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.

Low serum high-density lipoprotein cholesterol in obese subjects with normal serum triglycerides: the role of insulin resistance and inflammatory cytokines.

BACKGROUND: The cause of obesity-related low HDLc in the absence of hypertriglyceridemia is not known. SUBJECTS & METHODS: A total of 32 subjects with a body mass index (BMI)(kg/m(2)) greater than 30 and normal serum triglycerides (<150 mg/dl) were identified. RESULTS: People with low HDLc (n = 16) compared to those with normal HDLc (n = 16) had higher BMI (37.53 +/- 4.54 vs. 33.99 +/- 3.65 kg/m(2), p < 0.021), higher body fat weight (42.59 +/- 9.51 vs. 34.76 +/- 8.7 kg, p < 0.023), and higher insulin resistance index (3.75 +/- 2.51 vs. 1.95 +/- 1.10, p < 0.013). Seven subjects with low HDLc and none of those with normal HDLc, had elevated serum tumor necrosis factor alpha and/or interleukin-6 (p < 0.010). CONCLUSIONS: Low HDLc levels can occur in obesity independently of elevated serum triglycerides and may be secondary to elevated serum levels of inflammatory cytokines.

Possible association between high-dose fluconazole and adrenal insufficiency in critically ill patients.

OBJECTIVE: Whereas the antifungal azole ketoconazole interferes with steroidogenesis and can cause adrenal insufficiency, fluconazole in standard doses is thought to not interfere with cortisol production. The objective was to evaluate the effect of high-dose fluconazole therapy on adrenal function in critically ill patients in an intensive care setting. DESIGN: Descriptive case reports. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Two patients, a 77-yr-old man (case 1) with esophageal cancer and a 66-yr-old woman (case 2) with multiple organ failure developed reversible adrenal insufficiency temporally related to the institution and withdrawal of high-dose fluconazole. INTERVENTIONS: Short cosyntropin (adrenocorticotropic hormone; ACTH) stimulation tests. MEASUREMENTS AND MAIN RESULTS: Two days after high-dose fluconazole in case 1, the serum ACTH level was 121 pg/mL (normal range is 9-52 pg/mL), and the peak cortisol after ACTH stimulation was 15.5 microg/dL (normal response is >or=18 microg/dL). Eleven days after discontinuation of fluconazole, the peak cortisol level after ACTH stimulation was 43.4 microg/dL. Twenty-four hours after high-dose fluconazole in case 2, an ACTH stimulation test had a low peak serum cortisol of 16.8 microg/dL. Fluconazole was withdrawn, and 5 days later, the peak stimulated cortisol was 20.6 microg/dL. CONCLUSIONS: Although fluconazole is the therapy of choice for patients in the intensive care setting with Candida infections, two patients with multiple organ failure who received high-dose fluconazole appeared to develop adrenal insufficiency. Although preliminary and anecdotal, these data suggest a need to further investigate the possibility that high-dose fluconazole might cause adrenal insufficiency in already compromised critically ill patients.

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.

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.

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.

Adrenal insufficiency in an adult on inhaled corticosteroids; recovery of adrenal function with inhaled nedocromil sodium.

BACKGROUND: Whereas oral corticosteroids and high-dose inhaled corticosteroids may be associated with suppression of the hypothalamic-pituitary-adrenal axis, medium-dose inhaled corticosteroids have not been reported to be associated with clinically significant adrenal insufficiency in the adult. OBJECTIVE: A case study of adrenal responsiveness after prolonged medium-dose inhaled corticosteroids and after replacement of steroid therapy by inhaled nedocromil sodium is described. METHODS: Standard 250-microg dose ACTH (cosyntropin) stimulation tests were followed after replacement of inhaled triamcinolone acetonide therapy by nedocromil sodium. RESULTS: A 55-year-old woman who had been on inhaled triamcinolone acetonide, 1600 microg/day for 12 years, presented with symptoms of adrenal hypofunction upon inhaled corticosteroid taper. An ACTH stimulation test confirmed adrenal insufficiency. She was switched to inhaled nedocromil sodium with improvement in her clinical syndrome and normalization of her ACTH stimulation test. CONCLUSION: Withdrawal from prolonged use of inhaled medium-dose corticosteroids may be associated with clinically significant adrenal insufficiency in adults. Steroid sparing agents may be considered for those on long-term inhaled corticosteroid therapy.

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.

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.

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.

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.

Drinking behavior and vasopressin responses to hyperosmolality in Alzheimer's disease.

Individuals with Alzheimer's disease (AD) have been shown to have abnormalities in response to fluid restriction. Twelve subjects with AD and ten elderly controls underwent overnight fluid restriction followed by measurement of plasma and urine vasopressin and serum osmolality. Estimates of "thirst" were determined after one hour of ad libitum water intake. All subjects were tested with a Mini-Mental State Examination (MMSE) and Global Deterioration Scale (GDS). Individuals with AD had a greater degree of overnight dehydration than the elderly control group (serum osmolality 310 +/- 1 vs. 305 +/- 1 mosmol/kg, p = 0.02). There was no difference between the groups in the plasma or urinary levels of vasopressin. There was a direct correlation (r = 0.45, p = 0.03) of the amount of water intake as a measure of "thirst" with the MMSE score as a measure of cognitive functioning. Individuals with advanced cognitive impairment may be at risk of dehydration due to loss of protective "thirst" responses with secondary complications of dehydration.

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.

Personal and family stress in individuals with diabetes and vision loss.

The intrapersonal distress and the impact of diabetes and vision impairment on marital functioning were assessed. Significant degrees of intrapersonal distress were demonstrated by the Beck Depression Inventory, Rosenberg Self-Esteem Scale, and Rand Mental Health Index. Family functioning as assessed by the Family Assessment Device was significantly compromised. Vision impairment was a major stressor in the spousal relationship. Of 18 subjects who had been involved in a committed relationship at the onset of vision impairment, 9 had separated. Separation occurred at a mean of 1.6 years after the vision impairment. Totally blind individuals were at greater risk for separation than those who were legally, but not totally, blind. Psychological intervention was a limited benefit. Studies are necessary to identify the appropriate timing for further interventions.

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.