDDM (type 2) patients and its relation to treatment

Pancreatic beta cell function was assessed by estimation of fasting and post prandial plasma C-peptide in 183 non-insulin dependent diabetic patients, who were treated with oral hypoglycaemic drugs, for more than 10 years. One-hundred-and-forty-one patients, continued to respond to oral hypoglycaemic agents (Group I) and in 42 the control was not satisfactory and had to be changed over to insulin (secondary failure, Group II). Significant beta cell reserve (PP CP greater than or equal to 0.6 pmol/ml) was present in 89 out of 183 patients (48%) and 83 (93%) of them responded to oral hypoglycaemic agents. Among the 94 patients with low beta cell reserve, 58 (62%) were on oral hypoglycaemic agents and the other 36 (38%) were on insulin. Of the 42 patients with secondary failure to the oral drugs, 36 (86%) had low C-peptide while 6 (14%) had significant C-peptide values. Secondary failure to oral hypoglycaemic agents can also occur in spite of good beta cell reserve. Beta cell reserve was not correlated either to the duration of diabetes or the age at diagnosis of the patients.     

The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.     

Interrelation between glucose, insulin, C-peptide and 3-hydroxybutyrate in plasma and amniotic fluid in last trimester diabetic women without residual betacell function

The relationship between maternal plasma and amniotic fluid (AF) concentrations of glucose, insulin, C-peptide and 3-hydroxybutyrate (3-HB) was analysed between 45 to 140 minutes after a standardized breakfast in 8 type I diabetic women without residual betacell function and in 13 nondiabetic control women during the last trimester of gestation. AF levels of both glucose and C-peptide were slightly and AF insulin levels significantly (P less than 0.05) elevated above normal in the diabetic women. 3-HB levels in plasma and in AF were significantly (P less than 0.05) elevated in the diabetic group between 45 to 65 minutes after breakfast. AF insulin and glucose was significantly correlated in the diabetic group (r = 0.96, P less than 0.05). During the 2 hour study period AF levels of glucose, insulin and C-peptide remained essentially unchanged in both groups of women. Changes in maternal plasma 3-HB concentrations seemed to be more rapidly reflected in AF.     

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets

The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormalities of low density lipoproteins in normolipidemic type II diabetic and nondiabetic patients with coronary artery disease.

The characteristics of low density lipoproteins (LDL) of ten non-insulin-dependent diabetic (NIDDM) and ten nondiabetic patients with coronary artery disease (CAD) were investigated and compared to LDL of ten NIDDM patients without CAD and ten healthy persons. All subjects had LDL cholesterol below 160 mg/dl and serum triglycerides below 200 mg/dl. The mean LDL particle size and particle distribution profiles were analyzed by using nondenaturing polyacrylamide gradient gel electrophoresis. The LDL composition and hydrated density distribution were investigated by using density gradient ultracentrifugation. Both NIDDM and nondiabetic CAD patients tended to have larger LDL particles than NIDDM patients without CAD and healthy subjects. The increase of LDL particle size of CAD patients was due to marked enrichment of triglycerides (TG) in their LDL. The percentage content of TG in LDL of NIDDM patients with CAD was 14.5% and in LDL of nondiabetic CAD patients 13.4% compared with 7.9% in LDL of NIDDM patients without CAD and 7.2% in normal-LDL (P less than 0.05 or less between either CAD group and NIDDM without CAD or normals). The LDL TG/apolipoprotein (apo) B weight ratio was significantly higher in both CAD groups compared with LDL of the two groups without CAD (0.70 and 0.68 vs. 0.38 and 0.34, respectively, P less than 0.05, P less than 0.05 and P less than 0.01, P less than 0.01). The LDL total lipid to apoB weight ratio was similar in all four groups. Consistent with this, the hydrated density distributions of LDL in the four groups were similar, the average peak densities being 1.0346 g/ml, 1.0331 g/ml, 1.0331 g/ml, and 1.0331 g/ml, respectively. The findings of this study demonstrate that normolipidemic patients with CAD may have marked abnormalities in th eir LDL composition and these anomalies are present in both diabetic and nondiabetic patients.     

The thyroid reserve in children with chronic lymphocytic thyroiditis revealed by the thyrotropin-releasing hormone and thyroid-stimulating hormone tests

Serum thyroid hormone and TSH concentrations were measured before and after the administration of TRH (10 micrograms/kg body weight) and bovine TSH (10 IU) in 14 children with chronic lymphocytic thyroiditis. The TRH test showed that the responsiveness of TSH was positively correlated with the basal TSH (P less than 0.001) and inversely with the increase in serum thyroid hormones, for delta T3 (P less than 0.05) and for delta T4 (P less than 0.001). Overall, the patients had significantly lower mean values for basal T4, but not for T3. The TSH test revealed that the delta T3 was positively correlated with delta T4 (P less than 0.05). delta T3 after TSH administration was positively correlated with it after TRH (P less than 0.05). The patients were divided into three groups on the basis of their peak TSH values after TRH administration. In Group 1 (peak value below 40 microU/ml; N = 5); T3 increased significantly after TRH and TSH administrations (P less than 0.05 and P less than 0.025, respectively). In addition, delta T4 was significant after TSH administration. In Group 2 (peak TSH above 40 and less than 100 microU/ml; N = 6); only delta T3 after TRH was significant (P less than 0.05). In Group 3 (peak TSH above 100 microU/ml; N = 3); the response of thyroid hormones was blunted. Thus, the thyroid hormone responses to endogenous TSH coincided with that to exogenous TSH, and the exaggerated TSH response to TRH indicates decreased thyroid reserve.     

Interactions between oxytocin, glucagon and glucose in normal and streptozotocin-induced diabetic rats

Oxytocin has been suggested to have glucoregulatory functions in rats, man and other mammals. The hyperglycemic actions of oxytocin are believed to be mediated indirectly through changes in pancreatic function. The present study examined the interaction between glucose and oxytocin in normal and streptozotocin (STZ)-induced diabetic rats, under basal conditions and after injections of oxytocin. Plasma glucose and endogenous oxytocin levels were significantly correlated in cannulated lactating rats (r = 0.44, P less than 0.01). To test the hypothesis that oxytocin was acting to elevate plasma glucose, adult male rats were injected with 10 micrograms/kg oxytocin and killed 60 min later. Oxytocin increased plasma glucose from 6.1 +/- 0.1 to 6.8 +/- 0.2 mM (P less than 0.05), and glucagon from 179 +/- 12 to 259 +/- 32 pg/ml (P less than 0.01, n = 18). There was no significant effect of oxytocin on plasma insulin, although the levels were increased by 30%. A lower dose (1 microgram/kg) of oxytocin had no significant effect on plasma glucose or glucagon. To eliminate putative local inhibitory effects of insulin on glucagon secretion, male rats were made diabetic by i.p. injection of 100 mg/kg STZ, which increased glucose to greater than 18 mM and glucagon to 249 +/- 25 pg/ml (P less than 0.05). In these rats, 10 micrograms/kg oxytocin failed to further increase plasma glucose, but caused a much greater increase in glucagon (to 828 +/- 248 pg/ml) and also increased plasma ACTH. A specific oxytocin analog, Thr4,Gly7-oxytocin, mimicked the effect of oxytocin on glucagon secretion in diabetic rats. The lower dose of oxytocin also increased glucagon levels (to 1300 +/- 250 pg/ml), but the effect was not significant. A 3 h i.v. infusion of 1 nmol/kg per h oxytocin in conscious male rats significantly increased glucagon levels by 30 min in normal and STZ-rats; levels returned to baseline by 30 min after stopping the infusion. Plasma glucose increased in the normal, but not STZ-rats. The relative magnitude of the increase in glucagon was identical for normal and diabetic rats, but the absolute levels of glucagon during the infusion were twice as high in the diabetics. To test whether hypoglycemia could elevate plasma levels of oxytocin, male rats were injected i.p. with insulin and killed from 15-180 min later. Plasma glucose levels dropped to less than 2.5 mM by 15 min. Oxytocin levels increased by 150-200% at 30 min; however, the effect was not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reduction in urine C-peptide clearance rate after metabolic control in NIDDM patients

One hour urine C-peptide and creatinine clearance rates were determined simultaneously in 25 hospitalized patients with non-insulin-dependent diabetes mellitus (NIDDM) undergoing sulfonylurea and/or diet treatment. The studies had been performed after an overnight fast on the second day of admission and on a day soon before discharge, with intervals of 18.9 +/- 7.0 days. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) values decreased significantly at the second examination as compared to the initial values (FPG: 101 +/- 20 mg/dl vs. 161 +/- 47 mg/dl, p less than 0.005; HbA1c: 7.3 +/- 1.5% vs. 8.4 +/- 1.7%, p less than 0.005). The urine C-peptide clearance rate also decreased significantly after metabolic control (0.75 +/- 0.36 l/hr vs. 1.06 +/- 0.54 l/hr, p less than 0.005). Meanwhile, the urine creatinine clearance rate tended to decrease, but the difference was not significant (3.69 +/- 2.04 l/hr vs. 4.87 +/- 2.98 l/hr) at the second examination. The data suggest that the urine C-peptide clearance rate is susceptible to the effects of the fluctuation of metabolic states in NIDDM patients. In order to use urinary C-peptide for a follow up study of pancreatic B-cell secretion, the changes in C-peptide clearance under various metabolic conditions must be taken into account.     

Residual beta-cell function in type II diabetes and evaluation of the hepatic insulin extraction

Insulin and C-peptide (free insulin and C-peptide in insulin-treated patients) were measured after glucose stimulation in nine Type II diabetics on chlorpropamide, eleven insulin-treated maturity-onset diabetics and in 8 normal controls. Dissociation between C-peptide and insulin response to glucose was observed in several diabetics. The relation between incremental molar areas under C-peptide and insulin curves, after glucose challenge (delta CPR - delta IRI/delta CPR) were used to evaluate the hepatic insulin extraction in all but the insulin-treated diabetics. The lower insulin requirements and better control of the short-duration insulin-treated maturity-onset diabetics in relation to the long-term ones could not be explained either by the residual insulin secretion or by the level of "insulin antibodies". The chlorpropamide-responsive patients presented higher insulin levels after the glucose challenge and a lower hepatic insulin extraction than the non-responsive ones.     

Long term renal outcome of childhood haemolytic uraemic syndrome.

OBJECTIVE--To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING--The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS--103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES--Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS--The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS--After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group.     

Urinary platelet-activating factor excretion is elevated in non-insulin dependent diabetes mellitus.

Proteinuria is currently considered a very sensitive predictor of diabetic nephropathy, but 20-25% of all diabetic patients with negative Albustix reaction excrete higher than normal (< 20 mg/24 h) amounts of albumin in their urine. It is our hypothesis that platelet-activating factor (PAF), a potent glycerophospholipid that acts as a chemical mediator for a wide spectrum of biological activities, including increased vascular permeability, may be produced in significant amounts during periods preceding microalbuminuria. In this study, we compared urinary PAF excretion in Mexican-American subjects who were diagnosed with non-insulin dependent diabetes mellitus (NIDDM) with their healthy control counterparts. The age of the NIDDM subjects (45.9 +/- 2.1 years) was not significantly different from the healthy control group, which was 39.4 +/- 2.7 years (P < 0.0672). The NIDDM subjects (body mass index, 29.9 +/- 1.1 compared to 26.1 +/- 0.9 kg/m2 in healthy controls) were characterized by significantly increased (P < 0.05) fasting plasma glucose (192 +/- 11 vs. 97 +/- 4 mg/dl in healthy controls), fasting insulin (20.9 +/- 2.4 vs. 12.3 +/- 1.6 microU/ml), fasting C-peptide (2.93 +/- 1.26 vs. 1.48 +/- 0.51 ng/ml), and hemoglobin A1c (10.3 +/- 0.7 vs. 5.6 +/- 0.3%), respectively. The urine output for the NIDDM and control subjects were 1942 +/- 191 ml/24 h and 1032 +/- 94 ml/24 h, respectively, and urinary albumin excretion (UAE) rates were estimated to be 38 +/- 7 micrograms/min and 11 +/- 1 micrograms/min, respectively. The NIDDM subjects produced significantly increased levels of urinary PAF (2606.3 +/- 513.1 ng/24 h compared with 77.9 +/- 14.1 ng/24 h in controls (or 1706.3 +/- 420.8 ng/ml compared with 85.4 +/- 17.8 pg/ml of urine, in NIDDM and control subjects, respectively). We found that urinary PAF excretion was significantly correlated with microalbumin excretion (r = 0.7) especially at UAE rates greater than 30 mg/day and more importantly, some NIDDM patients with negative Albustix reaction (i.e. normal UAE) produced significantly more PAF, suggesting that PAF excretion may precede microalbuminuria and that subtle injury to the kidneys are present in NIDDM long before overt albuminuria ensues, urinary PAF measurements could potentially therefore serve as a sensitive indicator of renal injury in diabetes mellitus. These results lend further credence to our hypothesis that PAF may be the biochemical compound linking the various members of the insulin resistance syndrome.     

Influence of intrinsic sympathomimetic activity on respiratory function during chronic beta blockade: comparison of propranolol and pindolol.

The long term effect of beta blockers and the influence of intrinsic sympathomimetic activity on respiratory function were assessed in patients with chronic stable angina pectoris randomised to receive treatment with propranolol (n = 21) or pindolol (n = 19) for one year. Forced expiratory volume in one second (FEV1) had fallen by a mean of 240 ml after one year (p less than 0.001) in those treated with propranolol compared with 120 ml in those treated with pindolol (p less than 0.05). The difference between the groups was significant (p less than 0.01). Vital capacity fell significantly only in those treated with propranolol (p less than 0.05 at one year). In those in whom the basal ratio of FEV1 to forced vital capacity was low (less than 70%) propranolol, but not pindolol, caused a significant (p less than 0.05) fall in FEV1 throughout treatment. Long term administration of pindolol has a less adverse effect on respiratory function than propranolol, which results in a progressive deterioration in respiratory function over one year.