Screening for Vitamin D Deficiency in Black Americans: Comparison of Total, Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density.

OBJECTIVES: There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. DESIGN: Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. SETTING: The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. PARTICIPANTS: 122 men and 206 women, age 60.2 ± 4.3 years. INTERVENTION: Retrospective analysis. MEASUREMENTS: Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. RESULTS: Serum total 25(OH)D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. CONCLUSION: Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

Thyroid dysfunction during chronic amiodarone therapy.

Clinical and laboratory features of 99 patients receiving long-term amiodarone therapy were analyzed to determine which individuals may be at a high risk for developing amiodarone-induced thyroid dysfunction. The group of 68 men and 31 women was followed up for an average of 27 months (range 3 to 60). There were no differences in age, sex, dose of amiodarone, type or severity of underlying heart disease or baseline serum thyroxine levels in patients who developed hypothyroidism (n = 32) or hyperthyroidism (n = 5) or remained euthyroid (n = 62). Baseline serum thyrotropin levels were statistically higher in patients who became hypothyroid, but there was considerable overlap with the other patient groups. Serum reverse triiodothyronine (reverse T3), which has been suggested to be a marker of amiodarone efficacy, correlated directly with serum thyroxine levels, and was not an independent variable. There was no pattern to the time course for development of thyroid dysfunction, which occurred in 49% of those followed up and developed as early as 1 month or, in one individual, as late as after 3 years of amiodarone therapy. There are few guidelines for replacement therapy in patients with amiodarone-induced hypothyroidism. L-thyroxine dosage was adjusted cautiously in these high risk individuals to achieve serum thyroxine levels within the reference range of euthyroid individuals taking amiodarone: the mean dosage required was 136 micrograms/day. Normalization of serum thyrotropin (TSH) would have required doses of L-thyroxine that were judged to be excessively high.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoglycemia due to serum-complexed insulin in a patient with diabetes mellitus.

A 28-year-old woman with insulin-dependent diabetes mellitus presented with a "hyperlabile" state of hyperglycemia and ketoacidosis alternating with hypoglycemia. Measurements of total and free insulin levels suggested that the clinical syndrome may have been due to antibody binding of insulin. Equilibrium analysis of insulin binding to the patient's serum demonstrated two classes of anti-insulin activities. The first class was of high affinity (dissociation constant approximately equal to 10(-9) M) and low capacity (150 microU/ml). At low total serum insulin concentrations, most of the circulating insulin was bound to the high-affinity binding activity, and the patient presented with hyperglycemia or ketosis. The second class of insulin binding activity had a lower affinity (dissociation constant approximately equal to 5 X 10(-7) M). The insulin that was bound to this low-affinity serum substance still maintained biologic activity in vivo. Isophane insulin (NPH) had a markedly prolonged serum half-life, which resulted in delayed hypoglycemia. Serum insulin complexes--that is, bound insulin--may not be "inactive" but may contribute to total insulin action. A determination of insulin activity, not only free insulin levels, may help explain hypoglycemia in selected patients with diabetes mellitus.

Psychosocial profiles in patients with visual impairment due to diabetic retinopathy.

The psychological impact of vision loss due to diabetic retinopathy is compounded by the loss of diabetes self-management skills. The appropriate role and timing for rehabilitative intervention has not been determined. Twenty-nine individuals with diabetes mellitus, 16 with stable visual impairment and 13 with fluctuating and transitional visual impairment, underwent psychological assessment before and after entering into a specially designed rehabilitation program. Low levels of performance were rehabilitation program. Low levels of performance were demonstrated by the Rosenberg Self-Esteem Scale and the Diabetes Self-Reliance Test in both groups. The Minnesota Multiphasic Personality Inventory, the Zung Self-Rating Depression Scale, and the Rand Mental Health Index suggested that subjects with stable vision impairment were moderately compensated relative to the transitional group, although the former group may have been totally blind. Both groups demonstrated significant improvements in psychological profiles after the program. It is suggested that a rehabilitation program may be of clinical benefit early in the course of vision loss associated with diabetic retinopathy.

The effect of glipizide gastrointestinal therapeutic system on islet cell hormonal responses to a test meal in NIDDM.

OBJECTIVE: To determine whether the abnormal glucagon and amylin secretions in NIDDM are secondary to hyperglycemia and relative hypoinsulinemia. RESEARCH DESIGN AND METHODS: A total of 13 patients with NIDDM were studied before and after treatment with glipizide gastrointestinal therapeutic system (GITS) in a randomized double-blind placebo-controlled fashion. Of the 13 subjects, 9 were randomized to the glipizide GITS arm and 4 were randomized to the placebo arm of the study. Serum glucose, insulin, C-peptide, plasma glucagon, and plasma amylin concentrations were measured under fasting and postprandial (post-Sustacal ingestion) conditions. The Sustacal challenge was performed at baseline and after 12 weeks of treatment with either glipizide GITS or placebo. RESULTS: Glipizide GITS treatment resulted in a significant reduction in hyperglycemia and increases in insulin and C-peptide secretion. Hyperglucagonemia was not ameliorated, and amylin secretion was not altered after glipizide GITS treatment. Placebo-treated patients did not show significant changes in any of the parameters measured. CONCLUSIONS: Glipizide GITS treatment failed to ameliorate the hyperglucagonemia of NIDDM and did not alter amylin secretion even though it increased insulin secretion and significantly ameliorated the hyperglycemia. These observations suggest that NIDDM related abnormalities in some of the islet cell hormonal responses are the result of changes inherent in the islet cells and may be independent of hyperglycemia and relative hypoinsulinemia.

Cardiovascular conditioning in individuals with diabetic retinopathy.

The benefit of exercise for individuals with diabetes mellitus and high-risk complications of retinopathy has been questioned. Thirty-nine individuals with diabetes and visual impairment completed a 12-wk rehabilitation program that included cardiovascular conditioning. Pre- and postprogram assessment of exercise training in 30 subjects included a graded stress test with a bicycle ergometer. There were improvements in exercise tolerance as measured by the work load achieved (from 248 +/- 27 to 303 +/- 31 kilopond meter [kpm], P less than .05). There was a trend toward improvement in METS achieved (from 3.3 +/- 0.2 to 3.8 +/- 0.3, P = .06). There was no correlation of improvement in exercise tolerance with improvements in glycemic control, lipoprotein balance, and change in body weight. Individuals with diabetic retinopathy may be given the option of entering cardiovascular training programs with appropriate modifications to fit specific needs.

Cerebral and ophthalmic artery hemodynamic responses in diabetes mellitus.

OBJECTIVE: To address whether hemodynamic responses in the cerebral arteries and OAs may be altered in patients with diabetic retinopathy. We used TCD to evaluate the effects of changes in BP, posture, and exercise on MCA and OA blood flow velocities. RESEARCH DESIGN AND METHODS: We evaluated 13 patients with BDR, 19 with PDR, and 11 control subjects. Each was tested while supine, breathing 100% oxygen, sitting, and during exercise. RESULTS: Control subjects exhibited linear increases in velocity in the MCA and OA with increases in BP. Those with BDR had higher baseline sBP than control subjects. The MCA velocity response to BP in the BDR group was parallel to, but differed significantly from, the response in control subjects in compensation for the level of BP (ANCOVA F1,53 = 10.1, P = 0.003). The OA velocity response to BP was indistinguishable between the control subjects and the group with BDR. The group with PDR had more elevated BP than control subjects, and those with BDR had more advanced autonomic neuropathy. The PDR group had heterogenous velocity responses in the MCA and OA with respect to BP. None of the control subjects and 3 of 13 of the BDR group had abnormal autoregulatory velocity responses in the MCA or OA to 100% oxygen breathing, whereas 12 of 19 PDR patients were abnormal (P < 0.01). Of those with PDR, 4 had elevated MCA and 3 had elevated OA velocities while supine at rest. CONCLUSIONS: Patients with PDR demonstrated abnormal hemodynamic responses of the cerebral and ophthalmic circulation both at rest and with exercise.

Effectiveness of glucose monitoring systems modified for the visually impaired.

OBJECTIVE: To compare three glucose meters modified for use by individuals with diabetes and visual impairment regarding accuracy, precision, and clinical reliability. RESEARCH DESIGN AND METHODS: Ten subjects with diabetes and visual impairment performed self-monitoring of blood glucose using each of the three commercially available blood glucose meters modified for visually impaired users (the AccuChek Freedom [Boehringer Mannheim, Indianapolis, IN], the Diascan SVM [Home Diagnostics, Eatontown, NJ], and the One Touch [Lifescan, Milpitas, CA]). The meters were independently evaluated by a laboratory technologist for precision and accuracy determinations. RESULTS: Only two meters were acceptable with regard to laboratory precision (coefficient of variation < 10%)--the Accuchek and the One Touch. The Accuchek and the One Touch did not differ significantly with regard to laboratory estimates of accuracy. A great discrepancy of the clinical reliability results was observed between these two meters. The Accuchek maintained a high degree of reliability (y = 0.99X + 0.44, r = 0.97, P = 0.001). The visually impaired subjects were unable to perform reliable testing using the One Touch system because of a lack of appropriate tactile landmarks and auditory signals. CONCLUSIONS: In addition to laboratory assessments of glucose meters, monitoring systems designed for the visually impaired must include adequate tactile and audible feedback features to allow for the acquisition and placement of appropriate blood samples.

Diabetic neuropathy and braille ability.

Thirty-five individuals with visual impairment due to diabetic retinopathy underwent neurologic examination with special emphasis on two-point discrimination and nerve conduction studies to determine whether concomitant peripheral neuropathy would interfere with their ability to read braille. Twenty-two individuals with insulin-dependent diabetes mellitus (9 men and 13 women) and 13 with noninsulin-dependent diabetes mellitus (4 men and 9 women) were evaluated. All had peripheral neuropathy; there were 4 with stage 1, 29 with stage 2, and 2 with stage 3 neuropathy. Two-point discriminatory ability appeared to be relatively well-preserved and at least 25 of the 35 individuals were able to learn to read standard or jumbo braille. Individuals with abnormalities in two-point discrimination (greater than 5 mm) were found to have abnormalities in braille reading. Individuals with visual impairment due to diabetes should not be discouraged from undertaking braille on the basis of apparent polyneuropathy.

The age-related changes in lipogenic enzymes: the role of dietary factors and thyroid hormone responsiveness.

To determine whether resistance to insulin or to thyroid hormones rather than an inherent defect in enzyme activity expression account for the age-related changes in lipogenic enzymes, the activities of malic enzymes (ME), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G-6PD) and 6-phosphogluconate dehydrogenase (6-PGD) were assayed in hepatic, retroperitoneal fat and epididymal fat cytosol of male Fischer 344 rats at 3.5, 12 and 25 months of age. The rats were maintained on either regular rat chow with 62% of calories as complex carbohydrates or were given either high glucose or fructose diet with 65.7% of calories provided by glucose or fructose respectively. Additional groups of young and aged rats were treated with L-triiodothyronine (T3) (15 microg/100 g body weight) for 10 days. Treatment with T3 resulted in higher levels of hepatic ME activity regardless of the diet consumed or the age of the rats. T3 had no consistent effect on FAS, G-6PD or 6-PGD activities. ME response to T3 in young rats was significantly greater than that found in aged rats regardless of diet. The age-related decrease in basal hepatic ME activity was not apparent in rats maintained on the high glucose or the high fructose diets, yet the T3 responsiveness of ME in rats maintained on these diets was not normalized. In adipose tissue, with the exception of the age-related changes in basal activity of the lipogenic enzymes, neither T3 nor the feeding of the test diets had any consistent effects. Since insulin resistance induced by high fructose feeding did not reduce hepatic lipogenic enzymes, it is unlikely that the age-related increase in insulin resistance explains the reduced lipogenic enzyme activity in aged rats. However, resistance to thyroid hormone action found in aged rats may partly account for the reduced hepatic lipogenic enzyme activity.

Analysis of radiocontrast-induced nephropathy by dual-labeled radionuclide clearance.

RATIONALE AND OBJECTIVES: This study was devised to develop a method of measuring the acute effects of radiocontrast media on renal function and assessing the relationship of the dose of radiocontrast media infused with the incidence of radiocontrast-induced renal failure. In addition, the drug adenosine phosphate-magnesium chloride (ATP-MgCl2) was evaluated as a renoprotective agent. METHODS: Eighteen patients with pre-existing renal impairment, (serum creatinine greater than 133 mumol/L) were randomized to receive a continuous infusion of ATP-MgCl2 or placebo before and during a radiocontrast procedure. Subjects were monitored with daily serum creatinine and with radionuclide renal clearance studies at baseline, during, and 24 hours after the radiocontrast procedure. RESULTS: There was an initial deterioration in renal clearance in the entire study group (from 44.2 +/- 4.6 to 32.6 +/- 3.9 mL/min, P = .001) which was independent of the dose of radiocontrast infused. There was a persistent deterioration in renal clearance only in those who received greater than 135 mL of contrast media (from 48.6 +/- 7.8 to 37.1 +/- 3.9 mL/min, P = .05). There also was an increase in serum creatinine that persisted only in those subjects who received greater than 135 mL of contrast media (230 +/- 27 to 283 +/- 44 mumol/L, P = .01). CONCLUSION: Persistent deterioration in renal function after radiocontrast administration appears to be dose-dependent and is not prevented by the use of ATP-MgCl2. Radionuclide techniques are useful in monitoring acute changes in renal function during radiocontrast procedures and may be of value in assessing renal impairment in future intervention studies.

Focused assessment of foot care in older adults.

OBJECTIVES: The purpose of this study was to investigate the prevalence and characteristics of foot problems in non-diabetic individuals compared with those in a diabetic population in order to develop recommendations for preventive foot care in older people. DESIGN: Retrospective review of a convenience sample of all patients referred to a Foot Care Service during a 24-month period. SETTING: University Health Sciences Center. PARTICIPANTS: A total of 308 patients aged 33 to 95 years (176 women and 132 men), of whom 183 had diabetes mellitus (DM) and 125 were without DM. INTERVENTION: Each subject had a detailed history of foot care behavior and a thorough foot examination for peripheral neuropathy (PN), peripheral vascular disease (PVD), and foot deformities. PN was evaluated using the Semmes-Weinstein monofilament test. PVD was graded by clinical measures and Doppler examination (ankle:brachial index < 0.8). MEASUREMENTS: Forty-three percent of subjects with diabetes had PN, 32% had PVD, and 19% had both conditions. Eighteen percent of subjects without diabetes had PN, 21% had PVD, and 6% had both. The risk of foot abnormalities in those without DM increased with age (r = .99, P = .0002). Thirty-eight percent of non-diabetic patients older than age 60 had one or more of these major risk factors and would be considered at high risk for the development of foot ulcers or amputation. Ninety percent of the subjects reported inappropriate foot care practices. Forty-seven percent of non-diabetic individuals with PN or PVD wore inappropriate shoes. CONCLUSION: Older individuals without DM are at high risk for foot-related disease and should receive the same foot care screening, education, and follow-up as those with DM. Older people who have PN, PVD, or physical and psychosocial limitations, may require referral to foot care specialists.

Vasopressin response to dehydration in Alzheimer's disease.

Alzheimer's disease is a progressive deterioration of neuropsychological functioning. One of the main neuropathological correlates of the disease is a drop-out of cholinergic neurons within the central nervous system. The neuropeptide that is responsible for water homeostasis and defense against dehydration, vasopressin, is also under direct cholinergic control. Several studies have suggested that in Alzheimer's disease there has been a trend toward lower vasopressin levels than in age-matched controls. In order to improve discrimination of normal from diminished vasopressin levels, nine subjects with Alzheimer's disease (mean age 65 +/- 2 years) and nine age- and sex-matched controls (68 +/- 3 years) underwent a mild provocative challenge of overnight fluid restriction. Individuals with Alzheimer's disease had a greater degree of dehydration, with overnight serum osmolality of 313 +/- 4 vs 300 +/- 3 Mosmol/kg, P = .01, and diminished "thirst" as measured by water ingested in one hour of ad libitum water intake. Eight of the nine with Alzheimer's disease had levels of vasopressin which, by extrapolation, appear to be subnormal for their serum osmolalities, whereas seven of the nine control subjects has vasopressin levels within or above the reference range (P less than .05). Elderly individuals with Alzheimer's disease may be at increased risk of dehydration during periods of fluid restriction due to the loss of normal physiological responses of "thirst" and vasopressin secretion.

Venous thromboembolism and transient thrombocytopenia in a patient with diabetes insipidus treated with desmopressin acetate (DDAVP).

A 22 year-old woman with diabetes insipidus on chronic therapy with desmopressin acetate (DDAVP) developed recurrent venous thromboembolism and transient thrombocytopenia temporally related to the administration of DDAVP. Large increases in plasma von Willebrand factor (vWF), vWF-activity, and relative increases in the concentrations of the larger multimeric forms of vWF-antigen were observed, as well as a plasma factor which sensitized normal platelets to undergo spontaneous aggregation in vitro. Additional studies showed that the patient's plasma retained the platelet aggregation inducing activity after selective removal of vWF by immunoabsorption. The nature of the platelet activating factor and the relationship of this factor and the excessively increased and transiently abnormal vWF to the recurrent venous thromboembolism in this patient remain uncertain. Although the findings do not implicate definitively DDAVP in the elevation of vWF in this patient, it is suggested that its use be considered with caution in patients with diabetes mellitus and increased levels of vWF.

The effect of insulin on glucose transport in rabbit erythrocytes and reticulocytes.

Insulin binding and 3-0-Methylglucose transport have been studied in erythrocyte- and reticulocyte-enriched fractions of blood cells in order to determine if the increased number of insulin binding sites in reticulocytes is associated with a glucose transport response to insulin. In these experiments rabbit reticulocytes demonstrate an eightfold increase in total insulin receptors when compared to erythrocytes. Glucose transport activity in the erythrocyte has Km of 3.2 mM. Reticulocytes demonstrate a saturable glucose transport activity of lower affinity, Km 18.9 mM. Neither the erythrocyte, nor the the reticulocyte glucose transport activity, was capable of an increased response to insulin. the low affinity glucose transport activity in reticulocytes could allow a fourfold increase in facilitated glucose transport at supraphysiological glucose concentrations that might occur in poorly controlled diabetes mellitus.

Foot care assessment in patients with diabetes: a screening algorithm for patient education and referral.

The foot care behaviors of patients with diabetes were assessed by medical history, and their feet were examined for peripheral neuropathy, peripheral vascular disease, foot ulcers, and deformities. The sample consisted of 136 patients (14 with insulin-dependent diabetes and 122 with non-insulin-dependent diabetes). Mean age was 61 years and mean duration of diabetes was 13 years. Peripheral vascular disease was found in 25% of the patients, peripheral neuropathy in 33%, and 13% had both peripheral vascular disease and peripheral neuropathy. Potentially unsafe nail and foot care practices were identified, suggesting that routine diabetes care may not provide sufficient foot care education and follow-up for all patients. A screening algorithm was developed to provide guidelines for individualizing foot care education and referral of patients with diabetic foot disease. The recommendations included annual diabetes foot care assessments and education for those at low risk for foot amputation, intensive foot care education and more frequent follow-up for individuals with peripheral neuropathy or peripheral vascular disease, and referral to a foot care specialty clinic for individuals with peripheral neuropathy and peripheral vascular disease, or foot ulcers.

A model clinical program for patients with diabetes and vision impairment.

A program was developed to improve independence, self-esteem, and glycemic control in patients with diabetes and blindness. Twenty-nine individuals with both insulin-dependent and noninsulin-dependent diabetes mellitus entered 12-week programs that included education focusing on diabetes self-management skills for the visually impaired, monitored exercise sessions, and group support. Glycated hemoglobin values fell from 13.0% +/- 0.6% (SEM) to 11.4% +/- 0.5% (P = .001). Exercise tolerance in a 12-minute walk test improved from 0.48 +/- 0.04 to 0.64 +/- 0.05 miles (P = .001). Marked improvements occurred in psychosocial indices, demonstrated through changes in the Rand Mental Health Index from 155 +/- 6 to 174 +/- 5 (P = .0001), the Rosenberg Self-Esteem Scale from 22 +/- 1 to 19 +/- 1 (P = .001), the Zung Depression Scale from 0.50 +/- 0.02 to 0.44 +/- 0.02 (P = .001), and the Diabetes Self-Reliance Test from 60 +/- 3 to 74 +/- 2 (P = .0001).

Delayed recovery of thyrotropin responsiveness after radioactive iodine therapy for hyperthyroidism.

BACKGROUND: After radioactive iodine therapy for hyperthyroidism, an expected lag in the responsiveness of thyrotropin (TSH) is 60 to 90 days. In our experience, however, many patients seemed to have a more prolonged lag in TSH recovery. METHODS: A retrospective chart review was performed in 58 patients who underwent radioactive iodine therapy for hyperthyroidism (52 with Graves disease, 5 with toxic nodular goiters, and 1 with a toxic adenoma). RESULTS: Forty-nine patients (84%) had appropriate responses of TSH for their level of serum thyroid hormone. Thirty-one became hypothyroid, 12 became euthyroid, and 6 remained hyperthyroid. Nine patients (16%) had a lag in their TSH responsiveness. The TSH remained low for 3 months in 5 patients, for 9 months in 3 patients, and 1 patient had low levels of serum TSH for at least 12 months. CONCLUSIONS: After radioactive iodine therapy for hyperthyroidism, decisions upon further therapy must be based upon the clinical status as well as the serum levels of TSH and thyroid hormones.

Dose-response profile of acarbose in older subjects with type 2 diabetes.

OBJECTIVE: To examine the dose-response relationship of acarbose, an alpha-glucosidase inhibitor, in older subjects with type 2 diabetes. RESEARCH DESIGN: Fourteen subjects with type 2 diabetes who were over 65 years old were studied. Five subjects had been treated with diet alone and 9 were receiving a sulfonylurea. The subjects underwent a meal tolerance test in the presence of varying doses of acarbose (0, 25, 50, and 100 mg) on 4 occasions, each 1 week apart. The test meal was chosen to include food items commonly consumed during breakfast in the United States. The 483-kcal meal consisted of 51% of calories in the form of carbohydrates, 14% protein, and 35% fat. The serum glucose, insulin, and triglyceride levels were measured at 0, 1, and 2 hours after the meal. RESULTS: The postprandial hyperglycemic response to the test meal was significantly reduced with 25 mg of acarbose compared with baseline values. Increasing doses of acarbose to 50 or 100 mg had no significant additional ameliorating effects on postprandial hyperglycemia. Postprandial insulin or triglyceride levels were not significantly altered with single dose acarbose treatment. CONCLUSIONS: It is concluded that the acute efficacy of acarbose is near maximal at 25 mg when the meal size does not exceed 483 kcal and contains only 61 gm of carbohydrates.