Luther B. Travis

Barriers to Insulin Injection Therapy Patient and Health Care Provider Perspectives

Objective To compare patients’ perceptions of injection-related problems with clinicians’ estimates of those problems. Methods Data were obtained through 2 Internet surveys, one of US adults self-identified as taking insulin to treat diabe- tes and the second of health care professionals who treat people with diabetes who inject insulin, including pri- mary care physicians, endocrinologists, and diabetes educators. Results A substantial majority of patients would like to reduce the number of injections they take each day; almost half said that they would be more likely to take their insulin injections regularly if a product were available to ease the pain. A much smaller proportion of patients reported that (1) injections were a serious burden, (2) they were dissatisfied with the way they took insulin, (3) injections had a substantial negative impact on qual- ity of life, (4) they skipped injections they should take, or (5) injection-related problems affected the number of injections they were willing to take. Half of the patients said they mentioned injection-related problems to their provider; a similar number reported that their providers had not given them a solution to problems with injection- related pain and bruising. Although awareness of prod- ucts to ease injection pain was high among providers (especially diabetes educators), this information was not effectively transmitted to patients. Conclusions Patients should be encouraged to discuss their injection- related concerns, and providers should regularly ask about injection-related problems. Providers should offer patients information about tools to reduce injection- related worries, preferably by having them available to show and demonstrate

The association of idiopathic hypercalciuria and asymptomatic gross hematuria in children

Seven children with asymptomatic gross hematuria are described. Six had recurrent hematuria; one had a single episode. Occasional global glomerulosclerosis and/or mesangial electron dense deposits were present in the three patients in whom renal bipsy was performed; the changes were felt to be insufficient to account for the hematuria. None of the patients had urolithiasis or any significant urinary tract abnormality. One was an adopted child; a family history of urolithiasis was obtained in the other six. Idiopathic hypercalciuria was documented in six patients; the seventh subsequently passed a calcium oxalate calculus. One patient is 10 weeks of age at the time of this submission. Of the remainder, three patients received no specific therapy; renal calculi developed six months, six years, and eight years later. Three patients were treated with a thiazide diuretic soon after onset of hematuria and confirmation of idiopathic hypercalciuria; there was complete cessation of hematuria within five days with no recurrence as long as therapy was continued. We suggest that measurement of urinary calcium excretion as part of the initial evaluation of a child with gross hematuria may, in some cases, obviate invasive investigations and allow for effective therapy.

Progressive Retinopathy with Improved Control in Diabetic Dwarfism (Mauriac's Syndrome)

We report four children aged 11–18½ yr first seen 7–14 yr after the diagnosis of insulin-dependent diabetes. At presentation, all had marked short stature, two had hepatomegaly, and the older three had delayed adolescence. They had been severely underinsulinized. Initial funduscopy demonstrated only occasion microaneurysms in two children and a single intraretinal hemorrhage in another. The youngest was normal. Improved control required large increases in insulin dosage. Growth rate improved significantly and hepatomegaly regressed. Puberty progressed rapidly in two older patients with poor final height. Paradoxically, with improved control, retinopathy progressed rapidly with appearance of multiple microaneurysms, nerve fiber layer infarctions, intraretinal microangiopathic changes, hemorrhages, exudates, and macular edema in all the patients and severe proliferation changes in three. One child with proliferative retinopathy in both eyes developed vitreous hemorrhage and blindness in one eye. Two required panretinal photocoagulation with no further progression of their retinopathy. These rapidly progressive retinal changes remain unexplained. We advise caution when correcting metabolic derangements of diabetic patients who have been poorly controlled for a prolonged period.

Reliability and validity of the Diabetes Family Behavior Scale (DFBS).

The Diabetes Family Behavior Scale (DFBS) was designed to measure diabetes-specific family support. The purposes of this study were to refine the scale and to assess reliability and criterion validity in terms of relationship to metabolic control. The DFBS was administered to 321 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Blood was drawn for determination of glycosylated hemoglobin (HbA1c). Based on an item-analysis procedure, the DFBS was revised to include 47 items with two subscales, one to reflect guidance-control and one to reflect warmth-caring. Acceptable internal consistency was found for the DFBS total score (.86), and for the guidance-control (.81) and warmth-caring (.79) subscales. There was a statistically significant relationship in the expected direction between DFBS total score and HbA1c (r = -.12, P<.03), and between the guidance-control subscale and HbA 1c. (r=-.17, P<.002).

Mutants of 11β-Hydroxysteroid Dehydrogenase (11-HSD2) With Partial Activity: Improved Correlations Between Genotype and Biochemical Phenotype in Apparent Mineralocorticoid Excess

Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent mineralocorticoid excess, an autosomal recessive form of familial hypertension. We studied 4 patients with AME, identifying 4 novel and 3 previously reported mutations in the HSD11B2 (HSD11K) gene. Point mutations causing amino acid substitutions were introduced into a pCMV5/11HSD2 expression construct and expressed in mammalian CHOP cells. Mutations L179R and R208H abolished activity in whole cells. Mutants S180F, A237V, and A328V had 19%, 72%, and 25%, respectively, of the activity of the wild-type enzyme in whole cells when cortisol was used as the substrate and 80%, 140%, and 55%, respectively, of wild-type activity when corticosterone was used as the substrate. However, these mutant proteins were only 0.6% to 5.7% as active as the wild-type enzyme in cell lysates, suggesting that these mutations alter stability of the enzyme. In regression analyses of all AME patients with published genotypes, several biochemical and clinical parameters were highly correlated with mutant enzymatic activity, demonstrated in whole cells, when cortisol was used as the substrate. These included the ratio of urinary cortisone to cortisol metabolites (R(2)=0.648, P<0.0001), age at presentation (R(2)=0.614, P<0.0001), and birth weight (R(2)=0.576, P=0.0004). Approximately 5% conversion of cortisol to cortisone is predicted in subjects with mutations that completely inactivate HSD11B2, suggesting that a low level of enzymatic activity is mediated by another enzyme, possibly 11-HSD1.

Bone mineral density of the lumbar vertebrae in children and adolescents with insulin-dependent diabetes mellitus

To test the hypothesis that bone mineral density (BMD) is lower in children with insulin-dependent diabetes mellitus (IDDM), we measured BMD of the lumbar vertebrae (L-2 to L-4) by dual-photon absorptiometry in 31 boys and 25 girls, mean age 12.3 years, with IDDM of varying clinical duration (range 0.1 to 14.8 years). Mean standard deviation scores (z scores) were determined for L-2-L-4 BMD, weight, height, weight percentile, and weight-adjusted L-2-L-4 BMD index (L-2-L-4 BMD/weight), with reference data from a previously described white, nondiabetic, age-matched control group (n = 221). Compared with nondiabetic control subjects, male patients with short-term IDDM and all female patients with IDDM did not have significantly different L-2-L-4 BMD, weight, weight percentile, height, or BMD index. Boys with IDDM longer than 1 year had significantly lower weight, weight percentile, and height than did age-matched control subjects. When L-2-L-4 BMD of boys with long-term diabetes was corrected for weight, the L-2-L-4 BMD index was significantly greater than that of control subjects, indicating that weight was disproportionately lower than BMD. There were no significant linear correlations between metabolic control and L-2-L-4 BMD. When L-2-L-4 BMD was adjusted for differences in body weight, spinal BMD values in children with IDDM were not lower than in control subjects. These findings indicate that in children with IDDM, as in previously studied nondiabetic youths, body weight and spinal BMD are highly correlated; although BMD is reduced in some children with diabetes, the reduction parallels reductions in growth, and may simply reflect a normal response of the skeleton to a lower weight-bearing load.

Implications of psychological and family factors in the treatment of diabetes.

The authors delineate and discuss in detail those psychological and familial factors that have implications in treatment and in fostering the optimal emotional and physical health of children and adolescents with diabetes mellitus.

Psychosocial correlates of hemoglobin A1c in young adults with type I diabetes

To determine whether psychosocial variables are related to long-term glycemic control; trait anxiety, depression, loneliness and life stress were assessed in 48 Type I diabetic patients. Hemoglobin A1c (HbA1c), an indicator of long-term glycemic utilization, was assayed from blood samples drawn shortly before the self-report instruments were administered. Of the psychosocial variables, anxiety was significantly related to current values of HbA1c. The association between anxiety and current HbA1c remained after statistically controlling for potentially confounding variables, including the previous value of HbA1c. Despite the stability of HbA1c values over time, anxiety scores were not significantly correlated with follow-up HbA1c. The implications of the significant relationships between psychological constructs and glycemic control are discussed.

A practical primary care approach to hematuria in children

Abstract Although hematuria is a common finding in the unselected population of children, the approach to evaluation is quite variable. Changes in the practice of primary care medicine in the United States mandate an approach to common office problems that is practical and realistic. This review addresses three areas: the current approach to evaluation of hematuria in children, a classification of children with hematuria into four distinct and easily identified clinical categories, and the development of an algorithm for application in the primary care setting. Each category is discussed relative to the more-common etiologies of hematuria, with recommendations for appropriate evaluation as well as suggestions of an appropriate referral to the nephrologist. An algorithm is proposed that provides a practical, systematic approach to the problem without the requirement for a specific diagnosis in every patient. The proposed classification and approach to the evaluation of children with hematuria should help simplify and clarify a potentially complex process.

Immune deposits and mesangial hypercellularity in minimal change nephrotic syndrome: Clinical relevance

Occasional patients with nephrotic syndrome and minimal histologic change demonstrate glomerular deposition of small amounts of immunoglobulin and complement. Some consider this a disease distinct from MCNS. To investigate the clinical importance of immune deposits and mesangial hypercellularity in the initial biopsy, the clinical records, follow-up data, and renal biopsies of 68 patients (ages 6 months to 16 years) with MCNS by light microscopy were reviewed. Among 68 patients followed a mean of 6.2 years, eight of 25 patients with immune deposits on initial renal biopsy were steroid nonresponsive. Only one of 43 patients without immune deposits was steroid nonresponsive (P = 0.00005). Of 44 patients with normal mesangial cellularity, 31 experienced fewer than three relapses a year, whereas of 15 patients with mesangial hypercellularity, only six experienced fewer than three relapses a year (P = 0.035). The data suggest that immune deposits and increased mesangial cellularity in children with NS and minimal light microscopic change may predict the clinical course.