Elevated Albumin Excretion Rate Research Articles

Exercise versus overnight albumin excretion rates in subjects with type 1 diabetes

Diabetic nephropathy is the leading cause of new cases of renal failure in the US and Europe. An elevated albumin excretion rate (AER) on an overnight urine sample is considered an early predictor of end-stage renal failure. An elevated AER on a post-exercise urine sample has previously been considered to be an even earlier marker of renal damage. In a longitudinal prospective study, 373 subjects with insulin-dependent (type 1) diabetes mellitus had a total of 714 renal evaluations, each of which included one exercise and two overnight urine collections for AER determinations. All subjects were at least 13 years old and had diabetes for at least 4 years. There was a strong correlation between exercise and overnight AERs ( r = 0.74, P < 0.001). For the 60 subjects with an initial borderline increase of either overnight or exercise AER, the overnight AER values (7.6–20 μg/min) progressed first for 52% of subjects whereas the exercise AERs (41–114 μg/min) progressed first for 43% of subjects (5% had simultaneous elevations of both). For the 22 subjects in which an abnormal overnight (> 20 μg/min) or exercise (> 114 μg/min) value was detected first, 17 (77%) had an elevated exercise AER first, whereas only 4 (18%) had an elevated overnight AER first. This study shows that an increase of either the exercise or the overnight AER can occur first, dependent upon the level of abnormality being considered. The two tests correlate closely with one another. The previous misconception that an elevation in exercise AER preceded the elevation in overnight AER occurred because values for normal, borderline and abnormal exercise AERs had not been set to correspond with normal, borderline and abnormal overnight AERs.

Aspects of haemostatic function in healthy subjects with microalbuminuria — A potential atherosclerotic risk factor

Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6–150 μg/min) and 60 age- and sex-matched controls with normoalbuminuria (UAER < 6.6 μg/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1+2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors: plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2–8.3) vs. 7.2 (6.9–7.5) μmol/l; p<0.1). Neither did any of the haemostatic factors correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease.

Atherosclerotic risk factors are increased in clinically healthy subjects with microalbuminuria

Increased morbidity and mortality from atherosclerotic vascular disease were observed in subjects with slightly elevated urinary albumin excretion rate (UAER), known as microalbuminuria. Therefore, the association between microalbuminuria and established atherogenic risk factors was studied in clinically healthy subjects. All healthy 40–65 year-old participants with microalbuminuria, examined within the first 21 months of The Copenhagen City Heart Study, were invited, and 28 were studied. An age- and sex-matched group of 60 randomly chosen subjects with normoalbuminuria served as control. Microalbuminuria was defined as a UAER of 6.6–150 μg/min, and normoalbuminuria as a UAER ≤6.6 μg/min. In the microalbuminuric group, systolic and diastolic blood pressures were both elevated (mean (95% C.I.) 128 (123–134) vs. 119 (116–122) mmHg; P = 0.005, and 75 (71–78) vs. 69 (67–71) mmHg; P = 0.008, respectively), and serum apolipoprotein (apo) A-1 concentration was lower (1.30 (1.20–1.37) vs. 1.42 (1.36–1.47) g/l; P = 0.02) in comparison with the normoalbuminuric group. Furthermore, serum HDL-cholesterol concentration tended to be lower, whereas body weight, body mass index and fasting serum insulin concentration were slightly elevated in the microalbuminuric group but not statistically significant. It is concluded that microalbuminuria in clinically healthy subjects is associated with increased levels of atherogenic risk factors. This may contribute to the increased vascular morbidity and mortality observed in these individuals.

Microalbuminuria: An important diagnostic tool

The concept of microalbuminuria is reviewed. Measuring the urinary albumin excretion rate and testing for microalbuminuria is well established in the control and treatment of patients with insulin-dependent diabetes mellitus. Microalbuminuria predicts nephropathy and early cardiovascular death. In the presence of microalbuminuria frequent examinations are warranted for early detection of retinopathy, blood-pressure rise, and for optimizing the glycemic control. In patients with non-insulin-dependent diabetes, the independent value of microalbuminuria as a cardiovascular risk factor is not yet clarified. The urinary albumin excretion rate should be measured at diagnosis, because the indications are that presence of microalbuminuria reinforces the urge to intervene against other well-documented cardiovascular risk factors (hypertension, dyslipidemia, tobacco, and obesity). In the nondiabetic population, there is accumulating evidence that an elevated urinary albumin excretion rate is associated with early cardiovascular morbidity and mortality. Large scale cross-sectional and prospective studies are needed in order to clarify further the role of microalbuminuria as an independent risk factor in the background population.

The use of antihypertensive agents in prevention and treatment of diabetic nephropathy

Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h), a relentless decline in glomerular filtration rate, and elevated systemic blood pressure. The prevalence of an abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in patients with both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Diabetes has become the leading cause of end-stage renal failure in the United States and Japan and it is still the second leading cause in Europe. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30 to 300 mg/24 h). Randomized controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that angiotensin-converting enzyme (ACE) inhibitors diminish urinary albumin excretion rate and postpone or may even prevent progression to clinically overt diabetic nephropathy. These findings suggest that screening and intervention programs are likely to have life-saving effects and lead to considerable economic savings. High blood pressure is an early and frequent phenomenon that can accelerate the course of diabetic nephropathy. Besides ACE inhibitors, conventional antihypertensive treatment (mainly beta-blockers and diuretics) reportedly reduce albuminuria and diminish the loss of kidney function in IDDM patients with diabetic nephropathy. The same beneficial effect has been demonstrated using ACE inhibition combined with diuretics in hypertensive IDDM patients with overt nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary albumin excretion rate and puberty in non‐diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents.

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20-200 micrograms/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevated albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 micrograms/min, 95 percentile 15.1 micrograms/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a screening level for elevated albumin excretion (15 micrograms/min) showed a high positive (0.88) and negative (0.99) predictive value.

Relationship Between Ambulatory Blood Pressure and Albuminuria in Normal Subjects

Elevation of the urinary albumin excretion rate (AER) may be an important marker of vascular disease in nondiabetic as well as diabetic patients. Although hypertension is associated with an elevated AER, little is known regarding the relationship between AER and blood pressure in normal subjects. We studied 13 healthy, normotensive, nondiabetic subjects over 48 h. Urine was collected every 2 h and blood pressure was measured half hourly during the day using an ambulatory sphygmomanometric device. Overnight, blood pressure was measured hourly and a single overnight urine collection was obtained. Daytime blood pressures were higher than those overnight for systolic (122 +/- 9 v 105 +/- 8, P less than .01), diastolic (122 +/- 9 v 105 +/- 8, P less than .01) and mean arterial pressures (92 +/- 7 v 78 +/- 6 mm Hg, P less than .01). Similarly, AER fell overnight [day 5.9 (3.8 to 9.5) v night 3.6 (2.3 to 5.2) micrograms/min, median (interquartile range), P less than .01]. In the majority of subjects there was a significant positive correlation between AER and systolic (N = 9), diastolic (N = 10), and mean (N = 10) arterial pressure. We conclude that systemic blood pressure may influence AER in normal subjects.

Increased Urinary Transferrin Excretion in Exercising Normoalbuminuric Insulin-Dependent Diabetic Patients

The median rate of urinary transferrin excretion is greatly increased by exercise in subjects with uncomplicated type 1 (insulin-dependent) diabetes. This increase is proportionally far greater than that seen in urinary albumin excretion rate after the same exercise. Non-diabetic control subjects showed no rise in urinary transferrin excretion rate following exercise. N-acetyl-beta-D-glucosaminidase excretion rate was higher in diabetic than control groups but did not rise with exercise. Our results suggest that patients with apparently uncomplicated diabetes have abnormal renal function. In this group an elevated urinary transferrin excretion rate appears to be a more sensitive indicator of altered renal function than is elevated albumin excretion rate. The mechanism underlying exercise-induced urinary loss of transferrin remains to be elucidated.

Urinary Transferrin Excretion in Type 1 (Insulin‐dependent) Diabetes Mellitus

Urinary excretion of transferrin and albumin was studied by radioimmunoassay in 47 adult patients with Type 1 diabetes and 28 control subjects. Median (range) urinary transferrin excretion rate was significantly elevated in the diabetic group 0.58 (0.02-2663.3) micrograms min-1 compared with the control group 0.04 (0.01-0.28) micrograms min-1, p less than 0.001. Urinary transferrin:creatinine ratios (x 10(2)) were different in diabetic 47 (0.6-958.0) micrograms mmol-1 and control groups 0.7 (0.06-2.3) micrograms mmol-1, p less than 0.001). There were correlations between urinary transferrin and albumin excretion rates in diabetic (r = 0.78, p less than 0.001) and control groups (r = 0.81, p less than 0.05). Forty (85%) diabetic patients had elevated transferrin excretion rates, 18 (38.3%) had elevated albumin excretion rates. All diabetic patients with elevated albumin excretion rates had elevated transferrin excretion rates. Twenty-one (77.8%) of the patients with normal albumin excretion rates had elevated transferrin excretion rates. Urinary excretion of N-acetyl-beta-D-glucosaminidase was greater in diabetic patients than control subjects (142 vs 58 mumol h-1 l-1, p less than 0.001). There were correlation between transferrin and N-acetyl-beta-D-glucosaminidase excretion (r = 0.67, p less than 0.01) and albumin and N-acetyl-beta-D-glucosaminidase excretion (r = 0.63, p less than 0.01) in the diabetic group. Elevated urinary transferrin excretion rate may be a marker for renal dysfunction in diabetes mellitus.

Platelet Behaviour and Haemostatic Variables in Type 1 (Insulin‐dependent) Diabetic Patients With and Without Albuminuria

Abnormalities of haemostasis have been implicated in the development of both large and small vessel disease in diabetes. Platelet behaviour and coagulation factors were studied in 28 non-diabetic control subjects and 81 Type 1 diabetic patients with different degrees of albuminuria. Twenty-four (30%) patients had macro- or micro-albuminuria. These patients had elevated levels of beta-thromboglobulin compared with normo-albuminuric patients and control subjects (macro-albuminuric 113 (range 60-314), micro-albuminuric 88 (50-220), normo-albuminuric 55 (13-273), control 52 (18-210) micrograms l-1, p less than 0.001). Similar results were found for platelet factor 4 (macro-albuminuric 57 (9-350), micro-albuminuric 78 (12-205), normo-albuminuric 10 (2-135), control 9 (3-95) micrograms l-1, p less than 0.001). There were decreased beta-thromboglobulin:platelet factor 4 ratios in the albuminuric patients compared with control subjects and normo-albuminuric patients (p less than 0.001). There is abnormal platelet activity in Type 1 diabetic patients with elevated albumin excretion rates.

Blood glucose control and albuminuria in type 1 diabetes mellitus

The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop.

Diabetic nephropathy in insulin-dependent diabetes mellitus patients: How to measure progression of disease and effect of treatment

Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospitai, Aarhus, Denmark Usually, diabetic nephropathy with end-stage renal disease (ESRD) takes between 25 and 30 years to develop (Figure l), and three main stages may be defined,’ each lasting about a decade, starting with the acute changes (stage I) at diagnosis of diabetes, which also involve abnormalities in the kidney, probably not predictive of subsequent disease.’ Stage II usually lasts 10 years and is characterized by renal hyperfunction and hypertrophy without any clinical or laboratory signs of disease, but structural changes in glomeruli are developing. Longterm follow-up studies have shown, however, that patients with most severe early renal involvement (hyperfiltration) are those most prone to development of late nephropathy.3 In the next decade (stage Ill), a very characteristic abnormality develops, namely microalbuminuria (MA),4 which is defined as an elevated urinary albumin excretion rate (UAER), below the proteinuric range. Usually this too is a slow process, and the increase in albuminuria from normal to the proteinuric level may also last about 10 years, although with considerable variations in rate of progression. In the third decade (stage IV) diabetic nephropathy, well known since the thirties, becomes clinically apparent with proteinuria and eventually end-stage renal failure (ESRF) after a fairly linear decrease in glomerular filtration rate (GFR), lasting approximately 10 years, as shown in Figure 1.

Transferrinuria in Type 2 Diabetes: The Effect of Glycaemic Control

Urinary excretion rates of transferrin, albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha-1-microglobulin (A1M) were measured in type 2 (non-insulin-dependent) diabetic patients at diagnosis and after 6 and 12 weeks treatment. Initially 21 (53%) patients had elevated transferrin excretion rates. The proportion of patients with raised transferrin excretion rates fell to 30% at 6 weeks and 20% at 12 weeks with treatment of diabetes. At diagnosis 11 (28%) patients had elevated albumin excretion rates and 10 of these had elevated transferrin excretion rates. After 6 weeks treatment only six (15%) had elevated albumin excretion rates and by 12 weeks this number had fallen to four (10%). NAG and A1M levels also fell with treatment of diabetes. There were correlations between the transferrin excretion rate and albumin excretion rate (r = 0.86, P less than 0.0001), transferrin excretion rate and NAG (r = 0.46, P less than 0.0001), and transferrin excretion rate and A1M (r = 0.55, P less than 0.0001) at each visit. There were weaker correlations between the albumin excretion rate and A1M and NAG at each visit. The correlations between the transferrin excretion rate and markers of tubular function (NAG and A1M) suggest that tubular dysfunction may play a part in renal loss of transferrin in diabetes mellitus. There were no differences in transferrin excretion rates between patients with and without evidence of complications.

Glycemic control and longitudinal testing for exercise microalbuminuria in subjects with Type I diabetes

There is a need for better and earlier markers of clinical renal damage in subjects with Type I diabetes. In this prospective study, exercise albumin excretion rates (AERs) were studied longitudinally for a 4-year period in 187 young subjects with Type I diabetes. For this time period, 54% of subjects continued to have normal overnight and exercise AERs, 11% had continuously elevated exercise and overnight AERs, 11% developed an elevated exercise AER with the overnight AER remaining normal, and 12% had a normal overnight AER throughout the study, with initially elevated exercise levels later decreasing to normal. This improvement in exercise AER was associated with improved glycosylated hemoglobin (HbA 1) values for 64% of the subjects ( p = 0.0004, paired t test). Five percent of subjects, who initially had only an elevated exercise AER, developed a consistently elevated overnight AER. Seven of these nine subjects showed either worsening (>10%) or no improvement in their HbA 1 values from the initial to the final study periods. Five percent of subjects continued to have an elevated exercise and normal overnight AER throughout the study. These results show that the elevated exercise AER represents a definite transitional stage between a normal and an abnormal (>30 μg/min) overnight AER. In addition, a “window” exists during which an elevated exercise AER may be reversed by improved glucose control, but if this improvement does not occur, progression to an increased overnight AER is likely to result.

Correlation of Urinary Albumin andβ-2-Microglobulin and Growth Hormone Excretion in Patients with Diabetes Mellitus and Short Stature*

We examined the correlation between urinary GH, urinary albumin, and beta-2-microglobulin excretion to determine how the excretion of GH relates to markers of renal glomerular and tubular function. Urinary albumin and GH excretion was determined in timed daytime and nighttime urine collections obtained from both subjects with diabetes mellitus and subjects with short stature. For subjects with diabetes, urinary GH excretion rate correlated highly with urinary albumin concentration and excretion rate in both the range of 0 to 1.6 g/L (r = 0.75), P less than 0.001) and in the microalbuminuria range, 0 to 0.4 g/L (r = 0.53, P less than 0.001). Changes in GH and albumin excretion occurred in parallel in 71% of the subjects with diabetes and elevated albumin excretion. The mean GH excretion rate was higher in the group with elevated albumin excretion rate (AER) during both day and night compared to the group with microalbuminuria during the day and normal AER at night. For subjects with short stature, the mean albumin excretion rate was 0.7 +/- 1.3 micrograms/min (range 0.05-8.3 micrograms/min) using a sensitive enzyme-linked immunosorbent assay to measure albumin concentration. The correlation of GH and albumin excretion rates for the subjects with short stature was not statistically significant (r = 0.14, P less than 0.5). About half of the subjects with diabetes and elevated AER (greater than 10 micrograms/min) had a GH excretion rate within the range observed in subjects with short stature. The GH and albumin excretion rate were not correlated in this group. There was a positive correlation of both albumin and GH excretion rate with age in the subjects with diabetes. Urinary GH and beta-2-microglobulin excretion rates were determined in a larger group of subjects with diabetes and a separate group with short stature. Urinary GH and beta-2-microglobulin excretion were correlated both in subjects with diabetes (r = 0.46, P less than 0.001) and with short stature (r = 0.64, P less than 0.001). The association was present in urine collected either during the day or night. The mean GH excretion rate of the group with diabetes was greater than the group with short stature. In conclusion, there was an association of urinary GH and albumin excretion rate in subjects with abnormal glomerular function as indicated by elevated albumin excretion rate. An association of urinary GH and beta-2-microglobulin excretion was observed in subjects with normal tubular function.(ABSTRACT TRUNCATED AT 400 WORDS)

Prediction of Clinical Diabetic Nephropathy in IDDM Patients: Alternatives to Microalbuminuria?

This perspective deals with prediction of overt diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). The role of elevated urinary albumin excretion rate (microalbuminuria) in predicting diabetic nephropathy has been emphasized by new follow-up studies. Development of severe kidney impairment was seen in a large percentage of patients with microalbuminuria, but with more intensive care for diabetic patients, this percentage may be falling. Herein, I analyzed alternatives to microalbuminuria in predicting kidney disease in diabetes. 1) Parental predisposition to hypertension is not seen in all studies and therefore may not be a decisive factor, and it cannot be used in prediction of nephropathy. 2) Prediabetic blood pressure may predict nephropathy in certain non-insulin-dependent diabetic patients, but elevated blood pressure seems to develop after early microalbuminuria and is likely to be an aggravating factor in established microalbuminuria in IDDM patients. 3) At the clinical diagnosis of IDDM, diabetic nephropathy cannot be predicted. 4) Glycemic control is poor in normoalbuminuric patients with later development of microalbuminuria, and multiple glycosylated hemoglobin measurements are therefore important. 5) In diabetes, glomerular hyperfiltration is associated with late nephropathy, but it alone cannot be the decisive factor, because hyperfiltration in nondiabetic individuals does not produce kidney disease, according to new long-term follow-up studies. 6) Studies of glomerular structure and ultrastructure have not yet documented predictive values for overt nephropathy, but further studies are in progress. 7) Isolated blood pressure elevation without microabuminuria (probably representing essential hypertension in diabetes) has not been predictive. 8) It is clear that elevation of serum creatinine is a very late and insensitive parameter, occurring only with pronounced proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical characteristics associated with microalbuminuria in an adult diabetic population

A study was conducted to identify clinical characteristics which might distinguish individuals at risk for diabetic nephropathy. A cross-sectional survey measuring microalbuminuria in a population of 140 diabetic adults was performed and several clinical parameters among subgroups with different clinical types of diabetes, based upon age of onset and insulin treatment, were examined. In 67 insulin-treated patients with onset of diabetes at or after the age of 30 who had elevated albumin excretion rates, significantly greater duration of diabetes, age, blood pressure, serum creatinine, body mass index, and serum triglycerides were found. In this group of maturity onset insulin-treated diabetic patients, there was a significantly smaller proportion of smokers in the microalbuminuria group than in the group with normal excretion. No such distinctions were seen in 58 maturity onset patients with and without microalbuminuria who were not receiving insulin. In 15 insulin dependent patients with onset in early adulthood, only age and duration distinguished those with, or without, microalbuminuria. Analysis of microalbuminuria, taking into account diabetes therapy and other clinical and demographic data, may provide clues to the pathophysiology of renal disease in diabetes mellitus.

The effect of exercise on urinary excretion of different size proteins in patients with insulin-dependent diabetes mellitus

To examine whether exercise-induced proteinuria in diabetes is dependent upon the size of the excreted protein, we measured urinary excretion of beta 2-microglobulin, kappa light chains, albumin and IgG before and after 20 min of moderate ergometer exercise in 34 patients with insulin dependent diabetes mellitus (IDDM) and in eight healthy control subjects. Seventeen patients with newly diagnosed IDDM and 17 patients (seven of which had elevated albumin excretion rate) with longstanding IDDM were studied. Exercise did not significantly influence protein excretion in control and newly diagnosed IDDM subjects. In contrast, exercise enhanced excretion of beta 2-microglobulin (p less than 0.05-0.01), kappa light chains (p less than 0.001), albumin (p less than 0.005-0.001) and IgG (p less than 0.01-0.001) in patients with long-standing IDDM independently of whether the patient had proteinuria in the resting state or not. In conclusion, proteinuria induced by moderate exercise is not observed in the early stages of IDDM, and is independent of the size of the excreted protein. Therefore, moderate exercise does not appear to influence the size selectivity of the glomerular capillary wall in patients with longstanding IDDM.

Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM.

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.