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Purpose: To study the use and cost of bedside capillary glucose testing in a large teaching hospital., Patients and Methods: In a prospective study of 40 inpatient units and 10 outpatient units at Massachusetts General Hospital, records were maintained by each unit of the date, time, operator, and results of patient and quality control tests. Cost analysis was performed using data from time studies, test tallies in logbooks, and hospital administration records., Results: The number of glucose meters in the hospital increased from 10 to 54 over a 2-year period. In 1992, 67,596 tests were performed by the bedside method, representing 30.7% of all glucose measurements performed in the institution. The majority of tests (94.7%) were performed on inpatients, and 10.2% of all hospital admissions underwent bedside glucose testing. The impact on the number of glucose tests performed in the clinical laboratories was minimal, indicating that bedside glucose testing was added as an extra test rather than as a substitute for laboratory-based glucose measurements. The cost of bedside glucose testing was $4.19 per test compared with $3.84 in the clinical laboratory. The cost varied from one unit to another (median $5.52, range $3.08 to $48.16), an effect largely attributed to the difference in the volume of tests performed by different units. In seven high-volume units the cost per test was lower than the corresponding value in the laboratory. The cost of bedside glucose testing included labor (80.2%) and supplies (19.8%). The percent of costs attributed directly to patient testing was 57.7%, whereas the costs for all other related activities (training, quality control, and quality assurance) was 42.3%., Conclusions: Bedside capillary glucose testing is a rapidly expanding technology and is performed on a significant percentage of hospital admissions. Bedside glucose testing is not inherently more expensive than centralized laboratory measurements but implementation on inefficient care units with low utilization can add substantially to the cost. Much of the excess cost of the bedside method can be attributed to the high costs of quality control and quality assurance, training, and documentation.

Purpose: To study the implementation of bedside capillary glucose monitoring using a hospital-wide quality control (QC) program., Methods: A prospective study of QC performance in 7 outpatient and 39 inpatient treatment units was performed in a large teaching hospital over a 2-year period. Approximately 800 nurses were trained to perform bedside capillary glucose monitoring (Accu-Chek II, Boehringer-Mannheim, Indianapolis, IN). An eight-point QC program was instituted including proficiency testing, instrument maintenance, performance of daily controls, storage of reagent strips and supplies, instrument calibration, and documentation procedures., Results: Comparison of laboratory and bedside test results (split-sample proficiency testing) revealed Y = 1.004X + 7.26, r = 0.95, with a mean percent difference of -4.2% (p < 0.001). Less than 7% of results fell outside +/- 20% of the laboratory results. QC scores (0 = worst to 4 = best), based on adherence to the QC program, improved from 0 on the first inspection to 3.7 +/- 0.17 by the 11th inspection. The most common QC deficiencies were failure to perform split-sample testing (41.4%) and failure to perform instrument maintenance (30.2%). Significant differences were noted in the QC performance of different types of medical services. During the 2-year study period, the total number of glucose assays performed in the clinical laboratories decreased by 22.2% concurrent with initiation of bedside testing. The number of instruments in the hospital increased from 10 to 46., Conclusions: Bedside capillary glucose assays can be widely implemented in large hospitals with an acceptable degree of accuracy. QC programs with frequent inspections are necessary to identify units that function inadequately, and a formal disciplinary policy is required to ensure compliance with the program.

Objective: To evaluate the ability of diabetologists to screen diabetic patients for diabetic retinopathy., Research Design and Methods: Comparison of eye examination performed by diabetologists with direct ophthalmoscopy through an undilated pupil and by ophthalmologists through a dilated pupil with seven-field stereoscopic fundus photography (gold standard). The study consisted of 67 insulin-dependent and non-insulin-dependent diabetic outpatients attending a diabetes clinic., Results: On the basis of fundus photography, patients were classified as having no or insignificant (30%), minimal (31%), moderate (24%), or severe (15%) retinopathy. The diabetologists and ophthalmologists performed similarly in their ability to classify severity of diabetic retinopathy accurately. When no or insignificant retinopathy (isolated microaneurysms only) was detected by examination, clinically significant retinopathy detected by fundus photography was highly unlikely (less than 5%). On the other hand, if more than isolated microaneurysms were seen on examination, all examiners missed more severe lesions detected by fundus photography. Patients with corrected visual acuity worse than 20/30 had a high likelihood (100%) of moderate or severe retinopathy., Conclusions: Motivated well-trained diabetologists can screen for diabetic retinopathy. The absence of detectable lesions by direct ophthalmoscopy indicates that automatic referral to an ophthalmologist is not necessary. However, if any level of retinopathy is detected or corrected acuity is worse than 20/30, referral to an ophthalmologist is required. In this setting, fundus photography is advised because it is the most sensitive means of detecting clinically significant retinopathy. If other nonophthalmologists can be trained to achieve similar results, current recommendations for ophthalmologic referral that require annual ophthalmologic examinations for most diabetic patients may need to be reconsidered.

Non-insulin-dependent diabetes mellitus is predominantly a disease of aging, with more than 70 percent of non-insulin-dependent (type II) diabetic patients older than 55 years of age. The prevalence of macrovascular, microvascular, and neurologic complications in outpatients with type II diabetes between the ages of 55 and 74 was compared with that in a similarly aged nondiabetic group of patients. The association between duration of diabetes, hypertension, age, and other putative risk factors that are prevalent in this elderly diabetic population and the occurrence of complications was explored. This cross-sectional survey confirmed a significant increase in retinopathy, neuropathy, impotence, and macrovascular complications in patients with type II diabetes. Within the diabetic population, duration of disease was associated with the occurrence of retinopathy and neuropathy, but not associated with such macrovascular complications as coronary artery disease. Gender, type of therapy, and previously identified risk factors for vascular disease such as hypertension had little impact on the prevalence of complications in this population. The notion that type II diabetes in the elderly represents "mild" diabetes with regard to complications must be discarded. Further identification of risk factors within this diabetic population may suggest therapeutic approaches that will prevent or ameliorate the development of complications.

We investigated the pathophysiology of fasting hypoglycemia associated with large tumors of mesenchymal origin. We studied two patients with symptomatic fasting hypoglycemia (plasma glucose, 1.92 and 2.03 mmol/L) and a large mesenchymal neoplasm. Before therapy, the plasma insulin-like growth factor II (IGF-II) level measured by RIA was elevated (1879 and 1084 micrograms/L; normal range, 358-854 micrograms/L), the serum GH response to hypoglycemia was impaired, and the plasma IGF-I level was low in both patients. After treatment of the tumor, all of these abnormalities resolved in both patients. Northern blot analysis of tumor RNA revealed extremely high levels of IGF-II mRNA (greater than 100-fold higher than those in normal adult liver). Tumor fragments released IGF-II into tissue culture medium (2.1 and 7.2 micrograms IGF-II/g tissue.24 h). These findings indicate that secretion of IGF-II into the circulation by the tumor was the likely source of the elevated plasma IGF-II levels. We suggest that the primary event in tumor-induced hypoglycemia is overproduction of IGF-II by the tumor, which gives rise to hypoglycemia by a dual mechanism: increased glucose utilization mediated by the insulin-like actions of IGF-II and inhibition of GH secretion.

Study Objective: To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus., Design: Randomized, double-blind, placebo-controlled trial with a 9-month treatment period., Setting: University hospital., Patients: Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone., Interventions: Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia., Measurements and Main Results: Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin., Conclusions: Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.

Non-insulin-dependent (type II) diabetics over the age of 55 comprise most of the diabetic population and are at considerable risk for the development of both macrovascular and microvascular complications. We studied the prevalence of retinopathy and its association with putative risk factors for its development in an elderly (55- to 75-yr-old) population of type II diabetics. Our cross-sectional analysis revealed that duration of diabetes and hemoglobin A1c (HbA1c) concentration were the two major predictors of the presence of retinopathy. Duration effect was seen after 10 yr of diabetes, whereas HbA1c effect was linear over its entire range. Hypertension, which has been reported to be a risk factor for microvascular disease in younger diabetic patients, was not associated with retinopathy in the older type II population. Multiple logistic regression analysis revealed that both the duration of diabetes and HbA1c remained significant independent determinants of retinopathy even after taking age and blood pressure into account. Our results support an etiologic role for metabolic control in the development of retinopathy in the elderly type II population.

The accuracy of capillary blood glucose monitoring has been well demonstrated when applied by patients in the outpatient setting or by specially trained nurses on inpatient diabetes units. In order to determine the applicability of this technique in the more general hospital setting, a program was initiated for instructing general staff nurses in the use of Chemstrips bG strips and the Accu-Chek bG meter. As a pilot study, nurses on four general medical and surgical hospital floors performed capillary glucose determinations within 15 minutes of the drawing of venous blood samples for determination of plasma glucose in the hospital's Chemistry Laboratory. Two hundred ten paired measurements were made by 31 nurses. Linear regression analysis yielded a Pearson correlation coefficient of 0.96 between bedside and laboratory glucose measurements. The mean percent deviation between the two values was 7.9 percent. Acceptance by both nurses and patients was high. Properly supervised capillary glucose monitoring can provide a valuable adjunct to the care of hospitalized patients with diabetes.

Double-stranded complementary DNAs were constructed enzymatically from polyadenylated RNA extracted from pituitary glands of ovariectomized rats, were inserted into the Pst I site of plasmid pBR322 and were cloned in Escherichia coli chi 1776. Cloned cDNAs encoding the precursor to the alpha subunit (pre-alpha) of the glycoprotein hormones were identified by hybridization with a restriction fragment of a previously cloned and sequenced cDNA encoding the precursor to the alpha subunit of mouse thyrotropin (Chin, W. W., Kronenberg, H. M., Dee, P. C., Maloof, F., and Habener, J. F. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 5329-5333). The DNA sequences of the two largest rat cDNA inserts (591 and 554 base pairs) were determined and the amino acid sequence of the rat pre-alpha subunit was deduced from these sequences. The composite sequence determined from these cDNAs spans 610 base pairs, or almost the entire length of the messenger RNA (mRNA) of 800 bases, when account is taken of the 3' poly(A) tract. The rat alpha precursor consists of a 24 amino acid leader sequence and a 96 amino acid alpha subunit apoprotein. The amino acid homologies between the rat and mouse, and between the rat and human sequences are 95% and 74%, respectively. Nucleotide homologies between the rat and mouse cDNAs in the coding and untranslated regions are 94% and 80%, respectively. This cloned cDNA will be applied to analysis of the structure of the rat alpha subunit gene(s) and of the regulation of alpha subunit gene expression.

We describe a patient with type I diabetes mellitus and hypothyroidism who developed frank adrenocortical insufficiency while receiving a high-dose ketoconazole therapy for keratitis caused by Acanthamoeba species. While impaired cortisol responses to corticotropin and mildly symptomatic hypoadrenalism have been described previously with ketoconazole therapy, to our knowledge, this case represents the first documented article of an actual adrenal crisis associated with this drug. Two reasons are postulated for the development of this complication in our patient: high-dose ketoconazole therapy given in divided doses during the day, and a possibly impaired central response to stress because of hypothyroidism. Our article points to the need to monitor patients treated with high-dose ketoconazole for adrenal insufficiency, particularly if associated illnesses are present that may impair an adequate stress response.

Animal studies strongly support the notion that the microvascular complications of diabetes are a consequence of the metabolic derangements. The evidence from human studies is not nearly as persuasive, but controlled prospective clinical trials are examining this issue more incisively than has been possible previously.

We investigated the effect of ice cream ingestion on blood glucose control in conventionally treated and intensively treated insulin-dependent (type I) diabetic patients. After the ingestion of 100 g of ice cream, plasma glucose excursions as measured by the peak increment (90 +/- 30 mg/dL) and area under the curve (166 +/- 59 mg/dL X hour) were modest and not significantly different between the subgroups of intensively treated and conventionally treated diabetics. A small dose (3 to 5 units) of rapid-acting insulin given 30 minutes before ingestion of ice cream reduced the modest plasma glucose excursion. A modest amount of ice cream may be included in weight-maintaining diets of insulin-dependent diabetics. Small doses of rapid-acting insulin prevent any adverse effect of the ice cream on blood glucose control.

A suitable placebo for NPH insulin has not previously been available for clinical investigation. A series of organic and inorganic compounds were formulated as insulin placebos and analyzed according to the following criteria: (1) degree of visual similarity to insulin, (2) stability, (3) absence of local side effects, and (4) clinical safety. Dilute suspensions of cortisone acetate (1.25-2.5 mg/ml) were found to fulfill the criteria as acceptable insulin placebos. Placebo-controlled studies with NPH insulin can now be performed.

We have determined the nucleotide sequences of cDNAs encoding the precursor of the beta subunit of rat lutropin, a polypeptide hormone that regulates gonadal function, including the development of gametes and the production of steroid sex hormones. The cDNAs were prepared from poly(A)+ RNA derived from the pituitary glands of rats 4 weeks after ovariectomy and were cloned in bacterial plasmids. Bacterial colonies containing transfected plasmids were screened by hybridization with a 32P-labeled cDNA encoding the beta subunit of human chorionic gonadotropin, a protein that is related in structure to lutropin. Several recombinant plasmids were detected that by nucleotide sequence analyses contained coding sequences for the precursor of the beta subunit of lutropin. Complete determination of the nucleotide sequences of these cDNAs, as well as of cDNA reverse-transcribed from pituitary poly(A)+ RNA by using a synthetic pentadecanucleotide as a primer of RNA, provided the entire 141-codon sequence of the precursor of the beta subunit of rat lutropin. The precursor consists of a 20 amino acid leader (signal) peptide and an apoprotein of 121 amino acids. The amino acid sequence of the rat lutropin beta subunit shows similarity to the beta subunits of the ovine/bovine, porcine, and human lutropins (81, 86, and 74% of amino acids identical, respectively). Blot hybridization of pituitary RNAs separated by electrophoresis on agarose gels showed that the mRNA encoding the lutropin beta subunit consists of approximately 700 bases. The availability of cDNAs for both the alpha and beta subunits of lutropin will facilitate studies of the regulation of lutropin expression.

Polyadenylated RNA prepared from pituitary glands of normal and castrate rats was translated in membrane-free heterologous cell-free systems derived from wheat germ and rabbit reticulocytes. Sodium dodecyl sufate (SDS)-polyacrylamide gel electrophoresis and autoradiography demonstrated a major [35S]methionine-labeled translation product of castrate pituitary mRNA with apparent Mr = 14,000. This Mr = 14,000 product was specifically immunoprecipitated by anti-sera to the alpha subunit of rat and bovine luteinizing hormone (LH alpha) and was much reduced in the translation products of normal pituitary RNA. Additional minor translation products of normal pituitary RNA. Additional minor translation products with apparent Mr = 15,000 and 16,000 were identified by immunoprecipitation with antisera to rat LH beta and to the beta subunit of rat follicle-stimulating hormone (FSH beta), respectively. The immunological identity of the alpha, LH beta, and FSH beta precursors was confirmed by successful competition of these immunoprecipitation reactions by unlabeled homologous LH alpha, LH beta, and FSH, respectively. These results indicate that the gonadotropin subunits are synthesized as precursors from separate mRNAs. This system is responsive to endocrine manipulations and is appropriate for studies of the regulation of gonadotropin biosynthesis.

Polyadenylated RNA prepared from pituitary glands of ovariectomized rats was translated in heterologous cell-free systems derived from wheat germ and rabbit reticulocytes in the absence and in the presence of pancreatic microsomal membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that the major 14,000-dalton product immunoprecipitated by antisera to the alpha subunit of rat and bovine luteinizing hormone from membrane-free translations was processed to a major 21,000-dalton and a minor 17,000-dalton product in the presence of microsomal membranes. These membrane-dependent products were sensitive to cleavage by the glycosidase endo-beta-N-acetylglucosaminidase H, but the 14,000-dalton product was resistant. The 21,000-dalton product was sequestered within the microsomal vesicles as shown by its resistance to limited proteolysis capable of digesting the 14,000-dalton precursor. Glycosylated products with apparent Mr = 18,000 and 17,000 were identified from membrane-supplemented translations by immunoprecipitation using antisera to the beta subunit of rat luteinizing hormone. The immunological identity of the glycosylated subunits of luteinizing hormone was confirmed by showing competition of the immunoprecipitation reactions with unlabeled subunits.