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Biomedical subjects

S Vaaler

Publications and source records attributed to S Vaaler.

At least 37 records · Page 2Linked to original sources

Serum lipoprotein(a) and cardiovascular disease in non-insulin-dependent diabetes mellitus.

OBJECTIVE: To examine whether lp(a) can explain a) the increased cardiovascular morbidity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and b) the wide variation in the tendency for such complications to develop in the patients. DESIGN: Cross-sectional study. SETTING: General practice in a local community in Norway. SUBJECTS: One hundred and thirty NIDDM patients and a reference group drawn from a twin study. MAIN OUTCOME MEASURES: Lp(a), self-reported cardiovascular disease, urinary albumin excretion. RESULTS: The level of lp(a) was equally distributed in our NIDDM population and a reference group. We found no association between lp(a) and self-reported cardiovascular disease and urinary albumin excretion (UAE). CONCLUSION: Lp(a) cannot explain the increased risk for cardiovascular disease in NIDDM patients, nor can it explain the variation in the tendency for such complications to develop.

Adult↗

[Insulin treatment is of value--also in type 2 diabetes].

Consensus has not been reached about the optimal treatment of type 2 diabetes, and several authors have questioned the use of insulin for this disorder. The reasons are that an association has been found between hyperinsulinaemia and cardiovascular disease in non-diabetic men, and the sparse evidence of a beneficial effect from tight glycaemic control in prevention of late complications in type 2 diabetes. We discuss the pathophysiology of atherosclerosis in type 2 diabetes, and review some of the recent literature. We find it likely that, in the metabolic cardiovascular syndrome found in many patients with type 2 diabetes, insulin resistance is more important than the accompanying hyperinsulinaemia. Furthermore, evidence is emerging of a strong association between hyperglycaemia and atherosclerotic vascular disease in patients with type 2 diabetes. We conclude that insulin treatment should be used in type 2 diabetic patients when the hyperglycaemia cannot be controlled by oral agents.

Diabetes Mellitus, Type 2↗

NIDDM: a rapid progressive disease. Results from a long-term, randomised, comparative study of insulin or sulphonylurea treatment.

The objective of the present study was to assess the relative efficacy of insulin or glibenclamide treatment for non-insulin-dependent diabetes mellitus (NIDDM) over 42 months. We performed a randomised, controlled trial allocating patients treated with diet and oral antihyperglycaemic agents to treatment with glibenclamide or insulin to achieve HbAlc levels under 7.5%. We included 36 subjects with established NIDDM of more than 2 years' duration. Mean HbAlc levels were significantly reduced in patients allocated to insulin treatment from 9.1 +/- 1.4% before the start to 7.8 +/- 1.3% (p < 0.05) after 1 year, and did not change significantly thereafter throughout the study period. Mean HbAlc levels increased during the study in the patients allocated to glibenclamide treatment, and 11 of 18 patients had to be switched to insulin treatment due to increasing hyperglycaemia (HbAlc > 10%). Mean body weight increased in the subjects allocated to insulin by 7.2 +/- 4.1 kg during the study period. In conclusion, insulin was more effective than glibenclamide treatment in obtaining control over hyperglycaemia in these patients, and once improved, glycaemic control did not deteriorate over 42 months in the insulin-treated group. Two thirds of the patients allocated to glibenclamide treatment had to be given insulin due to inadequate glycaemic control.

Aged↗

Bone mass in non-insulin-dependent diabetes mellitus.

In view of the contradictory results of earlier reports regarding bone mass in patients with non-insulin-dependent diabetes, we measured bone mass using dual X-ray absorptiometry and ultrasound measurements of the right calcaneus in 36 type 2 diabetic subjects, i.e. 21 men and 15 postmenopausal women aged 40-65 years, and compared their bone mass to a sex- and age-matched control group. We also measured several metabolic parameters in the diabetic population and studied the relationship between these metabolic parameters and the bone parameters using correlation analysis. We found a tendency to higher bone mass in the diabetic subjects compared to the normal controls. In the Type 2 diabetic postmenopausal women, fat mass and lean body mass correlated positively with total body bone mineral density (BMD) (r = 0.53 and 0.68), and with total body bone mineral content (BMC) (r = 0.58 and 0.77). Insulin sensitivity (GDR/I) correlated negatively with total body BMC and BMD (r = -0.68 and -0.61). Serum insulin correlated positively with the same bone parameters. When controlling for fat mass or lean body mass using a multiple regression analysis, the correlation between insulin sensitivity and BMD became non-significant. This suggests that body mass is a more important determinant of BMD than hyperinsulinaemia or insulin resistance in diabetic women. Among the diabetic men there was a significant positive correlation between lean body mass and BMC (r = 0.66), between serum oestrone and BMD (r = 0.49) and between serum insulin and femoral neck BMD (r = 0.53).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Insulin-mediated increase in calf blood flow is not related to blood pressure levels in patients with type 2 diabetes mellitus.

An association between insulin resistance and blood pressure levels has been found both in non-diabetic subjects and in type 2 diabetic patients. In non-diabetic subjects, infusion of insulin increases skeletal muscle blood flow, and it has been suggested that an attenuated flow-response to insulin may cause insulin resistance and may also serve as a mechanism relating insulin resistance to elevated blood pressure. We wanted to explore whether these findings could be extended to patients with type 2 diabetes. The effect of insulin infusion during a hyperinsulinaemic euglycaemic glucose clamp investigation on calf blood flow and its relationship to average diastolic blood pressure (DBPAVG), insulin sensitivity (GFRIlbm), body fat and total exercise capacity (TEC) was examined in 11 patients with type 2 diabetes. We found that insulin infusion increased median calf blood flow from 2.3 to 2.7 ml/min.100 g (p = 0.01). The change in blood flow (delta flow) did not correlate to the subjects' average blood pressure levels or their insulin sensitivity. Significant correlations between delta flow and leg fat %, fasting and clamp-insulin levels and total exercise capacity were observed. In conclusion, we found that insulin infusion increased calf blood flow significantly in patients with type 2 diabetes. However, our hypothesis that a negative correlation exists between blood pressure levels and insulin stimulated blood flow, was invalidated. Leg fat was identified as an important predictor of delta flow, GDRILBM and TEC in these patients.

Aged↗

A long-term, randomized, comparative study of insulin versus sulfonylurea therapy in type 2 diabetes.

OBJECTIVES: To study the effect of insulin and sulfonylurea (SU) therapy on glycaemic control, insulin resistance and cardiovascular risk factors in type 2 diabetic subjects. DESIGN: A prospective, parallel, randomized, controlled, long-term study. SETTING: Outpatient clinic in tertiary referral centre. SUBJECTS: Thirty-six type 2 diabetic subjects treated with diet and SU, aged 44-69 years and a duration of diabetes of between 2 and 14 years. INTERVENTIONS: Individually adjusted doses of insulin and glibenclamide. MAIN OUTCOME MEASURES: Glycosylated haemoglobin (HbA1c), insulin resistance (euglycaemic glucose clamp), levels of lipids, lipoproteins and blood pressure. RESULTS: Glycaemic control improved during insulin treatment, but deteriorated on SU; HbA1c levels differed significantly between groups after 12 months of therapy (mean +/- SEM 7.9 +/- 0.3 vs. 9.5 +/- 0.4%, P = 0.004). Body mass index increased significantly during insulin treatment (26.4 +/- 0.7 to 27.8 +/- 0.7 kg/m2, P = 0.0001) and 30% of this increase was a result of an increase in lean body mass. The total glucose disposal rate showed a small increase in the insulin group. Levels of triglycerides and apolipoprotein B were significantly reduced during insulin treatment (1.8 +/- 0.2 to 1.5 +/- 0.2 mmol L-1, P = 0.03 and 1.58 +/- 0.1 to 1.40 +/- 0.08 g L-1, P = 0.003), and insulin prevented a reduction in the levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 and an increase in Lp(a) lipoprotein observed in the SU group. Blood pressure levels did not change during therapy. CONCLUSIONS: Insulin therapy was superior to SU treatment in achieving good metabolic control. Despite a modest improvement in cardiovascular risk factors in the insulin-treated group, no significant differences were observed between the groups after 1 year's treatment.

Aged↗

Increased plasma glucose levels after Hypnorm anaesthesia, but not after Pentobarbital anaesthesia in rats.

The effects of the fentanyl fluanisone combination (Hypnorm) and pentobarbitone sodium (Pentobarbital) anaesthesia on blood glucose, insulin and glucagon were tested in rats in the fed and fasted state. Blood glucose was measured before and at 10, 20 and 30 min after injection of the anaesthetic agents. At 30 min the rats were sacrificed, and blood was drawn for measurement of glucagon and insulin. Pre-anaesthetic values for insulin and glucagon were established in separate groups of fasted and fed rats. In fasting rats given Hypnorm, blood glucose and plasma insulin were unchanged while there was a non-significant increase in plasma glucagon. The fasted rats given Pentobarbital had unchanged blood glucose and plasma insulin and a non-significant depression of glucagon. The fed rats given Hypnorm had a significant increase in blood glucose at 10 min and nearly a doubling of glucose values at 20 and 30 min (P < 0.001). Glucagon increased far less than in the fasted group, whereas insulin was doubled from preanaesthetic values (P < 0.05). The fed rats given Pentobarbital, had unchanged blood glucose, a slight non-significant depression of glucagon and a significant increase in insulin (P < 0.01). Thus Hypnorm induced hyperglycaemia in fed but not in fasted rats, probably because more glucose was available in the fed state. Fed animals are a modification of the standard fasted animal model, and may be preferable when exploring hyperglycaemic or other reactions to anaesthetic agents.

Anesthesia↗

Long-term randomized placebo-controlled double-blind therapeutic comparison of glipizide and glyburide. Glycemic control and insulin secretion during 15 months.

OBJECTIVE: To examine the long-term (15 months) effects on glycemic control and insulin secretion of glipizide and glyburide treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Prospective, randomized, double-blind, placebo-controlled study on 46 NIDDM patients comparing fasting levels and test-meal responses of glucose and insulin during 15 months of follow-up. RESULTS: A comparable reduction in HbA1c levels by both agents versus placebo was observed throughout the study period, but after a marked initial reduction in both sulfonylurea groups, all three groups showed gradually increasing HbA1c levels. However, both glipizide and glyburide achieved and maintained lowered postprandial glucose levels and increased fasting and postprandial insulin levels compared with placebo. CONCLUSIONS: Both glipizide and glyburide may achieve and maintain glycemic reduction and stimulation of insulin secretion during long-term treatment. However, these agents do not prevent the gradual increase in overall glycemia that develops over time in NIDDM patients.

Blood Glucose↗

Hyperproinsulinemia of type II diabetes is not present before the development of hyperglycemia.

OBJECTIVE: To examine proinsulin and insulin levels in first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Comparison of insulin and proinsulin responses to an oral glucose tolerance test in four groups of individuals: 1) 31 patients with newly diagnosed NIDDM treated with diet alone, 2) 34 first-degree relatives of NIDDM patients with impaired glucose tolerance (IGT), 3) 26 relatives with normal glucose tolerance (NGT), and 4) 30 subjects without a family history of diabetes. RESULTS: Both fasting and post-glucose levels of proinsulin were elevated in patients with diabetes, but not in the relatives with IGT or NGT. Levels of true insulin were highest in the diabetic group, followed by the subjects with IGT, and were lowest among relatives with NGT. Proinsulin levels correlated with glucose levels, suggesting that hyperglycemia is the main stimulus for increased proinsulin secretion. CONCLUSIONS: First-degree relatives of NIDDM patients, who have a high risk of developing diabetes, do not exhibit elevated levels of fasting or glucose-stimulated proinsulin as long as their fasting glucose levels remain normal.

Blood Glucose↗

Fructosamine cannot replace HbA1c in the management of type 2 diabetes (NIDDM).

OBJECTIVE: To compare HbA1c, fructosamine, and blood glucose and discuss to what degree Hba1c can be replaced by fructosamine. DESIGN: Cross-sectional study. PATIENTS: 87 unselected patients coming for 112 consecutive consultations. MAIN OUTCOME MEASURES: Fructosamine, HbA1c, blood glucose. RESULTS: The following Pearson correlation coefficients were found: Blood glucose/fructosamine 0.45, HbA1c/blood glucose 0.64, and HbA1c/fructosamine 0.39. Sensitivity and specificity of fructosamine and blood glucose to detect HbA1c > or = 8.0% was shown. CONCLUSION: Our study indicates that fructosamine and fasting capillary blood glucose are poor indicators of the level of HbA1c in NIDDM patients.

Adult↗

Oral glucose tolerance test in general practice--when is it worthwhile?

OBJECTIVE: To examine the probability of impaired glucose tolerance and diabetes, diagnosed with oral glucose tolerance test, at different levels of fasting blood glucose. DESIGN: When indicated, fasting capillary whole blood glucose was measured. Patients with blood glucose ranging from 4.4 to 6.6 mmol/l had an oral glucose tolerance test. SETTING: General practice. SUBJECTS: 355 patients had an oral glucose tolerance test. RESULTS: 33% had impaired glucose tolerance and 12% had diabetes. One or more diabetics were found at every level of fasting blood glucose. The probability of finding a diabetic was ten times larger in the fasting blood glucose stratum 6.1 to 6.6 mmol/l than in the fasting blood glucose stratum 4.4 to 4.9 mmol/l. Likelihood ratio increased 30 times from the lowest to the highest stratum. No cutoff point in the interval 4.4 to 6.6 mmol/l had both a high sensitivity and a high specificity for the diagnosis of diabetes. CONCLUSION: If it is of great importance to find every patient with impaired glucose tolerance and diabetes, one has to do an oral glucose tolerance test in every fraction of the fasting blood glucose range 4.4 to 6.6 mmol/l (according to WHO's diagnostic criteria). Using 5.2 mmol/l as a cutoff point for an oral glucose tolerance test, the sensitivity is still high (0.95), but one would miss a few with diabetes.

Adolescent↗

Haemorrhage-induced increases in glucose, glucagon and insulin levels are blocked by naloxone in rats.

OBJECTIVE: To find out if the opioids that are liberated during bleeding influence the concentrations of glucagon, insulin, somatostatin, corticosterone and glucose in rats, and if naloxone has any regulatory effect. DESIGN: Laboratory study. SETTING: University hospital. MATERIAL: 56 Male Wistar rats. INTERVENTIONS: Removal of blood corresponding to 2% of body weight through a catheter in the internal jugular vein. Before bleeding (n = 8), and at 5, 15 and 30 minutes afterwards (n = 16 at each time point, half of which had received naloxone 0.04 mg/ml, 0.7 ml/hour, for 10 minutes before bleeding and up to 30 minutes afterwards) rats were killed and samples of heart blood taken. MAIN OUTCOME MEASURES: Concentrations of glucose, glucagon, insulin, somatostatin, and corticosterone in heart blood. RESULTS: In the control group (saline) concentrations of glucose, glucagon and insulin increased significantly after bleeding, and had returned to baseline concentration by 30 minutes. Naloxone blocked the increases in the treated group. CONCLUSION: Endogenous opioids, possibly endorphin, may be important in the acute regulation of blood glucose, glucagon and insulin concentrations after haemorrhage.

Animals↗

Glycemic thresholds for hypoglycemic responses in obese subjects.

The objective of this study was to compare glycemic thresholds for hypoglycemic responses in obese and control subjects. A modified glucose-clamp technique was used to produce a standardized fall in plasma glucose (0.5 mmol/l per 40 min) in nine morbidly obese and ten control subjects. The release of the counter-regulatory hormones was measured and a symptom questionnaire was filled out every 10 min. The hypoglycemic thresholds (taken as the plasma glucose level where the response exceeded the basal level +2 s.d.) were practically identical in the two groups both for the hormones and the symptoms (including hunger). Our results argue against the hypothesis that an increased sensitivity to a falling plasma glucose is of importance in the pathogenesis of obesity.

Adult↗

Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes.

The level of sex hormone-binding globulin (SHBG) is associated with glucose metabolism in nondiabetic women and men, and the finding of low SHBG levels is suggested to be a predictor of the development of type 2 (noninsulin-dependent) diabetes mellitus. To further assess the relationship between SHBG levels and glucose metabolism, we measured serum concentrations of sex hormones and SHBG in 23 well characterized diabetic men, and studied the relationship between these variables and parameters of glucose and lipid metabolism. Insulin sensitivity was estimated using the hyperinsulinemic euglycemic glucose clamp technique. There was a strong positive correlation between the level of SHBG and the sensitivity to insulin in these individuals (r = 0.74; P < 0.001), which was independent of obesity and abdominal fat accumulation. Controlling for the effect of fasting C-peptide and insulin levels did not change the correlation coefficient significantly. SHBG levels did not correlate with levels of free testosterone (F-T), free estradiol (F-E2), or F-T/F-E2 ratio. F-E2 was positively correlated with levels of diastolic blood pressure and triglycerides (r = 0.44; P < 0.05 and r = 0.62; P < 0.001, respectively). These findings support earlier observations that associate insulin resistance with levels of SHBG, and for the first time demonstrate a direct correlation between sensitivity to insulin and SHBG levels in men with type 2 diabetes.

Adipose Tissue↗

Reproducibility of glycaemic thresholds for activation of counterregulatory hormones and hypoglycaemic symptoms in healthy subjects.

Nine healthy subjects were studied on two separate occasions, at least two weeks apart, using the glucose clamp technique to produce a gradual hypoglycaemia. Glucose thresholds for neuroendocrine and symptom responses varied up to 1.5 mmol/l between subjects. There was a significant correlation between individual glucose thresholds on day 1 and 2 for adrenaline (p = 0.0008), growth hormone (p = 0.007) and pancreatic polypeptide (p = 0.02), and for autonomic (p = 0.018) and neuroglycopoenic (p = 0.023) symptoms, whereas no significant correlations were found for glucagon and cortisol. The mean intra-individual differences in glucose thresholds between day 1 and 2 were 0.22 mmol/l for the hormones and 0.25 mmol/l for the symptoms. We conclude that healthy subjects differ in hypoglycaemic thresholds, and that the difference reflects individual variation.

Adult↗

Relationship between blood pressure and in vivo action of insulin in type II (non-insulin-dependent) diabetic subjects.

In nondiabetic hypertensive subjects, a relationship has been found between insulin resistance and level of blood pressure. Since type II (non-insulin-dependent) diabetic subjects are often both insulin-resistant and hypertensive, we studied the relationship between insulin resistance and blood pressure level in a group of patients with type II diabetes. Fourteen women and 19 men with diabetes for 2 to 14 (mean, 7.4) years, treated with diet alone (five subjects) or combined with hypoglycemic agents, were studied. Their average hemoglobin A1c (HbA1c) levels during the study period were 6.6% to 11.7% (mean, 8.6%), and their body mass indexes (BMI) were 20.8 to 33.1 (mean, 26.3) kg/m2. Insulin sensitivity was measured using the hyperinsulinemic, euglycemic glucose clamp technique, and an insulin-sensitivity index was calculated as the ratio of the glucose disposal rate (GDR) to the insulin concentration during clamp (GDR/I). The average of three to eight measurements of diastolic blood pressure (DBP) during the study period (9 to 24 months) in each subject was 79 to 111 (mean, 95.1) mm Hg, and DBP also showed significant correlations to BMI (r = .54) and fasting C-peptide level (r = .38). In a multiple regression model, GDR/I, antihypertensive treatment, and known duration of diabetes were significant and independent predictors of variations in blood pressure, and GDR/I could account for 35% of the observed variations in DBP. We conclude that, in accordance with what has been found in nondiabetic hypertensives, DBP correlates significantly to insulin resistance in type II diabetic subjects.

Antihypertensive Agents↗

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations.

OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Adult↗

Pre- and postoperative glucose levels for eliciting hypoglycaemic responses in a patient with insulinoma.

Counterregulatory hormones and hypoglycaemic symptoms were studied during a gradual decline in plasma glucose in a 66-year-old man before and 9 weeks after removal of an insulin-producing tumour. Before surgery the adrenaline started to respond first at plasma glucose 2.8 mmol l-1. He reported no autonomic symptoms although plasma glucose fell to 2.3 mmol l-1 with a corresponding adrenaline rise to 4.64 nmol l-1. After surgery adrenaline responded at a plasma glucose of 3.7 mmol l-1 and he started to sweat and tremble at a plasma glucose of 3.1 mmol l-1 (corresponding adrenaline 2.63 nmol l-1). The lack of autonomic symptoms preoperatively may indicate adrenaline insensitivity, possibly as a result of repeated hypoglycaemia.

Aged↗