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Biomedical subjects

L Laffel

Publications and source records attributed to L Laffel.

9 recordsLinked to original sources

Sick-day management in type 1 diabetes.

Illness and stress are common occurrences. For the person with type 1 diabetes, these events can be triggers for counterregulation and [table: see text] subsequent metabolic deterioration if there is no attention to diabetes management tasks. Sick-day management requires increased monitoring of blood glucose and assessment for ketosis. Although urine testing for ketones has been the standard approach to sick-day management, new technology for self-monitoring of blood 3HB levels is now available. According to the American Diabetes Association, blood measurement of 3HB "may offer a useful alternative to urine ketone testing." This new technology may provide an opportunity to improve the management of uncontrolled diabetes and sick days in an attempt to reduce the human and economic burden of DKA.

Blood Glucose↗

von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.

OBJECTIVE: Although retinopathy is a common microvascular complication of type 1 diabetes, the mechanism for this complication is still unknown. Changes in retinal circulation have been noted before the development of overt retinal pathology. Because von Willebrand factor (vWF) is a marker for endothelial dysfunction and mediates platelet adhesion, we determined if there was an association between vWF and retinal circulation in the early stages of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Twenty subjects (aged 32.4 +/- 7.8 years) with type 1 diabetes and minimal or no retinopathy were studied. The mean duration of diabetes was 4.7 +/- 2.6 years. Data were collected at baseline and after 4 months of 1,800 IU vitamin E therapy or placebo. Retinal circulation was evaluated by video fluorescein angiography. Plasma vWF antigen levels were measured by enzyme-linked immunosorbent assay and fibrinogen by the Clauss method. RESULTS: Retinal blood flow was negatively correlated with vWF levels (r = -0.44, P = 0.008), whereas retinal circulation time was positively correlated with vWF levels (r = 0.33, P = 0.048). Fibrinogen levels were not significantly associated with either retinal index. However, fibrinogen levels were positively associated with HbA1c levels (r = 0.34, P = 0.01), indicating an association between poor glycemic control and higher fibrinogen levels. CONCLUSIONS: Increased vWF was associated with a prolonged retinal circulation time and reduced retinal blood flow in early-stage retinopathy of type 1 diabetes. Reduced blood flow associated with increased vWF levels may promote stasis in the retinal circulation and lead to local hypoxemia. These changes might contribute to the microvascular complications of diabetes. Whether the vWF levels predict retinal complications deserves further investigation.

Adult↗

High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes.

OBJECTIVE: To determine the effectiveness of vitamin E treatment in normalizing retinal blood flow and renal function in patients with <10 years of type 1 diabetes. RESEARCH DESIGN AND METHODS: An 8-month randomized double-masked placebo-controlled crossover trial evaluated 36 type 1 diabetic and 9 nondiabetic subjects. Subjects were randomly assigned to either 1,800 IU vitamin E/day or placebo for 4 months and followed, after treatment crossover, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized creatinine clearance from timed urine collections. RESULTS: After vitamin E treatment, serum levels of vitamin E were significantly elevated (P<0.01) in both type 1 diabetic and control patients. Hemoglobin A1c was not affected by vitamin E treatment. Diabetic patient baseline retinal blood flow (29.1+/-7.5 pixel2/s) was significantly (P = 0.030) decreased compared with that of nondiabetic subjects (35.2+/-7.2 pixel2/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5+/-7.8 pixel2/s) was significantly increased (P<0.001) and was comparable with that of nondiabetic subjects. Additionally, vitamin E treatment significantly (P = 0.039) normalized elevated baseline creatinine clearance in diabetic patients. CONCLUSIONS: Oral vitamin E treatment appears to be effective in normalizing retinal hemodynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy.

Adolescent↗

Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus.

OBJECTIVES: The goal of this study was to identify parental behaviors that relate to adherence and metabolic control in a population of young adolescents with insulin-dependent diabetes mellitus (IDDM), and to understand the interrelationships among the variables of parental involvement, adherence to blood glucose monitoring, and glycemic control. STUDY DESIGN: A cross-sectional design was used to investigate parental involvement in diabetes regimen tasks in 89 youth, aged 10 to 15 years, with IDDM. Levels of parental involvement in blood glucose monitoring (BGM) and insulin administration were evaluated through interviews. Assessment of adherence was made by physicians or nurses, independent of patient or parent reports of adherence. Glycemic control was assessed with glycosylated hemoglobin (HbA1c) (reference range, 4% to 6%). RESULTS: There were significant differences in the mean HbA1c values between the older (13 to 15 years of age) (HbA1c = 8.9% +/- 1.03%) and younger (10 to 12 years) patients (HbA1c = 8.4% +/- 1.06%) (p < 0.02). Parental involvement in BGM was significantly related to adherence to BGM (number of blood sugar concentrations checked daily) in both groups of adolescent patients. The younger patients monitored their blood glucose levels more frequently than did the older patients, 39% of the younger patients checked sugar concentrations four or more times daily compared with only 10% of the older group (p < 0.007). In a multivariate model controlling for age, gender, Tanner staging, and duration of diabetes, the frequency of BGM was a significant predictor of glycemic control (R2 = 0.19, p < 0.02). Increased frequency of BGM was associated with lower HbA1c levels. When the frequency of BGM was zero or once a day, the mean HbA1c level was 9.9% +/- 0.44 (SE); when the frequency of BGM was two or three times a day, the mean HbA1c level was 8.7% +/- 0.17; and when the frequency of BGM was four or more times daily, the mean HbA1c level was 8.3% +/- 0.22. CONCLUSIONS: Parental involvement in BGM supports more frequent BGM in 10- to 15-year-old patients with IDDM. This increased adherence to BGM is associated with better metabolic control (i.e., lower HbA1c levels). These findings suggest that encouraging parental involvement in BGM with 10- to 15-year-old patients with IDDM may help to prevent the well-documented deterioration in glycemic control and adherence to treatment that often occurs in later adolescence.

Adolescent↗

Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio.

The objective of this study was to determine the prevalence of stages of diabetic nephropathy, defined by the albumin/creatinine ratio (AC ratio) in repeated measurements in random urine samples. Over a 30-month interval, 1613 patients with Type I diabetes (IDDM) (aged 15 to 44 yr, IDDM duration 1 to 39 yr), and 218 healthy control subjects provided multiple urine specimens. AC ratios measured in urine samples taken 5 months apart were highly reproducible (Spearman r = 0.83). A criterion for the boundary between normoalbuminuria and microalbuminuria was obtained by searching for a cutpoint that optimized agreement between serial specimens on individuals. The result was lower in men than women: 17 as compared with 25 micrograms/mg. These two values corresponded to the 95th percentiles of the respective distributions of the AC ratio in healthy control subjects. Also these sex-specific cutpoints, when converted to albumin excretion rates, became almost equal: 30 and 31 micrograms/min. Microalbuminuria appeared early in the course of IDDM (6% of those with only 1 to 3 yr of diabetes) and then increased rapidly during two intervals, the first and third decades, before leveling off at 52%. By that time the cumulative risk of overt proteinuria had risen to 27%. Determinations of the AC ratio in random urine samples are easily obtained and are reliable indices of elevated urinary albumin excretion (microalbuminuria) in IDDM. The pattern of occurrence of microalbuminuria according to duration of IDDM suggests that there may be two subsets of diabetic nephropathy, one appearing early and the other late. Patients with microalbuminuria and 25 yr of postpubertal IDDM have low risk of progression to advanced diabetic nephropathy.

Adolescent↗

Application of denaturing gradient gel electrophoresis to detect DNA sequence differences encoding apolipoprotein E isoforms.

Apolipoprotein E (apoE) plays an important role in plasma lipid metabolism. Three common isoforms of this protein have been identified by the isoelectric focusing method. In this report we describe a new method for distinguishing these isoforms. Our method employs PCR amplification of the DNA sequence of exon 4 in the apoE gene followed by denaturing gradient gel electrophoresis (DGGE) to distinguish its different melting characteristics. Identification of the ApoE isoforms through DNA melting behavior rather than protein charge differences eliminates the problems associated with isoelectric focusing and facilitates screening for additional mutations at the apoE locus.

Apolipoproteins E↗

Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes.

Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies.

Animals↗