Implantable insulin infusion devices.
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Humans↗
Biomedical subjects
D M Nathan
Publications and source records attributed to D M Nathan.
Intensive conventional and insulin pump therapies in adult type I diabetes. A crossover study.
We examined the relative efficacy of two modes of insulin therapy in five patients with insulin-dependent diabetes. Using a crossover protocol, therapy with multiple insulin injections was compared with the use of continuous subcutaneous insulin infusion (pump therapy); both therapies were regulated by home blood glucose monitoring. Although both therapies were equally effective during 2 to 4 days of inpatient management, pump therapy was clearly superior in the outpatient setting. Mean plasma glucose and hemoglobin A1c concentrations and the frequency of hypoglycemic reactions were significantly less with pump therapy despite apparently equal compliance with both therapies. We conclude that in compliant adult patients with type I diabetes continuous insulin infusion is more effective in achieving normalization of plasma glucose concentration than intensified conventional therapy in the outpatient setting. Although these patients found pump therapy preferable to intensive conventional therapy, the superiority of pump therapy is not explained by this bias. Whether these results are applicable in a more standard treatment setting remains to be established.
Adult↗
Rapid method for eliminating labile glycosylated hemoglobin from the assay for hemoglobin A1.
The irreversible formation of stable glycosylated hemoglobin proceeds through a labile intermediate that is indistinguishable, by most methods, from the stable glycosylated product. The inclusion of the labile intermediate, which changes acutely with acute blood glucose changes, detracts from the utility of the assay as an index of chronic glucose concentration. We have developed a rapid, reliable chemical method for eliminating the labile intermediate: a 30-min incubation of whole-blood samples with semi-carbazide (30 mmol/L) and aniline (12 mmol/L) at pH 5 and 38 degrees C. The semicarbazide serves as a glucose trap; the transfer of glucose from the labile glycosylated hemoglobin to the semicarbazide is catalyzed by the acidic pH and aniline. This treatment is effective in the three most commonly used assays: "high-performance" liquid chromatography, electrophoresis, and a minicolumn kit.
Aniline Compounds↗
A rapid chemical means for removing labile glycohemoglobin.
We have devised a rapid and convenient method of eliminating the contribution of labile glycosylated hemoglobin in the hemoglobin A1 assay. The procedure requires a 30-min incubation of erythrocytes in 30 mM semicarbazide and 12 mM aniline (pH 5, 38 degrees C). This chemical means of eliminating the labile fraction is as effective as a 14-h incubation in isotonic saline as measured with high-pressure liquid chromatography or electrophoresis methods. The removal of the labile glycosylated hemoglobin fraction preserves the assay as a reliable index of chronic metabolic control.
Aniline Compounds↗
U-500 insulin in the treatment of antibody-mediated insulin resistance.
Three patients with antibody-mediated insulin resistance were treated with U-500 regular insulin subcutaneously. Insulin requirements decreased dramatically (55% to 75%) when therapy was changed from U-100 NPH pork to equivalent doses of U-500 regular pork insulin. There was no difference in antibody affinity for the insulin in these two preparations as shown by competition experiments. These observations demonstrate that U-500 insulin is a useful alternative in the treatment of antibody-mediated insulin resistance. The mechanism for this effect is yet to be determined.
Adult↗
Insulins for insulin resistance.
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Humans↗
Labile glycosylated hemoglobin contributes to hemoglobin A1 as measured by liquid chromatography or electrophoresis.
The utility of glycosylated hemoglobin (HbA1) measurement as an index of chronic control in diabetes can be adversely affected by interference from a labile glycosylated fraction that changes rapidly with acute changes in blood glucose concentration. I used a "high-pressure" liquid-chromatographic assay and a newly developed electrophoretic assay to quantitate the contribution of this labile fraction. If erythrocytes are incubated at 22 degrees C in isotonic saline for 12 h before hemolysis, the labile fraction is eliminated. Its contribution is similar as measured by both assays: 2-3.5% of total HbA1 in normal cells and 7-9.5% in diabetic cells. A 3-h incubation of erythrocytes with glucose produces acute changes in apparent HbA1 concentrations by both assays, but such changes can be eliminated by the incubation in saline. Although current methods are time consuming, the labile glycosylated hemoglobin must be removed when the sample is prepared for HbA1 measurement by liquid chromatography and electrophoresis if results are not to be factitiously high.
Blood Glucose↗
Gastrinoma and phaeochromocytoma: is there a mixed multiple endocrine adneoma syndrome?
A 51 year old man was found to have a malignant gastrinoma. A phaeochromocytoma had been diagnosed and removed previously. The occurrence of these two rare tumours in a single patient suggests the possibility of a crossover between MEA I and MEA II. Reported cases of the "crossover syndrome" are reviewed and the status of this phenomenon as a syndrome is discussed.
Adrenal Gland Neoplasms↗
Simultaneous nosocomial outbreaks caused by multiply resistant Klebsiella pneumoniae types 2 and 30.
Two simultaneous Klebsiella pneumoniae outbreaks resistant to multiple antibiotics are reported. The closely related strains were distinguished by comparing the zone diameters obtained by disk diffusion susceptibility testing but not by interpretations of susceptible, resistant, or intermediate. Similar conclusions were made when minimal inhibitory concentrations were considered. The separation was subsequently confirmed by capsular serotyping into types 2 and 30. The data presented suggest that routine antimicrobial susceptibility patterns obtained from disk diffusion and/or minimal inhibitory concentrations may serve as an inexpensive and reliable typing system for epidemiological investigations.
Amikacin↗
Acute methemoglobinemia and hemolytic anemia with phenazopyridine: possible relation to acute renal failure.
An 18-year-old woman with no prior history of renal or hematologic dysfunction developed severe, acute methemoglobinemia after an overdose of phenazopyridine hydrochloride (Pyridium). The methemoglobinemia was reversed acutely with methylene blue, and during the course of ten days, the patient developed a hemolytic anemia with "bite cells" and acute renal failure. The patient recovered fully with conservative management. Several putative pathophysiologic explanations for the development of methemoglobinemia, hemolytic anemia, and renal failure following oxidative stress are considered and include a direct toxic effect on the renal tubules or methemoglobin-caused damage. Renal failure as a complication of phenazopyridine-related methemoglobinemia and hemolytic anemia should be borne in mind in cases of overdosage with this common drug.
Acute Kidney Injury↗
The limited clinical value of home urine testing by diabetic patients.
To investigate the value of home urine glucose testing in assessing chronic diabetic glucose control, the authors compared patients' glycosuria patterns with their mean blood glucose (MBG) levels calculated from glycosylated hemoglobin (Hb Alc). One hundred and twenty-one patients who regularly checked their urines reported on the frequencies of glycosuria over the preceding ten weeks. There was substantial overlap in the glycosuria patterns of patients at different levels of MBG. Glycosuria was not detectable in only 44% of patients with good control (MBG less than or equal to 150 mg/dl). The probability of such good control given no glycosuria was only 26%. Similarly, frequent glycosuria was reported by only 27% of patients with poor control (MGB greater than 250 mg/dl). The probability of such poor control given frequent glycosuria was only 34%. Because home urine testing cannot reliably identify good or poor control, it has a very limited role in assessing patients' chronic glucose control.
Adolescent↗
Triglyceride levels affect cognitive function in noninsulin-dependent diabetics.
Noninsulin-dependent diabetes mellitus (NIDDM) is associated with decrements in several cognitive functions. Among the variables that apparently contribute to the decline in cognitive performance is poor glucose control, as measured by hemoglobin A1c. Elevated levels of triglycerides in diabetics may also contribute to this cognitive decline through the increased incidence of atherosclerosis in these patients. The authors examined the relationship between triglycerides and cognitive performance in 246 NIDDM outpatients, aged 55-74 years. The relationship between triglyceride levels and performance on three cognitive tasks and on a test of reaction time was measured. Elevated levels of triglycerides were associated with significant decrements in performance on the digit symbol substitution test, digit span (backward) test, and on a reaction time measure. High levels of triglycerides, independent of chronic glucose control, appear to contribute to the decreased ability to perform short-term memory tasks in NIDDM.
Blood Glucose↗
Age and diabetes related changes in verbal fluency.
Non-insulin-dependent diabetes mellitus is present in 7-10% of the aged. This disease appears to be associated with an acceleration of the aging process and results in compromised performance on learning and memory tasks. The present study used a verbal fluency test to examine semantic memory performance in two age groups (55-64 and 65-74 years) of diabetic subjects and controls. In addition, immediate and secondary memory were also examined using the digit symbol and digit span tests and a serial learning task. Results showed that digit symbol performance was poorer for older subjects and diabetics while serial learning was poorer only for diabetic subjects. However, the number of words generated on the verbal fluency test was similar for all groups. Qualitative analyses of the verbal output revealed that older subjects and diabetics produced the greatest number of previously recited words (repetitions). Repetitions may signal a failure to adequately monitor behavior which in turn could contribute to cognitive decline.
Aged↗
Single-void urine samples can be used to estimate quantitative microalbuminuria.
The excretion of small quantities of urinary albumin (microalbuminuria) may predict renal failure in diabetes. The measurement of microalbuminuria with radioimmunoassays has been based on 24-h, overnight, and 3- to 4-h collections. To determine whether single-void urine samples can be used to estimate 24-h excretion, we compared the results of 24-h outpatient urine collections with single-void samples corrected for creatinine from diabetic and nondiabetic subjects. The overall correlation of single-void sample results expressed as microgram albumin per milligram creatinine with 24-h excretion (mg/24 h) was excellent (r = .82, P less than .001). More important, in the diabetic patients the sensitivity and specificity of detecting 24-h microalbuminuria in the abnormal range were at least 94 and 96%, respectively. Single-void urine specimens adjusted for creatinine discriminate between normal and abnormal levels of microalbuminuria, as determined in 24-h urine collection, with high specificity and sensitivity.
Adult↗
The glycemic index: meat and potatoes or just gravy?
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Blood Glucose↗
Basal-rate intravenous insulin infusion compared to conventional insulin treatment in patients with type II diabetes. A prospective crossover trial.
We compared continuous basal-rate intravenous insulin infusion, delivered by means of a totally implantable pump, to two types of conventional insulin administration in patients with type II (non-insulin-dependent) diabetes in a prospective crossover trial. Ten patients entered the study, and 5 completed all three 8-mo study periods. When results from the infusion study period were compared with results from the period involving single daily injections of ultralente insulin, significant improvements were noted in the pump arm in glycosylated hemoglobin concentrations (which were nearly normal), M-component values, mean daily outpatient fasting blood glucose concentrations, mean fasting and 24-h blood glucose concentrations during an inpatient 24-h glycemic profile, and urinary glucose concentrations. When the pump arm was compared to a period of single daily injections of lente insulin, three of six monthly mean fasting blood glucose concentrations and overall means for the entire study period were significantly lower during the pump arm than during the lente arm; in addition, significantly fewer hypoglycemic reactions were noted during infusion therapy than during lente therapy. Finally, mealtime free-insulin and C-peptide excursions appeared to be greater during infusion treatment when compared with lente or ultralente treatment. In the 50% of patients who completed the study, it appeared that significant improvements in glycemic control could be achieved by simple basal-rate intravenous insulin infusion compared with conventional treatment with single daily injections of ultralente or lente insulin without an increased incidence of symptomatic hypoglycemia.
Adult↗
Nesidioblastosis associated with insulin-mediated hypoglycemia in an adult.
Nesidioblastosis, the process of differentiation of pancreatic islets from ductular epithelium, is a well-described cause of insulin-mediated hypoglycemia in neonates and infants, but not in adults. A 58-yr-old woman with characteristic clinical features of fasting hypoglycemia had inappropriately elevated plasma immunoreactive insulin levels during symptomatic episodes of fasting hypoglycemia. Angiography, palpation at laparotomy, and resection of the distal three-quarters of the pancreas provided no evidence of a tumor. Pathologic examination of the resected pancreas revealed the findings of nesidioblastosis, i.e., budding of islets from the wall of ductules, and also increased number and size of islets and abnormal shape and location of islets. An entire spectrum of islet cell abnormalities including nesidioblastosis can cause insulin-mediated hypoglycemia in adults, as it does in neonates and infants.
Adenoma, Islet Cell↗
Successful treatment of extremely brittle, insulin-dependent diabetes with a novel subcutaneous insulin pump regimen.
Brittle, insulin-dependent diabetic patients with extremely labile glucose control requiring frequent hospitalizations were treated with a continuous subcutaneous insulin infusion delivered with a programmable pump. As reported by others, the patients did not improve with a regimen of preprandial boluses superimposed on a continuous single-rate infusion. However, they demonstrated dramatic clinical and metabolic improvement with a modified pump regimen that delivered a variable square-wave insulin infusion and avoided any boluses. These very difficult patients can benefit by insulin pump therapy.
Adult↗