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Biomedical subjects

O Kolterman

Publications and source records attributed to O Kolterman.

At least 19 recordsLinked to original sources
PubMed2003

Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis.

An unresolved problem in the management of type 2 diabetes is that improvement of glycemic control with insulin, insulin secretagogues, and insulin sensitizers is often accompanied by undesired weight gain. This problem is of particular concern in ethnic groups with a high propensity for diabetes and obesity, such as African Americans and Hispanics. Two 1-year, randomized, double-blind, placebo-controlled clinical trials in insulin-treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide, an analog of the human beta-cell hormone amylin, reduces A(1C) with concomitant weight loss, rather than weight gain. To assess the effect of pramlintide in various ethnic groups with type 2 diabetes using insulin, we conducted a pooled post hoc analysis of the 2 trials, which included all Caucasian (n = 315), African American (n = 47), and Hispanic (n = 48) patients (age 57 years, A(1C) 9.1%, body mass index [BMI] 33 kg/m(2), mean values) who completed 52 weeks of treatment with either pramlintide (120 microg twice daily or 150 microg 3 times a day) or placebo. Primary endpoints included changes from baseline to week 52 in A(1C) and body weight. Collectively, pramlintide-treated patients achieved significant reductions from baseline in both A(1C) and body weight (placebo-corrected treatment effects at week 52: -0.5% and -2.6 kg, respectively, both P <.0001). The simultaneous reduction in A(1C) and body weight at week 52 was evident across all 3 ethnic groups and appeared to be most pronounced in African Americans (-0.7%, -4.1 kg), followed by Caucasians (-0.5%, -2.4 kg) and Hispanics (-0.3%, -2.3 kg). The glycemic improvement with pramlintide was not associated with an increased incidence of hypoglycemia over the entire study period (43% pramlintide v 40% placebo). Nausea, the most common adverse event associated with pramlintide treatment, was mostly mild and confined to the first 4 weeks of therapy (25% pramlintide v 16% placebo) with comparable patterns in the 3 ethnic groups. Thus, pending further experience, the combined improvement in glycemic and weight control with pramlintide treatment appears to be generalizable to a broad population of mixed ethnicity.

Black or African American↗
PubMed2003

Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets.

AIM: Two long-term, randomized, double-blind, placebo-controlled clinical trials in insulin-using patients with type 2 diabetes, spanning a wide range of baseline glycaemic control, have shown that the addition of pramlintide, an analogue of the beta-cell hormone amylin, to pre-existing insulin regimens results in reductions in HbA1c that are accompanied by weight loss. METHODS: To assess whether this profile of pramlintide is observed in patients approaching, but not yet reaching, glycaemic targets, we conducted a pooled post hoc analysis of the two trials, including all patients with an entry HbA1c between 7.0 and 8.5%. Within this subset of patients, 80 were treated with placebo + insulin [baseline HbA1c 8.0 +/- 0.3%, weight 87.3 +/- 19.3 kg (mean +/- s.d.)] and 86 with pramlintide (120 micro g bid) + insulin [HbA1c 8.0 +/- 0.4%, weight 92.5 +/- 20.4 kg (mean +/- s.d.)]. Endpoints included changes from baseline to Week 26 in HbA1c, body weight, and the event rate of severe hypoglycaemia. RESULTS: Adjunctive therapy with pramlintide resulted in significant reductions in both HbA1c and body weight from baseline to Week 26 (-0.43% and -2.0 kg differences from placebo, respectively, both p < 0.001). These changes were achieved without a concomitant increase in the overall rate of severe hypoglycaemic events (0.13 pramlintide vs. 0.19 placebo, events/patient year of exposure). CONCLUSIONS: The data from this post hoc analysis indicate that the addition of pramlintide to insulin therapy may help patients with type 2 diabetes who are approaching, but not yet reaching, glycaemic targets to achieve further reductions in HbA1c without concomitant weight gain and increased risk of severe hypoglycaemia.

Aged↗
PubMed1999

The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus.

To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 microg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 AM to 4:30 PM) was performed. Serum fructosamine was decreased after pramlintide (314+/-14 micromol/L) compared with placebo (350+/-14 micromol/L, P = .008). On the profile day, the mean plasma glucose (8.3+/-0.7 v 10.2+/-0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration (P < .01 for both) despite comparable circulating insulin levels (359+/-41 v 340+/-35 pmol/L). Mean blood glycerol values were reduced (0.029+/-0.004 v 0.040+/-0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274+/-0.012 v 0.246+/-0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8+/-7.3 v 72.4+/-8.0 ng/L, P = .005) and lunch (47.6+/-9.0 v 60.9+/-8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 microg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.

Adult↗
PubMed1996

Effect of race and hypertension on plasma amylin concentrations.

Amylin is a recently discovered peptide hormone composed of 37 amino acids that is cosecreted with insulin by pancreatic beta cells. Amylin has been reported to be present in increased amounts in insulin-resistant subjects who are hyper-insulinemic. Because blacks and whites differ in the prevalence of both hypertension and diabetes, we examined amylin levels in 77 individuals; 42 were black (11 hypertensive and 31 normotensive) and 35 were white (10 hypertensive and 25 normotensive) individuals who were either healthy control subjects or hypertensive subjects not receiving antihypertensive medication. Plasma amylin concentrations were measured in two separate monoclonal antibody-based immunofluorescent sandwich-type assays. The F002-2 capture antibody binds amylin plus at least two additional amylin-like peptides, and the F024-4 capture antibody detectably binds only the amylin peptide. There was a significant race-by-diagnosis interaction for levels of amylin immunoreactivity during a 2-hour glucose tolerance test (P<.005 for F002-2 antibody and P<.05 for F024-4 antibody). Highest levels were found in black hypertensive subjects. The results appear to fit with previously observed differences in metabolic status between blacks and whites and with the association between hypertension and alterations in metabolic status.

Adult↗
PubMed1996

Modulation of gastric emptying as a therapeutic approach to glycaemic control.

Amylin is a peptide hormone which is deficient in patients with Type 1 and late stage Type 2 diabetes. Evidence from studies in rats and humans has suggested that it is involved in glucose homeostasis by modulating gastric emptying and, possibly, by regulating the release of glucagon. These observations have led to the suggestion that amylin may be used clinically to improve glycaemic control in patients with diabetes. Preliminary studies with the human amylin analogue, pramlintide, have provided evidence of beneficial effects in terms of improved glycaemic control in these patients; these effects are currently being investigated in long term phase III studies.

Amino Acid Sequence↗
PubMed1992

Recovery and hypersecretion of insulin and reversal of insulin resistance after withdrawal of short-term cyclosporine treatment.

We have previously demonstrated decreased insulin release and insulin resistance in dogs treated with cyclosporine (20 mg/kg/day). In this study we examine the changes caused by a lower CsA dose and evaluate the reversal of these changes. Six animals were treated for 2 weeks with oral CsA (15 mg/kg/day), after which CsA was discontinued. Glucagon stimulation tests (GST) and euglycemic clamp studies (ECS) were used to evaluate changes in insulin release and insulin resistance. GST were performed before CsA, after 2 weeks of CsA, and 3, 9, and 15 days after discontinuing CsA. ECS were performed before CsA, after 2 weeks of CsA, and 2, 4, 8, and 14 days after discontinuing CsA. The mean serum CsA level after 2 weeks of treatment was 188 +/- 28 ng/ml. GST demonstrated decreased insulin release during CsA with recovery and hypersecretion after CsA withdrawal. ECS showed peripheral insulin resistance during CsA with a rapid recovery and a temporary increase in insulin sensitivity after CsA withdrawal. Comparisons were made with our previous study group given 20 mg/kg/day of CsA. In summary, CsA induces a dose-dependent impairment of glucose homeostasis due to inhibition of insulin release and development of peripheral insulin resistance. Withdrawal of short-term CsA at commonly used therapeutic doses results in reversal of and temporary overcompensation for these changes. CsA withdrawal after long-term treatment results in a slower normalization of the insulin response as compared with after short-term treatment. The hypersecretory reaction of the beta cell may be of help in further investigations of mechanisms of CsA- and FK506-induced inhibition of insulin release.

Animals↗
PubMed1991

Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles.

Mutations in the insulin receptor gene can lead to in vivo and in vitro insulin resistance and can be the cause of diabetes mellitus in selected patients. We have studied a 22-year-old diabetic woman with Type A insulin resistance and acanthosis nigricans. Insulin binding to the patient's erythrocytes, monocytes, adipocytes, fibroblasts, and transformed lymphocytes was decreased. Receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the proband's transformed lymphocytes. Determination of the nucleotide sequence of the patient's insulin receptor cDNA revealed that the subject was a compound heterozygote who inherited two different mutant insulin receptor gene alleles. The paternal allele contains a missense mutation encoding the substitution of glutamine for arginine at position 981 in the tyrosine kinase domain of the receptor. The maternal allele contains a nonsense mutation causing premature termination after amino acid 988 in the beta-subunit, thereby deleting most of the kinase domain. The mRNA encoded by the allele with the premature stop codon is likely to be unstable, since mRNA transcripts from this allele were decreased markedly compared with the other allele. The mother, who is heterozygous for the nonsense mutation, exhibited only mild insulin resistance, whereas the proband was severely insulin-resistant; this indicates that the missense mutation is biologically significant. In summary, (1) we have identified a patient and her family with a genetic form of insulin resistance and diabetes due to a defect at the level of the insulin receptor; (2) the proband is a compound heterozygote displaying a missense mutation (position 981) in one allele and a nonsense mutation (position 988) in the other insulin receptor gene allele; (3) the missense mutation is in the kinase domain and encodes a receptor with impaired in vitro kinase activity; and (4) based on the in vitro and in vivo phenotype, the kinase domain mutation at position 981 is biologically significant leading to insulin resistance.

Adult↗
PubMed1990

Inhibition of insulin release by cyclosporine and production of peripheral insulin resistance in the dog.

Cyclosporine has been shown to cause glucose intolerance in both humans and animals. This can result from alterations in insulin release, insulin metabolism, the sensitivity of peripheral or hepatic tissues to insulin, or a combination of these factors. The present study was designed to simultaneously evaluate the effect of CsA on these variables. A group of chronically catheterized dogs were administered oral CsA (20 mg/kg/day) for a period of 10 weeks. The glucagon stimulation test (GST) and the euglycemic glucose clamp technique, using a primed continuous infusion of 3H-3-glucose and a continuous insulin infusion (0.8 mU/kg/min), were employed to evaluate pancreatic insulin release, peripheral glucose disposal rate (Rd), hepatic glucose output (HGO), and metabolic clearance rate (MCR) of insulin. The dogs were tested before and after 2, 6, and 10 weeks of CsA administration. Serum CsA levels were 358 +/- 85, 244 +/- 48, and 355 +/- 81 ng/ml at 2, 6, and 10 weeks, respectively (P = NS). Elevated fasting glucose and an abnormal glucose response to an i.v. bolus of glucagon (0.25 U) were noted after 2, 6, and 10 weeks of CsA administration. The areas under the glucose curve (AUCG) for 0-60 min were 9605 +/- 773, 11634 +/- 1226, 12380 +/- 719, and 12626 +/- 1560 mg/min/dl at 0, 2, 6, and 10 weeks, P(F3, 15 = 5.1) = 0.012, demonstrating a CsA-induced disturbance of glucose homeostasis. The areas under the insulin curve (AUCI) for 0-20 min of the insulin response curve were 2033 +/- 203, 1089 +/- 187, 1038 +/- 179, and 972 +/- 161 uU/min/dl at 0, 2, 6, and 10 weeks, P(F3, 15 = 13.1) less than 0.001, indicating a 50% reduction during CsA treatment. CsA did not affect basal Rd, but peripheral insulin resistance was noted in the insulin-stimulated state. Rd during the third hour of the insulin infusion decreased from 6.72 +/- 0.69 to 4.42 +/- 0.44, 5.02 +/- 0.64, 4.47 +/- 0.52 mg/kg/min at 0, 2, 6, and 10 weeks, respectively, P(F3, 15 = 6.94) less than 0.004. HGO suppression by insulin and MCR of insulin were not altered by CsA. Similarly, glucagon secretion did not appear to be influenced by CsA. In conclusion, this study has simultaneously evaluated the effect of CsA on several aspects of glucose and insulin metabolism in the dog. CsA administration produces abnormal glucose homeostasis by reducing pancreatic insulin release, in addition to inducing peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Computerized ambulatory-care pharmacy information system for direct order entry by prescribers.

A computer system that links prescribers in a diabetes center to an ambulatory-care satellite pharmacy is described. In 1988 an ambulatory-care center serving the diabetic patients of a 437-bed university teaching hospital moved to a new location. To maintain efficient communication of prescription information from the diabetes center to a designated ambulatory-care satellite pharmacy, a program that enables diabetes center prescribers to enter their orders directly into the satellite pharmacy computer system was implemented. The pharmacy department's prescription-entry screen was reprogrammed so that it could be more easily used by prescribers, and a "default" list of the most frequently prescribed drugs was generated to simplify direct order entry. Prescription information entered at the diabetes center is transmitted to the satellite pharmacy; the filled prescriptions are usually ready by the time patients arrive. The average number of prescriptions entered into the computer per week remained steady during the first 14 weeks that the system was in use but increased substantially after diabetes center personnel were given a summary of use data and other information pertaining to the new system. However, because of the availability of only one terminal for order entry and the inherent ease and speed of writing prescriptions on paper, use of the system has not met expectations despite the benefits it offers. Prescribers in a diabetes center did not frequently enter prescription information into a computer system linked to the hospital's ambulatory-care pharmacy because the traditional method of writing prescriptions remained available and convenient.

California↗
PubMed1987

Selective suppression of hepatic glucose output by human proinsulin in the dog.

By using the euglycemic glucose-clamp technique we have observed the effects of comparable low dose proinsulin and insulin infusions on isotopically determined glucose turnover in 20 anesthetized dogs. In each animal somatostatin (SRIF) infusion was used to suppress endogenous pancreatic hormone secretion and basal glucagon was replaced. Peripheral proinsulin (0.083 micrograms X kg-1 X min-1) and insulin (350 microU X kg-1 X min-1) levels 15- to 20-fold higher than insulin on a molar basis, based on previous observations that proinsulin has only 5-10% the biologic potency of insulin. Three groups of infusion studies were performed: SRIF and glucagon (n = 5); SRIF, glucagon, and proinsulin (n = 10); and SRIF, glucagon, and insulin (n = 5). The mean serum proinsulin level of 2.43 +/- 0.36 pmol/ml achieved represented a 17-fold excess compared with the mean serum insulin level of 0.14 +/- 0.03 pmol (20 +/- 4 microU/ml). At these concentrations, both hormones reduced hepatic glucose production rates by approximately 50% to 2.0 +/- 0.2 mg X kg-1 X min-1 and 1.8 +/- 0.5 mg X kg-1 X min-1, respectively. In contrast, proinsulin failed to stimulate peripheral glucose utilization, whereas insulin led to a 2.0 +/- 0.3 mg X kg-1 X min-1 increment (approximately 50% increase) in glucose uptake (P less than 0.05). Thus at low infusion rates proinsulin exerts its effect predominantly by suppressing hepatic glucose production without measurable stimulation of peripheral glucose disposal. In contrast, for a comparable degree of hepatic glucose output suppression, insulin also significantly stimulates glucose disposal.

Animals↗
PubMed1987

Non-insulin-mediated glucose uptake predominates in postabsorptive dogs.

Overall glucose uptake represents the sum of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). In this study, we compared the rate of NIMGU in conscious and anesthetized dogs. Rates of glucose disposal were compared in the basal state and during severe insulinopenia after endogenous insulin suppression by high-dose somatostatin (SRIF) infusion. Steady-state NIMGU rates were calculated 2 h after commencing SRIF infusion. Three groups of studies were performed: 1) SRIF in conscious dogs; 2) SRIF in anesthetized dogs; and 3) SRIF plus glucagon, also in anesthetized dogs. In all three groups, serum insulin levels were reduced to below assay sensitivity after SRIF infusion. The basal metabolic clearance rate of glucose (MCRg) for each group was 3.8 +/- 0.4, 3.6 +/- 0.3, and 3.6 +/- 0.3 ml X kg-1 X min-1, respectively (P = NS, all groups). Steady-state NIMGU rates were 2.4 +/- 0.2 (conscious), 2.5 +/- 0.1 (anesthetized, SRIF only), and 2.4 +/- 0.1 ml/kg/min (anesthetized, SRIF plus glucagon). Thus, absolute rates of NIMGU expressed as MCRg in conscious and anesthetized animals do not differ and in the three groups studied comprise approximately the same proportion of the basal glucose uptake (approximately 64, approximately 69, and approximately 66%, respectively). We conclude that approximately 66% of basal postabsorptive glucose uptake occurs via NIMGU mechanisms and that this pathway is unaffected by anesthesia and surgery.

Absorption↗
PubMed1987

Continuous subcutaneous insulin infusion in an obese insulin-resistant pregnant woman with type II diabetes: accelerated fetal growth and neonatal complications.

This is the first report to describe prolonged continuous subcutaneous insulin infusion in a massively obese insulin-resistant pregnant woman with type II diabetes. Maternal 24-hour plasma glucose levels became normal by 48 hours, and normoglycemia was maintained with high daily doses of insulin (530 U-333 U/24 hours) from 29 weeks' gestation until delivery at 38.5 weeks. Excellent diabetic control was associated with euglycemia, normal glycosylated hemoglobin concentration, and a significant decrease in mean 24-hour plasma C-peptide (P less than .004) and glucagon (P less than .003) levels. Unexpectedly, fetal growth accelerated during constant insulin infusion despite normal maternal plasma glucose levels. The newborn infant was large (4530 g), with a striking truncal accumulation of fat, hypoglycemia (30-minute plasma glucose 11 mg/dL), and polycythemia (central venous hematocrit 71%). Normalization of maternal plasma glucose levels failed to ameliorate established macrosomia, and did not prevent the neonatal complications that are common in infants of diabetic mothers.

Adult↗
PubMed1984

Biosynthetic human insulin and proinsulin have additive but not synergistic effects on total body glucose disposal.

Recent studies from our laboratory have demonstrated that human biosynthetic proinsulin has a much slower MCR than insulin as well as a greater effect on hepatic than on peripheral tissues. Since both of these features make proinsulin potentially useful as an adjunct to insulin, the present study was undertaken to characterize the biological effects of combined infusions of insulin and proinsulin. As an initial study, multiple euglycemic clamp studies were performed in six normal subjects to construct dose-response curves for insulin- and proinsulin-mediated glucose disposal. Insulin infusion rates of 0.63, 1.67, 5, and 10 micrograms/M2 X min were compared to proinsulin infusion rates of 2.75, 7.5, 22.5, and 45 micrograms/M2 X min. Analysis of these dose-response curves indicated that proinsulin-mediated glucose disposal was approximately 7% that of insulin. Each subject also received a combined infusion of insulin (0.63 micrograms/M2 X min) and proinsulin (2.75 micrograms/M2 X min). The mean (+/- SE) glucose disposal rate obtained during the combination study (319 +/- 21 mg/M2 X min) was similar to that predicted by adding the results from the individual hormone infusions (307 +/- 21 mg/M2 X min). Analysis of the dose-response curves for insulin and proinsulin was also useful in predicting the glucose disposal rate during the combination study (290 +/- 19 mg/M2 X min). Thus, using either approach to predict the glucose disposal rates, insulin and proinsulin appeared to have additive effects on total body glucose disposal.

Adult↗
PubMed1984

The metabolic effects of biosynthetic human proinsulin in individuals with type I diabetes.

To assess the significance of deficiency of circulating proinsulin in patients with type I diabetes mellitus, we studied the metabolic effects of biosynthetic human proinsulin in 24 patients. After withdrawing insulin, an infusion of proinsulin to physiological plasma levels did not prevent elevations of plasma glucose or beta-hydroxybutyrate. During steady state infusions of insulin and proinsulin, 13.7 times the steady state plasma level of proinsulin compared to insulin was required to maintain euglycemia. This finding indicates that proinsulin is approximately 7.3% as biologically active as insulin on a molar basis in maintaining glucose control. The MCRs of insulin and proinsulin during these steady state infusions were 12.5 +/- 2.2 (+/- SEM) and 2.62 +/- 0.33 ml/kg X min, respectively. After maintaining euglycemia overnight with an infusion of insulin or proinsulin and then acutely stopping these infusions, the rise in plasma glucose after proinsulin was delayed significantly compared to insulin, consistent with proinsulin's slower clearance. Further studies are necessary to determine whether biosynthetic human proinsulin has a specific role in the treatment of diabetes.

Blood Glucose↗
PubMed1984

The effects of biosynthetic human proinsulin on carbohydrate metabolism.

Large quantities of biosynthetic human proinsulin have recently become available through recombinant DNA technology. Since the in vivo effects of human proinsulin have not been studied in man, we compared the dose-response relationship for stimulation of glucose disposal and suppression of hepatic glucose output by proinsulin and insulin. Ten normal subjects were studied using the euglycemic glucose clamp technique. The human proinsulin and insulin infusion rates were chosen to achieve steady-state proinsulin levels 10-fold higher than insulin levels on a molar basis, based on previous observations that porcine proinsulin has approximately 10% the potency of insulin. Proinsulin infusion rates of 2.75, 7.5, 22.5, and 45 micrograms/m2/min were compared with insulin infusion rates of 0.63, 1.67, 5, and 10 micrograms/m2/min. Primed, continuous infusions of insulin yielded steady-state levels within 25 min, whereas proinsulin levels did not reach a steady state for 120-180 min. The metabolic clearance rate of insulin was 11-12 ml/kg/min at the lower infusion rates but fell to 8.4 ml/kg/min at the highest infusion rate. The metabolic clearance rate of proinsulin was 3.0-3.5 ml/kg/min at all infusion rates. Dose-response analysis demonstrated that proinsulin-mediated glucose disposal was approximately 8% that of insulin. In contrast, proinsulin-mediated suppression of hepatic glucose output was approximately 12% that seen with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Insulin binding in human pregnancy: comparisons to the postpartum, luteal, and follicular states.

We have studied insulin binding to isolated erythrocytes from 28 nondiabetic, pregnant women and have compared these results to similar data obtained in nonpregnant, nondiabetic women. In the nonpregnant subjects insulin binding was 35% higher during the follicular stage of the menstrual cycle as compared to the luteal phase. In the pregnant women insulin binding was comparable to that seen in the nonpregnant women during the follicular phase but was higher than that seen during the luteal phase of the menstrual cycle. Insulin binding was measured in 5 pregnant women during the third trimester and in the postpartum period. In these subjects insulin binding to erythrocytes declined by 31% after delivery. These results demonstrate that erythrocyte insulin receptors are not decreased in normal human pregnancy despite the presence of hyperinsulinemia and insulin resistance. Providing erythrocyte insulin receptors are reflective of insulin receptors in other tissues in human pregnancy, these findings suggest that some factor exists in pregnancy that modulates insulin receptors in a positive manner and are consistent with the possibility that the insulin resistance in pregnancy is related to a postreceptor abnormality.

Adolescent↗
PubMed1980

Diabetes due to secretion of an abnormal insulin.

A 51-year-old, nonobese man with diabetes mellitus had marked hyperinsulinemia (70 to 120 muU per milliliter; 502 to 860 pmol per liter) and fasting hyperglycemia (140 to 170 mg per 100 ml; 7.8 to 9.4 mmol per liter). Plasma proinsulin, glucagon, growth hormone, and cortisol levels were normal; insulin antibodies and insulin-receptor antibodies were not detected. The patient showed relatively normal insulin sensitivity, and insulin receptors on circulating monocytes were within the normal range. Insulin from the patient's serum bound to IM-9 lymphocytes and rat adipocytes approximately 40 per cent as well as insulin standards. Its biologic activity on rat adipocytes averaged 15 per cent of that expected from its immunologic concentration. The impaired biologic activity of this patient's circulating insulin was probably due to a structural abnormality. Subsequent studies of the patient's insulin (fortuitously obtained from his pancreas during a laparotomy for a pancreatic cyst) have confirmed this conclusion. (N Engl J Med 302:129-135, 1980).

Blood Glucose↗