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Biomedical subjects

L Groop

Publications and source records attributed to L Groop.

At least 163 records · Page 9Linked to original sources
PubMed1986

Therapeutic equivalence of once- and thrice-daily glipizide.

Two cross-over studies were carried out in 23 patients with Type 2 diabetes, to examine whether glipizide, a potent sulphonylurea with fast and complete absorption and rapid elimination (t1/2 less than 5 h), can be given once-daily without loss of therapeutic effect. In both studies, patients were randomly assigned to an initial dose of 7.5 mg once daily or 2.5 mg three-times daily, which was increased to 15 mg o.d. or 5 mg t.i.d. if the fasting plasma glucose remained over 10 mmol/l on the lower dosage. In Study 1 (n = 11), administration once a day before breakfast was compared with intake before breakfast, lunch and early dinner (5 p.m.) and in Study 2 (n = 12) the comparison was between intake once-daily before breakfast and dosing before breakfast, lunch, and at bedtime (10 p.m.). Neither the 24-hour urinary glucose excretion nor HbA1, fasting plasma glucose, insulin or C-peptide levels differed between the once and three times daily administration with the third dose given before early dinner. The nadir plasma levels of glipizide were not significantly different and were often too low to be detected. Postponing the third dose until 10 p.m. did not produce any improvement in HbA1 or in fasting plasma glucose, insulin or C-peptide. The mean nadir glipizide levels following this schedule were twice as high as those after once-daily administration. As expected, the plasma glipizide after breakfast was higher when the whole dose was taken before breakfast than when it was divided. The corresponding plasma level of insulin was higher and that of plasma glucose was lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Relationship between B-cell function and HLA antigens in patients with type 2 (non-insulin-dependent) diabetes.

In order to study the heterogeneity of Type 2 (noninsulin-dependent) diabetes, we determined HLA antigens and measured B-cell function as C-peptide response to intravenous glucagon in 217 patients with onset of non-ketotic diabetes after the age of 40 years. Their HLA frequencies were compared with those of Type 1 (insulin-dependent) diabetic patients and of healthy blood donors. The Type 1 diabetic patients showed a typical HLA pattern, with increased frequencies of B15, DR3, DR4, B8/B15 and DR3/DR4 and decreased frequencies of B7 and DR2. The Type 2 diabetic patients could be distinguished from blood donors by increased frequencies of Cw4, DR4, DR5 and DR3/DR4, and from Type 1 diabetic patients by increased frequencies of B7, DR2, DR5 and decreased frequency of A9, Bw22 and DR4. Age at onset and body mass index were unrelated to HLA antigens, but the Type 2 diabetic patients with HLA-Cw4, DR5 and DR6 showed a strong family history for Type 2 diabetes. Type 2 diabetic patients with HLA-B8, DR4, B8/B15 and DR3/DR4 showed significantly lower C-peptide concentrations (p less than 0.05) than patients without these HLA antigens. In contrast, patients with DR5 and DRw8 presented with high C-peptide levels. Twelve patients who were positive for both DR3 and DR4 and 23 patients who were DR3/DR4 negative were followed with repeated C-peptide determinations during a period of three years. The C-peptide concentrations of the DR3/DR4 positive patients decreased during this period, whereas there was no change in C-peptide levels in the DR3/DR4 negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of acarbose on the relationship between changes in GIP and insulin responses to meals in normal subjects.

The relationship between changes in gastric inhibitory polypeptide (GIP), C-peptide and insulin responses to meals was studied in 8 normal subjects after 2 weeks of Acarbose treatment. Acarbose caused a significant reduction of GIP and insulin responses (P less than 0.05). The decrease in insulin response could not be explained by changes in the glycaemic stimulus of insulin secretion, as Acarbose did not significantly change the plasma glucose response to meals during the study. The reduced insulin response was seen without a concomitant reduction in the C-peptide response to the meals, thus resulting in a decreased insulin/C-peptide ratio after Acarbose treatment (P less than 0.05). The changes in GIP response after Acarbose correlated positively with the change in insulin/C-peptide ratio (r = 0.69; P less than 0.05). Our data thus challenge the concept that Acarbose therapy affects the secretion of insulin. The positive relationship between changes in GIP response and changes in the insulin/C-peptide ratio rather suggests that GIP affects the metabolism of insulin or C-peptide.

Acarbose↗
PubMed1986

Relationship between changes in GIP concentrations and changes in insulin and C-peptide concentrations after guar gum therapy.

In order to elucidate the mechanisms of the action of gel-forming fibre in diabetes, we measured insulin, C-peptide and GIP responses to meals during treatment with guar gum and placebo in normal and non-insulin-dependent diabetic (NIDD) subjects. Dietary supplementation with guar gum caused a sustained reduction of the GIP response in normal and diabetic subjects (p less than 0.05), but did not influence insulin responses. On the other hand, guar gum increased the C-peptide response to meals in normal subjects (p less than 0.05) resulting in a 40% decrease of the insulin/C-peptide ratio (p less than 0.01). Assuming that the insulin/C-peptide ratio reflects the hepatic extraction of insulin, this would be compatible with increased hepatic removal of insulin. The change in insulin/C-peptide ratio was positively correlated with the change in GIP response after guar gum (r = 0.75; p less than 0.001) and this correlation was strengthened in normal subjects (r = 0.91; p less than 0.001). Our data thus suggest that guar gum stimulates rather than suppresses insulin secretion. The apparent insulinotropic action of GIP may partly be explained by a reduced hepatic extraction of insulin.

Adult↗
PubMed1986

The usefulness of micro- and macrochromatographic determinations of glycohemoglobin in diabetic patients with nephropathy.

Determination of glycohemoglobin in blood (HbA1) represents an established measure of glycemic control in diabetic patients. In patients with uremia, however, the determination can be subject to pitfalls which may limit its reliability. In order to evaluate the clinical usefulness of HbA1 determinations in diabetic patients with nephropathy, concentrations of HbA1 and its subfractions HbA1c and HbA1a+b were measured by micro- and macrocolumn chromatography in 58 diabetic and 80 non-diabetic patients with impaired renal function. Fifteen diabetic patients without nephropathy and 15 healthy subjects served as controls. The concentrations of HbA1 and its subfractions were significantly higher in non-diabetic patients with nephropathy than in healthy controls. A positive correlation was seen between HbA1 and plasma glucose concentrations in all subjects, and between HbA1 and serum urea and creatinine concentrations in the non-diabetic subjects. When measured repeatedly in the same patient there was a positive correlation between HbA1 and plasma glucose concentrations in diabetic patients with azotemia. There was no change in HbA1 concentrations measured immediately before and after hemo- or peritoneal dialysis. The increase of chromatographically determined HbA1 concentrations in azotemic patients is most likely due to the joint action of carbamylation of hemoglobin with urea derived cyanate and deterioration of glycemic control induced by azotemia. Despite these problems, chromatographically determined HbA1 is still a clinically useful measure of glycemic control in diabetic patients with nephropathy. This presumes repeated measurements in the same patient and the use of appropriate reference levels which consider the degree of renal impairment.

Adult↗
PubMed1985

Pharmacokinetics and metabolic effects of glibenclamide and glipizide in type 2 diabetics.

Fifteen Type 2 diabetics were treated for 4-week periods with once daily (10 mg) glibenclamide, glipizide and placebo according to a double-blind cross-over protocol. Post-dose glipizide concentrations were three times higher than those of glibenclamide, due to the incomplete bioavailability of the latter. On the other hand, pre-dose drug levels were similar, as an expression of the slower absorption and/or elimination of glibenclamide. Both active treatments reduced postprandial blood glucose concentrations and 24-hour urinary glucose excretion to a similar degree, but fasting blood glucose concentrations were slightly lower during glibenclamide treatment. Both active treatments enhanced fasting and postprandial insulin and C-peptide concentrations, the C-peptide response being greater after glipizide than after glibenclamide. Plasma glucagon and GIP concentrations were not significantly affected. Insulin sensitivity was increased by glibenclamide but not by glipizide. Neither therapy affected insulin binding to erythrocytes. It appears that both glibenclamide and glipizide improved glucose metabolism by sustained stimulation of insulin secretion, which was most pronounced with glipizide. Only glibenclamide improved insulin sensitivity and was slightly more active than glipizide on fasting blood glucose levels. The differences may be consequences of the pharmacokinetics, but differences in pharmacodynamics cannot be excluded.

Aged↗
PubMed1985

Transient effect of the combination of insulin and sulfonylurea (glibenclamide) on glycemic control in non-insulin dependent diabetics poorly controlled with insulin alone.

In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p less than 0.001), 24-hour urinary glucose (p less than 0.01) and glycohemoglobin (HbA1) concentrations (p less than 0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p less than 0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA1 concentrations (r = 0.56, p less than 0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.

Blood Glucose↗
PubMed1985

Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy.

The urinary excretion of beta2-microglobulin, albumin, kappa light chains, transferrin, and IgG as well as their concentration ratios were assessed in 27 nondiabetic patients with proteinuria and in 72 IDDM patients, 41 with proliferative retinopathy (PR) and 31 without retinopathy, matched for age, duration of diabetes, and treatment. The mean excretions of albumin, transferrin, and IgG were similar in patients with nondiabetic proteinuria and in IDDM patients with PR and were significantly higher than in IDDM patients without retinopathy. Despite similar albumin excretion, the amount of excreted kappa light chains was significantly higher in IDDM patients than in patients with nondiabetic proteinuria, resulting in an elevated kappa chain/albumin ratio. Furthermore, diabetic subjects without microalbuminuria showed increased kappa chain/albumin ratio, indicating that increased urinary excretion of kappa chains may be an early sign of diabetic nephropathy. Determination of kappa light chain excretion may have clinical implications in the differentiation between proteinuria of diabetic and nondiabetic origin. The ratio kappa chain/albumin was independent of the excretion of beta2-microglobulin in patients with PR, suggesting that the reduced ability to reabsorb immunoglobulin light chains may occur earlier than that of beta2-microglobulin in the development of tubular dysfunction in insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1985

Combination of insulin and glibenclamide in the treatment of elderly non-insulin dependent (type 2) diabetic patients.

A double-blind crossover study was undertaken to determine whether glibenclamide could improve glycaemic control in patients not adequately controlled by insulin. Nine elderly outpatients with non-insulin dependent (type 2) diabetes participated in the study. In addition to their regular insulin treatment, the patients were given either glibenclamide 5 mg twice daily or placebo tablets for 2 months followed by the opposite combination for a further 2 months. The fasting plasma glucose concentrations were lower during the insulin plus glibenclamide period than during the insulin plus placebo period and the difference tended to increase at the end of each study period (p less than 0.01 and 0.001). The level of haemoglobin A, (HbA1) decreased significantly from 13.8 +/- 0.6% (mean +/- SE) to 12.4 +/- 0.6% during the insulin + glibenclamide period (p less than 0.01); in contrast, there was no change during the insulin + placebo period. The 24-hour urinary glucose excretion was reduced during the insulin + glibenclamide period compared with insulin + placebo (p less than 0.05). Basal and glucagon stimulated C-peptide concentrations did not significantly differ between the two treatment regimens. The results suggest that glibenclamide can improve the glycaemic control in insulin-treated elderly diabetics by mechanisms which still are to be elucidated.

Aged↗
PubMed1984

Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush.

The value and reproducibility of the chlorpropamide-alcohol flush (CPAF) have been questioned, and objective measures of the test are required. Recording of facial skin temperature, measurement of chlorpropamide, ethanol and acetaldehyde concentrations have been proposed for this purpose. The present study was designed to evaluate the relative contributions of these variables in determining CPAF. Twenty-one Type 2 (non-insulin-dependent) diabetic patients (11 CPAF-positive and 10 CPAF-negative according to previous tests with standard amounts of alcohol and chlorpropamide) were investigated in a random fashion with either chlorpropamide or placebo given on three subsequent evenings before a two-step alcohol challenge with increasing body-weight-matched amounts of alcohol. Higher rises in facial skin temperature and heart rate, higher flush-score and higher acetaldehyde levels resulted from chlorpropamide therapy than followed placebo. After smaller alcohol challenges (with chlorpropamide pretreatment) there were positive intercorrelations between flush-score, rise in facial skin temperature, and plasma concentrations of chlorpropamide and blood acetaldehyde. The increased alcohol dose abolished most of these correlations and a minimum temperature rise of 1.8 degrees C appeared in all but two subjects regardless of previous CPAF classification. During the current experimental conditions, the previously-classified CPAF-positive and CPAF-negative patients did not differ with respect to flush-score, rise in skin temperature, heart rate, blood acetaldehyde or ethanol concentrations, whereas they differed with respect to chlorpropamide concentrations. The present results support the view that CPAF is associated with elevated blood acetaldehyde levels due to inhibition of aldehyde dehydrogenase by chlorpropamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1984

Chlorpropamide-alcohol flush: significance of body weight, sex and serum chlorpropamide level.

Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.

Body Weight↗
PubMed1984

Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients.

The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double-blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p = 0.037 and p = 0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p = 0.0036 and p = 0.0003), respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.

Adrenergic beta-Antagonists↗
PubMed1984

Characterization of patients with chlorpropamide-alcohol flush.

One hundred and sixty patients with onset of non-ketotic diabetes at the ages of 35-70 were investigated for chlorpropamide-alcohol flush (CPAF), beta-cell function, insulin sensitivity, human leucocyte antigens (HLA), organ specific antibodies and diabetic complications. A positive flush reaction was defined as an increase in facial skin temperature by at least 1.5 degrees C, which was associated with a visible flush reaction in all patients. In accordance with these criteria, 38% of the patients were considered CPAF-positive with a mean rise in facial skin temperature of 2.3 +/- 0.1 degrees C compared with 0.6 +/- 0.1 degrees C in the CPAF-negative patients (p less than 0.001). The CPAF-positive patients could be distinguished from the CPAF-negative with respect to: 1) higher frequency of first degree family history of diabetes (p less than 0.05), 2) lower basal and glucagon-stimulated C-peptide concentrations (p less than 0.02 and p less than 0.001), 3) increased frequency of HLA-A2 (p less than 0.01) and decreased frequency of HLA-B7 (p less than 0.01). The findings thus support the genetically determined nature of CPAF. Considering the criteria for maturity onset diabetes in the young, it is unlikely that CPAF acts as a genetic marker for this particular form of genetic diabetes.

Adult↗
PubMed1984

The combination of insulin and sulphonylurea in the treatment of secondary drug failure in patients with type II diabetes.

Thirteen patients (6 females and 7 males) who were secondary failures on oral drug therapy were randomly allocated to either 2 months of treatment with insulin + glibenclamide or insulin + placebo. Thereafter the treatment schedules of the two groups were switched over for another two months. The combination of insulin and glibenclamide was more effective in lowering the fasting blood glucose (P = 0.026) and 24 h urine glucose (P = 0.042) than the combination of insulin and placebo. The combination therapy with insulin and glibenclamide revealed higher basal (P = 0.021) and glucagon-stimulated C-peptide concentrations (P = 0.037) than therapy with insulin and placebo. However, insulin binding to erythrocytes did not differ between the two study periods. The results indicate that the addition of glibenclamide to insulin in type II diabetics poorly controlled by oral antidiabetics alone may slightly improve diabetic control. The mechanism of this action is due at least partly to sulphonylurea-induced stimulation of endogenous insulin secretion. The effectiveness of the combination treatment during long-term therapy still remains to be proven, however.

Adult↗
PubMed1984

Factors influencing beta-cell function and insulin sensitivity in patients with type 2 (non-insulin-dependent) diabetes.

This study was designed to evaluate the influence of age, duration of diabetes, relative body weight and glycaemic control on beta-cell function and insulin sensitivity in 250 patients with onset of nonketotic diabetes between the age of 35 and 70 years (Type 2 diabetes). Beta-cell function was assessed by measuring serum C-peptide concentrations after 1 mg of glucagon iv. It was not influenced by age, age at onset of diabetes nor by the duration of the disease. This suggests that progressive deterioration of beta-cell function with time is not a consistent finding in Type 2 diabetes. Insulin sensitivity, measured as the glucose disappearance rate, KITT, in response to iv-insulin, was not significantly influenced by age or age at onset, but decreased consistently with the duration of the disease (P less than 0.001). Beta-cell function was not correlated to fasting blood glucose and HbA1 concentrations. In contrast, there was a strong inverse relationship between glycaemic control and insulin sensitivity (P less than 0.001) indicating that decreased insulin sensitivity contributes to poor glycaemic control in these patients. Attempts to improve glycaemic control in patients with Type 2 diabetes should therefore include means to improve insulin sensitivity.

Adult↗
PubMed1983

Influence of beta-blocking drugs on glucose metabolism in hypertensive, non-diabetic patients.

Two beta-blocking agents, non-selective propranolol and beta 1-selective metoprolol, were investigated with respect to their effect on glucose metabolism in 11 hypertensive, non-diabetic patients. They were randomly treated for two weeks in a double-blind cross-over manner with propranolol, metoprolol and placebo. Both drugs caused a small but significant increase in basal blood glucose values as compared with placebo (p less than 0.01). Metoprolol increased the blood glucose concentrations during the first 10 min of an i.v. glucose tolerance test (IVGTT) as compared with placebo (p less than 0.02) and propranolol (p less than 0.05). Propranolol raised only the blood glucose values during the later part of the IVGTT (p less than 0.01). The increase in blood glucose concentrations was, however, not associated with significant changes in peripheral insulin levels. The mean basal glucagon concentrations were lower during propranolol and metoprolol than during placebo (p less than 0.01). Propranolol also induced a more pronounced reduction of plasma glucagon than placebo (p less than 0.05) at 10 min of the IVGTT. The mean basal free fatty acid (FFA) concentrations were lower during propranolol (p less than 0.001) and metoprolol (p less than 0.05) than during placebo. Both drugs decreased the plasma levels of FFA during the first 10 min of the IVGTT as compared with placebo (p less than 0.01 and p less than 0.02, respectively). Pharmacological doses of propranolol and metoprolol increased blood glucose concentrations, decreased plasma glucagon and FFA concentrations, but had no effect on serum insulin levels in hypertensive, non-diabetic subjects.

Adult↗