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Biomedical subjects

T J Berg

Publications and source records attributed to T J Berg.

At least 19 recordsLinked to original sources
PubMed2005

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

Blood Flow Velocity↗
PubMed2003

Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes.

A time-delayed fluorescence immunoassay was developed for the determination of serum levels of methylglyoxal (MG)-derived hydroimidazolone using a monoclonal antiserum raised against Nalpha-acetyl-Ndelta-(5-hydro-5-methyl)-4-imidazolone, Europium-labeled anti-mouse IgG antiserum as indicator, and MG modified bovine serum albumin (BSA) as standard. Serum levels of hydroimidazolone were measured in 45 patients with type 2 diabetes aged 59.4 +/- 6.1 (mean +/- SD) years and with duration of diabetes of 7.3 +/- 3.1 years, and in 19 nondiabetic controls aged 56.3 +/- 4.3 years. The serum levels of hydroimidazolone were significantly higher in patients compared to controls: median, 3.0 (5-95 percentile, 1.6 to 5.4) U/mg protein versus 1.9 (1.2 to 2.8) U/mg protein (P =.0005). Significant positive correlations were observed between the serum levels of hydroimidazolone and serum levels of advanced glycation end products (AGEs), measured with a polyclonal anti-AGE antibody: r = 0.59 for patients (P <.0001), and r = 0.65 for controls (P =.002). Similarly, significant correlations were also found between serum levels of hydroimidazolone and N(epsilon)-(carboxymethyl)-lysine (CML): r = 0.36 in patients and r = 0.55 for controls (both P =.02). Serum hydroimidazolone levels did not correlate with fasting plasma glucose or hemoglobin A(1c) (HbA(1c)) levels. The observed differences between patients with diabetes and nondiabetic controls seem to be comparable to differences measured for other AGE compounds.

Diabetes Mellitus, Type 2↗
PubMed2001

The AGE product N epsilon-(carboxymethyl)lysine serum albumin is a modulator of proteoglycan expression in polarized cultured kidney epithelial cells.

AIMS/HYPOTHESIS: Changes in kidney function in diabetes could be due to changes in the kidney basement membranes. Proteoglycans are important constituents of this kidney extracellular matrix. This study explored the possibility that advanced glycation end products affect proteoglycan synthesis in cultured kidney epithelial cells. METHODS: Madin Darby Canine Kidney (MDCK) epithelial cells were cultured with either low glucose (5 mmol/l), low glucose with 10 micrograms/ml of N epsilon-(carboxymethyl)lysine bovine serum albumin (CML-BSA) or high glucose (25 mmol/l). From day 7-8 cells were labelled with either [35S]sulphate or [3H]glucosamine for 24 h. Labelled macromolecules were purified by gel and ion exchange chromatography, and isolated proteoglycans analysed by gel chromatography and electrophoresis. RESULTS: The CML-BSA treatment reduced the proteoglycan synthesis in MDCK cells. Neither the type of glycosaminoglycan chains made nor the molecular size of the chains was affected. CONCLUSION/INTERPRETATION: At concentrations found in the plasma of diabetes patients CML-BSA, decreases proteoglycan expression in kidney epithelial cells. Advanced glycation end products could, accordingly, promote pathological changes in kidneys of diabetics.

Animals↗
PubMed2000

[Can type 2 diabetes be prevented?].

BACKGROUND: The prevalence of type 2 diabetes among Norwegian men increased from 2.6% to 3.3% from 1986 to 1997. The most important environmental risk factors for type 2 diabetes are obesity and reduced physical activity. Genetic factors are also strongly involved. Biochemical risk factors are impaired glucose tolerance and decreased insulin response. MATERIAL AND METHODS: Only a few small studies have investigated the possibility of primary prevention of type 2 diabetes. RESULTS: In a six-year intervention study on persons with impaired glucose tolerance in China, diet and/or increased physical activity reduced the risk of type 2 diabetes by 30 to 50%. Similar results were found in a study from Sweden. No drug is shown to prevent type 2 diabetes. Possible candidates are metformin and thiazolidinediones which increase insulin sensitivity, and pancreatic lipase inhibitors which reduce the absorption of fat from the gut. Three large, randomised, prospective studies are investigating whether life style intervention or medication can prevent the disease. The results of these studies will be available in about five years. INTERPRETATION: Present evidence clearly indicates that increased physical activity and diet can prevent the development of type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed1999

Central and peripheral arteriovenous passage times of the retina in glaucoma.

The purpose of this paper was to estimate arteriovenous passage (AVP) times, taking into account the non-uniform distribution of arrival times over the vessel diameter, and assessment of respective differences between 15 normal controls (N), 30 primary open-angle glaucoma (POAG) and 30 normal-pressure glaucoma (NPG) patients. Arrival times in retinal vessels were assessed from digitized scanning laser fluorescein angiograms. The arrival times were assessed as a function of position (juxtamural versus axial) in the vessel. This differentiation, based on the measurement position in the vessel, enabled the estimation of AVP times of the posterior pole and of the peripheral retina. The overall, juxtamural and axial AVP times were prolonged in POAG as compared to both N and NPG (P<0.03). The difference in axial AVP times between POAG and normal subjects was considerably larger than the juxtamural values. The distribution of AVP times was considerably larger in POAG patients than in N subjects and NPG patients. Retinal AVP times are prolonged in POAG patients as compared to N and NPG. The wider distribution of AVP times in POAG patients may point to a generalized microvascular alteration. Since the axial AVP times seem to provide the largest differences between NPG and POAG patients, this measurement may be preferred over more general AVP times. The axial AVP times may possibly reflect peripheral vascular changes, e.g. increased vascular resistance. The underlying mechanisms causing these differences are at present unknown.

Blood Circulation↗
PubMed1999

A colorimetric microtiter plate PCR system detects respiratory syncytial virus in nasal aspirates and discriminates subtypes A and B.

We developed a colorimetric microtiter plate (MTP) PCR system for specific detection of the respiratory syncytial virus (RSV) nucleocapsid gene and differentiation of viral subtypes A and B. Of 47 pediatric nasal aspirate specimens, the sensitivity and specificity were 94.4% (17 of 18) and 100% (15 of 15), respectively, when compared with RSV cell culture isolation in HEp-2 cells. An additional 14 specimens positive for adenoviruses, rhinoviruses, influenza, or parainfluenza viruses did not give positive reactions. PCR testing detected a mean of 0.15 (0.01 to 7.00) plaque-forming units of RSV virions. Inhibition of PCR amplification was detected in 33.3% (6/18) of undiluted specimens and could be avoided by a dilution (1:10) of extracted RNA without decreasing test sensitivity. RSV subtype, as determined by allele-specific probes, was identical to that determined by an immunofluorescence assay. These results indicate that the MTP PCR system provides a sensitive and specific test for clinical laboratory diagnosis and simultaneous subgroup classification of RSV infection.

Cell Culture Techniques↗
PubMed1999

Population-based study of the relationship among muscle morphology, insulin action, and hypertension.

To examine whether changes in muscle morphology are linked to the metabolic abnormalities associated with the insulin resistance syndrome, muscle morphology and the metabolic profile were examined in 52 individuals with untreated hypertension (mean arterial pressure [MAP] = 117+/-7 mm Hg) and 38 carefully matched controls (MAP = 89+/-5 mm Hg). Oral glucose tolerance tests and hyperglycemic clamps were performed for measurements of insulin action on glucose disposal and suppression of nonesterified fatty acids (NEFA). Fully automated, computer-aided techniques were used for morphometric measurements of muscle biopsies from m. vastus lateralis. The hypertensive and normotensive groups did not differ in insulin sensitivity to glucose disposal (0.18+/-0.16 v. 0.19+/-0.13 micromol/kg/min/pmol/L; P = .20) and NEFA suppression (87.5+/-7.3 v. 87.2+/-9.4%, P>0.30) during a hyperglycemic clamp. The groups were similar in the proportion of types 1, 2a, and 2b muscle fibers, fiber size, and capillary density. Fiber roundness (ratio of fiber perimeter squared to fiber area) differed in the hypertensive (1.51+/-0.07) and normotensive (1.58+/-0.12, P = .004) groups, showing that the muscle fibers in the hypertensive group were more rounded in shape, a nonspecific change often seen after minimal ischemic lesions. The quotient expressing fiber roundness was associated with systolic (r = -0.29, P = .01) and diastolic (r = -0.32, P = .005) blood pressure. We conclude that persons with mild and moderate hypertension do not have abnormalities in muscle morphology that could explain the impairment of insulin action often observed in this condition. However, hypertensive individuals have increased muscle fiber roundness. It is wondered whether hypertension may be a condition with defects in the regulation of the transmembranous ion transport, leading to raised intracellular sodium concentration, swelling of the cytoplasma, and roundening of the fibers.

Adult↗
PubMed1999

Severity of glomerulopathy predicts long-term urinary albumin excretion rate in patients with type 1 diabetes and microalbuminuria.

OBJECTIVE: To investigate whether the degree of glomerular structural lesions in young patients with type 1 diabetes and microalbuminuria was associated with urinary albumin excretion rate (AER) 6 years later and whether the AER level was influenced by blood glucose control, blood pressure, or glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS: There were 17 young adults with type 1 diabetes and microalbuminuria, 8 men and 9 women with mean age 20 years (95% CI: 18-22) and duration of diabetes of 11 years (10-13), who participated in a 6-year prospective study. Kidney biopsies (measurements of basement membrane thickness [BMT] and mesangial and matrix volume fractions) and GFR were performed at baseline. AER and HbA1c were measured at least three times a year and blood pressure once a year. RESULTS: In a multivariate analysis, baseline BMT and mean 6-year HbA1c contributed significantly to AER at the end of the study (R2 = 0.69, P < 0.01). When mesangial volume fraction replaced BMT as the independent variable, this parameter and AER at baseline predicted the AER at 6 years (R2 = 0.55, P < 0.55). Mesangial volume fraction and BMT (in separate analysis) contributed significantly to change in AER during the study. During the study, neither AER (30 micrograms/min [19-40] to 16 micrograms/min [7-90]) nor blood pressure (96 mmHg [92-102] to 95 mmHg [91-98]) changed significantly in the group. However, HbA1c was reduced from 10.3 (9.6-11.0) to 8.4% (7.8-9.1) (P < 0.01). CONCLUSIONS: In young patients with microalbuminuria, the long-term urinary AER was predicted by the degree of glomerular structural changes and associated with blood glucose control, but not with blood pressure or GFR.

Adolescent↗
PubMed1999

Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes.

OBJECTIVE: Impairment of left ventricular diastolic function, possibly caused by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanced glycation end products (AGEs) cross-link tissue collagen and are found within myocardial fibers. The aim of this study was to examine for a possible association between circulating AGEs and left ventricular cardiac function. RESEARCH DESIGN AND METHODS: Left ventricular diastolic and systolic function were assessed by M-mode and Doppler echocardiography in 52 patients with type 1 diabetes, age 40 +/- 13 (mean +/- SD) years, diabetes duration 17 +/- 13 years, and HbA1c 8.3 +/- 1.1%. Serum levels of AGEs and N epsilon-(carboxymethyl)lysine (CML) were measured by newly developed competitive immunoassays. RESULTS: A positive correlation was found between serum levels of AGEs and isovolumetric relaxation time (IVRT), r = 0.46 (P < 0.0008), and left ventricular diameter during diastole, r = 0.37 (P < 0.008). The systolic parameters did not correlate with serum levels of AGEs. Stepwise regression analysis showed that 21% of the IVRT variation could be explained by serum levels of AGEs (F = 11.4, P < 0.002), whereas serum levels of CML, HbA1c, albumin excretion rate, diabetes duration, and mean arterial blood pressure were of no importance. AGE levels were significantly increased in men compared with women (P < 0.03) and present or former smokers (P < 0.04). CONCLUSIONS: Increased serum levels of AGEs, unlike serum levels of CML, are associated with heart stiffness in patients with type 1 diabetes, possibly mediated by the cross-linking properties of AGEs.

Adult↗
PubMed1999

Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease.

OBJECTIVE: To investigate whether serum levels of advanced glycation end products (AGEs) and the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) are increased in patients with type 2 diabetes compared with nondiabetic control subjects and whether levels of AGEs and/or CML differ in patients with type 2 diabetes with or without coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Serum levels of AGEs and CML were measured with an immunoassay in 32 men and 21 women aged 59.3+/-6.2 years (means +/- SD) with type 2 diabetes for 7.3 + 3.1 years and in 17 men and 17 women aged 56.2+/-4.2 years without diabetes. Of the patients with diabetes, 18 had CHD. RESULTS: The serum levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects (median [5th-95th percentile]: AGEs 7.4 [4.4-10.9] vs. 4.2 [1.6-6.4] U/ml, P < 0.0001; CML 15.6 [5.6-29.9] vs. 8.6 [4.4-25.9] U/ml, P < 0.0001). The median level of AGEs but not CML was significantly increased in patients with type 2 diabetes and CHD compared with patients without CHD (8.1 [6.4-10.9] vs. 7.1 [3.5-9.8] U/ml, P = 0.03). There were significant positive correlations between serum levels of AGEs and CML in both patients and control subjects. CONCLUSIONS: Levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects, and levels of AGEs but not CML were significantly higher in patients with type 2 diabetes and CHD than in patients without diabetes. These results may indicate a role for non-CML AGEs in the development of macrovascular disease in patients with type 2 diabetes.

Aged↗
PubMed1998

The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes.

OBJECTIVE: To investigate whether children and adolescents with type 1 diabetes have increased serum levels of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) at an early stage of the disease. RESEARCH DESIGN AND METHODS: The serum levels of CML in 38 patients with type 1 diabetes aged 14+/-3.2 (mean+/-SD) years were compared with those in 26 control subjects aged 16+/-1.7 years. The mean duration of diabetes was 5+/-4.7 years, ranging from 0.5 to 15 years. The mean levels of HbA1c were 10.3+/-2.5% in the patient group. The serum levels of CML were measured using a monoclonal anti-CML antibody in a fluoremetric immunoassay. Serum protein levels of advanced glycation end products (AGEs) were assayed using a polyclonal antibody from rabbit immunized with AGE-RNase (pAGE). RESULTS: The serum levels of CML and pAGE were significantly increased in the patient group versus the control group: 1.08 (0.45-2.97) U/ml CML (median 10-90 percentiles) vs. 0.70 (0.36-1.79) U/ml CML, P < 0.03, and 6.6 (5.1-9.9) U/ml pAGE vs. 5.5 (3.7-8.2) U/ml AGEs, P < 0.01. A significant relationship between CML and pAGE was found in the IDDM group, r = 0.76, P < 0.001. The CML levels were not associated with the HbAlc levels (n = 23, r = -0.02, NS), cholesterol levels (n = 21, r = 0.07, NS), age, sex, or diabetes duration. CONCLUSIONS: Serum levels of CML are increased in patients with type 1 diabetes. This increase precedes the development of micro- and macrovascular complications.

Adolescent↗
PubMed1998

Hydroperoxides in plasma are reduced by intensified insulin treatment. A randomized controlled study of IDDM patients with microalbuminuria.

OBJECTIVE: An association between reactive oxygen species and diabetic micro- and macrovascular complications has been proposed. In the present study, we have examined the effect of an improved blood glucose control on plasma levels of hydroperoxides in patients with IDDM. RESEARCH DESIGN AND METHODS: Subjects included 30 young IDDM patients with microalbuminuria who were randomized to receive either continuous subcutaneous insulin infusion (CSII) by a portable insulin pump (n = 15) or conventional insulin treatment (CIT) (n = 15) for 24 months. Plasma levels of hydroperoxides were measured by the ferrous oxidation with Xylenol Orange, version 2 (FOX2) assay. This method measures total lipid hydroperoxides and, unlike other methods, does not suffer from extraction losses. RESULTS: The mean HbA1c level was lower in the CSII group at the end of the study than in the CIT group: (mean [95% CI]) 8.6 (8.1-9.1) vs. 9.6 (9.0-10.3)%, respectively (P < 0.002). The level of plasma hydroperoxides was very similar at the start of the study but was significantly lower in the CSII group compared with the CIT group at the end of the study: 2.9 (2.1-3.7) vs. 4.3 (3.2-5.4) mumol/l, respectively (P < 0.02). In the CSII group, hydroperoxides were reduced by 31% from baseline (P < 0.001), whereas there was no change in levels of hydroperoxides in the CIT group. Mean hydroperoxide levels correlated with mean HbA1c during the study (r = 0.39, P < 0.04). Hydroperoxide levels were associated with the levels of microalbuminuria (r = 0.45, P < 0.02). CONCLUSIONS: This study provides support for the hypothesis that hyperglycemia is an important factor in the generation of hydroperoxides, and, thus, reactive oxygen species, in the circulation of IDDM patients.

Adolescent↗
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

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↗
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

The effects of vasoactive intestinal polypeptide and substance P on methacholine-induced sweating and vascular flare in diabetic neuropathy.

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.

Adult↗