OBJECTIVE —Conflicting evidence of a decline in incidence of microvascular complications in type 1 diabetes during the last decades has been reported. To assess recent trends in the cumulative incidence of diabetic microangiopathy in type 1 diabetes, we analyzed data from long-term prospective observational studies lasting ≥20 years.

RESEARCH DESIGN AND METHODS —A total of 600 Caucasian patients with onset of type 1 diabetes between 1965 and 1984 were followed until death or until the year 2000. Patients were divided into four groups based on the year of diabetes onset: group A, 1965–1969 ( n = 113); group B, 1970–1974 ( n = 130); group C, 1975–1979 ( n = 113); and group D, 1979–1984 ( n = 244). Group A, B, and C are prevalence cohorts identified in 1984; group D is an inception cohort.

RESULTS —In patients followed for ≥20 years, the cumulative incidence (95% CI) of diabetic nephropathy after 20 years of diabetes (urinary albumin excretion >300 mg/24 h) was reduced in patients with more recent diabetes onset (groups A–D): 31.1% (22.5–39.7) vs. 28.4% (19.8–37.0) vs. 18.9% (10.9–26.9) vs. 13.7% (6.2–21.2) ( P = 0.015). Similarly, the cumulative incidence of proliferative retinopathy was as follows: 31.2% (22.2–39.8) vs. 30.3% (22.2–38.4) vs. 19.3% (11.2–27.4) vs. 12.5% (5.2–19.8) ( P < 0.01). In the latter groups, antihypertensive treatment was started earlier, blood pressure and HbA1c were lower, and fewer patients smoked.

CONCLUSIONS —Our study demonstrates a decrease in the cumulative incidence of diabetic microangiopathy in type 1 diabetes over the past 35 years. Improved glycemic control, lower blood pressure (in part due to early aggressive antihypertensive treatment), and reduced prevalence of smoking rates were associated with the improved prognosis.

https://care.diabetesjournals.org/content/diacare/26/4/1258.full.pdf

Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes.

Early glycemic control, age at onset and development of microvascular complications in childhood-onset type 1 diabetes : A population-based study in Northern Sweden

https://care.diabetesjournals.org/content/diacare/27/4/955.full.pdf

Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden

Immunological studies of homosexual men with immunodeficiency and Kaposi's sarcoma.

OBJECTIVE Experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension and kidney disease. Whether uric acid has a causal role in the development of diabetic nephropathy is not known. The objective of the present study is to evaluate uric acid as a predictor of persistent micro- and macroalbuminuria. RESEARCH DESIGN AND METHODS This prospective observational follow-up study consisted of an inception cohort of 277 patients followed from onset of type 1 diabetes. Of these, 270 patients had blood samples taken at baseline. In seven cases, uric acid could not be determined; therefore, 263 patients (156 men) were available for analysis. Uric acid was measured 3 years after onset of diabetes and before any patient developed microalbuminuria. RESULTS During a median follow-up of 18.1 years (range 1.0–21.8), 23 of 263 patients developed persistent macroalbuminuria (urinary albumin excretion rate >300 mg/24 h in at least two of three consecutive samples). In patients with uric acid levels in the highest quartile (>249 μmol/l), the cumulative incidence of persistent macroalbumnuria was 22.3% (95% CI 10.3–34.3) compared with 9.5% (3.8–15.2) in patients with uric acid in the three lower quartiles (log-rank test, P = 0.006). In a Cox proportional hazards model with sex and age as fixed covariates, uric acid was associated with subsequent development of persistent macroalbuminuria (hazard ratio 2.37 [95% CI 1.04–5.37] per 100 μmol/l increase in uric acid level; P = 0.04). Adjustment for confounders did not change the estimate significantly. CONCLUSIONS Uric acid level soon after onset of type 1 diabetes is independently associated with risk for later development of diabetic nephropathy.

https://diabetes.diabetesjournals.org/content/diabetes/58/7/1668.full.pdf

Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840080332

Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis

We have developed a new automated immunonephelometric method for determination of albumin in urine, by exploiting the polymer-enhancing effect on the immunological reaction. The original continuous-flow manifold has been simplified and the reaction time shortened to about 3 min. The antiserum was diluted 100-fold in a solution (100 g/liter) of polyethylene glycol (av mol wt, 6000) and mixed with the prediluted sample in the continuous-flow system. The method is highly sensitive and is unaffected by high blank and (or) high absorbance values of the specimens. Day-to-day variation was 3.8-4.3% (CV). Accuracy, as estimated from recovery experiments, was also good. A comparative study of 176 urines with the single radial immunodiffusion technique showed a correlation coefficient of 0.994. We therefore suggest the new method for routine use for determination of urinary albumin, because it is fast, accurate, precise, and sensitive, and requires only small amounts of antiserum.

Polymer Enhancement of Automated Immunological Nephelometric Analysis, as Illustrated by Determination of Urinary Albumin

A manual immunonephelometric method for proteins has been developed by using an ordinary fluorometer as a nephelometer. By applying the enhancing effect of polyethylene glycol (av mol wt, 6000) on the immunological reaction, albumin and fibrinogen were quantitated after a 10-min reaction time. Under the present conditions the sensitivity was increased and thus antiserum consumption was decreased. The reaction conditions were carefully studied with respect to optimal time and concentration of the reactants. The precision of the method was 2.6-3.6% (CV). The lower detection limit in the albumin-antialbumin system was 0.1 mg/liter. Comparative studies showed a correlation coefficient of 0.991 with an automated immunonephelometric method for urinary albumin, and of 0.908 with a thrombin clottable method for plasma fibrinogen. We especially suggest use of this manual immunonephelometric method where small series of samples are to be analyzed.

Manual Immunonephelometric Assay of Proteins, with Use of Polymer Enhancement

We describe a high-speed immunonephelometric continuous-flow system. The mechanical timing assembly and cams of the sampler were replaced by an external electronic control unit. Improved sampling precision, speeds of 2 to 900 samples per hour, and a wide variety of sample-to-wash ratios are the most important advantages of the unit. We analyzed albumin and fibrinogen at speeds of 150, 180, and 210 samples per hour. Carry-over studies showed that, in clinical practice, it should be possible to run the system at 150 samples per hour with an interaction of less than 5% and a precision (CV) of around 4%. Comparative studies with a previously described method, run at 60 samples per hour, showed correlation coefficients of 0.968 and 0.935 for albumin and fibrinogen, respectively. The electronic control unit can be used to increase speed and improve sampling precision of any continuous-flow system. An immunonephelometric system equipped with this device provided fast and reliable results, and required less antiserum than other systems described.

Electronic Timing of a High-Speed Immunonephelometric Continuous-Flow System

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Polymer Enhancement of Automated Immunological Nephelometric Analysis, as Illustrated by Determination of Urinary Albumin

Manual Immunonephelometric Assay of Proteins, with Use of Polymer Enhancement

Electronic Timing of a High-Speed Immunonephelometric Continuous-Flow System