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Biomedical subjects

B Zinman

Publications and source records attributed to B Zinman.

At least 145 records · Page 8Linked to original sources
PubMed1984

Long term open loop intravenous insulin infusion in type I diabetes: feasibility, problems and promise.

The response of four Type I diabetic patients to long term (1,4,4, and 8 months) intravenous insulin infusion is reported. As compared to their usual subcutaneous depot insulin treatment, glycosylated hemoglobin (HbAl) decreased from 12.2 +/- 0.7 to 8.8 +/- 0.9 (p less than 0.05). However, only 49 to 76.5% of self blood glucose monitoring results were between 60-179 mg/dl range. Although 6.3 to 15.2% of capillary blood glucose levels were less than 60 mg/dl, severe hypoglycemia occurred only on one occasion. Plasma cholesterol, triglyceride and high density lipoprotein all decreased significantly (p less than 0.005). The major motivating factors for participation in this study were: (1) the hope of preventing diabetic complications; (2) the wish for more knowledge about diabetes; (3) a sense of special purpose and (4) a general interest in science and research. Catheter obstruction as a result of insulin aggregation terminated the study in two subjects. A third subject requested the study be stopped primarily because of imposed travel restrictions. In one subject, the study was stopped because of a disrupted personal life and developing depression. Diabetic ketoacidosis or sepsis from the centrally placed intravenous catheter did not occur. Although long term intravenous insulin infusion is feasible in a clinical research setting, insulin aggregation continues to be a major limiting factor. The widespread clinical use of implantable pumps will have to await the development of a suitable insulin formulation.

Adult↗
PubMed1984

Endocrine, cytogenetic and psychometric features of patients with X-isochromosome 46, X, i(Xq) Turner's syndrome: a preliminary study in nine patients.

The 46, X, i(Xq) karyotype of isochromosome for the long arm of the X chromosome has been found to be a frequent structural abnormality in Turner's syndrome. To characterize the endocrine, metabolic, and psychometric features of such patients, nine subjects, aged 12 to 49 years, with this specific cytogenetic abnormality were studied. Although eight of the nine patients had a mosaic chromosome pattern, five had a greater proportion of i(Xq) cells than XO cells, and in four of these the proportion of i(Xq) cells was over 80%. Eight of the nine isochromosomes were metacentric and most had a single C-band. Two subjects were hypothyroid, six had thyroid antibodies present and five had parietal cell antibodies. Oral glucose tolerance testing was abnormal in three and elevated insulin levels were present in an additional two subjects. Psychometric testing showed some discrepancy between verbal and performance I.Q. scores, the performance scores generally being lower. Thus, thyroiditis, insulin insensitivity and diabetes mellitus, parietal cell antibodies, and a relatively low performance I.Q. are found in some of the 46, X, i(Xq) Turner's syndrome patients. The highest thyroid antibodies were present in the four subjects in whom more than 80% of cells were 46, X, i(Xq). Two of these subjects also had diabetes mellitus and three had antiparietal cell antibodies. These findings suggest an association of autoimmune disease with this particular cytogenetic abnormality.

Adolescent↗
PubMed1983

Intravenous infusions of sulfated insulin normalize plasma glucose levels in pancreatectomized dogs.

Sulfated insulin (SI) differs radically from regular crystalline zinc insulin (CZI). To date, SI has been used mainly for the subcutaneous treatment of diabetics with resistance or local allergic reactions to CZI. In this regard, SI exists as a soluble monomer at pH 7.4 and is not inclined to self-association even when agitated and exposed for long periods to materials known to aggregate CZI. To compare its stability and biologic activity when used in conjunction with intravenous infusion pumps, diabetic dogs were infused portally for 140 days with SI and for 140 days with CZI. These studies demonstrated a significant improvement of glycemic control obtainable with SI compared with CZI. Mean +/- SD fasting glycemias were normalized for the SI group (99 +/- 19 mg/dl) and were significantly (P less than 0.001) less than the mean of 148 +/- 64 mg/dl for the CZI group. Mean +/- SD coefficient of variation of the fasting plasma glucose concentrations was 18 +/- 1% for the SI- versus 43 +/- 3% for the CZI-infused dogs, both significantly greater than normal values of 4.5 +/- 0.5%. Basal insulin requirements under these conditions also differed significantly (P less than 0.001). The CZI group received 0.35 +/- 0.07 mU/kg/min compared with 0.20 +/- 0.05 mU/kg/min for the SI group, the former resulted in mean +/- SD plasma levels of 14 +/- 7 microU/ml and the latter resulted in concentrations of 47 +/- 12 microU/ml. Insulin clearance rates were 28 +/- 11 ml/kg/min with CZI compared with 5 +/- 3 ml/kg/min with SI (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Exercise in diabetic man: glucose turnover and free insulin responses after glycemic normalization with intravenous insulin.

The metabolic response to moderate exercise in postabsorptive insulin-dependent diabetics receiving insulin by constant intravenous infusion was compared with that of normal controls. The diabetics were infused with insulin overnight and were normoglycemic (89 +/- 6 mg/dL, controls: 90 +/- 6 mg/dL). With exercise, glycemia remained constant in both groups. In the diabetic subjects, glucose production was 166 +/- 11 mg/min at rest, increased to 230 +/- 27 mg/min with exercise (p less than 0.05), and returned to base line during recovery. Glucose disappearance changed in a synchronous and parallel fashion. In the normal controls, insulin concentration was 0.44 +/- 0.03 ng/mL at rest and decreased significantly with exercise (p less than 0.01) while in the diabetic free insulin was fourfold higher (1.70 +/- 0.32) and did not change with exercise. Lactate increased similarly (twofold) with exercise in both groups. In summary, (i) complete normalization of glycemia, glucose turnover, and the lactate response to postabsorptive exercise can be achieved by the intravenous infusion of insulin adjusted to obtain normoglycemia before the onset of exercise; (ii) this response was obtained with an associated elevation in circulating free insulin which probably reflects the peripheral intravenous route rather than the physiologic (portal) site of insulin administration.

Adult↗
PubMed1982

Metabolic response of normal man and insulin-infused diabetics to postprandial exercise.

Physical exercise is often performed during absorption of meals. We have characterized the metabolic response to 45 min of moderate exercise (approximately 55% of estimated maximal oxygen uptake) beginning 30 min after breakfast in seven healthy controls. Nine insulin-dependent diabetes were studied in an identical manner, with glycemia controlled by a closed-loop "artificial endocrine pancreas" controlled by a closed-loop "artificial endocrine pancreas" (AEP). Responses were compared to those during breakfast without exercise. In the controls, onset of exercise rapidly reversed the rise in both glycemia and insulin (IRI) that occurred with breakfast alone, both returning to fasting levels (glycemia, 80 +/- 3 mg/dl; IRI, 0.38 +/- 0.10 ng/ml). After exercise, small and transient increments occurred (glycemia, 33 +/- 6 mg/dl; IRI, 0.81 +/- 0.15 ng/ml). In the diabetics, prior overnight intravenous insulin normalized fasting glycemia (98 +/- 4 mg/dl), and its postbreakfast excursion was identical to that of controls, as were those of most measured substrates. Similarly, with exercise, glycemia returned rapidly to fasting levels, accompanied by an appropriate decrease in insulin infusion rates. "Free" IRI levels mirrored changes in infusion rates by the AEP, with a decrease in insulin requirement of 30% during exercise as compared to breakfast alone (P less than 0.05). Thus, in both diabetics treated with the AEP and in normals, the responses to postprandial exercise required rapid modulation of insulin delivery. To demonstrate the effect of postprandial exercise on preprogrammed open-loop insulin replacement, four diabetic subjects were studied during breakfast with and without exercise while receiving a fixed open-loop insulin infusion pattern (6.1 +/- 0.7 U over 140 +/- 8 min). The glycemic response to breakfast alone was entirely normalized. However, symptomatic hypoglycemia occurred in all subjects when exercise was initiated 30 min after breakfast. The diabetic responses to closed-loop insulin infusion provide important data in defining the appropriate preprogrammed open-loop insulin infusion pattern for postprandial exercise.

Adult↗
PubMed1982

Responses to mixed meals in pancreatectomized dogs deprived of postprandial insulin.

Insulin plays a central role in metabolic control after a mixed meal. In the absence of adequate meal insulin release, abnormal circulating concentrations of most meal-derived metabolic substrates can be expected. To quantify these abnormalities in depth, responses of six pancreatectomized dogs on long-term intravenous insulin replacement were compared to those of five normal control dogs. Blood samples were drawn hourly for 24 h via a chronic indwelling catheter, and all animals ate a single mixed meal. To establish whether there were route-related differences, insulin was delivered into either the portal or the peripheral circulation of the diabetic animals at constant rates. These insulin infusion rates resulted in premeal fasting normoglycemia and in normal levels of insulin, glucagon, lactate, pyruvate, 3-hydroxybutyrate, nonesterified fatty acids, and 9 of 13 amino acids. In the absence of enhanced meal insulin infusion, the subsequent responses of glucose, lactate, pyruvate, alanine, and 10 of 13 other blood amino acids were exaggerated in terms of both amplitude and duration. Only minor or transient differences were attributable to the routes of insulin infusion. Remarkably, in spite of these abnormal postmeal responses, basal insulin alone (with constant circulating levels) succeeded in restoring all metabolite and hormonal levels during the postabsorptive period 16-23 h after the meal. Thus, with intravenous insulin infusions, the requirements for fasting metabolic normalization may be considered independently of those for metabolic control following caloric intake. It remains to be shown how prolonged deprivation of the postprandial insulin supplement results in metabolic decompensation under these conditions.

Animals↗
PubMed1981

The metabolic and hormonal responses to a mixed meal in unrestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion.

The metabolic and hormonal consequences of long term intravenous insulin replacement were studied in 11 pancreatectomised dogs. Insulin was delivered into the portal circulation of six animals for 164-224 days and into the peripheral circulation of the remainder for 123-365 days. Infusion rates were initially adjusted to achieve normoglycaemia in the fasting (0.37 +/- 0.01 mU Kg-1 min-1 portal; 0.45 +/- 0.03 mU kg-1 min-1 peripheral) and post-prandial states (2.57 +/- 0.07 mU kg-1 min-1 for 7 1/2 h portal; 3.16 +/- 0.18 mU kg-1 min-1 for 7 h peripheral). Animals were fed their usual mixed diet and blood samples were drawn from indwelling catheters at regular intervals for 24 h. A matched group of six normal dogs was similarly studied. Significantly less insulin was needed for glycaemic normalisation with portal (1.05 +/- 0.03 U kg-1 day-1) compared with peripheral (1.27 +/- 0.08 U kg-1 day-1) infusions, but post-prandial insulin levels were not normalised. Glucagon levels were normal and unaffected by the route of insulin infusion. Lactate and pyruvate responses were exaggerated post-prandially in the diabetic compared with the normal dogs. Fasting non-esterified fatty acid levels were suppressed with peripheral but normal with portal insulin infusion. There were only minor differences in the branched chain, essential and other non-essential amino acids except for alanine which was significantly above normal in the diabetic animals. Fasting levels of insulin, lactate, pyruvate and non-esterified fatty acids were normalised only with portal infusion while glucose, glucagon, 3-hydroxybutyrate and most amino acids were normalised regardless of the route of infusion. We conclude that the metabolic regulation achieved with portal insulin replacement is closer to normal than that achieved with peripheral infusion.

3-Hydroxybutyric Acid↗
PubMed1981

Glucoregulatory and metabolic response to exercise in obese noninsulin-dependent diabetes.

The metabolic response to exercise in obese postabsorptive noninsulin-dependent diabetics was compared to that of obese nondiabetics. Exercise consisted of 45 min on a cycle ergometer at 60% maximum oxygen consumption. Six diabetic subjects were studied during oral hypoglycemic therapy and four on diet alone. The sulfonylurea therapy had no effect on the response. Glycemia was elevated at rest in both diabetic subgroups (192 +/- 24 mg/dl for diet alone, 226 +/- 36 mg/dl for sulfonylurea treatment) and a similar fall (35 and 37 mg/dl, respectively) occurred with exercise. In control subjects, glycemia was 86 +/- 4 mg/dl and did not change with exercise. In the diabetics at rest, glucose production was elevated (220 +/- 25 mg/min), whereas the metabolic clearance of glucose was suppressed. During exercise the increase in glucose utilization was similar to that in controls, but glucose production failed to increase significantly, thus accounting for the decline in plasma glucose. At rest, plasma immunoreactive insulin (IRI) was elevated to 0.90 ng/ml in the controls and decreased to 0.65 ng/ml with exercise. In the diabetics IRI was similarly elevated (0.89 ng/ml) but failed to decrease normally with exercise. Lactate, pyruvate, alanine, and free fatty acids increased similarly in diabetics and controls, whereas the increase in 3-hydroxybutyrate during recovery was less in diabetics. The sustained insulinemia, the basal overproduction of glucose, and hyperglycemia itself may all contribute to the observed differences in glucose flux during exercise in noninsulin-dependent diabetics.

Adult↗