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T Tuomi

Publications and source records attributed to T Tuomi.

At least 19 recordsLinked to original sources
PubMed2006

Common variants in HNF-1 alpha and risk of type 2 diabetes.

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor 1-alpha gene (HNF-1alpha, now known as the transcription factor 1 gene [TCF1]) cause the most common monogenic form of diabetes, MODY3, but it is not known if common variants in HNF-1a are associated with decreased transcriptional activity or phenotypes related to type 2 diabetes, or whether they predict future type 2 diabetes. SUBJECTS AND METHODS: We studied the effect of four common polymorphisms (rs1920792, I27L, A98V and S487N) in and upstream of the HNF-1alpha gene on transcriptional activity in vitro, and their possible association with type 2 diabetes and insulin secretion in vivo. RESULTS: Certain combinations of the I27L and A98V polymorphisms in the HNF-1alpha gene showed decreased transcriptional activity on the target promoters glucose transporter 2 (now known as solute carrier family 2 [facilitated glucose transporter], member 2) and albumin in both HeLa and INS-1 cells. In vivo, these polymorphisms were associated with a modest but significant impairment in insulin secretion in response to oral glucose. Insulin secretion deteriorated over time in individuals carrying the V allele of the A98V polymorphism (n = 2,293; p = 0.003). In a new case-control (n = 1,511 and n = 2,225 respectively) data set, the I27L polymorphism was associated with increased risk of type 2 diabetes, odds ratio (OR) = 1.5 (p = 0.002; multiple logistic regression), particularly in elderly (age > 60 years) and overweight (BMI > 25 kg/m(2)) patients (OR = 2.3, p = 0.002). CONCLUSIONS/INTERPRETATION: This study provides in vitro and in vivo evidence that common variants in the MODY3 gene, HNF-1alpha, influence transcriptional activity and insulin secretion in vivo. These variants are associated with a modestly increased risk of late-onset type 2 diabetes in subsets of elderly overweight individuals.

Adult↗
PubMed2006

Occupational asthma caused by stainless steel welding fumes: a clinical study.

The aim of the present study was to describe the cases of occupational asthma (OA) due to stainless steel welding fumes diagnosed at the Finnish Institute of Occupational Health during the period 1994-2003. OA was diagnosed according to patient history, lung function examinations and welding challenge tests with measurements of the forced expiratory volume in one second (FEV(1)) and peak expiratory flow (PEF) values. The present series comprised 34 patients, all male, with a mean age of 44.7 yrs (range 22-57), mainly working as welders. The mean duration of exposure was 22.4 yrs, and the mean duration of exposure before the onset of respiratory symptoms was 18 yrs. Dyspnoea was the most frequently reported work-related respiratory symptom. During the inhalation challenge tests, the mode of the asthmatic FEV(1)/PEF reaction was delayed in 16 (47%) patients, immediate in nine (26%) patients and dual (both immediate and delayed) in nine (26%) patients. In the follow-up assessment 6 months later, only six patients were considered able to continue performing welding tasks, whereas occupational injury pension was recommended for seven, and measures of vocational rehabilitation for 14 patients. In most cases, after the diagnosis of occupational asthma, the continuation of welding work was not possible.

Adult↗
PubMed2005

A male-specific quantitative trait locus on 1p21 controlling human stature.

BACKGROUND: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. OBJECTIVE: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. METHODS: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. RESULTS: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. CONCLUSIONS: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sex-specific locus affecting human stature.

Adult↗
PubMed2005

Genetic testing for maturity onset diabetes of the young: uptake, attitudes and comparison with hereditary non-polyposis colorectal cancer.

AIMS/HYPOTHESIS: Mutations in hepatic nuclear factor 1alpha cause a monogenic form of diabetes, maturity onset diabetes of the young type 3 (MODY3). Our aim was (1) to assess the uptake of genetic testing for MODY3 and to determine factors affecting it, and (2) to compare attitudes to predictive genetic testing between families with MODY3 and a previously studied group at risk of hereditary non-polyposis colorectal cancer (HNPCC). METHODS: Adult members of two extended MODY3 pedigrees, either with diabetes or a 50% risk of having inherited the mutation (n=144, age 18-60 years), were invited to an educational counselling session followed by a possibility to obtain the gene test result. Data were collected through questionnaires before counselling and 1 month after the test disclosure. RESULTS: Eighty-nine out of 144 (62%) participated in counselling, and all but one wanted the test result disclosed. No significant sociodemographic differences were observed between the participants and non-participants. The counselling uptake was similar among diabetic and non-diabetic subjects. Uncertainty about the future and the risk for the children were the most common reasons to take the gene test. At follow-up, most subjects in both MODY3 (100%) and HNPCC (99%) families were satisfied with their decision to take the test and trusted the result. The majority of both diabetic and non-diabetic subjects considered that the MODY3 gene test should be offered either in childhood (50 and 37%) or as a teenager (30 and 37%). CONCLUSIONS: Genetic testing for MODY3 was well accepted among both diabetic and non-diabetic participants. The subjects found the gene test reliable and they were satisfied with their decision regarding the predictive test.

Adult↗
PubMed2005

Occupational asthma due to manual metal-arc welding of special stainless steels.

Occupational asthma (OA) can be induced by fumes of manual metal-arc welding on stainless steel. In recent years, the use of special stainless steels (SSS) with high chromium content has increased. This study presents two cases of OA caused by manual metal-arc welding on SSS. In both cases, the diagnosis of OA was based on respiratory symptoms, occupational exposure and positive findings in the specific challenge tests. In the first case, a 46-yr-old welder had experienced severe dyspnoea while welding SSS (SMO steel), but not in other situations. Challenge tests with both mild steel and stainless steel using a common electrode were negative. Welding SSS with a special electrode caused a delayed 37% drop in forced expiratory volume in one second (FEV1). In the second case, a 34-yr-old male had started to experience dyspnoea during the past few years, while welding especially SSS (Duplex steel). The workplace peak expiratory flow monitoring was suggestive of OA. Challenge tests with both mild steel and stainless steel using a common electrode did not cause bronchial obstruction. Welding SSS with a special electrode caused a delayed 31% drop in FEV1. In conclusion, exposure to manual metal-arc welding fumes of special stainless steel should be considered as a new cause of occupational asthma.

Adult↗
PubMed2004

Reducing the risks of children living near the site of a former lead smeltery.

The sources of lead exposure, soil, household dust, diet and ambient air near a former lead smeltery were studied. The blood lead level of small children was also determined. The aim of the study was to define, based primarily on blood lead measurements, whether children living in the contaminated area may be at risk. Within 500 m from the site of the smeltery, there were several areas where the Finnish limit value for soil Pb, i.e. 300 mg/kg, was exceeded. In the recently built areas, the surface soil has been replaced and soil remediation has taken place in schoolyards and the playgrounds of children's day-care centres. Lead content in household dust was clearly elevated in the contaminated areas. In approximately 20 years, after the smeltery was closed in 1984, the lead concentrations of the fruits and berries in local gardens have decreased to one-tenth. In some samples, the limit values are still exceeded. The lead concentration in ambient air is now 50 times lower than in the 1970s. The blood lead level of the children living in the area is slightly but statistically significantly higher than that of the children in the control areas. The critical blood lead level, i.e. 10 microg/100 ml, was not exceeded in any of the children examined. The average and maximum lead concentrations of 63 analysed blood samples were 2.2 and 5 microg/100 ml, respectively. In contrast, the average and maximum blood lead levels of school children in 1981 were 6.7 and 13.0 microg/100 ml, respectively. The risk reduction measures undertaken during the past 20 years are described.

Child↗
PubMed2004

The genetic variant of lactase persistence C (-13910) T as a risk factor for type I and II diabetes in the Finnish population.

OBJECTIVE: Lactase persistence (LP), the ability to maintain a high lactase activity throughout life, has been suggested to be a possible risk factor for diabetes. Recently, a single nucleotide polymorphism C (-13910) T, residing 14 kb from the 5' end of the lactase (LCT) gene was shown to be associated with LP. Here we have studied the relationship between C (13910) T polymorphism and diabetes in the Finnish population. PATIENTS AND DESIGN: In all, 1455 patients with type I and 615 with type II diabetes and 446 nondiabetic controls in the Finnish population were genotyped for the C (-13910) T polymorphism by PCR minisequencing. RESULTS: No differences were detected in the LP genotype frequencies (CT&TT) between diabetic and nondiabetic subjects. CONCLUSIONS: We conclude that the C (-13910) T polymorphism associated with lifelong LP is not a risk factor for type I or type II diabetes in the Finnish population.

Adult↗
PubMed2003

Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband.

To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first-degree relatives, we studied 2,100 first-degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH-). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion [30-min incremental insulin/glucose (I/G 30)] and insulin sensitivity [homeostasis model assessment (HOMA) of insulin resistance (IR)]. A subset participated in a euglycemic clamp (n = 75) and an intravenous glucose tolerance test (n = 300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first-degree relatives of diabetic probands with high and low waist-to-hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant, as seen from a higher HOMA-IR index (P = 0.006) and a lower rate of insulin-stimulated glucose uptake (P = 0.001) and had more features of the metabolic syndrome (P = 0.02, P = 0.0002) compared with FH- subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs. FH- subjects (P = 0.04). Relatives of diabetic probands with a high WHR had reduced insulin-mediated glucose uptake compared with relatives of probands with a low WHR (P = 0.04). Relatives of diabetic patients with age at onset <44 yr had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yr (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the nondiabetic first-degree relative.

Adolescent↗
PubMed2003

Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin-independent mechanisms.

BACKGROUND: Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established. OBJECTIVE: To examine the mechanism by which exposure to spores of satratoxin producing and non-producing S. chartarum strains induce inflammatory responses in murine lungs. METHODS: BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin-producing and a non-producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real-time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole-body plethysmography and serum antibody levels by ELISA. RESULTS: A dose-dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin-producing and the non-producing strains. Infiltration of inflammatory cells was associated with an induction of pro-inflammatory cytokine (IL-1beta, IL-6 and TNF-alpha) and chemokine (CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL2/MCP-1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin-producing strain compared with the non-producing strain. MCh-induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure. CONCLUSION: These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro-inflammatory cytokines and leucocyte-attracting chemokines. The data also imply that S. chartarum-derived components, other than satratoxins, are mediating the development of this inflammatory response.

Administration, Intranasal↗
PubMed2002

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes.

AIMS/HYPOTHESIS: Autoantibodies against CD 38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i). overlaps with anti-GAD autoimmunity, (ii). identifies an insulin-deficient phenotype, (iii). is under the influence of genetic factors. METHODS: We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). RESULTS: CD 38-autoantibodies were found in 8.4% of Type II diabetic patients ( p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD 38 ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti- CD 38 positive had DQB1*02 compared with 38% of anti-CD 38 negative ( p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired ( p=0.02) only in association with anti-GAD positivity (3.2+/-3.1 U/mol, mean +/- SD) but not in anti- CD 38 positive patients (5.6+/-2.9) as compared with patients free of autoimmunity (4.5+/-4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti- CD 38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD 38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. CONCLUSION: Anti-CD 38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.

ADP-ribosyl Cyclase↗
PubMed2002

Rare variants identified in the HNF- 4 alpha beta-cell-specific promoter and alternative exon 1 lack biological significance in maturity onset diabetes of the young and young onset Type II diabetes.

AIMS/HYPOTHESIS: The recently identified alternative promoter (P2) of HNF-4 alpha is the major HNF-4 alpha transcription start site in pancreatic beta cells. The significance of the P2 promoter was shown by the identification of a mutation in the IPF-1 binding site of the alternative promoter which cosegregated with diabetes in a large MODY family. The role of the P2 promoter and the associated alternative exon 1 in both MODY and polygenic Type II (non-insulin-dependent) diabetes mellitus is not known. Linkage to this region in studies of Type II diabetes makes the P2 region a strong candidate for a role in Type II diabetes susceptibility. METHODS: To assess the role of the P2 region we screened MODY, young-onset Type II diabetic subjects, and probands from Type II diabetes families linked to chromosome 20 for variants of the P2 promoter and associated exon of HNF-4 alpha. RESULTS: Two variants were found that were not present in the control subjects. The -79 C/T substitution was present in a MODY family but did not perfectly cosegregate with diabetes. A -276 G/T substitution was identified in two UK young-onset diabetes probands but did not co-segregate with diabetes. Reporter gene studies did not indicate changes in transcriptional activity caused by either the -79 C/T or -276 G/T single nucleotide substitutions. CONCLUSION/INTERPRETATION: We found no evidence to suggest that variation in the P2 proximal promoter region and associated alternative exon 1 of HNF-4 alpha contribute to young onset Type II diabetes susceptibility in Northern Europeans.

Adolescent↗
PubMed2002

Synchrotron X-ray topography of electronic materials.

Large-area transmission, transmission section, large-area back-reflection, back-reflection section and grazing-incidence topography are the geometries used when recording high-resolution X-ray diffraction images with synchrotron radiation from a bending magnet, a wiggler or an undulator of an electron or a positron storage ring. Defect contrast can be kinematical, dynamical or orientational even in the topographs recorded on the same film at the same time. In this review article limited to static topography experiments, examples of defect studies on electronic materials cover the range from voids and precipitates in almost perfect float-zone and Czochralski silicon, dislocations in gallium arsenide grown by the liquid-encapsulated Czochralski technique, the vapour-pressure controlled Czochralski technique and the vertical-gradient freeze technique, stacking faults and micropipes in silicon carbide to misfit dislocations in epitaxic heterostructures. It is shown how synchrotron X-ray topographs of epitaxic laterally overgrown gallium arsenide layer structures are successfully explained by orientational contrast.

Journal Article↗
PubMed2002

Genomewide search for type 2 diabetes mellitus susceptibility loci in Finnish families: the Botnia study.

Type 2 diabetes mellitus is a heterogeneous inherited disorder characterized by chronic hyperglycemia resulting from pancreatic beta-cell dysfunction and insulin resistance. Although the pathogenic mechanisms are not fully understood, manifestation of the disease most likely requires interaction between both environmental and genetic factors. In the search for such susceptibility genes, we have performed a genomewide scan in 58 multiplex families (comprising 440 individuals, 229 of whom were affected) from the Botnia region in Finland. Initially, linkage between chromosome 12q24 and impaired insulin secretion had been reported, by Mahtani et al., in a subsample of 26 families. In the present study, we extend the initial genomewide scan to include 32 additional families, update the affectation status, and fine map regions of interest, and we try to replicate the initial stratification analysis. In our analysis of all 58 families, we identified suggestive linkage to one region, chromosome 9p13-q21 (nonparametric linkage [NPL] score 3.9; P<.0002). Regions with nominal P values <.05 include chromosomes 2p11 (NPL score 2.0 [P<.03]), 3p24-p22 (NPL score 2.2 [P<.02]), 4q32-q33 (NPL score 2.5 [P<.01]), 12q24 (NPL score 2.1 [P<.03]), 16p12-11 (NPL score 1.7 [P<.05]), and 17p12-p11 (NPL score 1.9 [P<.03]). When chromosome 12q24 was analyzed in only the 32 additional families, a nominal P value <.04 was observed. Together with data from other published genomewide scans, these findings lend support to the hypothesis that regions on chromosome 9p13-q21 and 12q24 may harbor susceptibility genes for type 2 diabetes.

Aged↗
PubMed2002

The genetic abnormality in the beta cell determines the response to an oral glucose load.

AIMS/HYPOTHESIS: We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT). METHODS: We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor -1 alpha ( HNF-1alpha) gene mutations. RESULTS: BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2 % glucokinase subjects and 46 % HNF-1 alpha subjects ( p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1 alpha subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38 % vs 22 %, glucokinase vs HNF-1 alpha) or 2-h values (19 % vs 44 %) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects ( r = -0.047, p = 0.65) but were strongly correlated in HNF-1 alpha subjects ( r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT. CONCLUSION/INTERPRETATION: The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.

Adult↗
PubMed2002

Glutamic acid decarboxylase antibody positivity is associated with an impaired insulin response to glucose and arginine in nondiabetic patients with autoimmune thyroiditis.

To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical beta-cell damage and impaired insulin secretion, we screened 441 nondiabetic patients with autoimmune thyroiditis (AT) for GADab, and 15 (3.4%) were found positive. Antibodies to IA-2 were found in two GADab+ and one GADab- patients. We matched 11 GADab+ and 13 GADab- AT patients who were euthyroid on thyroxin supplementation, and 13 control subjects for sex, age, and body mass index and measured insulin, C-peptide, and glucagon response to glucose and arginine at three blood glucose concentrations (fasting, 14 mmol/liter, >25 mmol/liter). In the fasting state, all groups had similar blood glucose concentration and HbA1c level, but the serum insulin concentration was higher in the AT patients compared with the control subjects (P < 0.04). The acute insulin response to arginine was lower in GADab+ than in GADab- thyroiditis subjects at glucose concentration of 14 and >25 mmol/liter (AIR(14): 76.8 +/- 52.0 vs. 158.2 +/- 118.2 mU/liter, P = 0.040; AIR(>25): 84.3 +/- 64.4 vs. 167.9 +/- 101.5 mU/liter, P = 0.035). In conclusion, GADab were associated with a decreased insulin secretion capacity in nondiabetic subjects with thyroiditis, which suggests that GADab positivity could be a marker of subclinical insulitis.

Adult↗
PubMed2001

The metabolic syndrome influences the risk of chronic complications in patients with type II diabetes.

AIMS/HYPOTHESIS: We examined features of the metabolic syndrome to see if they modified the risk of chronic diabetic complications in patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: A total of 85 randomly selected patients with the metabolic syndrome (WHO definition) were compared with 85 Type II diabetic patients matched for age, sex, duration of diabetes, glycaemic control and without the syndrome to assess the microvascular and macrovascular complications. RESULTS: The patients with the metabolic syndrome had a higher prevalence of cardiovascular disease (52 vs 21%, p < 0.001), microalbuminuria or macroalbuminuria (23 vs 7%, p = 0.003) and distal neuropathy (16 vs 6%, p = 0.048) than patients without the syndrome. The patients with the metabolic syndrome had smaller LDL particle size (25.4+/-1.4 vs 26.4+/-1.1 nm; p < 0.001), which correlated with the ratio of serum triglycerides to HDL cholesterol (r = -0.64, p < 0.001). In a multiple logistic regression analysis the metabolic syndrome was associated with coronary heart disease (RR 3.84, p < 0.001) and microalbuminuria (RR 3.99, p = 0.01). Small LDL particle size was independently associated with neuropathy (RR 0.58; p = 0.04), whereas a high HbA1c was related to neuropathy (RR 1.69, p = 0.04), retinopathy (RR 1.53, p = 0.002) and microalbuminuria (RR 1.54, p = 0.01). CONCLUSION/INTERPRETATION: Although chronic hyperglycaemia is the main predictor of microvascular complications in patients with Type II diabetes, this risk is modified by some of the components of the metabolic syndrome.

Aged↗
PubMed2001

Classifying diabetes according to the new WHO clinical stages.

AIMS/HYPOTHESIS: To test the usefulness of the new WHO criteria for clinical staging of diabetes in the characterization of 1977 diabetic patients. METHODS: The following clinical stages were used: patients on diet and/or oral antidiabetic agents 2 years after diagnosis were considered as non-insulin requiring (NIR; n = 711) and patients who required insulin therapy after 1 year as insulin requiring for control (IRC; n = 543). Patients who because of deteriorating hyperglycemia within 1 year required insulin therapy were considered as insulin requiring for survival (IRS; n = 743). RESULTS: The NIR patients had the highest age at onset (52 +/- 12 years; mean +/- SD), BMI (29.3 +/- 5.2 kg/m2) and C-peptide concentrations (median 0.98 nmol/l; interquartile range 0.72-1.31 nmol/l) but the lowest frequency of GAD antibodies (5.5%) compared to the IRC and IRS groups. The IRC group had a high age at onset (49 +/- 13 years), BMI (28.0 +/- 4.8 kg/m2), frequency of GAD antibodies (16.8%), intermediate C-peptide concentrations (0.56 nmol/l, interquartile range 0.28 +/- 0.94), and the highest prevalence of nephropathy (31.5%) and neuropathy (68.1%). The IRS group had the lowest age at onset (23 +/- 15 years), BMI (24.2 +/- 3.4 kg/m2), C-peptide concentrations (0.05 nmol/l, interquartile range below detection limit 0.01) and highest frequency of GAD antibodies (44.5%). Retinopathy was more common in IRS than in IRC patients (62.1 vs. 43.9%;p < 0.001). CONCLUSIONS: The new WHO criteria seem to discriminate three distinct subgroups and thus provide a useful tool for clinical staging. The IRC patients seem to have a more severe disease than the IRS patients, which has not been clearly acknowledged in the etiological classification. However, because of the cross-sectional nature of these data, they need to be confirmed in a prospective study with defined cut-off limits for when insulin should be initiated.

Aged↗