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Biomedical subjects

A H Rubenstein

Publications and source records attributed to A H Rubenstein.

At least 127 records · Page 7Linked to original sources
PubMed1979

The infant of the diabetic mother: correlation of increased cord C-peptide levels with macrosomia and hypoglycemia.

C peptide is secreted by pancreatic beta cells in amounts equimolar with insulin, and its levels provide a direct indication of endogenous fetal levels of insulin despite the presence of maternal insulin antibodies. To determine the presence of hyperinsulinemia and its relation to the development of complications in infants of diabetic mothers, we measured cord serum levels of C peptide in 79 infants of diabetic mothers and 62 infants of nondiabetic mothers. Infants of diabetic mothers had higher cord levels of C peptide, which were significantly associated with neonatal hypoglycemia and macrosomia (P less than 0.001) but not with hyaline-membrane disease. Cord levels of C peptide in infants of diabetic mothers were elevated at the earliest gestational age studied (less than 34 weeks) and were directly related to the severity of maternal diabetes, as assessed by the White classification. We conclude that hyperinsulinemia is present in infants of diabetic mothers and that it is related to some major complications in such infants.

Birth Weight↗
PubMed1979

Detection and possible functional influence of antibodies directed againt the pancreatic islet cell surface.

Antibodies directed towards determinants on the surface of rat islet cells can be detected qualitatively by the indirect immunofluorescence or quantitatively by a specific radioassay for IgG. Antibodies are found in insulin-dependent diabetics or in rabbits immunized with islet cells. Such antibodies may affect the B-cell function as indicated by the inhibition of incorporation of radioactive leucine into proinsulin/insulin in vitro.

Animals↗
PubMed1979

Use of a glucose controlled insulin infusion system (artificial beta cell) to control diabetes during surgery.

An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose +/- SEM: 185 +/- 16 mg/dl) and, to a greater degree, diabetics (247 +/- 36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p less than 0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128 +/- 21 mg/dl) as normal subjects receiving saline (110 +/- 7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.

Blood Glucose↗
PubMed1979

Metabolic control in diabetic patients: assessment by hemoglobin A1 values.

Hemoglobin A1 concentrations were measured in 230 patients with diabetes mellitus. Diabetic patients controlled by diet alone had significantly lower HbA1 levels compared to the insulin or oral hypoglycemic treated groups. Only 13% of insulin-treated patients had HbA1 levels below 10%, while 26% of the oral agent treated group and 70% of the diet treated group fell into this range. The HbA1 levels correlated with fasting and nonfasting plasma glucose concentrations. However, in certain patients, discrepant results between these two variables were found. Hemoglobin A1 was measured on three or more occasions in 60 patients over a 1-yr period. An improvement was noted in 40%, no change in 38%, and a deterioration in 22%. Hemoglobin A1 measurements have proved to be useful in the follow-up and treatment of diabetic patients.

Adolescent↗
PubMed1979

Familial nesidioblastosis: severe neonatal hypoglycemia in two families.

Severe neonatal hypoglycemia with pathologic findings of diffuse nesidoblastosis of the pancreas is described in five children of both sexes from two families with unaffected parents. This appears to represent an autosomal recessive disorder of pancreatic development. Despite extensive testing, the diagnosis of hyperinsulinism was difficult in the index case of each family and delayed definitive treatment. Medical therapy with steroids and diazoxide was unsuccessful; pancreatectomy was required to treat persistent hypoglycemia. An abnormality of circulating glucagon found in one child with this disorder suggested that hyperinsulinism may not be the sole hormonal imbalance present, but rather that this disease is one of generalized disturbance of islet cell function. The history of severe, persistent neonatal hypoglycemia in an older sibling should lead the physician to investigate subsequent children for the presence of asymptomatic hypoglycemia.

Chromosome Aberrations↗
PubMed1979

Evaluation of insulin secretory capacity in diabetes mellitus.

The capacity of the pancreatic beta cells to secrete insulin can be evaluated in vivo by measurement either of circulating immunoreactive insulin or of C peptide, a by-product of insulin synthesis. Evaluation of serum levels is complicated, however, by the variable degradation rates and distribution spaces of these peptides. Also, interpretation of peripheral vein concentrations of insulin, and perhaps C peptide, is more difficult because of hepatic catabolism. Quantitation of these peptides in the urine may provide an integrated measure of insulin secretion. In insulin treated diabetic patients who develop circulating insulin antibodies, beta cell secretory capacity may be assessed by C peptide measurement, or by techniques that allow separate determinations of "free" and "total" insulin. A variety of stimulatory tests may be used to investigate insulin secretory capacity.

Adult↗
PubMed1979

Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.

Familial hyperproinsulinemia is an autosomal dominant defect that is associated with strikingly elevated levels of serum proinsulin-like material. Our studies show that trypsin converts familial hyperproinsulinemia proinsulin to insulin more slowly than it converts a 131I-labeled porcine proinsulin marker. Molar yields of insulin indicated that the material may be an intermediate proinsulin. Studies with two human C-peptide antisera that differ in their relative immunoreactivity with human C-peptide and proinsulin showed that the two antisera reacted equally with familial hyperproinsulinemia proinsulin, suggesting that it is a partially cleaved proinsulin intermediate. Sulfitolysis of highly purified material to break the inter- and intra-chain disulfide bridges and subsequent adsorption on a specific B-chain antibody covalently bound to Sepharose beads showed that the C-peptide was still connected to the B-chain. These data indicate that familial hyperproinsulinemia proinsulin is normally cleaved at the C-peptide-A-chain linkage site. A structural abnormality appears to underlie familial hyperproinsulinemia proinsulin, which impairs its cleavage at the B-chain-C-peptide linkage site.

Amino Acid Sequence↗
PubMed1979

Calcium infusion: a new provocative test for insulinomas.

Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas.

Adenoma, Islet Cell↗
PubMed1979

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Five patients with fasting and(or) postprandial hypoglycemia were found to have insulin antibodies in the absence of previously documented immunization. Studies on the equilibrium-binding of insulin to the autoantibodies revealed two classes of binding sites with association constants and binding capacities analogous to those of insulin antibodies from insulin-treated diabetic patients. Similarly, no consistent differences in these parameters were found in both groups of patients with insulins of bovine, porcine, and human origin. Proinsulin (C-segment directed) antibodies capable of binding bovine or porcine proinsulin were present in 10 of 10 and 9 of 10 insulin-treated diabetics serving as controls, respectively, and, when present, provide incontrovertible evidence of exogenous insulin administration. No such antibodies could be detected in the hypoglycemic patients with autoimmune insulin antibodies. The kinetics of dissociation of the insulin-antibody complexes were consistent with the existence of two classes of antibody sites. The corresponding dissociation rate constants were large enough to predict that significant amounts of free hormone may be generated by this mechanism and provide a plausible pathogenesis for the hypoglycemia in these patients.

Adult↗
PubMed1979

C-Peptide and insulin secretion in Pima Indians and Caucasians: constant fractional hepatic extraction over a wide range of insulin concentrations and in obesity.

Peripheral serum insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 10 nondiabetic Pima Indians and 10 nondiabetic Caucasians with varying degrees of obesity. Although both insulin and C-peptide levels were elevated in the Indians compared to the Caucasians (p less than 0.05), hepatic insulin extraction, measured by comparing the C-peptide to insulin ratios, was similar over a wide range of insulin concentrations in both groups. The ratios of C-peptide to insulin were independent of the degree of obesity. These studies indicate that the peripheral hyperinsulinemia in Pima Indians and obese subjects is due in general to pancreatic hypersecretion rather than to diminished hepatic extraction of insulin.

Adult↗
PubMed1979

Gastric inhibitory polypeptide response to hyper- and hypoglycemia in insulin-dependent diabetics.

The response of gastric inhibitory polypeptide (GIP) levels to oral glucose in 11 insulin-dependent diabetics was compared to that in 8 age- and sex-matched healthy controls to determine whether they would show the pattern of GIP hypersecretion reported by other workers in maturity-onset, insulin-independent diabetes. One gram of glucose per kg bw resulted in a higher level of glycemia and a significantly diminished GIP response in diabetics when compared to controls (6,018 +/- 1,337 vs. 11,343 +/- 2,353 pg/ml.180 min min, respectively). There was virtually no beta cell response in the diabetics, as measured by changes in the levels of free insulin and connecting peptide. A significant lowering of glucagon levels occurred in the controls, while an inconsistent response was seen in the diabetics. An insulin infusion test was administered to test the hypothesis that insulin suppresses GIP secretion. Although hyperinsulinism, hypoglycemia, and suppression of endogenous insulin secretion were produced in the controls, no suppression of baseline GIP was detected. Similarly, hyperinsulinism and hypoglycemia failed to suppress baseline GIP levels in the diabetics. These results do not support a direct role for insulin in suppressing GIP in normal or diabetic subjects.

Adult↗
PubMed1979

Pancreatic alpha-cell function in diabetic hemochromatotic subjects.

To clarify further the etiology of the carbohydrate intolerance in idiopathic hemochromatosis, we investigated the glucose, insulin, C-peptide, and glucagon responses to arginine (0.5 g/kg) infused during 30 min in lean normal subjects; in insulin-requiring subjects with hemochromatosis, genetic diabetes, and total pancreatectomy; and in nondiabetic cirrhotic subjects without portosystemic shunting. Serum insulin, C-peptide, and glucagon responses (30K antibody) were determined by RIA, and glucose level was determined by a glucose oxidase technique. Hemochromatotic and genetic diabetic subjects had similar basal glucose (157 +/- 25 vs. 168 +/- 40 mg/dl) and C-peptide (0.73 +/- 0.42 vs. 0.65 +/- 0.22 ng/ml) values, with subnormal C-peptide peak responses to stimulation (1.05 +/- 0.38 and 1.40 +/- 0.83 vs. 3.95 +/- 0.4 ng/ml in normals; P less than 0.05). No glucagon or C-peptide response to arginine was seen in any pancreatectomized subject. Similar but excessive glucagon levels were present in hemochromatosis, diabetes, and cirrhosis under basal conditions (166 +/- 24, 232 +/- 111, and 263 +/- 116 vs. 76 +/- 15 pg/ml; P less than 0.05) and after arginine stimulation (782 +/- 80, 834 +/- 123, and 902 +/- 275 vs. 489 +/- 81 pg/ml; P less than 0.05) when compared with normals. The excessive glucagon levels found in hemochromatosis, diabetes mellitus, and cirrhosis contrast to the absent response in pancreatectomized subjects and indicate that generalized islet cell destruction is not the major factor in diabetic hemochromatotic subjects.

Adult↗
PubMed1979

Metabolic control in diabetic patients. Effect of insulin-secretory reserve (measured by plasma C-peptide levels) and circulating insulin antibodies.

We measured circulating hemoglobin A1 (HbA1) and fasting plasma C-peptide concentrations in 100 diabetic patients. Pancreatic insulin reserve showed a negative correlation with HbA1 concentrations in nonobese, insulin-treated patients but not in obese patients, whether they were treated with insulin, oral agent, or diet alone. Patients with fasting C-peptide concentrations above 0.1 pmol/ml had significantly better metabolic control than did those with lower values. Anti-insulin antibodies were measured in 37 patients. There was no correlation between metabolic control and the affinity constants or binding capacities of these antibodies.

Adult↗
PubMed1978

Islet-cell-surface antibodies in juvenile diabetes mellitus.

Using an indirect immunofluorescence test on suspensions of viable, insulin-producing islet cells from rats, we found that 32 per cent (28/88) of insulin-treated patients with juvenile diabetes have islet-cell-surface antibodies in their circulation. These antibodies also occurred in four of nine children with glucose intolerance, in one of 24 healthy children and in nondiabetic children with thyroid disorders. In the diabetic children, the immunofluorescent reaction was inhibited by preadsorption of serum to islet cells but was little affected by preadsorption to rat hepatocytes or erythrocytes or to acetone powders of various rat tissues, including pancreas. These results show that organ-specific, nonspecies-specific antibodies reactive with the cell surface of the islet cells can be present in serum from diabetic children, and provide an approach to investigation of immunopathological aspects of diabetes mellitus.

Adolescent↗