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Biomedical subjects

O K Faber

Publications and source records attributed to O K Faber.

At least 19 recordsLinked to original sources
PubMed1991

The effect of acute hyperglycemia on the plasma C-peptide response to intravenous glucagon or to a mixed meal in insulin-dependent diabetes mellitus.

The dose-response relationships between prestimulatory blood glucose concentration and the plasma C-peptide responses to stimulation with 1 mg of glucagon iv or a standard mixed meal were studied in 8 C-peptide positive patients with insulin-dependent diabetes mellitus. Hyperglycemia was maintained for 90 min before stimulation using a hyperglycemic clamp technique. Each test was performed at the steady state blood glucose levels approximately 5, approximately 12, and approximately 20 mmol/l. The glucose potentiation of the incremental plasma C-peptide area under the curve at the two levels of hyperglycemia in percent of the area at normoglycemia (median and range) was 343% (53-1053) (p less than 0.05) and 341% (267-1027) (p less than 0.05) after glucagon and 140% (76-227) (NS) and 251% (95-1700) (p less than 0.05) after the meal. The corresponding relative glucose potentiation of plasma C-peptide 6 min after stimulation with glucagon was 124% (100-427) (p less than 0.02) and 144% (100-209) (p less than 0.05). There was no significant difference in the degree of glucose potentiation at approximately 12 or approximately 20 mmol/l. Furthermore, there was no significant difference in the degree of glucose potentiation of the different estimated values of B-cell function. In conclusion, the plasma C-peptide responses to iv glucagon or to a standard test meal were markedly potentiated by acute hyperglycemia in insulin-dependent diabetes mellitus. No further potentiation was, however, obtained when the prestimulatory blood glucose concentration was raised above 12 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Sulfonylureas. Why, which, and how?

Although controversies remain as to the usefulness of sulfonylureas, most evidence is in favor of their use in many if not patients with non-insulin-dependent diabetes mellitus. When used properly, sulfonylureas improve insulin secretion and action, and these effects may be maintained for years. If combined with hypocaloric dietary regulation, rapid- and short-acting sulfonylureas may help patients reach and maintain euglycemia without provoking chronic hyperinsulinemia or weight increase. There is no evidence that sulfonylurea treatment causes beta-cell exhaustion; instead, the antihyperglycemic effect helps improve beta-cell function. Sulfonylurea "failures" are often dietary failures or may be due to late introduction of these drugs, i.e., when beta-cell function is already attenuated. Desensitization of the insulinotropic effect of sulfonylureas may occur but might be avoided by discontinuous (less than 24 h/day) sulfonylurea exposure, i.e., once-daily administration of a short-acting sulfonylurea in a moderate dose. The most important adverse effect of sulfonylureas is long-lasting hypoglycemia, which may lead to permanent neurological damage and even death. This is mainly seen in elderly subjects who are exposed to some intercurrent event, e.g., acute energy deprivation or a drug interaction, i.e., aspirin. Long-acting sulfonylureas may be more likely to promote long-lasting hypoglycemia. The dose-response relationships of sulfonylureas have been poorly investigated, and sulfonylurea therapy should always be initiated and maintained at the lowest possible dose.

Diabetes Mellitus, Type 2↗
PubMed1990

Acute actions of sulfonylurea drugs during long-term treatment of NIDDM.

The acute effect of sulfonylurea drugs during long-term treatment was evaluated in two separate studies. In the first study, the levels of plasma glucose, insulin, and C-peptide were measured after intake of 10 mg glyburide alone or together with a standardized mixed meal in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients treated with 10-20 mg glyburide/day for greater than 2 yr. There was no acute effect of glyburide on the insulin and C-peptide responses to the meal or during continued fasting, indicating the absence of an acute insulinotropic action of glyburide during chronic treatment. The glucose increase after the meal was also unchanged, but a significant glucose reduction was found after glyburide intake during continued fasting, suggesting a sustained acute extrapancreatic (hepatic) effect. In the second study, the diurnal glycemic excursions in 8 NIDDM patients chronically and continuously (24 h/day) exposed to glipizide (2.5-7.5 mg 3 times/day) were similar when the drug was taken 30 min before each of the three main meals and when taken immediately before the meals. It is concluded that there is no acute insulinotropic action of sulfonylurea drugs during chronic continuous exposure, whereas an acute extrapancreatic action may prevail. During such exposure, there seems to be no clinical benefit in taking a sulfonylurea 30 min before rather than at the start of a meal.

Aged↗
PubMed1989

Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes.

Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis less than or equal to 40 years, and 4) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients with a fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide levels above these values mainly were Type 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Metabolic effect of islet B-cell function in insulin-treated diabetes.

We studied the relationship between endogenous insulin secretion and fasting levels of plasma free fatty acids (FFA), plasma acetoacetate plus plasma 3-hydroxybutyrate (total ketone bodies), blood glucose, and HbA1 in 132 diabetic outpatients treated with conventional insulin regimens. Patients were divided into four groups according to plasma C-peptide concentration after intravenous stimulation with glucagon: one group with C-peptide stimulation less than 0.06 nmol/l, one group with C-peptide stimulation 0.06- less than 0.32 nmol/l, one group with C-peptide stimulation 0.32- less than 0.60 nmol/l, and one group with C-peptide stimulation greater than 0.60 nmol/l. According to clinical criteria the prevalence of insulin-dependent diabetes mellitus was approximately 90% in patients with C-peptide stimulation less than 0.32 nmol/l, approximately 25% in patients with C-peptide stimulation from 0.32- less than 0.60 nmol/l, and approximately 10% in patients with C-peptide stimulation greater than 0.60 nmol/l. All metabolic variables were significantly higher in patients without detectable C-peptide in plasma when compared to values found in patients with C-peptide stimulation from 0.06- less than 0.32 nmol/l. These two patient groups also had similar peripheral plasma free insulin levels and were comparable according to age, sex, and body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The beta-cell response to glucagon and mixed meal stimulation in non-insulin dependent diabetes.

The aim of this study was to evaluate the correlations of the C-peptide and insulin responses after stimulation with glucagon intravenously as well as the 24-h urinary excretion of C-peptide to the C-peptide response to a standard mixed meal in 30 patients with non-insulin dependent diabetes mellitus (NIDDM). Fasting plasma C-peptide as well as the C-peptide and insulin responses to glucagon, showed similar but only modest correlations with the C-peptide response to the meal. Urinary C-peptide showed no correlation with the C-peptide response to the meal, but correlated modestly with fasting plasma C-peptide (r = 0.55, p less than 0.01). The C-peptide and insulin responses after meal stimulation correlated modestly inversely with HbA1. In conclusion, measurement of C-peptide in fasting state, as well as measurements of C-peptide and insulin after glucagon stimulation, only modestly predict the C-peptide response to physiologic stimulation in NIDDM. Twenty-four-hour urinary C-peptide excretion does not predict this response. Patients with NIDDM seem to show a better metabolic control if they have a more pronounced beta-cell response to physiologic stimulation.

Aged↗
PubMed1986

ELISA for human proinsulin.

A micro enzyme-linked-immunosorbent-assay (ELISA) for monitoring circulating human proinsulin (hPI) was developed. A micro test plate was coated with guinea pig anti-insulin antibody. As labelling system peroxidase-labelled F(ab1)2-fragments of a guinea pig anti-human-C-peptide was used. The detection limit in buffer (95% level) was 0.6 pmol/l corresponding to 0.06 fmol/incubation well and to 1.2 pmol/l in serum, since samples were diluted 50%. Standard operating range was from 0-160 pmol/l. Interassay variation was 9% estimated from two human control materials (assayed within the range 6-9 pmol/l and 9-14 pmol/l, respectively). Insulin in samples did not interfere in concentrations below 400 pmol/l. Human C-peptide, porcine, and bovine proinsulins did not cross-react even at 10 000 pmol/l. In 38 healthy fasting subjects a reference range less than 1.2-13 pmol/l with a median of 4.1 pmol/l was found. Serum from total pancreatectomised patients showed values below the detection limit. The value from a patient with an insulinoma was 263 pmol/l. When stored at -20 degrees C human proinsulin appeared stable in serum or plasma for at least 9 mth. This ELISA, although among the most sensitive immunoassays for human proinsulin, is still not sensitive enough to measure the concentrations expected in samples from IDDM patients in the fasting state. In spite of this the method is useful in characterising beta-cell function in stimulated situations, as well as in the diagnosis of insulinoma.

Animals↗
PubMed1986

C-peptide: an index of insulin secretion.

Insight into the natural history of beta cell function in IDDM patients obtained by C-peptide measurements is reviewed. It is argued that residual insulin secretion of metabolic importance is present in all IDDM patients during the initial course of the disease. After some months, beta cell function reaches its maximum; thereafter it declines at different rates dependent on the age at onset of diabetes and, possibly, on the presence of ICA and HLA-antigens. As many as 15% of IDDM patients retain life-long beta cell function that persists at approximately 10% of that observed in nondiabetic individuals. The residual endogenous insulin secretion is characterized by reduced capacity, as well as abnormal insulin secretory kinetics; these defects in residual insulin secretion can be modulated by changes in metabolic regulation as well as by immunosuppression during the initial course of the disease.

Age Factors↗
PubMed1986

The effect of residual beta-cell function on the development of diabetic retinopathy.

The effect of residual B-cell function on retinopathy was evaluated in a cross-sectional study of 533 insulin-dependent diabetic patients (disease duration 0 to 45 years). One hundred and fifty-three patients with residual B-cell function, as evaluated by stimulated plasma C-peptide concentration, had lower prevalence of retinopathy than patients without B-cell function. The patients with B-cell function had a shorter duration of diabetes and were older at onset, but there was no difference in age at the time of the study. When patients with similar duration of diabetes were compared, no differences in the degrees of retinopathy could be demonstrated between patients with and without B-cell function. These results indicate that residual B-cell function does not protect against or delay the development of diabetic microvascular lesions.

Adolescent↗
PubMed1985

Beta-cell function and diabetic control in insulin dependent diabetes melletus.

Beta-cell function, as evaluated from plasma C-peptide measurements, is found in all insulin dependent diabetic patients the first months of disease and in about 15% of patients with more than 15 years of treatment. The beta-cells are capable of modulating their secretory activity in response to changes in blood glucose. Even a minimal residual insulin secretion is of metabolic significance.

Blood Glucose↗
PubMed1985

The effect of insulin deprivation on fasting levels of 5000 dalton gastric inhibitory polypeptide in type 1 (insulin-dependent) diabetics.

To investigate whether metabolic decompensation has an effect on gastric inhibitory polypeptide (GIP), 8 fasting male type 1 diabetics were deprived of insulin for 12 h. An overnight insulin infusion aiming at normoglycaemia was stopped at 08.00 h. During the following 12 h blood glucose increased from 7.0 +/- 0.4 to 14.9 +/- 1.0 mmol/l, P less than 0.01, 3-hydroxy-butyrate from 0.18 +/- 0.07 to 4.00 +/- 0.74 nmol/1, P less than 0.01, and immunoreactive GIP (IR-GIP) from 16.7 +/- 2.6 to 21.9 +/- 2.9 pmol/1, P less than 0.05. The antiserum employed, R65, only measures 5000 dalton IR-GIP. The final IR-GIP concentrations were not significantly different from fasting IR-GIP concentrations in 13 normal male subjects (17.4 +/- 1.5 pmol/1). Short term insulin deprivation therefore is associated with a slight increase in fasting IR-GIP concentrations. Whether this modest increase in IR-GIP significantly enhances insulin secretion is unknown.

3-Hydroxybutyric Acid↗
PubMed1979

Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes.

The role of preserved beta-cell function in preventing ketoacidosis in type I insulin-dependent diabetes was assessed in eight patients with and seven patients without residual beta-cell function as determined from C-peptide concentrations. After 12 hours of insulin fatty-acid, and glycerol concentrations were all significantly higher in patients without beta-cell function than in those with residual secretion. Mean blood glucose concentrations reached 17.2 +/- SE of mean 1.3 mmol/l (310 +/- 23 mg/100 ml) in the first group compared with 8.8 +/- 1.4 mmol/l (159 +/- 25 mg/100 ml) in the second (P less than 0.01), while 3-hydroxybutyrate concentrations rose to 5.5 +/- mmol/l (57 +/- 5 mg/100 ml) and 1.4 +/- 0.3 mmol/l (15 +/- 3 mg/100 ml) in the two groups respectively (P less than 0.01). Individual mean C-peptide concentrations showed a significant inverse correlation with the final blood glucose values (r = -0.91; P less than 0.02). These findings strongly suggest that even minimal residual insulin secretion is important for metabolic wellbeing in diabetes and may prevent the development of severe ketoacidosis when insulin delivery is inadequate.

Adolescent↗
PubMed1979

C-peptide response to glucagon in diabetics with and without complications.

Beta cell function has been studied by measurement of C-peptide responses to intravenous glucagon in 11 diabetics with advanced complications and compared with nine long-term diabetics without complications. The majority had no C-peptide responses, but there was evidence of beta cell function in one patient from each group. These observations suggest that some factor other than continuing beta cell function is involved in the complications of insulin-requiring diabetics.

Adult↗
PubMed1979

Bone loss in diabetes: effects of metabolic state.

The significance of different risk factors for the development of bone loss in diabetes mellitus was evaluated in a cross sectional study of 215 insulin treated diabetic outpatients. Bone mineral content in the forearms was measured by photon absorptiometry and the metabolic status was evaluated by three indices: residual B-cell function, insulin dosage and fasting blood glucose. The mean bone mineral content was reduced to 90.2% of sex- and age-matched normal mean values (P less than 0.001). Stratification of the patients showed that bone mineral content was 99.3% of that found in sex- and age matched normal subjects in the group with residual B-cell function, low insulin dosage and low fasting blood glucose; it was only 79.3% of normal in the group with no detectable insulin secretion, high insulin dosage and more severe hyperglycaemia. Thus, residual insulin secretion and the quality of metabolic control are major factors in determining bone mineral content in insulin treated diabetic patients.

Blood Glucose↗
PubMed1979

Variation in 125I-insulin absorption and blood glucose concentration.

The absorption of monocomponent porcine 125I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125I-insulin dose. A significant correlation (p less than 0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.

Absorption↗
PubMed1979

Pancreatic beta cell secretion during oral and intravenous glucose administration.

The contribution of decreased hepatic insulin extraction to the relative hyperinsulinemia after oral glucose load as compared to intravenous glucose load was studied in 6 normal weight male volunteers by means of an analysis of the relationship between peripheral venous concentrations of insulin and C-peptide following similar glycemic stimuli after oral and intravenous glucose administration. The incremental areas under the insulin and C-peptide curves were higher during oral as compared to intravenous glucose administration, 436 (251--762) per cent and 267 (124-378) per cent respectively (mean and range). The ratio between corresponding incremental areas of insulin and C-peptide were 53 (17--103 per cent higher during oral glucose load. These findings suggest that the augmented peripheral insulin levels after oral glucose administration are caused by a combination of increased beta cell secretion and decreased hepatic insulin extraction.

Adult↗