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Biomedical subjects

G Sundkvist

Publications and source records attributed to G Sundkvist.

At least 91 records · Page 5Linked to original sources
PubMed1996

Alcohol abuse exaggerates autonomic dysfunction in chronic liver disease.

BACKGROUND: Advanced chronic liver disease is characterized by peripheral arterial vasodilation and increased plasma catecholamine concentrations. These haemodynamic alterations may reflect impaired vascular responsiveness due to autonomic nerve dysfunction. METHODS: Three established non-invasive tests based on the heart reactions to deep breathing (expiratory/inspiratory (E/I) ratio) and to tilt (acceleration and brake indices) were used to evaluate age-related autonomic nerve function in 27 patients with chronic alcoholic and non-alcoholic liver disease. Liver function was estimated by demethylating capacity. The results were compared with a control group consisting of 56 healthy individuals. RESULTS: Overall, 12 patients (52%) had autonomic neuropathy (10 of 13 (77%) patients with alcoholic and 2 of 14 (14%) with non-alcoholic liver disease). Variance analysis showed that the age-corrected E/I ratio, but not the acceleration and brake indices, was significantly decreased compared with controls both in patients with alcoholic and non-alcoholic liver disease, indicating vagal nerve dysfunction (P < 0.0001 and 0.0133, respectively). The decrease in E/I ratio was also significantly more pronounced (-1.77 (0.62) (median (interquartile range)) versus 0.76 (0.70); P = 0.049) in patients with alcoholic compared with non-alcoholic liver disease. Furthermore, in contrast to non-alcoholics, patients with alcoholic liver disease were unable to increase their diastolic blood pressure after return to upright from a tilted position, indicating additional sympathetic neuropathy. CONCLUSIONS: Autonomic, mainly vagal, nerve dysfunction is common in patients with liver diseases and is further exaggerated by alcohol abuse. Autonomic neuropathy may contribute to altered vascular responsiveness in patients with chronic liver diseases.

Autonomic Nervous System Diseases↗
PubMed1995

Autonomic nerve dysfunction in patients with bolus-specific esophageal dysmotility.

The pathogenetic mechanisms causing esophageal dysmotility is not well understood. We examined 13 patients with solid bolus dysphagia in a radiologic barium study including the swallowing of a 14-mm tablet. In all 13 patients the tablet was caught in the proximal or midesophagus. In 8 patients, the entrapment was associated with symptoms (Group 1) whereas in 5 patients (Group 2), no symptoms were reported. All 13 patients together with a control group of 56 healthy, nondysphagic subjects were tested for autonomic nerve function. Autonomic nerve function tests included registration of electrocardiographic R-R interval variation during deep breathing test (E/I ratio), a test of parasympathetic, vagal, nerve function. The results showed that the E/I ratio was significantly lower in patients with symptoms of bolus-specific esophageal dysmotility (-2,19 [1.76]) (median [interquartile range]) compared with patients without symptoms (0.05 [2, 87], p = 0.0192) and controls (-0.25 [1.26], p = 0.0009). In conclusion, symptomatic bolus-specific esophageal dysmotility is associated with vagal nerve dysfunction.

Adolescent↗
PubMed1995

Increased arterial stiffness in women, but not in men, with IDDM.

For unknown reasons, there is a greater increase in the risk for cardiovascular complications in diabetic women than in diabetic men. Our aim was to study gender-related differences in the mechanical properties of the great arteries in patients with insulin-dependent diabetes mellitus (IDDM) but free from known cardiovascular and cerebrovascular complications. We measured arterial stiffness (beta, inversely related to arterial compliance) in the abdominal aorta and the common carotid artery non-invasively using echo-tracking sonography in 30 women (mean age 34 years, range 20-61) and 26 men (mean age 38 years, range 22-56) with IDDM. The results were compared with those of healthy individuals of corresponding age and gender. The results showed a marked gender-difference in changes of arterial stiffness. Arterial stiffness was increased in both the abdominal aorta and the common carotid artery in diabetic women compared to control women (p = 0.0001 and p = 0.0076, respectively). In contrast, there was no significant difference in stiffness of the abdominal aorta or the common carotid artery between the diabetic men and the control men (p = 0.69 and p = 0.39, respectively). In conclusion, this study has shown that stiffness of the aorta and the common carotid artery is increased in diabetic women but not in diabetic men. Increased arterial stiffness in diabetic women may be a pathogenic factor which could help to explain the gender-related differences in the risk for cardiovascular and cerebrovascular complications in diabetic subjects.

Adult↗
PubMed1995

Long-term effects of alloxan in mice.

The long-term effects of subdiabetogenic doses of alloxan monohydrate (< 70 mg/kg) were studied in the mouse. When injected intravenously at 50 and 60 mg/kg, alloxan induced a marked albeit transient hyperglycemia; plasma levels gradually declined after 15 d and were normal after 60 d in 20 of 31 animals. After injection of alloxan at the dose of 40 mg/kg, only a slight transient hyperglycemia was seen during the first 15 d. At 2 mo after alloxan injection, however, glucose- and carbachol-stimulated insulin secretion were markedly impaired in all animals treated with alloxan, including those with normoglycemia. The pancreatic content of insulin was significantly reduced at 2 mo after treatment of alloxan at 50 or 60 mg/kg, but, however, not after 40 mg/kg. It is concluded that (1) Subdiabetogenic doses of alloxan (50 and 60 mg/kg) induce a persistent hyperglycemia only in approx 25% of the animals; (2) The insulin secretory responses to glucose and carbachol are impaired after alloxan treatment; and (3) Alloxan-induced B-cell toxicity is evident also in animals not developing permanent diabetes. Hence, although a repair process may be initiated after alloxan to normalize the hyperglycemia, insulin secretion and pancreatic insulin content do not normalize.

Alloxan↗
PubMed1995

Glutamate decarboxylase antibody levels predict rate of beta-cell decline in adult-onset diabetes.

Glutamate decarboxylase autoantibodies (GAD65Ab) and beta-cell function were evaluated at and 3 years after diabetes onset in consecutive subjects over 15 years of age. At onset, 21/32 (66%) insulin-treated patients (mean age 43, range 16-79 years) had GAD65Ab; all GAD65Ab persisted 3 years later. At onset, 20/82 (24%) non-insulin-treated patients (mean age 56, range 20-79 years) had GAD65Ab. Of those with persistent GAD65Ab, 8 non-insulin-treated and 11 insulin-treated patients consented to follow-up glucose and glucagon stimulation tests. For non-insulin-treated patients, quantitative GAD65Ab index at onset correlated inversely with 1 + 3 min C-peptide response to glucose (r = -0.68, P < 0.05) and to glucagon (r = -0.79, P < 0.05) 3 years later. Those with high (> 0.50) initial GAD65Ab index had lower C-peptide (fasting, 1 + 3 min after glucose and after glucagon) 3 years later, versus those with low (< 0.50) initial GAD65Ab index (P < 0.05). In conclusion, not only did GAD65Ab presence predict future insulin dependence, but higher GAD65Ab levels may mark more rapid decline in beta-cell function in apparent non-insulin-dependent diabetes.

Adolescent↗
PubMed1995

Prospective study of autonomic nerve function in type 1 and type 2 diabetic patients: 24 hour heart rate variation and plasma motilin levels disturbed in parasympathetic neuropathy.

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

Adolescent↗
PubMed1995

Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children.

Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not DQA1*0301/B1*0302 (DQ8), and IAA with DQA1*0301/B1*0302 (DQ8; P = 0.03) but not DQA1*0501/B1*0201 (DQ2). GAD65ab were more prevalent in females than males (79 vs. 63%; P < 0.0001) but did not vary with onset age nor season. Combining the three antibody assays yielded sufficient sensitivity for screening. GADab were relatively sensitive/specific for diabetes, but even with HLA marker combinations yielded predictive values insufficient for early immunointervention in the low-prevalence general population.

Adolescent↗
PubMed1995

Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of IDDM. Members of the Swedish Childhood Diabetes Study.

The association between human leukocyte antigen (HLA) and insulin-dependent diabetes was studied in a large population-based investigation using genotyping of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. As many as 97% of patients compared with 75% of control subjects were positive for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB was present among 28% of patients, indicating that this residue alone does not confer protection. Combining Asp-57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1 did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQ8) and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid substitutions in the beta-chain, but DQ8 was positively (odds ratio 8.07; P < 0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the disease. Molecular modeling was used to determine whether physiochemical properties such as steric factors and surface electrostatic potentials also differ in a systematic way for various DQ molecules. Amino acids were substituted systematically at the four polymorphic sites, and the solvent-accessible surfaces and electrostatic potentials were computed for each molecule. Dramatic alterations in electrostatic potential were seen for double substitutions at position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical properties due to polymorphic substitutions may be significant to the mechanism of HLA-DQ association with insulin-dependent diabetes, via the effect these property variations have on peptide antigen binding selectivity and subsequent interactions with specific T-cell receptors.

Adolescent↗
PubMed1994

Islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface antibodies (ICSA) and C-peptide in 1031 school children in a population with a high background incidence of IDDM.

Islet cell antibodies (ICA), insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) together with C-peptide were determined in 1031 healthy schoolchildren to evaluate the frequency of autoimmune reactions towards endocrine pancreas and its relation to insulin secretion in non-diabetic children. The prevalence of ICA (levels > 6 JDF units) was 1.4% (14/1012) while 44 children (4.3%) were ICSA-positive and 40 (4%) had IAA. Girls had higher titres of ICSA than boys. Young children (7-8 years) more often had IAA than 12-13-year-old children who, however, had ICA three times more often than the young children. There were no clear associations between the different antibodies. Of the children, 2.4% had very low post-prandial serum C-peptide values (< or = 0.25 nmol/l). Serum C-peptide was higher in girls than in boys (P < 0.001) and in older children than in younger (P < 0.001). Girls with low levels of ICA had high C-peptide values, while girls with high ICA titers had low C-peptide values, the latter perhaps indicating partial beta cell loss. IAA and ICSA were not related to C-peptide values but both positive ICSA and high C-peptide values were most common in the autumn (P < 0.02 and P < 0.0001, respectively). One of the ICA-positive children developed diabetes in 1991, 4 years after the blood sample was taken. Since after 5 years only one of the children has developed IDDM, it can be concluded autoimmune reactions towards endocrine pancreas and insulin may occur in many children without the development of manifest diabetes. Those with high ICA titers may have lost so many beta cells that their insulin secretion is affected, which in some cases might lead to diabetes many years later.

Adolescent↗
PubMed1994

Glutamic acid decarboxylase antibodies, autonomic nerve antibodies and autonomic neuropathy in diabetic patients.

To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GAD-ab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p < 0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures.

Adrenal Medulla↗
PubMed1994

Islet cell antibodies are associated with beta-cell failure also in obese adult onset diabetic patients.

To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43 +/- 3 years), 55 nonobese ICA-negative (mean age at diagnosis 58 +/- 2 years), 7 obese ICA-positive (mean age at diagnosis 57 +/- 5 years), and 139 obese ICA-negative (mean age at diagnosis 58 +/- 1 years). Fasting C-peptide decreased (P < 0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6 +/- 0.6 versus 24.5 +/- 0.4; P < 0.05), lower fasting C-peptide (0.14 +/- 0.06 nmol/l versus 0.71 +/- 0.07 nmol/l; P < 0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%); P < 0.001] than nonobese ICA-negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Diabetes mellitus but not impaired glucose tolerance is associated with dysfunction in peripheral nerves.

To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.

Age Factors↗
PubMed1994

Relationships between diabetes duration, metabolic control and beta-cell function in a representative population of type 2 diabetic patients in Sweden.

To clarify whether metabolic control and beta-cell function deteriorate with increasing duration of diabetes, we investigated in a cross-sectional study Type 2 diabetic patients in an area-based population. Type 2 diabetic patients (n = 231: 112 males, 119 females) were identified by age at onset > or = 35 years, fasting levels of C-peptide > 0.04 nmol l-1, and absence of islet cell antibodies. Body weight was slightly elevated (BMI 26.8 +/- 0.3 kg m-2), however 76/210 (36%), had normal weight (BMI < 25 kg m-2). Fasting blood glucose rose significantly during the first 10 years of known diabetes from 8.2 +/- 0.3 mmol l-1 in patients with 0-5 years of duration to 9.9 +/- 0.7 mmol l-1 in those with 5-10 years of duration, p < 0.01 and HbA1c from 6.4 +/- 0.2 to 7.4 +/- 0.4%, p < 0.05. Fasting C-peptide levels decreased after 10 years duration from 0.90 +/- 0.06 nmol l-1 during 5-10 to 0.69 +/- 0.08 nmol l-1 during 10-15 years of diabetes, p < 0.05. The proportion of insulin treated patients increased from 13% (12/94) with 0-5 years of duration to 33% (13/39) with 10-15 years and 60% (18/30) with more than 15 years of duration. In conclusion in Type 2 diabetic patients without signs of autoimmunity, metabolic control, and beta-cell function deteriorate with increasing duration of diabetes, leading to common but not inevitable occurrence of 'secondary failure'.

Adult↗
PubMed1994

Islet cell antibodies, but not glutamic acid decarboxylase antibodies, are decreased by plasmapheresis in patients with newly diagnosed insulin-dependent diabetes mellitus.

The effects of plasmapheresis on islet autoantibody levels, C-peptide (beta-cell function), and hemoglobin-A1c (HbA1c, metabolic control) were tested in a prospective blinded study of 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients randomly assigned to receive plasmapheresis (P), carried out as double filtration, or sham (S) treatment at diagnosis and 3 months thereafter. At diagnosis, 6 of 8 patients (75%) in group P and 9 of 10 patients (90%) in group S had islet cell antibodies (ICA), whereas 4 of 8 (50%) and 7 of 10 (70%) patients, respectively, had glutamic acid decarboxylase antibodies (GAD65-Ab), with no significant differences between the groups in ICA and GAD65-Ab levels. After 6 months, P patients showed significantly lower ICA levels than S patients (11 +/- 6 and 128 +/- 47 Juvenile Diabetes Foundation International Units, respectively; P < 0.02) due to an increase in ICA levels in 8 of 9 (88%) of the S patients not seen in P patients (P < 0.002). Concurrently, HbA1c stabilized in P, but not in S, patients and was significantly lower by 24 months (6.58 +/- 0.54% vs. 9.76 +/- 1.21%; P < 0.05). Moreover, fasting C-peptide increased significantly (214 +/- 11 pmol/L; P < 0.05) over the first 6 months in P. After the initial 6 months, ICA levels tended to decrease in all patients and were not detected after 60 months. GAD65-Ab levels were not influenced by plasmapheresis and, also in contrast to ICA, increased significantly (P < 0.05) in the whole study population after 60 months. In fact, 4 initially negative patients became GAD65-Ab positive after diagnosis (in 2 patients > 24 months after diagnosis). We conclude that plasmapheresis of newly diagnosed IDDM patients does not change subsequent GAD65-Ab levels, but ICA are significantly decreased with associated improved C-peptide and HbA1c levels.

Adolescent↗
PubMed1993

HLA-DR3, DQ2 homozygosity in two patients with insulin-dependent diabetes mellitus superimposed with ulcerative colitis and primary sclerosing cholangitis.

Two unrelated young males with the unusual simultaneous presence of insulin-dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi-organ autoimmune disease.

Adolescent↗
PubMed1993

HLA DR and DQ RFLP analysis in Crohn's disease.

A study of 109 Swedish patients and 85 healthy Swedish controls with Crohn's disease (CD) by HLA class II RFLP genotyping was carried out. There was no significant association for any single DR or DQ specificity or phenotypic combination of DR and/or DQ specificities among our study group of Caucasian extraction.

Base Sequence↗