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Biomedical subjects

K F Hanssen

Publications and source records attributed to K F Hanssen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus.

The biochemical mechanisms that cause the development and progression of diabetic nephropathy are unknown. Advanced glycation end products (AGEs) might play a role, as shown by increased levels of tissue-bound and circulating AGEs that correlate with the severity of diabetic nephropathy. The aim of the present study was to investigate if circulating AGEs predict the progression of morphological pathology in patients with diabetic nephropathy. We have developed an immunoassay to determine serum levels of AGEs. In a prospective clinical trial of young insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria, kidney biopsies were taken at baseline and after 24 to 36 months. The biopsies were analyzed for structural changes in the glomeruli by quantitative morphometry (electron microscopy). We have retrospectively analyzed serum AGEs. The mean serum level of AGEs at the start of the study was 18.7 U/mL (95% confidence interval [CI], 16.9 to 20.5). A positive correlation between serum AGE levels at the start of study and changes from baseline to follow-up study in basement membrane thickness (r = .56, P < .02) and matrix/glomerular volume fraction (r = .57, P < .02) was demonstrated. In a stepwise regression analysis with changes in the matrix/glomerular volume fraction as the dependent variable, serum AGE levels at the start of the study proved to be a significant independent variable (P < .02), whereas the mean hemoglobin A1c (HbA1c) or HbA1c at the start was not. This study shows that serum AGEs predict the progression of early morphological kidney damage during 2.5 years in patients with IDDM.

Adolescent↗
PubMed1997

Blood glucose control and microvascular and macrovascular complications in diabetes.

High blood glucose levels for several years is the major factor in the development and progression of microvascular complications in IDDM. Reducing mean blood glucose reduces the risk of progression of diabetic microvascular complications substantially. A curve-linear relationship exists between HbA1c levels and progression of diabetic retinopathy. Recent evidence also points to a close relationship between high blood glucose levels and progression of microvascular complications in NIDDM. The relationship between mean blood glucose and cardiovascular disease in diabetes has been unclear. Recent population-based studies give evidence for a linear association of glycemic control with the risk for cardiovascular disease in patients with NIDDM. However, randomized studies comparing different degrees of glycemic control in NIDDM and their impact on cardiovascular morbidity and mortality are urgently needed.

Blood Glucose↗
PubMed1997

Increased serum levels of advanced glycation end products (AGEs) in children and adolescents with IDDM.

OBJECTIVE: To investigate whether the serum levels of advanced glycation end products (AGEs) are increased in IDDM children and adolescents and to study the effect of puberty on serum levels of AGEs (S-AGEs). RESEARCH DESIGN AND METHODS: A total of 68 children and adolescent IDDM patients (age, 13.3 +/- 4.0 years; duration of diabetes, 5.0 +/- 3.6 years; HbA1c, 8.2 +/- 2.0%; Tanner stage [public hair], 1 vs. 2-5, 24/42) recruited from the pediatric outpatient clinic at Aker University Hospital were compared with 25 healthy nondiabetic control subjects. S-AGEs were measured by a fluoremetric immunoassay. RESULTS: S-AGEs were significantly elevated in the diabetic group when compared with the control group (14.4 +/- 3.5 vs. 11.7 +/- 3.0 U/ml, P < 0.002). A significant correlation (r = 0.26, P < 0.04) was found between S-AGEs and HbA1c in the diabetic group but not in the control group. No significant correlation was found between S-AGEs and the duration of diabetes in the diabetic group or S-AGEs and blood glucose concentration or age in either group. We found no difference between S-AGEs in boys and girls and in prepubertal and pubertal diabetic or control subjects. CONCLUSIONS: S-AGEs are increased in young patients with diabetes before puberty. Since AGEs are linked to the pathogenesis of vascular complications, this observation suggests that the pathological processes leading to diabetic late complications start even before puberty.

Adolescent↗
PubMed1996

[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↗
PubMed1996

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↗
PubMed1995

[ACE inhibitors and early diabetic nephropathy].

At present we are able to disclose diabetic nephropathy in the very early stages, i.e. when urinary albumin excretion is only slightly increased (20-200 micrograms/min = microalbuminuria). Good blood glucose control and active antihypertensive treatment may stop or retard the further development towards renal failure. Angiotensin-converting-enzyme (ACE)-inhibitors seem to have a renoprotective effect. In this article we suggest guidelines for the use of ACE-inhibitors in patients with type 1 diabetes and early diabetic nephropathy. Special concerns are included in respect of adolescents, pregnant women and persons with type 2 diabetes.

Albuminuria↗
PubMed1995

Glomerular epithelial foot processes and filtration slits in IDDM patients.

Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p<0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p<0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p<0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r=0.65, p<0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients.

Adolescent↗
PubMed1995

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↗
PubMed1994

The effect of 8 years of strict glycaemic control on peripheral nerve function in IDDM patients: the Oslo Study.

We have investigated the effect of long-term strict glycaemic control on peripheral and autonomic nerve function in 45 IDDM patients (age 18-42 years, diabetes duration 7-23 years) without clinical signs of neuropathy or other neurological disease. They were randomly assigned to treatment either with continuous insulin infusion, multiple injections (4-6 times daily), or conventional treatment (twice daily) for 4 years and followed prospectively for 8 years. Motor and sensory nerve conduction velocities were measured at the start and after 8 years. Autonomic nerve function tests were performed only once, after 8 years. A significant reduction of nerve conduction velocity was observed during 8 years in patients with mean HbA1 more than 10% (n = 12, group mean 10.9%, range 10.1-13.2%) compared to patients with HbA1 less than 10% (n = 33, group mean 9.0%, range 7.5-9.9%). Change of motor nerve conduction velocity in the peroneal nerve was: -4.8 +/- 4.9 (SD) vs -2.2 +/- 5.3 m/s (p < 0.01). Change of motor nerve conduction velocity in the posterior tibial nerve was: -6.8 +/- 5.7 vs- 3.9 +/- 5.1 m/s (p < 0.05). No significant changes were observed in the ulnar nerve. Change of sensoric nerve conduction velocity in the sural nerve was: -8.9 +/- 8.0 vs -4.6 +/- 5.3 m/s (p < 0.05). Multiple regression analysis showed that a change in HbA1 of 1% resulted in a 1.3 m/s change in nerve conduction velocity during 8 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy.

We investigated in a randomized, prospective study the influence of improved blood glucose control during 2-3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n = 9) or CT (n = 9). Kidney biopsies were taken at baseline and after 26-34 months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p = 0.01) during the study in the CSII-group as glycated haemoglobin (HbA1c) fell from 10.1% ([95% CI] 8.9-11.3) to 8.6% (7.9-9.2), but not in the CT-group, 10.1% (8.3-11.9) vs 9.7% (8.7-10.8). Mean HbA1c during the study period was significantly lower in the CSII-group than in the CT-group, 8.7% (8.1-9.3) vs 9.9% (8.5-11.3), p = 0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p = 0.03) in the CT-group: 140 nm (50-230) vs CSII: 56 nm (27-86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p = 0.006) and matrix star volume (p = 0.04). Furthermore, a positive correlation between mean HbA1c during the study and change from baseline in BMT (r = 0.70, p = 0.001) and matrix/glomerular volume fraction (r = 0.33, p = 0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

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↗
PubMed1994

Impaired contrast sensitivity in adolescents and young type 1 (insulin-dependent) diabetic patients with microalbuminuria.

We compared neurosensorial visual function by psychophysical tests (macular recovery time and contrast sensitivity) in two well matched groups of young Type 1 (insulin-dependent) diabetic patients with micro- and normoalbuminuria, respectively. The patients had normal visual acuity (> or = 1.0) and either no retinopathy or non-proliferative retinopathy. Thirty patients with microalbuminuria (albumin excretion > or = 15 micrograms/min in a least two out of three timed overnight urine samples) were matched (age, diabetes duration, mean one-year HbA1c, gender) with normoalbuminuric (n = 27) patients. Retinopathy (50 degree colour fundus photography) was assessed by counting microaneurysms and hemorrhages as 'red spots'. Contrast sensitivity was examined for the spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree (cpd). Macular recovery time (nyctometry) refers to the time-related (2 min) ability of the retina to regain visual acuity following exposure to bright light (photostress). Contrast sensitivity score was reduced in patients with microalbuminuria compared to those without; 18 cpd (mean and 95% confidence intervals): [4.2 (3.8-4.7) vs 5.0 (4.6-5.4), p = 0.03]. Macular recovery performance was not significantly reduced: [21.0 arbitrary units (17.5-24.6) vs 26.0 (22.6-30.7), p = 0.12]. We conclude that impaired contrast sensitivity independent of background retinopathy is shown in a group of young Type 1 (insulin-dependent) diabetic patients with low-grade microalbuminuria compared to a group of patients with normoalbuminuria.

Adolescent↗
PubMed1993

Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria.

Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18-29) years, duration of diabetes 12 (8-15) years, mean blood pressure 93 (87-115) mm Hg, glomerular filtration rate 132 (101-209) ml.min-1.1.73 m2 -2, albumin excretion rate (mean over 1 year) 32 (15-194) micrograms/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549-641 nm) vs 305 nm (287-325 nm), p = 0.0001; mesangial volume fraction 0.22 (0.21-0.23) vs 0.19 (0.18-0.21), p = 0.04, and matrix volume fraction 0.13 (0.12-0.13 vs 0.09 (0.08-0.10), p = 0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗