Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linköping Diabetes Complications Study.

AIMS/HYPOTHESIS: In a previous study conducted over the last decades we found a decreased incidence of nephropathy but unchanged incidence of severe retinopathy among patients with Type 1 diabetes diagnosed in childhood and with 20 years duration of diabetes. The aim of our current study was to investigate the incidence 5 to 10 years later in the same population. METHODS: We studied all 269 patients in whom Type 1 diabetes was diagnosed in childhood between 1961 and 1985 in a district in southeastern Sweden. Ninety-one percent were monitored for retinopathy until at least 1997 and 95% were monitored for nephropathy. Severe retinopathy was defined as laser-treated retinopathy and nephropathy as persistent proteinuria. Survival analysis was used and the patients divided into five cohorts according to the time of onset of diabetes. RESULTS: The cumulative proportion of severe retinopathy had declined ( p=0.006). After 25 years it was 47% (95% CI 34-61), 28% (15-40) and 24% (12-36) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years it was 53% (40-66) and 44% (28-59) in the oldest cohorts. The cumulative proportion of nephropathy after 25 years duration was 30% (18-42), 8% (1-16) and 13% (4-23) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years, it was 32% (20-44) and 11% (2-20) for the oldest cohorts ( p<0.0001). CONCLUSIONS/INTERPRETATION: In an unselected population with Type 1 diabetes diagnosed in childhood, modern diabetes care markedly reduced the incidence of severe retinopathy and nephropathy.

Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes.

OBJECTIVE: To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). RESULTS: Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. CONCLUSIONS: Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.

The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes.

Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA(1c) during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA(1c) >8.4% compared with those with mean HbA(1c) <7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

Unchanged incidence of severe retinopathy in a population of Type 1 diabetic patients with marked reduction of nephropathy.

The incidence of nephropathy in Type 1 diabetes mellitus has declined during the past decade, probably as a result of improved glycaemic control. We wanted to investigate whether the incidence of severe retinopathy has changed during the same time period and to evaluate the importance of glycaemic control in relation to the development of severe retinopathy and nephropathy. All 213 patients in whom Type 1 diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden were studied. Ninety-two per cent of the patients were followed from the onset of diabetes to 1991 or to death. The cumulative incidence of severe retinopathy was not significantly different between the patients with diabetes onset 1961-65, 1966-70, 1971-75, and 1976-80. The risk of developing severe retinopathy or nephropathy was higher in patients with very poor glycaemic control (HbA1c > or = 8.4%) vs patients with poor control (HbA1c > or = 7.2 < 8.4%; p < 0.001). Patients with poor control had an increased risk of developing severe retinopathy vs patients with good control (HbA1c < 7.2%; p < 0.008) but there was no difference in the risk of nephropathy. No patients with good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes.

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria.

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

Glycemic control and prognosis in type I diabetic patients with microalbuminuria.

OBJECTIVE: To investigate the course of microalbuminuria during the 1980s in type I diabetes patients. RESEARCH DESIGN AND METHODS: This was a 10-year follow-up of 109 patients in whom type I diabetes was diagnosed between 1961 and 1980 before 15 years of age and who were initially investigated between 1977 and 1983 after a diabetes duration of > or = 3 years. Microalbuminuria was defined as an albumin excretion rate (AER) of 20-200 micrograms/min in two of three consecutive urine samples. RESULTS: At the initial investigation, 81 patients had normal AER, 27 had microalbuminuria, and 1 had macroalbuminuria. Between 1989 and 1992, 99 (91%) patients were reinvestigated. Only 5 (19%) of the initially microalbuminuric patients developed macroproteinuria during the 10-year follow-up period, and in 15 (58%) patients, AER decreased to normal. Three (4%) of the normoalbuminuric patients developed microalbuminuria but none macroproteinuria. The initially microalbuminuric patients, in whom AER normalized, improved their glycemic control from 1980-1983 to 1989-1991 (mean +/- SE HbA1c 7.5 +/- 0.2 to 6.6 +/- 0.3%; P = 0.01). CONCLUSIONS: In the majority of patients with microalbuminuria in whom it is possible to obtain good glycemic control, microalbuminuria will disappear and the risk of developing nephropathy will be markedly reduced.

Declining incidence of nephropathy in insulin-dependent diabetes mellitus.

BACKGROUND: The high relative mortality among patients with insulin-dependent diabetes mellitus results mainly from diabetic nephropathy. The cumulative incidence of nephropathy of 25 to 30 percent among patients who had had diabetes for 25 years remained stable from 1950 to the early 1980s. In a population study, we assessed recent trends in the incidence of diabetic nephropathy. METHODS: We studied all 213 patients in whom insulin-dependent diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden. Ninety-two percent of the patients were followed from the onset of diabetes to 1991 or to death. Patients with persistent albuminuria (positive Albustix test) were considered to have diabetic nephropathy. Glycosylated hemoglobin was measured periodically in all patients, beginning in 1980. RESULTS: The cumulative incidence of persistent albuminuria after 25 years of diabetes decreased from 30.0 percent among the patients in whom diabetes developed in the period 1961 to 1965 to 8.9 percent among those in whom it developed from 1966 to 1970 (P = 0.01). After 20 years of diabetes, the cumulative incidence decreased from 28.0 percent among the patients in whom diabetes developed from 1961 to 1965 to 5.8 percent among those in whom it developed from 1971 to 1975 (P = 0.01). Persistent albuminuria has not yet developed in any patient in whom diabetes was diagnosed in the period 1976 to 1980. The average glycosylated hemoglobin value decreased from 7.4 percent in the period 1980 to 1985 to 7.0 percent from 1986 to 1991 (P < 0.001). The mean glycosylated hemoglobin value was higher in the patients with persistent albuminuria than the patients with no albuminuria (8.1 percent vs. 7.1 percent, P < 0.001). CONCLUSIONS: During the past decade the cumulative incidence of diabetic nephropathy, as manifested by persistent albuminuria, among patients who have had diabetes for 25 years has decreased substantially, probably as a result of improved glycemic control.