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1.
Diabet Med ; 23(11): 1180-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17054592

ABSTRACT

AIMS: To determine differences in pancreatic B-cell function in relation to islet antibodies at diagnosis of diabetes and 3 years later in subjects aged 35-64 years old compared with those aged 0-34 years. METHODS: From a population-based diabetes register, 46 (0-34 years old) and 323 (35-64 years old) incident diabetic patients were investigated at diagnosis and 3 years later. Islet cell antibodies (ICA, GADA and IA-2A) and fasting plasma C-peptide were measured. RESULTS: Islet antibodies were found in 80% of the subjects aged 0-34 years and in 11% of those aged 35-64 years at diagnosis. ICA and GADA was the only combination of two islet antibodies detected in those aged 35-64 years and was, with or without IA-2A, associated with significantly lower median fasting C-peptide values than in those without or with only one antibody [0.35 nmol/l, interquartile range (IQR) 0.63 vs. 0.85 nmol/l, IQR 0.49; P = 0.0004]. However, fasting C-peptide in subjects aged 35-64 years old with multiple islet antibodies was higher than in those aged 0-34 years with islet antibodies (median 0 nmol/l, IQR 0.16, P = 0.0019). After 3 years' follow-up, fasting C-peptide was even lower in subjects aged 35-64 years old with three islet antibodies (median 0.14 nmol/l, IQR 0.27; P = 0.05). CONCLUSIONS: Islet antibodies were common in adults at diagnosis of diabetes. The combination of ICA and GADA indicates impaired B-cell function at diagnosis of diabetes in those aged 35-64 years old.


Subject(s)
Autoantibodies/immunology , Diabetes Mellitus/immunology , Insulin-Secreting Cells/immunology , Islets of Langerhans/immunology , Adolescent , Adult , C-Peptide/blood , Child , Child, Preschool , Diabetes Mellitus/physiopathology , Humans , Infant , Infant, Newborn , Middle Aged
2.
Diabetologia ; 49(8): 1785-94, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16783473

ABSTRACT

AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.


Subject(s)
Autoantibodies/analysis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/genetics , HLA-DQ Antigens/genetics , Insulin-Secreting Cells/physiology , Adolescent , Adult , C-Peptide/blood , DNA Primers , Diabetes Mellitus/pathology , Female , Genotype , Glutamate Decarboxylase/analysis , HLA-DQ beta-Chains , Humans , Isoenzymes/analysis , Male , Sweden/epidemiology
3.
Scand J Clin Lab Invest ; 65(7): 585-94, 2005.
Article in English | MEDLINE | ID: mdl-16271990

ABSTRACT

OBJECTIVE: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. MATERIAL AND METHODS: Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. RESULTS: Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). CONCLUSIONS: Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Hyperinsulinism/complications , Hyperinsulinism/diagnosis , Adolescent , Adult , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Hyperinsulinism/blood , Insulin/blood , Male
4.
BJU Int ; 92 Suppl 2: 39-43, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14983953

ABSTRACT

OBJECTIVE: To report the initial results from Sweden of a large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven. METHODS: From the population registry men aged 50-66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus f/tPSA assay (Perkin-Elmer, Turku, Finland). Men with a tPSA of < 3.0 ng/mL were not further investigated, while those with a tPSA of > or = 3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies. RESULTS: Of those invited, 60% accepted PSA testing and 11.3% had a tPSA of > or = 3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3-4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2-4, 71% 5-6, 19% 7 and 2% Gleason score 8-10. A threshold tPSA of > or = 4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of > or = 3.0 ng/mL combined with a f/tPSA threshold of < or = 18%. CONCLUSIONS: PSA screening detects early-stage low-grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of < 4 ng/mL.


Subject(s)
Mass Screening/methods , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Aged , Biopsy/methods , Humans , Male , Middle Aged , Prostate/pathology , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Sensitivity and Specificity , Sweden
5.
Pediatr Diabetes ; 3(3): 149-54, 2002 Sep.
Article in English | MEDLINE | ID: mdl-15016155

ABSTRACT

BACKGROUND: Insulin autoantibodies (IAA), antibodies against endogenous insulin, may be detected in type 1 diabetic children before the start of insulin treatment. OBJECTIVE: To relate IAA to islet antibodies (i.e., islet cell antibodies [ICA], and antibodies against two ICA-related islet antigens, glutamic acid decarboxylase 65 [GADA] and protein tyrosine phosphatase IA-2 [IA-2 A]) at diagnosis, and to endogenous beta-cell function at follow-up after diagnosis in diabetic children. SUBJECTS: We investigated 74 children, aged 1-15 yr, at the diagnosis of diabetes and 1-10 yr later. Insulin treatment may induce antibody development against exogenous insulin. Patients with insulin treatment > or = 1 wk (n = 5) were therefore excluded from the final analysis. METHODS: Radioligand-binding assays based on human recombinant antigen were used to measure IAA, GADA, and IA-2 A. ICA were determined with indirect immunofluorescence. RESULTS: IAA were detected at a significantly lower frequency (43%; p < or = 0.001) than ICA (86%), GADA (72%), and IA-2 A (80%). In agreement, IAA measurements only marginally increased the frequency of positive autoimmune markers at diagnosis of diabetes (from 97 to 99% positive for at least one autoantibody). Preserved beta-cell function (detectable fasting p-C-peptide levels) was found in only nine patients, who were older (13 +/- 3 vs. 7 +/- 6 yr, p = 0.002) and had fewer of the antibodies (IAA, GADA, IA-2 A, ICA) in high titer (> median) compared with 60 patients with undetectable p-C-peptide levels. CONCLUSIONS: Insulin autoantibodies are of less clinical value compared with islet antibodies in the diagnosis of autoimmune type 1 diabetes in children.

6.
Lakartidningen ; 98(41): 4444-8, 4450-2, 2001 Oct 10.
Article in Swedish | MEDLINE | ID: mdl-11699251

ABSTRACT

The heart is increasingly being recognised as a major endocrine organ involved in haemodynamic homeostasis. Natriuretic peptides, i.e. atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), affect renal, adrenal and central nervous system functions as well as vessel tonus and permeability thus causing decreased preload and afterload. Natriuretic peptides, BNP in particular, are independent risk factors for morbidity and mortality. They also have high negative predictive values for cardiac insufficiency indicating high diagnostic sensitivity for heart failure in outpatient practice. Monitoring of therapy for heart failure may be improved if BNP measurement is used in conjunction with clinical assessment. However, several problems remain to be solved, such as optimal decision limits in relation to sex and age for the assessment of heart failure.


Subject(s)
Atrial Natriuretic Factor/blood , Drug Monitoring/methods , Heart Failure/blood , Natriuretic Peptide, Brain/blood , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Biomarkers/blood , Heart Failure/diagnosis , Heart Failure/drug therapy , Humans , Natriuretic Peptide, Brain/genetics , Natriuretic Peptide, Brain/metabolism , Predictive Value of Tests , Prognosis
7.
J Clin Endocrinol Metab ; 86(7): 3032-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11443164

ABSTRACT

It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.


Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 1/immunology , Islets of Langerhans/immunology , Islets of Langerhans/physiopathology , Adult , Aged , C-Peptide/blood , Diabetes Mellitus, Type 1/physiopathology , Fasting , Female , Glucagon , Glucose Tolerance Test , Glutamate Decarboxylase/immunology , Glycated Hemoglobin/analysis , Humans , Kinetics , Male , Membrane Proteins/immunology , Middle Aged , Nerve Tissue Proteins/immunology , Prospective Studies , ROC Curve , Receptor-Like Protein Tyrosine Phosphatases, Class 8 , Sensitivity and Specificity
8.
Diabetes Res Clin Pract ; 51(1): 51-7, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11137182

ABSTRACT

In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes.


Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 1/epidemiology , Adolescent , Child , Diabetes Mellitus, Type 1/immunology , Female , Glutamate Decarboxylase/immunology , Humans , Islets of Langerhans/immunology , Male , Predictive Value of Tests , Prospective Studies , Registries , Risk Factors , Sweden/epidemiology
9.
Lakartidningen ; 97(37): 4001-5, 2000 Sep 13.
Article in Swedish | MEDLINE | ID: mdl-11036358

ABSTRACT

Measurement of gastrin in serum or plasma in patients with gastrinoma may be complicated by the presence of circulating biosynthetic intermediates which may not be detected by commonly available immunoassays. In contrast, the "processing-independent analysis" of gastrins developed by professor Jens Rehfeld et al in Copenhagen detects gastrin forms irrespective of their size. The authors review gastrinoma pathophysiology, the biochemistry of gastrin and other biomarkers of gastrinoma, the differential diagnosis of hypergastrinemia as well as other methods currently employed in the workup of gastrinoma patients, and illustrate with a clinical case.


Subject(s)
Gastrinoma/diagnosis , Multiple Endocrine Neoplasia Type 1/diagnosis , Prostatic Neoplasms/diagnosis , Quality Assurance, Health Care , Biomarkers, Tumor/analysis , Diagnosis, Differential , Gastrinoma/diagnostic imaging , Gastrinoma/metabolism , Gastrinoma/surgery , Gastrins/biosynthesis , Gastrins/metabolism , Humans , International Cooperation , Male , Middle Aged , Multiple Endocrine Neoplasia Type 1/metabolism , Practice Guidelines as Topic , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/surgery , Radionuclide Imaging , Scandinavian and Nordic Countries
11.
Acta Paediatr ; 89(1): 46-51, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10677057

ABSTRACT

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency.


Subject(s)
Autoantibodies/analysis , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/immunology , Glutamate Decarboxylase/immunology , Islets of Langerhans/immunology , Protein Tyrosine Phosphatases/immunology , Adolescent , Autoimmunity , Biomarkers , Child , Child, Preschool , Data Interpretation, Statistical , Fluorescent Antibody Technique , Follow-Up Studies , Humans , Infant , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Radioimmunoassay , Sensitivity and Specificity , Time Factors
12.
Diabetes Care ; 22(12): 1944-9, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10587823

ABSTRACT

OBJECTIVE: To determine the impact of improved glycemic control on the development and progression of retinopathy after the institution of insulin therapy in patients with type 2 diabetes and to assess the relation to IGF-1 and hemostatic variables. RESEARCH DESIGN AND METHODS: In a prospective observational study, 45 type 2 diabetic patients were examined at baseline and 1, 3, 6, 12, and 24 months after change to insulin therapy. Retinopathy was graded on fundus photographs using the Wisconsin scale; HbA1c, IGF-1, and hemostatic variables were measured. RESULTS: During the observation period of 2 years, 23 patients progressed in the retinopathy scale; 8 progressed > or = 3 levels. After 2 years of insulin treatment, HbA1c and IGF-1 were significantly lower than at baseline, whereas the hemostatic variables had not changed significantly. Progression of retinopathy > or = 3 levels was related to the degree of HbA1c reduction, the duration of diabetes, a higher prothrombin fragment 1 + 2 levels (F1 + 2), but not to other hemostatic variables or IGF-1. The relative risk for progression > or = 3 levels was 2.6 when HbA1c had been reduced > or = 3 percent units (95% CI 1.1-6.1). CONCLUSIONS: The magnitude of improvement of HbA1c by the institution of insulin treatment over a 2-year period may be associated with progression of retinopathy in patients with type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Diabetic Retinopathy/physiopathology , Hemostasis , Insulin-Like Growth Factor I/analysis , Diabetes Mellitus, Type 2/drug therapy , Diabetic Retinopathy/drug therapy , Disease Progression , Female , Fluorescein Angiography , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Middle Aged , Prospective Studies
14.
Lakartidningen ; 96(38): 4028-31, 1999 Sep 22.
Article in Swedish | MEDLINE | ID: mdl-10526463

ABSTRACT

Recent developments in medical care and research involve the increased use of immunochemical assays for hormones, tumour markers, vitamins and drugs. External quality assurance programmes using pooled human sera usually fail to detect analytical interference due to substances (e.g. anti-immunoglobulin or anti-ligand antibodies) present in individual serum specimens. The article reports on experience gained during a three-year period when specimens from individual patients attending a thyroid unit were distributed to hospital laboratories in Sweden for analysis. Specimen selection criteria were based on contradictory findings at the initial clinical or laboratory evaluation. The programme has given rise to the formation of a network of the laboratories involved, under the co-ordination of EQUALIS (External quality assurance in laboratory medicine in Sweden).


Subject(s)
Chemistry, Clinical/standards , Laboratories, Hospital/standards , Quality Assurance, Health Care , Antibodies/analysis , Biomarkers/analysis , False Positive Reactions , Female , Humans , Male , Thyroid Diseases/blood , Thyroid Diseases/diagnosis , Thyroid Function Tests/standards , Thyroid Hormones/analysis , Thyroid Hormones/immunology
15.
Digestion ; 60(5): 440-8, 1999.
Article in English | MEDLINE | ID: mdl-10473968

ABSTRACT

Gastric carcinoid disease may have a highly varying clinical course depending on the malignancy of the tumour. Many biochemical markers, such as peptides and biogenic amines, have been found in carcinoid tumour tissue but none has been reported to be useful as a predictor of the degree of malignancy of the carcinoid. beta-Microseminoprotein is a small disulphide-rich protein with unknown function present in the secretions on most mucosal surfaces in the body, including the stomach where it is also found in some endocrine cells. We have studied beta-microseminoprotein by immunohistochemistry in the tumour tissue of 29 patients with gastric carcinoid disease. Beta-Microseminoprotein was present in the tumour tissue in 62% of the patients and its presence was correlated to tumour diameter and tissue invasion depth. The presence of beta-microseminoprotein in tumour tissue was corroborated by in situ hybridisation. All 4 patients with the solitary sporadic type of tumour and all 6 patients with metastasis had positive immunostaining of the tumour tissue. The serum concentration of beta-microseminoprotein, measured by radioimmunoassay, was increased in all but 2 of 13 patients with gastric carcinoid disease. To a large part the increase was due to the concomitant atrophic corpus gastritis. We conclude that beta-microseminoprotein in tumour tissue is a marker of tumour progression and that measurement of beta-microseminoprotein in serum is less informative than immunohistochemistry.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoid Tumor/metabolism , Gastritis, Atrophic/metabolism , Peptides/metabolism , Prostatic Secretory Proteins , Stomach Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Anemia, Pernicious/complications , Carcinoid Tumor/pathology , Enterochromaffin Cells/metabolism , Enterochromaffin Cells/pathology , Female , Gastrins/blood , Gastritis, Atrophic/pathology , Humans , Hyperplasia , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Peptides/blood , Retrospective Studies , Statistics, Nonparametric , Stomach Neoplasms/pathology
16.
Diabet Med ; 16(1): 49-54, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10229293

ABSTRACT

AIMS: To clarify whether parasympathetic neuropathy in Type 2 diabetic patients is associated with features of the insulin resistance syndrome. METHODS: Blood pressures, glycaemic control (HbA1c), plasma lipids, residual beta-cell function (fasting plasma C-peptide), autonomic nerve function, urinary albumin excretion and glomerular filtration rate (Cr-EDTA clearance) were evaluated in 82 Type 2 diabetic patients (age 63+/-years) 5 years after diagnosis of diabetes. RESULTS: Parasympathetic neuropathy (an abnormal age corrected E/I ratio) was found in 24/82 (29%) patients. After adjustment for body mass index (BMI), patients with parasympathetic neuropathy had elevated fasting plasma C-peptide (P < 0.001) and triglyceride (Tg) (P < 0.05) levels compared with patients without parasympathetic neuropathy. In addition, the age corrected E/I ratio correlated inversely with Tg (r=-0.31; P<0.01) and fasting plasma C-peptide (r=-0.32; P < 0.01) in the Type 2 diabetic patients. CONCLUSION: Autonomic neuropathy 5 years after diagnosis of Type 2 diabetes is associated with an unfavourable metabolic risk profile.


Subject(s)
Autonomic Nervous System Diseases/complications , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/complications , Hyperinsulinism/complications , Hypertriglyceridemia/complications , Body Mass Index , Humans , Insulin Resistance , Middle Aged , Parasympathetic Nervous System , Prospective Studies , Risk Factors , Syndrome
17.
Scand J Gastroenterol ; 33(9): 911-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9759944

ABSTRACT

BACKGROUND: Beta-microseminoprotein is a 94-kDa protein present on most mucosal surfaces in the body. It is produced in mucin cells but is also found in a particular type of cells (E-cells) in the gastric antral mucosa. Most of these cells also contain gastrin. In atrophic corpus gastritis the gastrin-producing cells become hyperplastic, and the patients have hypergastrinemia. We wanted to ascertain whether there is a similar effect on the E-cells and on the concentration of beta-microseminoprotein in serum. METHODS: Antral biopsy specimens from 10 patients with atrophic corpus gastritis and 10 controls were stained immunohistochemically for beta-microseminoprotein and gastrin. beta-Microseminoprotein and gastrin were measured by radioimmunoassay in serum from 15 women with atrophic corpus gastritis and 31 healthy female blood donors. RESULTS: There was a 3.5-fold increase of the number of E-cells (which also were hypertrophic) and a 2.1 times higher serum concentration of beta-microseminoprotein in the patients with atrophic corpus gastritis than in the control subjects. Gastrin was seen in 28% of the E-cells in patients with atrophic corpus gastritis, compared with 87% in normal antral mucosa. There was no correlation between the serum concentrations of beta-microseminoprotein and gastrin. CONCLUSIONS: In atrophic corpus gastritis antrum E-cells undergo hyperplasia and hypertrophy, and the proportion of E-cells containing gastrin decreases. Increased amounts of beta-microseminoprotein are secreted to the blood but uncorrelated with gastrin.


Subject(s)
Gastritis, Atrophic/metabolism , Gastritis, Atrophic/pathology , Peptides/analysis , Prostatic Secretory Proteins , Pyloric Antrum/pathology , Adult , Aged , Female , Gastric Mucosa/chemistry , Gastrins/analysis , Humans , Hyperplasia , Immunohistochemistry , Male , Middle Aged , Peptides/blood , Pyloric Antrum/chemistry , Radioimmunoassay
18.
Diabetes Care ; 21(2): 250-5, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9539991

ABSTRACT

OBJECTIVE: To evaluate the frequency of autoimmune markers (islet cell antibodies (ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in newly diagnosed people with diabetes aged 40-75 years. RESEARCH DESIGN AND METHODS: Two hundred fifty-nine consecutive patients (aged 40-75 years) with newly suspected diabetes diagnosed during a 2-year period were studied. The diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender, BMI, HbA1c, fasting C-peptide, ICA, and GADA were evaluated. The frequency of obesity was estimated using two different sets of criteria: 1) National Diabetes Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference population. RESULTS: The annual incidence of diabetes was 106 per 100,000 people. The incidence of diabetes in those patients who were 40-54 years old was significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+; 10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203 diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in NIDDM was high but varied with its definition; the frequency of obesity was highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of 109 [41%] for men). CONCLUSIONS: A striking male preponderance was found among incident cases of diabetes in people aged 40-54 years. Autoimmune markers were detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a conservative estimation, as many as 10 of 100,000 middle-aged and elderly subjects developed IDDM. The frequency of obesity in NIDDM was high but this was also the case in the reference population.


Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Obesity , Adult , Aged , Body Mass Index , C-Peptide/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Fasting , Female , Glutamate Decarboxylase/immunology , Glycated Hemoglobin/metabolism , Humans , Islets of Langerhans/cytology , Islets of Langerhans/immunology , Male , Middle Aged , Sex Factors , Sweden/epidemiology
19.
J Intern Med ; 244(2): 149-54, 1998 Aug.
Article in English | MEDLINE | ID: mdl-10095801

ABSTRACT

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetic Retinopathy/blood , Diabetic Retinopathy/epidemiology , Glycated Hemoglobin/metabolism , Adolescent , Adult , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/diagnosis , Diabetic Retinopathy/diagnosis , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Severity of Illness Index , Sweden/epidemiology , Time Factors
20.
Proteins ; 29(4): 478-91, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9408945

ABSTRACT

Protein S (PS) and growth arrest specific factor 6 (GAS6) are vitamin K-dependent proteins with similar structures. They are mosaic proteins possessing a carboxyl-terminal region presenting sequence similarity with plasma sex hormone binding globulin (plasma SHBG), although apparently not involved in steroid binding. The SHBG-like modules have sequence similarity with the G repeats of the chain A of laminin. Laminin G repeats have been reported to contain mainly beta-strands (about 40-50%) but no or little alpha structure by circular dichroism (CD) spectroscopy. Secondary structure predictions carried out in the present work unexpectedly showed a 20 to 27% helices content in the SHBG region of PS/GAS6 (about 100 residues), while plasma SHBG and laminin G repeats had around 10% helices. CD measurements for human PS indicated also that its SHBG region had about 100 residues in alpha-helical structure. These data suggest that the SHBG region of PS/GAS6 on the one hand, and the laminin G repeats and possibly plasma SHBG on the other hand, could present important structural differences. Previously reported polymorphisms and point mutations leading to PS deficiency and thrombophilia have been analyzed with our structural predictions. We found a good agreement between these structural predictions, CD measurements, experimental and clinical data. This information allows us to gain insights into the three-dimensional structure of PS that will be helpful for the design of new experiments and future clinical investigations.


Subject(s)
Mutation , Protein S/chemistry , Protein S/genetics , Protein Structure, Secondary , Sex Hormone-Binding Globulin/chemistry , Sex Hormone-Binding Globulin/genetics , Amino Acid Sequence , Animals , Cattle , Cell Membrane/metabolism , Circular Dichroism , Complement C4b/metabolism , DNA Mutational Analysis , Haplorhini , Histocompatibility Antigens/metabolism , Humans , Leucine/genetics , Mice , Molecular Sequence Data , Proline/genetics , Protein S Deficiency/genetics , Rabbits , Rats , Receptors, Steroid/metabolism , Sequence Homology, Amino Acid , Solvents , Swine
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