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Impairment of insulin sensitivity of glucose metabolism, a prominent feature of type 1 diabetes (DM), is also well documented in adolescence and obesity. Overweight is frequently present during adolescence in females. Spurt in growth is significantly reduced during puberty in females with type 1 DM, while it is normal in males. In this study we assessed the effect of the coexistence of type 1 DM, adolescence, overweight, and their possible interference with growth. Moreover, we evaluated whether dietetic control associated with physical exercise improved insulin sensitivity in adolescence. The study enrolled 11 female adolescents and young adults (aged 18.5±0.6 years), affected by type 1 DM for 8.3±0.9 years, who were overweight (BMI, 27.3±0.8 kg/m2) and receiving conventional insulin therapy (0.78±0.10 U/kg day). We used the euglycemic hyperinsulinemic clamp technique coupled to [2H2]glucose and [13C]leucine infusion. The results show a striking increase in insulin resistance of glucose metabolism: the suppression of endogenous glucose production (EGP) was 59% in comparison to 90%–100% recorded by others at similar insulin levels in subjects at different periods of life. Insulin resistance in type 1 DM overweight adolescents was also present on protein metabolism: the postabsorptive plasma leucine (146.9±10.1 μM) and the endogenous leucine flux (ELF, 88.8±4.5 µmol/kg min) were higher than in healthy controls. The suppression of ELF during hyperinsulinemia was defective in diabetic adolescents (27%, p

Osteopenia has been described as a complication of insulin-dependent diabetes mellitus (IDDM). We measured bone modeling indexes during the first year of IDDM. At each time point the values obtained from diabetic children have been compared with those of control subjects. We selected 27 prepubertal children with IDDM (6.35 +/- 2.16 years). We also enrolled 30 healthy prepubertal children of comparable age (5.85 +/- 3.05 years). Height, height standard deviation scores, glycated haemoglobin (HbA(1C)), basal c-peptide concentrations, insulin dose, serum concentrations of procollagen type I C-terminal propeptide (PICP), and collagen type I C-terminal telopeptide (ICTP) were measured at onset of IDDM and at 3, 6 and 12 months. ICTP was in the normal range at onset of IDDM and decreased during the follow-up to reach a significant difference compared to controls after 3, 6 and 12 months of insulin treatment (P < 0.04). PICP concentrations increased significantly at 3 months (P = 0.05) compared to onset. At 3 and 12 months PICP values were significantly higher than those of control children (P = 0.04). Correlations were found be tween PICP concentrations and HbA(1C) and c-peptide at onset of diabetes (r = -0.45 and r = 0.47, respectively). Bone formation at onset of IDDM is not impaired; the introduction of insulin therapy, together with the achievement of a good metabolic control, determines an increase of bone matrix formation coupled with a decrease of bone resorption, that determines a positive balance of bone modeling.

The prevalence of obesity, according to sex and pubertal stage, and the correlations between obesity and metabolic data were investigated in 286 diabetic patients (164 boys, 122 girls) with mean (SD) age 15.3 (3.2) years and mean (SD) duration of diabetes 7.5 (4.1) years. Prevalence of obesity according to the body mass index (BMI) criteria was 6.3%. Girls were more often obese than boys but the prevalence approached statistical significance only for the BMI criteria, at 9.8% v 3.7% (chi 2 = 3.5; p = 0.06); obesity was independent of pubertal stage. Distribution of BMI values of diabetic girls was skewed towards the high centiles of the INSERM tables: < 25th centile, 8.6%; 25th-50th centile, 17.3%; 50th-75th centile, 25.9%; > 75th centile, 48.2% (chi 2 = 19.17, p < 0.0005). BMI values of diabetic boys were homogeneously distributed. Age, duration of diabetes, insulin requirement, daily number of insulin injections, and metabolic control (HbA1c) were comparable in obese and non-obese diabetic patients. Moreover metabolic control and insulin requirements were comparable between diabetic patients with BMI above and below the 50th centile of the INSERM tables after matching for sex. In conclusion the prevalence of obesity in diabetic children and adolescents is quite similar to the prevalence reported in their non-diabetic peers. Obesity and BMI excess correlate with female gender but are independent of insulin requirement and metabolic control.

Recent data provided by the EURODIAB ACE study group have confirmed wide variation in the incidence of insulin-dependent diabetes mellitus (IDDM) across Europe. The aim of this report is to compare age-specific incidence and seasonality at clinical onset of IDDM between study regions. Using a uniform methodology, the EURODIAB ACE framework ascertained 3,168 newly-diagnosed cases of IDDM in children under the age of 15 years during 1989–1990. Eighteen percent of the cases were age 0–4 years at diagnosis, 34 % were age 5–9 years and 48 % were age 10–14 years. Poisson regression analysis suggested that there were highly significant statistical differences in incidence between the three age groups and between the 24 regions. Although incidence rates in the 0–4 year and 5–9 year age groups varied from region to region in a similar fashion, the pattern of variation in the older age group was different. Seasonality of diagnosis conformed to a sinusoidal model with a peak occurring in winter, a feature which was consistently observed in both sexes and in all age groups. However, a statistically significant heterogeneity in the seasonal distribution was present among regions, those in Scandinavia showing the smallest relative amplitude. The first insulin injection was given the same day or the day after diagnosis in 93 % of the cases for whom data were available.

Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). The aim of this study was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)65, 37,000/ 40,000 Mr islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with pre-IDDM, GAD65 antibodies in 70 % of IDDM patients and 89 % with pre-IDDM, and antibodies to 37,000/40,000 Mr islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were found only in conjunction with islet cell antibodies and were more frequent in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD65 antibodies had antibodies to 37,000/40,000 Mr islet tryptic fragments, and all but one had disease onset before age 15 years. No sera strongly immunoprecipitated in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients had anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of the control subjects. The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD65 antibodies and antibodies to 37,000/40,000 Mr islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace islet cell antibodies in population screening for IDDM risk assessment.

Cardiovascular responses to cold pressor test and associated changes in blood concentrations of renin, aldosterone, and catecholamines were measured in 11 type I diabetic patients with microalbuminuria; 11 type I diabetic patients with normoalbuminuria matched for age, duration of diabetes, metabolic control; and in nine normal control subjects. Heart rate, renin, aldosterone, and catecholamines concentrations in diabetic patients and controls at baseline were similar, but higher mean blood pressure was evident in microalbuminuric than normoalbuminuric patients (p < 0.01) and controls (p < 0.05). Heart rate and mean blood pressure during cold pressor test in control subjects and type I diabetic patients increased significantly but similarly, regardless of the presence of microalbuminuria. Catecholamines, but not renin-aldosterone release, was associated to blood pressure modifications during the test. Peak values of mean blood pressure induced by cold test were positively correlated to baseline values in control subjects (r = 0.658, p < 0.05) and normoalbuminuric (r = 0.725, p < 0.01), but not microalbuminuric diabetics. These data suggest that the higher blood-pressure values at rest observed in microalbuminuric than normoalbuminuric diabetics are not associated with a higher cardiovascular response to cold hypertensive stimulus.

HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. The frequency of heterozygosity for HLA-DR3/DR4 was significantly higher in patients who developed the disease in the first 2 years of life and DR3+/DR4-, DQw2 and DQw3 alleles were higher in those aged less than 14 years at onset. The HLA-DR4 allele was associated with onset of diabetes in autumn and HLA-B18 with onset in Autumn-winter. Diabetic children who were breast fed had a later onset of insulin-dependent diabetes mellitus than those who were bottle fed but these differences were independent of HLA typing (11.8 +/- 0.72 years vs 9.23 +/- 0.42 years; mean +/- SEM). We conclude that: (1) in general, HLA distribution in Italian insulin-dependent diabetic patients reflects previous data reported in other European and North American populations; (2) HLA-DR3 and DR4 are strongly associated with insulin-dependent diabetes in Italy as well, and these alleles seem to predispose to an earlier onset of the disease; and (3) breast feeding may delay the onset of the disease.

An impaired pancreatic polypeptide response (PP) after hypoglycemia has been described in type I diabetic patients with overt autonomic neuropathy. Some authors have suggested that PP release might be useful as sensitive indicator of autonomic neuropathy. The meal test is safer and simpler than the insulin infusion test as PP stimulus. The aim of this study was to compare PP response to insulin infusion and protein meal test and to correlate these responses to the presence of measurable neuropathic disturbances. We thus studied 13 IDDM children and adolescents and 6 normal children. In diabetics the PP response to both tests was not different from that of the control subjects, but PP response to insulin infusion was inversely correlated to the duration of illness and was significantly lower in subjects with pathological heart rate response when compared to the control group. PP responses to the two stimuli were not correlated. We suggest that reduced PP response to hypoglycemia is an early sign of autonomic neuropathy as well as impairment of beat-to-beat variation when impaired PP response to meal test is still not evident.

The renal response to 100 g/1.73 m2 protein load in the form of a meat meal was studied in 19 normal subjects and 35 normoalbuminuric insulin-dependent diabetic patients (IDDs) under conditions of sustained euglycemia. The area under the glomerular filtration rate (GFR) curve rose above base line by 1,904 +/- 292 in normals and 502 +/- 237 ml/1.73 m2 in IDDs (P less than 0.01). The meat meal induced a greater increment in the area under the glucagon curve in normals (14,930 +/- 186 pg.ml-1.min-1) than in IDDs (7,227 +/- 67, P less than 0.01); similarly urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha rose by 119 and 98%, respectively, in normals but only by 2% (P less than 0.01 vs. normals) and 10% (P less than 0.01 vs. normals) in IDDs. The fractional albumin clearance rose by 102 and 251% in normals and IDDs, respectively. In five normal subjects indomethacin administration abolished the GFR, glucagon, prostaglandin, and albuminuric response to meat ingestion. Glucagon replacement under indomethacin treatment failed to restore these responses. In five diabetic patients, selected for having a flat glucagon and GFR response to a meat meal, replacement of glucagon to postprandial levels increased urinary vasodilatory prostaglandins and restored a normal GFR response. Thus in normal subjects renal vasodilatory prostaglandins appear to be the final effector of the renal hemodynamic and albuminuric response to a meat meal. The prostaglandin increase is likely to be mediated under physiological conditions by a glucagon rise, which, however, has no effect per se on renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 ± 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 ± 52.6 vs. 281.4 ± 46.1 vs. 236.8 ± 41.6 ml/1.73 m2, P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P = 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P = 0.003), along with a faster decline of GFR (P = 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy.

We report the case of a child with hypoglycaemia due to insulin auto-immunity. Insulin auto-immunity is the third most frequent cause of hypoglycaemia in Japan where the first cases were described. The child has been followed for the past 10 years with recurrence of hypoglycaemic symptoms and high titres of insulin antibodies.

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c

To investigate the role of puberty on spontaneous clinical remission and on secretion of residual C-peptide during the first year of type 1 diabetes mellitus, we studied 77 pre-pubertal, 39 pubertal and 41 post-pubertal type 1 diabetic patients. Spontaneous partial clinical remission (HbA1c within the normal range and insulin dose less than 0.3 U x kg(-1) body weight x day(-1) lasting for at least 10 days) decreased with duration of diabetes: months 3 vs 6 vs 12, respectively 13 vs 7 vs 4% (P

OBJECTIVE Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 ± 4.1 years) and control subjects (8.5 ± 4.2 years) at recruitment in the study was similar. RESULTS At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (−0.12 ± 2.1; −0.76 ± 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.

Frequency and correlates of severe hypoglycaemia have been retrospectively analysed in a cohort of diabetic children and adolescents with median (range) age 14.5 (3.2-25.5) years followed from the onset of the disease by the same diabetic clinic. During the years 1992-1994, 53 of the 187 patients reported 74 hypoglycaemic episodes: the average frequency of hypoglycaemia during the 3 years surveyed was 14.9 episodes/100 patients per year. Frequency of hypoglycaemia decreased significantly with age (chi(2) = 24.1; P < 0.0001) and was independent of duration of diabetes. Glycosylated haemoglobin and insulin dose were similar in patients with and without hypoglycaemia, matched for age and duration of diabetes. One out of two hypoglycaemic episodes occurred during sleep and no explanation was available for 50% of episodes. Conclusion In this study severe hypoglycaemia was more frequent in young children than in adolescents and was independent of metabolic control and insulin dose.

The prevalence and correlates of the early signs of renal, retinal and neurological microvascular complications were evaluated in 317 young patients with type I diabetes mellitus. Microalbuminuria was detected in 11% of patients and appeared to be strongly and positively related to HbA1c (p < 0.01) and less significantly to duration of diabetes (p < 0.02). Retinopathy was detected in 22.7% of patients and it was associated with duration of diabetes (p < 0.001). Peripheral neuropathy was detected in 18.5% of patients and there was a strong association with HbA1c (p < 0.01) and a weaker one with duration of diabetes (p < 0.05). Microalbuminuria was not detected in prepubertal patients while a similar frequency of retinopathy and neuropathy was observed in prepubertal and postpubertal patients. These results suggest that: 1) In short-term type I diabetic patients neuropathy is the most frequent microvascular complication, but after 10 years of diabetes, retinopathy exceeds the other complications; 2) Short-term metabolic control may influence the frequency of neuropathy and microalbuminuria but not retinopathy; 3) Puberty is involved in the appearance of microalbuminuria.

Insulin-dependent diabetes mellitus is associated to important micro and macro vascular complications. A good metabolic control can reduce the risk of complications. Aim of the study was to evaluate the metabolic control in adolescent diabetic patients using an educational system with graphic visualisation of capillary glycaemia. 40 (22 males, 18 females) insulin-dependent diabetic patients (age: 16.9 +/- 3.5 yrs; duration of diabetes: 6.7 +/- 4.6 yrs) were divided in two groups matched for age, sex, duration of diabetes and metabolic control. Patients of group 1 used One Touch II Video for three months. One Touch II Video is an educational program for diabetes mellitus linked to a meter for glycaemia assessment. Patients of group 2 were used as control group. All data were expressed as a mean +/- SD and were analysed by parametric t-Student test. In group 1 HbA1c at the end of the study was significantly reduced compared to the initial value: 8.58 +/- 1.65% vs 7.9 +/- 1.0% (p0.05). In group 2 HbA1c at end of the study was no different from the initial value. At short term One Touch II Video could be a useful instrument to improve metabolic control in insulin-dependent diabetic adolescents.

To investigate whether post-exercise urinary albumin excretion in Type 1 diabetic children and adolescents may prospectively predict the development of microalbuminuria, we have assessed post-exercise urinary albumin excretion before and after 6.2 +/- 1.7 years of follow-up in 66 diabetic children and adolescents. Post-exercise urinary albumin excretion rose significantly above the pre-exercise values in diabetic patients by 2.7 (-3.8 to 84.2) micrograms min-1 (p < 0.001) and in a group of 9 healthy individuals by 3.9 (-0.7 to 13.7) micrograms min-1 (p < 0.02) without significant differences between groups. Post-exercise albuminuria was greater in postpubertal than prepubertal 9.8 vs 4.3 micrograms min-1 (p < 0.03) and pubertal 9.8 vs 6.0 micrograms min-1 (p < 0.02) patients; post-exercise changes in urinary albumin excretion were also positively related to glycated haemoglobin (r = 0.293; p < 0.05). Eight out of 66 patients developed microalbuminuria at follow-up. Urinary albumin excretion at follow-up was comparable between patients with normal and abnormal post-exercise urinary albumin excretion; moreover post-exercise urinary albumin excretion was within the normal range in 5 out of 8 patients with microalbuminuria at follow-up. In conclusion post-exercise albuminuria does not seem to be a useful predictor of the onset of microalbuminuria in Type 1 diabetic children and adolescents.

Objective— This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE. Research Design and Methods— The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 ± 10.4 mo of follow-up. Results— GFR decreased in the two groups but Δ GFR of patients with glomerular hyperfiltration was greater than Δ GFR of patients with normal GFR (0.83 ± 0.55 vs. 0.28 ± 0.63 ml·min−1·mo−1; P < 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P < 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up. Conclusions— Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.

Blood sugar profiles after administration of pasta with (PG) and without (P) guar have been evaluated in 30 young type I diabetic children. Maximum increase of blood sugar was observed at 30' (mean = 21 mg/dl) after P and at 90' (mean = 6 mg/dl) after PG. Maximum decrease in blood sugar levels was reached at 180' in both groups (50 mg/dl after P and 25 mg/dl after PG). Blood sugar level was significantly different only at 180'. No significant difference was observed analyzing rates of increase.

Disseminated intravascular coagulation is a very rare complication of diabetic ketoacidosis. Central nervous system plasy but not peripheral neuropathy has been reported in these patients. On the other hand, signs of peripheral neuropathy may also be present at the onset of diabetes, but they are usually reversible within a few days after correction of the metabolic derangement. We describe an unusual case of mononeuritis multiplex syndrome still present after 2 months of follow-up in a child with diabetic ketoacidosis complicated by disseminated intravascular coagulation at the onset of insulin-dependent diabetes. These neurological impairments may be consistent with functional neural lesions due to vasa nervorum thrombosis and prolonged ischaemia.

Glomerular filtration rate, renal plasma flow and urinary albumin excretion rate were measured during insulin-induced euglycaemia in 12 male Type 1 (insulin-dependent) diabetic patients after a 3-week period of low protein diet (45 g/day) or a similar period on unchanged conventional diet (103 g/day). No changes in glycaemic control, indicated by home blood glucose profiles and serum fructosamine concentration, or in arterial pressure, were noted on either diet. On low protein diet, glomerular filtration rate was lower (p less than 0.001) in all patients, but there was no difference in renal plasma flow between low protein diet and normal protein diet; filtration fraction fell significantly on low protein diet (p less than 0.001). Fractional clearance of albumin was also lower (p less than 0.05) on low protein diet. This study suggests that reduction of dietary protein induces, independently of changes in plasma glucose and arterial pressure, modifications in glomerular filtration rate, filtration fraction and fractional clearance of albumin, which may be associated with a beneficial effect on the evolution of diabetic renal disease.

Overt diabetic nephropathy is a well-established clinical picture characterized by macroproteinuria and irreversible decline of glomerular function. The first phase of renal involvement has been widely investigated in the last decade in the hope to individuate early lesions. Five stages of glomerular damage have been identified by morphological abnormalities and clinical tests. Although renal hypertrophy, hyperfiltration, and microalbuminuria are present in all diabetics at onset, subsequent evolution shows different patterns: some patients may present no further progression, while others show a rapid and irreversible decline of kidney function. This suggests that other factors, i.e., risk factors, may play important roles in the renal involvement in diabetics. The predictive role of microalbuminuria and of hyperfiltration was investigated, and, so far, only an albumin excretion rate above 30 micrograms/min had been proved to be associated with a decline of renal function. Actually no practical hints can be given to prevent the disease apart from persistent strict glycometabolic control during the course of diabetes. Antihypertensive treatment can slow glomerular damage when overt diabetic nephropathy and hypertension are present. Aggressive treatment in the early phases of renal involvement might change the natural history of the disease.

To study the influence of preceding dietary protein intake on the renal response to a protein meal we examined renal hemodynamic and excretory responses to a meat meal in six normal human subjects either taking their normal-protein diet (NPD, 75 +/- 5 g/day) or after 3 wk of a low-protein diet (LPD, 43 +/- 3 g/day; P less than 0.005). Glomerular filtration rate (GFR) was lower on LPD than on NPD (107 +/- 7 vs. 124 +/- 5 ml X min-1 X 1.73 M-2, respectively; P less than 0.01), as was renal plasma flow (RPF) (NPD, 666 +/- 44; LPD, 605 +/- 43 ml X min-1 X 1.73 M-2; P less than 0.05). Filtration fraction (FF) was not different (NPD, 0.19 +/- 0.01; LPD, 0.18 +/- 0.01). Urinary excretion of albumin was also lower after LPD than NPD (2.1 +/- 0.5 vs. 4.2 +/- 0.8 micrograms/min; P less than 0.05). After an 80-g protein meat meal, GFR rose to a ceiling significantly higher on NPD than on LPD (132 +/- 4.8 vs. 120 +/- 5.2 ml X min-1 X 1.73 M-2; P less than 0.02), even though the percent changes were greater on LPD than on NPD (12.7 +/- 3.3 vs. 6.6 +/- 1.5%, respectively; P less than 0.05). There was a rise in RPF that was entirely attributable to a fall in renal vascular resistance, and FF did not change. On both diets, oral protein loading produced a 200-300% increase in the urinary excretion and fractional clearance of albumin and IgG, but failed to alter that of beta 2-microglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

The evolution of diabetic renal disease is hardly affected by correction of the metabolic disturbance of diabetes [1] and appears to recognize other determinants of progression [2]. Levels of arterial pressure seem important in this respect and have been shown to influence considerably the rate of decline of the glomerular filtration rate (GFR) [3, 4]. This supports the view that hemodynamic factors may have become predominant at this stage of nephropathy [5] and suggests that maneuvers capable of modifying renal and/or systemic vascular dynamics may have independent beneficial effects on the relentless deterioration of renal function in this condition.

212 insulin dependent young diabetics with mean age of 16 yr and mean diabetes duration of 9 yr, have been examined for prevalence of subclinical signs of microvascular disease. Prevalence of retinopathy is increased in subjects of older age when matched for diabetes duration. Subclinical abnormalities of peripheral nervous system, identified by neurophysiological techniques, are present in about 20% of patients. These abnormalities are mainly related to metabolic control as evaluated by HbA1c determination. Albumin excretion rate over 10 mcg/min is observed in about 40% of subjects and is related to increased blood pressure values and poor metabolic control.